ChEMBL ID
stringlengths 13
13
| Journal
stringclasses 37
values | Source ID
stringclasses 12
values | Source Description
stringclasses 12
values | Title
stringlengths 3
383
| PubMed ID
stringlengths 3
8
| DOI
stringlengths 3
30
| Patent ID
stringclasses 9
values | Authors
stringlengths 3
1.01k
| Year
stringclasses 49
values | Volume
stringclasses 260
values | Issue
stringclasses 63
values | First Page
stringlengths 1
6
| Last Page
stringlengths 1
6
| Document Type
stringclasses 3
values | Abstract
stringlengths 3
3.44k
| Compounds
stringclasses 143
values | Targets
stringclasses 90
values | Activities
stringclasses 625
values | ChEMBL Release
stringclasses 34
values | ChEMBL Release Creation Date
stringclasses 34
values |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CHEMBL1143059 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis. | 17451962 | 10.1016/j.bmc.2007.04.011 | nan | El-Hamamsy MH, Smith AW, Thompson AS, Threadgill MD. | 2007 | 15 | 13 | 4552 | 4576 | PUBLICATION | Tuberculosis is an increasing threat, owing to the spread of AIDS and to the development of resistance of the causative organism, Mycobacterium tuberculosis, to the currently available drugs. Dihydrofolate reductase (DHFR) is an important enzyme of the folate cycle; inhibition of DHFR inhibits growth and causes cell death. The crystal structure of M. tuberculosis DHFR revealed a glycerol tightly bound close to the binding site for the substrate dihydrofolate; this glycerol-binding motif is absent from the human enzyme. A series of pyrimidine-2,4-diamines was designed with a two-carbon tether between a glycerol-mimicking triol and the 6-position of the heterocycle; these compounds also carried aryl substituents at the 5-position. These, their diastereoisomers, analogues lacking two hydroxy groups and analogues lacking the two-carbon spacing linker were synthesised by acylation of the anions derived from phenylacetonitriles with ethyl (4S,5R)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane-4-propanoate, ethyl (4S,5S)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane-4-propanoate, tetrahydrooxepin-2-one and 2,3-O-isopropylidene-d-erythronolactone, respectively, to give the corresponding alpha-acylphenylacetonitriles. Formation of the methyl enol ethers, condensation with guanidine and deprotection gave the pyrimidine-2,4-diamines. Preliminary assay of the abilities of these compounds to inhibit the growth of TB5 Saccharomyces cerevisiae carrying the DHFR genes from M. tuberculosis, human and yeast indicated that 5-phenyl-6-((3R,4S)-3,4,5-trihydroxypentyl)pyrimidine-2,4-diamine selectively inhibited M. tuberculosis DHFR and had little effect on the human or yeast enzymes. | 19 | 3 | 57 | CHEMBL_1 | 2009-09-03 |
CHEMBL1146288 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Thiosialoside clusters using carbosilane dendrimer core scaffolds as a new class of influenza neuraminidase inhibitors. | 17095224 | 10.1016/j.bmcl.2006.10.085 | nan | Sakamoto J, Koyama T, Miyamoto D, Yingsakmongkon S, Hidari KI, Jampangern W, Suzuki T, Suzuki Y, Esumi Y, Hatano K, Terunuma D, Matsuoka K. | 2007 | 17 | 3 | 717 | 721 | PUBLICATION | An efficient synthesis of a series of carbosilane dendrimers uniformly functionalized with alpha-thioglycoside of sialic acid was accomplished. The results of a preliminary study on biological responses against influenza virus sialidases using thiosialoside clusters showed that some of the glycodendrimers have inhibitory potencies against the sialidases. | 8 | 1 | 16 | CHEMBL_1 | 2009-09-03 |
CHEMBL2346649 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Novel pseudopeptides incorporating a benzodiazepine-based turn mimetic--targeting Mycobacterium tuberculosis ribonucleotide reductase. | 23395111 | 10.1016/j.bmc.2013.01.020 | nan | Nurbo J, Ericsson DJ, Rosenström U, Muthas D, Jansson AM, Lindeberg G, Unge T, Karlén A. | 2013 | 21 | 7 | 1992 | 2000 | PUBLICATION | Peptides mimicking the C-terminus of the small subunit (R2) of Mycobacterium tuberculosis ribonucleotide reductase (RNR) can compete for binding to the large subunit (R1) and thus inhibit RNR activity. Moreover, it has been suggested that the binding of the R2 C-terminus is very similar in M. tuberculosis and Salmonella typhimurium. Based on modeling studies of a crystal structure of the holocomplex of the S. typhimurium enzyme, a benzodiazepine-based turn mimetic was identified and a set of novel compounds incorporating the benzodiazepine scaffold was synthesized. The compounds were evaluated in a competitive fluorescence polarization assay and in an RNR activity assay. These studies revealed that the compounds incorporating the benzodiazepine scaffold have the ability to compete for the M. tuberculosis R2 binding site with low-micromolar affinity. | 7 | 2 | 11 | CHEMBL_17 | 2013-08-29 |
CHEMBL1139091 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Synthesis and antimycobacterial evaluation of benzofurobenzopyran analogues. | 17208445 | 10.1016/j.bmc.2006.12.009 | nan | Prado S, Janin YL, Saint-Joanis B, Brodin P, Michel S, Koch M, Cole ST, Tillequin F, Bost PE. | 2007 | 15 | 5 | 2177 | 2186 | PUBLICATION | We recently reported that 3,3-dimethyl-3H-benzofuro[3,2,f][1]-benzopyran and its hydrogenated analogue are selective in vitro inhibitors of mycobacterial growth. However, their lack of in vivo activity on a murine model of Mycobacterium tuberculosis infection due to their poor bioavailability led to a structure-activity relationship investigation. We wish to report here the preparation of some structural analogues along with their biological effect on the growth of Mycobacterium smegmatis, M. tuberculosis, as well as on VERO cells for the most active compound. | 31 | 2 | 62 | CHEMBL_1 | 2009-09-03 |
CHEMBL1142193 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Dual targeting of GyrB and ParE by a novel aminobenzimidazole class of antibacterial compounds. | 17116675 | 10.1128/aac.00596-06 | nan | Grossman TH, Bartels DJ, Mullin S, Gross CH, Parsons JD, Liao Y, Grillot AL, Stamos D, Olson ER, Charifson PS, Mani N. | 2007 | 51 | 2 | 657 | 666 | PUBLICATION | A structure-guided drug design approach was used to optimize a novel series of aminobenzimidazoles that inhibit the essential ATPase activities of bacterial DNA gyrase and topoisomerase IV and that show potent activities against a variety of bacterial pathogens. Two such compounds, VRT-125853 and VRT-752586, were characterized for their target specificities and preferences in bacteria. In metabolite incorporation assays, VRT-125853 inhibited both DNA and RNA synthesis but had little effect on protein synthesis. Both compounds inhibited the maintenance of negative supercoils in plasmid DNA in Escherichia coli at the MIC. Sequencing of DNA corresponding to the GyrB and ParE ATP-binding regions in VRT-125853- and VRT-752586-resistant mutants revealed that their primary target in Staphylococcus aureus and Haemophilus influenzae was GyrB, whereas in Streptococcus pneumoniae it was ParE. In Enterococcus faecalis, the primary target of VRT-125853 was ParE, whereas for VRT-752586 it was GyrB. DNA transformation experiments with H. influenzae and S. aureus proved that the mutations observed in gyrB resulted in decreased susceptibilities to both compounds. Novobiocin resistance-conferring mutations in S. aureus, H. influenzae, and S. pneumoniae were found in gyrB, and these mutants showed little or no cross-resistance to VRT-125853 or VRT-752586 and vice versa. Furthermore, gyrB and parE double mutations increased the MICs of VRT-125853 and VRT-752586 significantly, providing evidence of dual targeting. Spontaneous frequencies of resistance to VRT-752586 were below detectable levels (<5.2x10(-10)) for wild-type E. faecalis but were significantly elevated for strains containing single and double target-based mutations, demonstrating that dual targeting confers low levels of resistance emergence and the maintenance of susceptibility in vitro. | 5 | 5 | 130 | CHEMBL_1 | 2009-09-03 |
CHEMBL1140281 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma. | 15664822 | 10.1016/j.bmcl.2004.11.044 | nan | Zablocki J, Kalla R, Perry T, Palle V, Varkhedkar V, Xiao D, Piscopio A, Maa T, Gimbel A, Hao J, Chu N, Leung K, Zeng D. | 2005 | 15 | 3 | 609 | 612 | PUBLICATION | Adenosine has been suggested to play a role in asthma, possibly via activation of A(2B) adenosine receptors on mast cells and other pulmonary cells. We describe our initial efforts to discover a xanthine based selective A(2B) AdoR antagonist that resulted in the discovery of CVT-5440, a high affinity A(2B) AdoR antagonist with good selectivity (A(2B) AdoR K(i)=50 nM, selectivity A(1)>200: A(2A)>200: A(3)>167). | 33 | 4 | 101 | CHEMBL_1 | 2009-09-03 |
CHEMBL3351429 | Journal of medicinal chemistry. | 1 | Scientific Literature | Phenyl substituted 4-hydroxypyridazin-3(2H)-ones and 5-hydroxypyrimidin-4(3H)-ones: inhibitors of influenza A endonuclease. | 25225968 | 10.1021/jm500958x | nan | Sagong HY, Bauman JD, Patel D, Das K, Arnold E, LaVoie EJ. | 2014 | 57 | 19 | 8086 | 8098 | PUBLICATION | Seasonal and pandemic influenza outbreaks remain a major human health problem. Inhibition of the endonuclease activity of influenza RNA-dependent RNA polymerase is attractive for the development of new agents for the treatment of influenza infection. Our earlier studies identified a series of 5- and 6-phenyl substituted 3-hydroxypyridin-2(1H)-ones that were effective inhibitors of influenza endonuclease. These agents identified as bimetal chelating ligands binding to the active site of the enzyme. In the present study, several aza analogues of these phenyl substituted 3-hydroxypyridin-2(1H)-one compounds were synthesized and evaluated for their ability to inhibit the endonuclease activity. In contrast to the 4-aza analogue of 6-(4-fluorophenyl)-3-hydroxypyridin-2(1H)-one, the 5-aza analogue (5-hydroxy-2-(4-fluorophenyl)pyrimidin-4(3H)-one) did exhibit significant activity as an endonuclease inhibitor. The 6-aza analogue of 5-(4-fluorophenyl)-3-hydroxypyridin-2(1H)-one (6-(4-fluorophenyl)-4-hydroxypyridazin-3(2H)-one) also retained modest activity as an inhibitor. Several varied 6-phenyl-4-hydroxypyridazin-3(2H)-ones and 2-phenyl-5-hydroxypyrimidin-4(3H)-ones were synthesized and evaluated as endonuclease inhibitors. The SAR observed for these aza analogues are consistent with those previously observed with various phenyl substituted 3-hydroxypyridin-2(1H)-ones. | 18 | 1 | 18 | CHEMBL_21 | 2016-02-01 |
CHEMBL1146381 | European journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis, stereochemistry and antimicrobial evaluation of t(3)-benzyl-r(2),c(6)-diarylpiperidin-4-one and its derivatives. | 17241703 | 10.1016/j.ejmech.2006.11.009 | nan | Jayabharathi J, Manimekalai A, Consalata Vani T, Padmavathy M. | 2007 | 42 | 5 | 593 | 605 | PUBLICATION | In a wide research program toward new and efficient antimicrobial agents, a series of t(3)-benzyl-r(2),c(6)-diarylpiperidin-4-ones (1-7) were synthesised and tested for their in vitro antibacterial and antifungal activities. Also, the structures and their stereochemistry of these synthesised compounds 1-7 were characterized by IR, high resolution (1)H NMR, (13)C NMR and (1)H-(13)C COSY spectra. The analysis of coupling constants of compounds 1-5 reveals that they exist in normal chair conformation with equatorial orientations of all the substituents. The spectra of 6 and 7 reveal the presence of two isomers labeled as E (carbonyl carbon is anti to benzyl group at C-3) and Z (carbonyl carbon is syn to benzyl group at C-3) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values the favoured conformation for the Z- and E-isomers of 6 and 7 was found to be the boat conformations. Their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against Cryptococcus neoformans, Candida 6, Candida 51, Aspergillus niger and Aspergillus flavus were also evaluated. | 9 | 9 | 78 | CHEMBL_1 | 2009-09-03 |
CHEMBL1142186 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Multistep resistance selection and postantibiotic-effect studies of the antipneumococcal activity of LBM415 compared to other agents. | 17116666 | 10.1128/aac.01150-06 | nan | Kosowska-Shick K, Credito KL, Pankuch GA, DeWasse B, McGhee P, Appelbaum PC. | 2007 | 51 | 2 | 770 | 773 | PUBLICATION | LBM415 is a peptide deformylase inhibitor active against gram-positive bacterial species and some gram-negative species. In multiselection studies, LBM415 had low MICs against all Streptococcus pneumoniae strains tested, regardless of their genotype, and selected resistant clones after 14 to 50 days. MIC increases correlated with changes mostly in the 70GXGXAAXQ77 motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h. | 10 | 1 | 271 | CHEMBL_1 | 2009-09-03 |
CHEMBL1142198 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Diversity of ampicillin resistance genes and antimicrobial susceptibility patterns in Haemophilus influenzae strains isolated in Korea. | 17116681 | 10.1128/aac.00960-06 | nan | Kim IS, Ki CS, Kim S, Oh WS, Peck KR, Song JH, Lee K, Lee NY. | 2007 | 51 | 2 | 453 | 460 | PUBLICATION | By Etest determination of the susceptibilities of 229 Haemophilus influenzae strains isolated in Korea to 10 antibiotics, the isolates were found to be antibiotic nonsusceptible in the following order: ampicillin (58.1%), trimethoprim-sulfamethoxazole (52%), cefaclor (41.1%), clarithromycin (25.8%), chloramphenicol (14.0%), amoxicillin-clavulanic acid (13.5%), meropenem (11.7%), cefixime (10.9%), cefuroxime (9.2%), and levofloxacin (1.3%). The prevalences of each resistance class were 23.6% for beta-lactamase-negative ampicillin-susceptible (BLNAS) strains; 37.6% for strains with the TEM-1 type beta-lactamase gene; 1.3% for strains with the ROB-1 type beta-lactamase gene; 29.3% for the beta-lactamase-negative ampicillin-resistant (BLNAR) strains with a mutation in the ftsI gene, which encodes PBP 3; and 8.3% for beta-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) strains, which showed both resistance mechanisms (i.e., a beta-lactamase gene and a mutation in the ftsI gene). The MIC50s of all beta-lactams, including cephem and meropenem agents, for the BLNAR strains were two to three times higher than those for the BLNAS strains. This study confirms that the prevalence of BLNAR and BLPACR strains is relatively high and for the first time confirms the presence of H. influenzae strains carrying blaROB-1 in Korea. Even though mutations in another gene(s) might be involved in beta-lactam resistance, these results suggest that mutations in the ftsI gene are important for the development of resistance to beta-lactams in H. influenzae strains in Korea. | 8 | 1 | 96 | CHEMBL_1 | 2009-09-03 |
CHEMBL3352116 | Journal of medicinal chemistry. | 1 | Scientific Literature | Discovery heralds new approach to the treatment of cystic fibrosis. | 25384240 | 10.1021/jm5016928 | nan | Lowe JA. | 2014 | 57 | 23 | 9774 | 9775 | PUBLICATION | nan | 3 | 3 | 7 | CHEMBL_21 | 2016-02-01 |
CHEMBL3351768 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | 7-(4-Alkylidenylpiperidinyl)-quinolone bacterial topoisomerase inhibitors. | 25455493 | 10.1016/j.bmcl.2014.10.014 | nan | Grant EB, Foleno BD, Goldschmidt R, Hilliard JJ, Lin SC, Morrow B, Paget SD, Weidner-Wells MA, Xu X, Xu X, Murray WV, Bush K, Macielag MJ. | 2014 | 24 | 23 | 5502 | 5506 | PUBLICATION | Novel antibacterial fluoroquinolone agents bearing a 4-alkylidenylpiperidine 7-position substituent are active against quinolone-susceptible and quinolone-resistant gram-positive bacteria, including Streptococcus pneumoniae and MRSA. Analogs 22b, 23c, and 24 demonstrated superior in vitro and in vivo efficacy to ciprofloxacin against these cocci. | 20 | 4 | 116 | CHEMBL_21 | 2016-02-01 |
CHEMBL1131215 | Journal of medicinal chemistry. | 1 | Scientific Literature | Anhydrolide macrolides. 1. Synthesis and antibacterial activity of 2,3-anhydro-6-O-methyl 11,12-carbamate erythromycin A analogues. | 9572890 | 10.1021/jm970547x | nan | Elliott RL, Pireh D, Griesgraber G, Nilius AM, Ewing PJ, Bui MH, Raney PM, Flamm RK, Kim K, Henry RF, Chu DT, Plattner JJ, Or YS. | 1998 | 41 | 10 | 1651 | 1659 | PUBLICATION | A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate analogues have been synthesized and evaluated for antibacterial activity. These compounds were found to be potent antibacterial agents against Gram-positive organisms in vitro, many having MIC values below 1 microg/mL for the macrolide-susceptible Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae, as well as improved activity compared to erythromycin A against the inducibly MLS (macrolide, lincosamide, and streptogramin B)-resistant organisms. Structure-activity studies revealed that arylalkyl carbamates with two and four carbon atoms between the aromatic moiety and carbamate nitrogen have the best in vitro activity. All of the C-10 epi analogues evaluated were found to have substantially less activity than the corresponding natural C-10 isomer. Several analogues demonstrated moderate antibacterial activity against the constitutively resistant S.aureus A-5278, S. pneumoniae5979, and S.pyogenes 930. However, despite potent in vitro activity, these analogues showed only moderate in vivo activity in mouse protection studies. | 36 | 6 | 428 | CHEMBL_1 | 2009-09-03 |
CHEMBL2434922 | European journal of medicinal chemistry. | 1 | Scientific Literature | Microwave assisted synthesis of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones; synthesis, in vitro antimicrobial and anticancer activities of novel coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones. | 24056147 | 10.1016/j.ejmech.2013.07.015 | nan | Puttaraju KB, Shivashankar K, Chandra, Mahendra M, Rasal VP, Venkata Vivek PN, Rai K, Chanu MB. | 2013 | 69 | nan | 316 | 322 | PUBLICATION | The present article describes the synthesis of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2a-h) under microwave irradiation. The product was obtained in excellent yield (74-94%) in a shorter reaction time (2 min). These molecules (2a, b) further reacted with various substituted 4-bromomethylcoumarins (3a-f) to yield a new series of coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones (4a-h). The structure of all the synthesized compounds were confirmed by spectral studies and screened for their in vitro antibacterial activity against three Gram-positive bacteria viz., Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and three Gram-negative bacteria viz., Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Fusarium oxysporum, Penicillium chrysogenum and anticancer activity against Dalton's Ascitic Lymphoma (DAL) cell line. In general, all the compounds possessed better antifungal properties than antibacterial properties. The coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (4g) (R = i-Pr, R₁ = 6-Cl) was found to be the most potent cytotoxic compound (88%) against Dalton's Ascitic Lymphoma cell line at the concentration of 100 μg/mL. | 19 | 13 | 221 | CHEMBL_18 | 2014-03-12 |
CHEMBL2429843 | Journal of medicinal chemistry. | 1 | Scientific Literature | Selective inhibitors of bacterial t-RNA-(N(1)G37) methyltransferase (TrmD) that demonstrate novel ordering of the lid domain. | 23981144 | 10.1021/jm400718n | nan | Hill PJ, Abibi A, Albert R, Andrews B, Gagnon MM, Gao N, Grebe T, Hajec LI, Huang J, Livchak S, Lahiri SD, McKinney DC, Thresher J, Wang H, Olivier N, Buurman ET. | 2013 | 56 | 18 | 7278 | 7288 | PUBLICATION | The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA. | 48 | 6 | 217 | CHEMBL_18 | 2014-03-12 |
CHEMBL2046407 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthesis and in vitro antitubercular activity of 4-aryl/alkylsulfonylmethylcoumarins as inhibitors of Mycobacterium tuberculosis. | 22726933 | 10.1016/j.bmcl.2012.05.054 | nan | Jeyachandran M, Ramesh P, Sriram D, Senthilkumar P, Yogeeswari P. | 2012 | 22 | 14 | 4807 | 4809 | PUBLICATION | A series of 4-aryl/alkylsulfonylmethylcoumarins have been synthesized and screened for in vitro antitubercular activity against Mycobacterium tuberculosis H(37)Rv (MTB). Four of the compounds showed MIC in the range of 0.78-3.13 μg/mL proving their potential activity. | 20 | 1 | 20 | CHEMBL_15 | 2013-01-23 |
CHEMBL3244373 | Journal of medicinal chemistry. | 1 | Scientific Literature | Stereoselective effects of cis- and trans-cyclopropylbis (dioxopiperazines) related to ICRF-159 on metastases of hamster lung adenocarcinoma. | 722727 | 10.1021/jm00210a004 | nan | Witiak DT, Lee HJ, Goldman HD, Zwilling BS. | 1978 | 21 | 12 | 1194 | 1197 | PUBLICATION | The synthesis for cis-4,4' (1,2-cyclopropanediyl)bis(2,6-piperazinedione) (cis-3) is discussed. Stereoselective effects on metastases of cis-3 and the previously reported trans-2 isomer were compared to conformationally mobile ICRF-159 using a Syrian hamster lung adenocarcinoma (LG1002). Whereas ICRF-159 and cis-3 significantly inhibited lung metastases the trans-2 isomer significantly increased the number of metastatic nodules in the lung. Thus, these studies have revealed that, at least in one tumor model, antimetastatic activity can be separated from metastatic potentiating activity by controlling drug geometry. | 3 | 2 | 9 | CHEMBL_20 | 2015-01-14 |
CHEMBL3046253 | Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents. | 1 | Scientific Literature | Design, synthesis and in vitro PDE4 inhibition activity of certain quinazolinone derivatives for treatment of asthma | nan | 10.1007/s00044-011-9846-3 | nan | Elansary AK, Kadry HH, Ahmed EM, Sonousi ASM | 2012 | 21 | 11 | 3327 | 3335 | PUBLICATION | nan | 10 | 1 | 10 | CHEMBL_19 | 2014-07-03 |
CHEMBL3272138 | Journal of medicinal chemistry. | 1 | Scientific Literature | Prostaglandins and congeners. 16. Synthesis and bronchodilator activity of dl-11-doexy-3-thiaprostaglandins. | 592330 | 10.1021/jm00222a024 | nan | Skotnicki JS, Schaub RE, Weiss MJ, Dessy F. | 1977 | 20 | 12 | 1662 | 1665 | PUBLICATION | The interesting bronchodilator activity of certain dl-11-deoxy-3-thiaprostaglandins and their preparation by the conjugate addition of appropriately substituted (E)-1-alkenyllithio cuprate reagents to requisite cyclopentenones are described. | 15 | 2 | 41 | CHEMBL_20 | 2015-01-14 |
CHEMBL3272064 | Journal of medicinal chemistry. | 1 | Scientific Literature | Mode of action and quantitative structure-activity correlations of tuberculostatic drugs of the isonicotinic acid hydrazide type. | 817022 | 10.1021/jm00226a007 | nan | Seydel JK, Schaper KJ, Wempe E, Cordes HP. | 1976 | 19 | 4 | 483 | 492 | PUBLICATION | Quantitative structure-activity studies have been performed for a series of 2-substituted isonicotinic acid hydrazides by correlating electronic, steric, and lipophilic properties of the substituents with the biological activity date (MIC) from serial dilution tests with Mycobacterium tuberculosis (strain H 37 Rv). The reaction rates for the quaternization of 2-substituted pyridines with methyl iodide were also determined. The rate constants show a similar dependence on the steric and electronic effects of the substituents as the antibacterial activities of the corresponding pyridine-4-carboxylic acid hydrazides. The obtained correlations give evidence that the reactivity of the pyridine nitrogen atom is essential for the biological activity of 2-substituted isonicotinic acid hydrazides and seem to support the hypothesis that isonicotinic acid derivatives are incorporated into an NAD analogue. | 39 | 2 | 83 | CHEMBL_20 | 2015-01-14 |
CHEMBL3396957 | European journal of medicinal chemistry. | 1 | Scientific Literature | Heteroatom insertion into 3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase. | 25528333 | 10.1016/j.ejmech.2014.12.022 | nan | Grombein CM, Hu Q, Rau S, Zimmer C, Hartmann RW. | 2015 | 90 | nan | 788 | 796 | PUBLICATION | Aldosterone synthase (CYP11B2) catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone. CYP11B2 is regarded as a new target for several cardiovascular diseases which are associated with chronically elevated aldosterone levels such as hypertension, congestive heart failure and myocardial fibrosis. In this paper, we optimized heterocycle substituted 3,4-dihydropyridin-2(1H)-ones as CYP11B inhibitors by systematic introduction of heteroatoms and by bioisosteric exchange of the lactame moiety by a sultame moiety. The most promising compounds regarding inhibition of human CYP11B2 and selectivity versus human enzymes CYP11B1, CYP17, and CYP19 were tested for inhibition of rat CYP11B2. Thus, we discovered compounds 4 and 9 which show potent inhibition of hCYP11B2 (IC50 < 1 nM) and the corresponding rat enzyme (4: 64%, 9: 51% inhibition, at 2 μM). | 20 | 6 | 96 | CHEMBL_21 | 2016-02-01 |
CHEMBL1140558 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | An atom efficient, solvent-free, green synthesis and antimycobacterial evaluation of 2-amino-6-methyl-4-aryl-8-[(E)-arylmethylidene]-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitriles. | 17933535 | 10.1016/j.bmcl.2007.09.095 | nan | Kumar RR, Perumal S, Senthilkumar P, Yogeeswari P, Sriram D. | 2007 | 17 | 23 | 6459 | 6462 | PUBLICATION | An atom efficient, green protocol for the synthesis of fifteen 2-amino-6-methyl-4-aryl-8-[(E)-arylmethylidene]-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitriles in quantitative yields from the reaction of 1-methyl-3,5-bis[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones with malononitrile in presence of solid sodium ethoxide under solvent-free condition is described. The compounds were tested for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant tuberculosis (MDR-TB), and Mycobacterium smegmatis using agar dilution method. 2-Amino-4-[4-(dimethylamino)phenyl]-8-(E)-[4-(dimethylamino)phenyl]methylidene-6-methyl-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]-pyridine-3-carbonitrile was found to be the most potent compound (MIC: 0.43microM) against MTB and MDR-TB, being 100 times more active than standard, isoniazid against MDR-TB. | 17 | 2 | 51 | CHEMBL_1 | 2009-09-03 |
CHEMBL1141641 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the catechol moiety and aspects of the B-ring structure. | 18065231 | 10.1016/j.bmc.2007.11.055 | nan | Dalence-Guzmán MF, Berglund M, Skogvall S, Sterner O. | 2008 | 16 | 5 | 2499 | 2512 | PUBLICATION | Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro-1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a conformational constrain (as a fused ring) is important and that compounds with a six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more potent than the corresponding isoindoline, 2,3,4,5-tetrahydro-1H-2-benzazepine and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives. | 19 | 1 | 19 | CHEMBL_1 | 2009-09-03 |
CHEMBL1123709 | Journal of medicinal chemistry. | 1 | Scientific Literature | Affinity labels for beta-adrenoceptors: preparation and properties of alkylating beta-blockers derived from indole. | 2882025 | 10.1021/jm00387a005 | nan | Pitha J, Buchowiecki W, Milecki J, Kusiak JW. | 1987 | 30 | 4 | 612 | 615 | PUBLICATION | New alkylating ligands derived from indole with high affinity for beta-adrenoceptors were synthesized and their properties examined. N8-(Bromoacetyl)-N1-[3-(4-indolyloxy)-2-hydroxypropyl]-(Z)-1,8-dia mino-p- menthane (8) and its N1,N8 isomer (9) were prepared by the reaction of bromoacetyl bromide with a product of the condensation of 4-indolyl glycidyl ether with (Z)-1,8-diamino-p-menthane. A similar reaction employing 2-cyano-4-indolyl glycidyl ether yielded the respective cyano derivatives 10 and 11. Apparent affinities (Ki, M) for beta-adrenoceptors on membrane preparations from rat heart and lung were 4.6 X 10(-10) and 1.34 X 10(-9) for 8, 2.3 X 10(-8) and 4.5 X 10(-9) for 9, 6.1 X 10(-10) and 1.49 X 10(-9) for 10, and 1.83 X 10(-9) and 2.78 X 10(-9) for 11, respectively. When membranes were preincubated with the above ligands (1 X 10(-8) M, 30 min, 30 degrees C) and then washed extensively, reduction in the concentration of specific binding sites of [3H]dihydroalprenolol ranged from 7% to 76% and there was no change in KD of the remaining binding sites. (+/-)-Alprenolol and (-)-isoproterenol, but not (+)-isoproterenol, when included with the alkylating ligands in the preincubation mixtures, prevented the reduction in concentration of [3H]dihydroalprenolol binding sites. Compounds 8-11 alone did not stimulate adenylate cyclase activity in rat heart homogenates. However, these compounds inhibited (-)-isoproterenol-stimulated adenylate cyclase activity with Ki values ranging between 5 X 10(-9) and 60 X 10(-9) M. These results suggest that high-affinity irreversible beta-adrenergic antagonists were obtained that may be useful for in vivo studies of beta-adrenoceptors. | 10 | 1 | 55 | CHEMBL_1 | 2009-09-03 |
CHEMBL1122984 | Journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis and beta-lactamase inhibitory properties of 2 beta-[(acyloxy)methyl]-2-methylpenam-3 alpha-carboxylic acid 1,1-dioxides. | 3872369 | 10.1021/jm00382a025 | nan | Gottstein WJ, Haynes UJ, McGregor DN. | 1985 | 28 | 4 | 518 | 522 | PUBLICATION | p-Nitrobenzyl 2 beta-[(benzoyloxy)methyl]-2 alpha-methylpenam-3 alpha-carboxylate was prepared by reaction of p-nitrobenzyl 2-[2-oxo-3 alpha-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl] -2-isopropenylacetate with silver benzoate in the presence of iodine. The resulting diester was oxidized to the sulfone with potassium permanganate and hydrogen peroxide, and the bromine and p-nitrobenzyl groups were removed by hydrogenolysis to give potassium 2 beta-(benzoyloxy)methyl 2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide. A series of related compounds, including the pivaloyl, methoxybenzoyl, p-fluorobenzoyl, and p-aminobenzoyl derivatives, were prepared in a similar way. All of these compounds were potent beta-lactamase inhibitors in vitro against the TEM beta-lactamase from Klebsiella pneumoniae A22695 and Bacteroides fragiles A22695 but less active against the beta-lactamase from Staphylococcus aureus A9606. All compounds when administered orally in a 1:1 combination with amoxicillin did not show any significant protection of mice infected with S. aureus A9606. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid was prepared and reacted with silver nitrate to give the nitrate ester. Oxidation with potassium permanganate and catalytic reduction afforded 2 beta-(hydroxymethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide was found to be a strong beta-lactamase inhibitor, while the 2 beta-hydroxymethyl compound showed only weak beta-lactamase-inhibiting properties. | 11 | 5 | 82 | CHEMBL_1 | 2009-09-03 |
CHEMBL1122020 | Journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis and enzymic activity of various substituted pyrazolo[1,5-a]-1,3,5-triazines as adenosine cyclic 3',5'-phosphate phosphodiesterase inhibitors. | 6279842 | 10.1021/jm00345a010 | nan | Senga K, O'Brien DE, Scholten MB, Novinson T, Miller JP, Robins RK. | 1982 | 25 | 3 | 243 | 249 | PUBLICATION | A series of various pyrazolo[1,5-a]-1,3,5-triazines have been prepared and studied as inhibitors of cAMP phosphodiesterase isolated from bovine brain, bovine heart, and rabbit lung. A number of compounds were found to be superior to theophylline. 2-Ethyl-7-phenylpyrazolo[1,5-a]-1,3,5-triazine (35) was found to be 97 times more potent than theophylline as an inhibitor of bovine brain PDE. 8-Bromo-2,4-dimethyl-7-phenylpyrazolo[1,5-a]-1,3,5-triazine (52) showed alpha lung = 40 compared to alpha heart = 3.0. Thus, various substituents could increase or decrease the inhibition relative to the type and source of tissue from which the PDE was isolated. The most active compound was 8-bromo-4-(diethylamino)-7-phenylpyrazolo[1,3-a]-1,3,5-triazine (25), which was 185 times more potent than theophylline as an inhibitor of PDE isolated from rabbit lung. The stepwise synthesis via ring-closure procedures of requisite pyrazole intermediates, followed by electrophilic substitution in the pyrazole ring and/or nucleophilic substitution in the 1,3,5-triazine moiety, resulted in the various pyrazolo[1,5-a]1,3,5-triazines listed in Tables I and II. Structure-activity relationships are reviewed. | 55 | 4 | 128 | CHEMBL_1 | 2009-09-03 |
CHEMBL1146365 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Synthesis and biological evaluation of new N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamides and phenylacetamides as antimicrobial agents. | 17223562 | 10.1016/j.bmc.2006.12.035 | nan | Ertan T, Yildiz I, Ozkan S, Temiz-Arpaci O, Kaynak F, Yalcin I, Aki-Sener E, Abbasoglu U. | 2007 | 15 | 5 | 2032 | 2044 | PUBLICATION | A new series of N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamide and phenylacetamide derivatives (1a-1n, 2a-2n) were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and their drug-resistant isolate. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 500 and 1.95 microg/ml. Benzamide derivative 1d exhibited the greatest activity with MIC values of 1.95, 3.9, and 7.8 microg/ml against drug-resistant B. subtilis, B. subtilis, and S. aureus, respectively. | 34 | 6 | 380 | CHEMBL_1 | 2009-09-03 |
CHEMBL1140116 | Journal of medicinal chemistry. | 1 | Scientific Literature | Potent s-cis-locked bithiazole correctors of DeltaF508 cystic fibrosis transmembrane conductance regulator cellular processing for cystic fibrosis therapy. | 18788728 | 10.1021/jm800533c | nan | Yu GJ, Yoo CL, Yang B, Lodewyk MW, Meng L, El-Idreesy TT, Fettinger JC, Tantillo DJ, Verkman AS, Kurth MJ. | 2008 | 51 | 19 | 6044 | 6054 | PUBLICATION | N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound 15Jf) was found previously to correct defective cellular processing of the cystic fibrosis protein DeltaF508-CFTR. Eight C4'-C5 C,C-bond-controlling bithiazole analogues of 1 were designed, synthesized, and evaluated to establish that constraining rotation about the bithiazole-tethering has a significant effect on corrector activity. For example, constraining the C4'-C5 bithiazole tether in the s-cis conformation [N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6 H-cyclohepta[1,2- d:3,4- d']bithiazole-2'-yl)pivalamide, 29] results in improved corrector activity. Heteroatom placement in the bithaizole core is also critical as evidenced by the decisive loss of corrector activity with s-cis constrained N-(2-(5-chloro-2-methoxyphenylamino)-5,6-dihydro-4 H-cyclohepta[1,2- d:3,4- d']bithiazole-2'-yl)pivalamide 33. In addition, computational models were utilized to examine the conformational preferences for select model systems. Following our analysis, the ' s-cis-locked' cycloheptathiazolothiazole 29 was found to be the most potent bithiazole corrector, with an IC50 of approximately 450 nM. | 6 | 1 | 6 | CHEMBL_2 | 2009-11-30 |
CHEMBL1147864 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthesis of new sugar derivatives from Stachys sieboldi Miq and antibacterial evaluation against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus. | 17331717 | 10.1016/j.bmcl.2007.02.024 | nan | Chiba T, Takii T, Nishimura K, Yamamoto Y, Morikawa H, Abe C, Onozaki K. | 2007 | 17 | 9 | 2487 | 2491 | PUBLICATION | A series of sugar derivatives (7-14) were synthesized from stachyose, a sugar compound of Stachys sieboldi Miq, and evaluated for antibacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus, and their structure-activity relationships were studied. The results showed that the compound OCT359 (allyl O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl)-(1-->6)-O-(2,3,4-tri-O-acetyl-alpha-D-galactopyranosyl)-(1-->6)-O-2,3,4-tri-O-acetyl-beta-D-glucopyranoside) (12) exhibited in vitro antibacterial activity. The allyl group at C-1 and the acetoxy groups of the manninotrioside were requisite for the antibacterial activity. | 18 | 3 | 169 | CHEMBL_1 | 2009-09-03 |
CHEMBL1141288 | Journal of natural products. | 1 | Scientific Literature | Antimalarial and antituberculous poly-O-acylated jatrophane diterpenoids from Pedilanthus tithymaloides. | 17844996 | 10.1021/np070174v | nan | Mongkolvisut W, Sutthivaiyakit S. | 2007 | 70 | 9 | 1434 | 1438 | PUBLICATION | Six new poly-O-acylated jatrophane diterpenes (1- 6) have been isolated along with five known compounds from the white latex of Pedilanthus tithymaloides. The structural identification was accomplished on the basis of 2D NMR and MS investigations. Some of these highly oxygenated jatrophane diterpenes possess a rare O-acetyl enol moiety. Compounds 1 and 3- 5 showed antiplasmodial activity with IC(50) values of 3.4-4.4 microg/mL and antimycobacterial activity against Mycobacterium tuberculosis with minimum inhibition concentration (MIC) values ranging from 12.5 to 100 microg/mL. | 9 | 3 | 17 | CHEMBL_1 | 2009-09-03 |
CHEMBL1140022 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Adenosine phosphonate inhibitors of lipid II: alanyl tRNA ligase MurM from Streptococcus pneumoniae. | 17548193 | 10.1016/j.bmcl.2007.05.071 | nan | Cressina E, Lloyd AJ, De Pascale G, Roper DI, Dowson CG, Bugg TD. | 2007 | 17 | 16 | 4654 | 4656 | PUBLICATION | Adenosine and 2'-deoxyadenosine phosphonate transition state analogues act as the first inhibitors for the MurMN/FemABX family of tRNA-dependent ligases implicated in high-level penicillin resistance in gram-positive bacteria. | 3 | 2 | 4 | CHEMBL_1 | 2009-09-03 |
CHEMBL1131190 | Journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis of 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine and novel derivatives free of positional isomers. Potent inhibitors of cAMP-specific phosphodiesterase and of malignant tumor cell growth. | 9822544 | 10.1021/jm981021v | nan | Merz KH, Marko D, Regiert T, Reiss G, Frank W, Eisenbrand G. | 1998 | 41 | 24 | 4733 | 4743 | PUBLICATION | 7-Benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine (7a) is a potent inhibitor of the cAMP-specific phosphodiesterase isoenzyme family PDE4 and induces growth inhibition in a panel of tumor cell lines. In this study, we describe a synthesis that yields 7a and novel derivatives free of positional isomers. The synthesis of alkylamino substituted pteridines is based on the successive nucleophilic aromatic substitution of the chlorine atoms of 2,4,6, 7-tetrachloropteridine. For the reaction with secondary amines, the positional order of reactivity was found to be C4 > C7 > C2 > C6. Final structural proof is given by X-ray crystallography. To unravel structural elements of 7a crucial for the interaction with the target enzyme, the compound was modified systematically. The impact of the modifications on activity was tested by evaluating the ability of the compounds to inhibit cAMP hydrolysis by cAMP-specific phosphodiesterase (PDE4) purified from the solid human large cell lung tumor xenograft LXFL529. Growth inhibitory properties were determined by in vitro treatment of the respective cell line LXFL529L using the sulforhodamine B assay (SRB). The results show that for high activity, the heterocyclic substituent in position 2 of the pteridine ring system requires the presence of a basic nitrogen in 4'-position, as represented by piperazine. | 15 | 2 | 30 | CHEMBL_1 | 2009-09-03 |
CHEMBL1137250 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Novel 6-O-acylated vitamin C derivatives as hyaluronidase inhibitors with selectivity for bacterial lyases. | 16908142 | 10.1016/j.bmcl.2006.07.087 | nan | Spickenreither M, Braun S, Bernhardt G, Dove S, Buschauer A. | 2006 | 16 | 20 | 5313 | 5316 | PUBLICATION | Previously, we identified ascorbic acid 6-O-hexadecanoate as an up to 1500 times more potent inhibitor of bacterial and bovine hyaluronidases than the parent compound, vitamin C, and determined a crystal structure of hyaluronidase from Streptococcus pneumoniae in complex with the inhibitor. As the alkanoyl chain interacts with a hydrophobic patch of the enzyme we synthesized other 6-O-acylated vitamin C derivatives bearing various lipophilic residues and investigated the inhibition of Streptococcus agalactiae strain 4755 hyaluronidase (SagHyal(4755)) and of bovine testicular hyaluronidases (BTH) in a turbidimetric assay. All compounds showed selectivity for the bacterial enzyme. Whereas vitamin C 6-O-hexanoate only weakly inhibited SagHyal(4755), the inhibition of both enzymes increased with the length of the aliphatic chain. In the case of the 6-O-octadecanoate, IC(50) values of 0.9 and 39microM for SagHyal(4755) and BTH, respectively, were determined. Partial replacement of the aliphatic chain with a phenyl, p-phenylene or p-biphenylyl group resulted in inhibitors with activity in the lower micromolar range, too. The title compounds are among the most potent inhibitors of both enzymes known to date. | 27 | 1 | 55 | CHEMBL_1 | 2009-09-03 |
CHEMBL1131863 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthesis and antibacterial activity of HMR 3647 a new ketolide highly potent against erythromycin-resistant and susceptible pathogens. | 10560728 | 10.1016/s0960-894x(99)00534-x | nan | Denis A, Agouridas C, Auger JM, Benedetti Y, Bonnefoy A, Bretin F, Chantot JF, Dussarat A, Fromentin C, D'Ambrières SG, Lachaud S, Laurin P, Le Martret O, Loyau V, Tessot N, Pejac JM, Perron S. | 1999 | 9 | 21 | 3075 | 3080 | PUBLICATION | In the search for new ketolides with improved activities against erythromycin-resistant S. pneumoniae and H. influenzae we synthesized a new 11,12 carbamate ketolide substituted by an imidazo-pyridyl side chain: HMR 3647. This compound demonstrated a potent activity against erythromycin susceptible and resistant pathogens, including penicillin G/erythromycin A-resistant S. pneumoniae and H. influenzae. In vivo, HMR 3647 displayed good pharmacokinetic parameters (Cmax = 2.9 microg/ml, bioavailability=49%, AUC0.8 = 17.2 microg.h/l, t1/2=1h) and was shown to have a high therapeutic efficacy in mice infected by various respiratory pathogens, including multi-resistant S. pneumoniae and Gram negative bacteria such as H. influenzae. HMR 3647 appears to be a very promising agent for the treatment of respiratory infections and is currently in clinical trials. | 10 | 8 | 164 | CHEMBL_1 | 2009-09-03 |
CHEMBL1143791 | European journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis of isonicotinoylhydrazones from anacardic acid and their in vitro activity against Mycobacterium smegmatis. | 17112641 | 10.1016/j.ejmech.2006.09.009 | nan | Swamy BN, Suma TK, Rao GV, Reddy GC. | 2007 | 42 | 3 | 420 | 424 | PUBLICATION | Isonicotinoylhydrazones were synthesized from a natural product anacardic acid, a major constituent of cashew nut shell liquid. The unsaturated side chain in anacardic acid and its 5-nitro derivative were converted into C(8')-aldehydes by oxidative cleavage. C(8')-aldehydes are then coupled with isoniazid (an anti-TB drug) to obtain N-isonicotinoyl-N'-8-[(2'-carbohydroxy-3'-hydroxy) phenyl] octanal hydrazone (5) and N-isonicotinoyl-N'-8-[(2'-carbohydroxy-3'-hydroxy-6-nitro) phenyl] octanal hydrazone (6). These isonicotinoylhydrazones of anacardic aldehydes showed potent antimycobacterial activity against Mycobacterium smegmatis mc(2)155. The synergistic studies of 5 and 6 with isoniazid showed more inhibitory activities than isoniazid alone. Compounds 5 and 6 also showed activity against Mycobacterium tuberculosis H(37)Rv. | 5 | 2 | 12 | CHEMBL_1 | 2009-09-03 |
CHEMBL1140570 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthesis and antimicrobial evaluation of guanylsulfonamides. | 17942305 | 10.1016/j.bmcl.2007.09.060 | nan | Patel PR, Ramalingan C, Park YT. | 2007 | 17 | 23 | 6610 | 6614 | PUBLICATION | A series of guanylsulfonamides, 2-amino-9-[2-substituted-4-(4-substituted piperidin-1-sulfonyl)phenyl]-1,9-dihydropurin-6-ones, was synthesized by adopting reductive aminoformylation of 2-amino-5-nitro-6-[4-(piperidin-1-sulfonyl)phenylamino]-3H-pyrimidin- 4-one and subsequent intramolecular ring condensation as key steps. All the guanylsulfonamides were assayed for their in vitro antibacterial activities against Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Streptococcus faecalis, and their antifungal activities against Aspergillus flavus, Aspergillus niger, and Candida albicans. Of the guanylsulfonamides, 13e and 13f displayed better antibacterial activities than that of Norfloxacin against the bacterial strains S. aureus and S. faecalis except 13f against S. faecalis, which exhibited the activity similar to that of Norfloxacin. Against the fungal strains A. flavus and A. niger, 13g and 13h showed similar activities to that of Griseoflavin-16 except 13h against A. niger, which displayed a profound drop in the activity compared to that of Griseoflavin-16. The remarkable inhibition of the growth of the bacterial and fungal strains makes these substances promising microbial agents. | 9 | 9 | 79 | CHEMBL_1 | 2009-09-03 |
CHEMBL1154429 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Identifying mutator phenotypes among fluoroquinolone-resistant strains of Streptococcus pneumoniae using fluctuation analysis. | 17664329 | 10.1128/aac.00336-07 | nan | Gould CV, Sniegowski PD, Shchepetov M, Metlay JP, Weiser JN. | 2007 | 51 | 9 | 3225 | 3229 | PUBLICATION | The occurrence of mutator phenotypes among laboratory-generated and clinical levofloxacin-resistant strains of Streptococcus pneumoniae was determined using fluctuation analysis. The in vitro selection for levofloxacin-resistant mutants of strain D39, each with point mutations in both gyrA and parC or parE, was not associated with a significant change in the mutation rate. Two of eight clinical isolates resistant to levofloxacin (MIC, >8 microg/ml) had estimated mutation rates of 1.2 x 10(-7) and 9.4 x 10(-8) mutations per cell division, indicating potential mutator phenotypes, compared to strain D39, which had an estimated mutation rate of 1.4 x 10(-8) mutations per cell division. The levofloxacin-resistant isolates with the highest mutation rates showed evidence of dysfunctional mismatch repair and contained missense mutations in mut genes at otherwise highly conserved sites. The association of hypermutability in levofloxacin-resistant S. pneumoniae clinical isolates with mutations in DNA mismatch repair genes provides further evidence that mismatch repair mutants may have a selective advantage in the setting of antibiotic pressure, facilitating the development of further antibiotic resistance. | 1 | 1 | 9 | CHEMBL_2 | 2009-11-30 |
CHEMBL1147973 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Ligand based virtual screening and biological evaluation of inhibitors of chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv. | 17418569 | 10.1016/j.bmcl.2007.03.053 | nan | Agrawal H, Kumar A, Bal NC, Siddiqi MI, Arora A. | 2007 | 17 | 11 | 3053 | 3058 | PUBLICATION | We have identified new lead candidates that possess inhibitory activity against Mycobacterium tuberculosis H37Rv chorismate mutase by a ligand-based virtual screening optimized for lead evaluation in combination with in vitro enzymatic assay. The initial virtual screening using a ligand-based pharmacophore model identified 95 compounds from an in-house small molecule database of 15,452 compounds. The obtained hits were further evaluated by molecular docking and 15 compounds were short listed based on docking scores and the other scoring functions and subjected to biological assay. Chorismate mutase activity assays identified four compounds as inhibitors of M. tuberculosis chorismate mutase (MtCM) with low K(i) values. The structural models for these ligands in the chorismate mutase binding site will facilitate medicinal chemistry efforts for lead optimization against this protein. | 4 | 1 | 4 | CHEMBL_1 | 2009-09-03 |
CHEMBL1146351 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthesis and biological evaluation of thiazolidine-2-one 1,1-dioxide as inhibitors of Escherichia coli beta-ketoacyl-ACP-synthase III (FabH). | 17189694 | 10.1016/j.bmcl.2006.11.067 | nan | Alhamadsheh MM, Waters NC, Huddler DP, Kreishman-Deitrick M, Florova G, Reynolds KA. | 2007 | 17 | 4 | 879 | 883 | PUBLICATION | A series of cyclic sulfones has been synthesized and their activity against beta-ketoacyl-ACP-synthase III (FabH) has been investigated. The compounds are selectively active against Escherichia coli FabH (ecFabH), but not Mycobacterium tuberculosis FabH (mtFabH) or Plasmodium falciparum KASIII (PfKASIII). The activity against ecFabH ranges from 0.9 to >100microM and follows a consistent general SAR trend. Many of the compounds were shown to have antimalarial activity against chloroquine (CQ)-sensitive (D6) P. falciparum (IC(50)=5.3microM for the most potent inhibitor) and some were active against E. coli (MIC=6.6microg/ml for the most potent inhibitor). | 17 | 5 | 72 | CHEMBL_1 | 2009-09-03 |
CHEMBL1141630 | Journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis, stability, and antimicrobial studies of electronically tuned silver acetate N-heterocyclic carbenes. | 18288795 | 10.1021/jm0708679 | nan | Hindi KM, Siciliano TJ, Durmus S, Panzner MJ, Medvetz DA, Reddy DV, Hogue LA, Hovis CE, Hilliard JK, Mallet RJ, Tessier CA, Cannon CL, Youngs WJ. | 2008 | 51 | 6 | 1577 | 1583 | PUBLICATION | A series of methylated imidazolium salts with varying substituents on the 4 and 5 positions of the imidazole ring were synthesized. These salts were reacted with silver acetate to afford their corresponding silver N-heterocyclic carbene (NHC) complexes. These complexes were then evaluated for their stability in water as well as for their antimicrobial efficacy against a variety of bacterial strains associated with cystic fibrosis and chronic lung infections. | 4 | 7 | 173 | CHEMBL_1 | 2009-09-03 |
CHEMBL1152986 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | The macrolide resistance genes erm(B) and mef(E) are carried by Tn2010 in dual-gene Streptococcus pneumoniae isolates belonging to clonal complex CC271. | 17709465 | 10.1128/aac.00598-07 | nan | Del Grosso M, Northwood JG, Farrell DJ, Pantosti A. | 2007 | 51 | 11 | 4184 | 4186 | PUBLICATION | The genetic elements carrying macrolide resistance genes in Streptococcus pneumoniae isolates belonging to CC271 were investigated. The international clone Taiwan(19F)-14 was found to carry Tn2009, a Tn916-like transposon containing tet(M) and mef(E). The dual erm(B) mef(E) isolates carried Tn2010, which is similar to Tn2009 with the addition of a putative new transposon, the erm(B) genetic element. | 1 | 1 | 1 | CHEMBL_3 | 2010-04-16 |
CHEMBL1136243 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthetic dihydropacidamycin antibiotics: a modified spectrum of activity for the pacidamycin class. | 12951115 | 10.1016/s0960-894x(03)00682-6 | nan | Boojamra CG, Lemoine RC, Blais J, Vernier NG, Stein KA, Magon A, Chamberland S, Hecker SJ, Lee VJ. | 2003 | 13 | 19 | 3305 | 3309 | PUBLICATION | Dihydropacidamycins having an antibacterial spectrum modified from that of the natural product pacidamycins and mureidomycins have been synthesized. Synthetic dihydropacidamycins with noteworthy antibacterial activity against wild-type and resistant Escherichia coli have been identified (MIC=4-8 microg/mL). Some dihydropacidamycins are shown to have activity against multi-resistant clinical strains of Mycobacterium tuberculosis. Compounds of this class are inhibitors of the cell wall biosynthetic enzyme, MraY. | 11 | 10 | 59 | CHEMBL_1 | 2009-09-03 |
CHEMBL1145480 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Horizontal gene transfer of ftsI, encoding penicillin-binding protein 3, in Haemophilus influenzae. | 17325223 | 10.1128/aac.01545-06 | nan | Takahata S, Ida T, Senju N, Sanbongi Y, Miyata A, Maebashi K, Hoshiko S. | 2007 | 51 | 5 | 1589 | 1595 | PUBLICATION | Horizontal gene transfer has been identified in only a small number of genes in Haemophilus influenzae, an organism which is naturally competent for transformation. This report provides evidence for the genetic transfer of the ftsI gene, which encodes penicillin-binding protein 3, in H. influenzae. Mosaic structures of the ftsI gene were found in several clinical isolates of H. influenzae. To identify the origin of the mosaic sequence, complete sequences of the corresponding gene from seven type strains of Haemophilus species were determined. Comparison of these sequences with mosaic regions identified a homologous recombination of the ftsI gene between H. influenzae and Haemophilus haemolyticus. Subsequently, ampicillin-resistant H. influenzae strains harboring identical ftsI sequences were genotyped by pulsed-field gel electrophoresis (PFGE). Divergent PFGE patterns among beta-lactamase-nonproducing ampicillin-resistant (BLNAR) strains from different hospitals indicated the potential for the genetic transfer of the mutated ftsI gene between these isolates. Moreover, transfer of the ftsI gene from BLNAR strains to beta-lactamase-nonproducing ampicillin-susceptible (BLNAS) H. influenzae strains was evaluated in vitro. Coincubation of a BLNAS strain (a rifampin-resistant mutant of strain Rd) and BLNAR strains resulted in the emergence of rifampin- and cefdinir-resistant clones at frequencies of 5.1 x 10(-7) to 1.5 x 10(-6). Characterization of these doubly resistant mutants by DNA sequencing of the ftsI gene, susceptibility testing, and genotyping by PFGE revealed that the ftsI genes of BLNAR strains had transferred to BLNAS strains during coincubation. In conclusion, horizontal transfer of the ftsI gene in H. influenzae can occur in an intraspecies and an interspecies manner. | 4 | 3 | 68 | CHEMBL_1 | 2009-09-03 |
CHEMBL1146360 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase. | 17218104 | 10.1016/j.bmc.2006.12.024 | nan | Neres J, Bonnet P, Edwards PN, Kotian PL, Buschiazzo A, Alzari PM, Bryce RA, Douglas KT. | 2007 | 15 | 5 | 2106 | 2119 | PUBLICATION | Benzoic acid and pyridine derivatives inhibit recombinant trans-sialidase from Trypanosoma cruzi with I50 values between 0.4 and 1mM. The best compounds, 4-acetylamino-3-hydroxymethylbenzoic acid and 5-acetylamino-6-aminopyridine-2-carboxylic acid, provide new leads to inhibitors not containing the synthetically complex sialic acid structure. The weak inhibition by such compounds contrasts with their much stronger inhibition of neuraminidase from Influenza virus. | 31 | 1 | 32 | CHEMBL_1 | 2009-09-03 |
CHEMBL1135313 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol-S-conjugate amidase. | 12161164 | 10.1016/s0960-894x(02)00385-2 | nan | Nicholas GM, Eckman LL, Ray S, Hughes RO, Pfefferkorn JA, Barluenga S, Nicolaou KC, Bewley CA. | 2002 | 12 | 17 | 2487 | 2490 | PUBLICATION | A series of bromotyrosine-derived compounds, including marine natural products and members of a psammaplin A-inspired combinatorial synthetic library, were screened for their ability to inhibit the Mycobacterium tuberculosis detoxification enzyme mycothiol-S-conjugate amidase (MCA). Correlations between the structures and their respective IC(50) values (which range from 3 microM to 2.7 mM) should prove valuable when optimizing more potent inhibitors of MCA. | 16 | 1 | 16 | CHEMBL_1 | 2009-09-03 |
CHEMBL1142033 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthesis of isonicotinic acid N'-arylidene-N-[2-oxo-2-(4-aryl-piperazin-1-yl)-ethyl]-hydrazides as antituberculosis agents. | 15745799 | 10.1016/j.bmcl.2005.01.073 | nan | Sinha N, Jain S, Tilekar A, Upadhayaya RS, Kishore N, Jana GH, Arora SK. | 2005 | 15 | 6 | 1573 | 1576 | PUBLICATION | A new series of antituberculosis agents 6-9 was designed, synthesized and evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv and clinical isolates in an agar dilution method. Compound 9h showed comparable in vitro activity (MIC) to isoniazid against M. tuberculosis H37Rv and clinical isolates (sensitive strains) and superior activity against resistant strains of M. tuberculosis. | 34 | 1 | 102 | CHEMBL_1 | 2009-09-03 |
CHEMBL2021773 | Journal of natural products. | 1 | Scientific Literature | Isolation, structure elucidation, and antibacterial activity of methiosetin, a tetramic acid from a tropical sooty mold (Capnodium sp.). | 22288374 | 10.1021/np200857y | nan | Herath K, Jayasuriya H, Zink DL, Sigmund J, Vicente F, de la Cruz M, Basilio A, Bills GF, Polishook JD, Donald R, Phillips J, Goetz M, Singh SB. | 2012 | 75 | 3 | 420 | 424 | PUBLICATION | Drug-resistant bacteria continue to make many existing antibiotic classes ineffective. In order to avoid a future epidemic from drug-resistant bacterial infections, new antibiotics with new modes of action are needed. In an antibiotic screening program for new drug leads with new modes of action using antisense Staphylococcus aureus Fitness Test screening, we discovered a new tetramic acid, methiosetin, from a tropical sooty mold, Capnodium sp. The fungus also produced epicorazine A, a known antibiotic. The structure and relative configuration of methiosetin was elucidated by 2D NMR and ESIMS techniques. Methiosetin and epicorazine A showed weak to modest antibacterial activity against S. aureus and Haemophilus influenzae. The isolation, structure elucidation, and antibacterial activity of both compounds are described. | 2 | 5 | 13 | CHEMBL_15 | 2013-01-23 |
CHEMBL2412959 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Investigations on synthesis and structure elucidation of novel [1,2,4]triazolo[1,2-a]pyridazine-1-thiones and their inhibitory activity against inducible nitric oxide synthase. | 23810674 | 10.1016/j.bmc.2013.05.064 | nan | Schulz U, Grossmann A, Witetschek M, Lemmerhirt C, Polzin M, Haertel B, Wanka H, Morgenstern O. | 2013 | 21 | 17 | 5518 | 5531 | PUBLICATION | The inducible nitric oxide synthase (iNOS) is a target of great research interest due to its importance in a number of diseases, for example, septic shock and inflammatory lung diseases. A variety of 3-substituted [1,2,4]triazolo[1,2-a]pyridazine derivatives was synthesized by ring closure with hexahydropyridazine-1-carbothioamide by using aliphatic and aromatic aldehydes. The activity of the new substances was tested on the insulin-secreting rat insulinoma cell line RINm5F. iNOS was expressed through exposure to interleukin-1β (IL-1β) and interferon-γ (IFN-γ). A number of the investigated compounds were more active than the reference inhibitor aminoguanidine (AG). Structure-activity relationships showed that a phenyl substituent in position 3 is apparently essential for inhibition. | 21 | 3 | 79 | CHEMBL_18 | 2014-03-12 |
CHEMBL1140332 | Journal of medicinal chemistry. | 1 | Scientific Literature | Design, synthesis, and enzymatic evaluation of N1-acyloxyalkyl- and N1-oxazolidin-2,4-dion-5-yl-substituted beta-lactams as novel inhibitors of human leukocyte elastase. | 16033266 | 10.1021/jm0501331 | nan | Moreira R, Santana AB, Iley J, Neres J, Douglas KT, Horton PN, Hursthouse MB. | 2005 | 48 | 15 | 4861 | 4870 | PUBLICATION | Human leukocyte elastase (HLE) is a serine protease that very efficiently degrades various tissue matrix proteins such as elastin. The imbalance between HLE and its endogenous inhibitors leads to excessive elastin proteolysis and is considered to be responsible for the onset of chronic obstructive pulmonary disease (COPD). A novel series of C-3-, C-4-, and N-1-substituted azetidin-2-ones were prepared as potential mechanism-based inhibitors of HLE to restore the protease/antiprotease imbalance. N-Acyloxyalkylazetidin-2-ones, 4, and their carbamate counterparts, 5, are weak HLE inhibitors, being 5 times less active than their bicyclic oxazolidin-2,4-dione-substituted analogues, 6, containing an electron-withdrawing substituent at C-4. Compounds 6 containing a C-4 substituent exist as two diastereomeric pairs of enantiomers, each pair presenting similar inhibitory activity against HLE. Comparative docking experiments with the C-4-substituted oxazolidin-2,4-dione inhibitors 6 suggest that only the 4R,5'S and 4S,5'S diastereomers consistently interact with the beta-lactam carbonyl carbon atom accessible to the serine hydroxyl oxygen. | 12 | 1 | 18 | CHEMBL_1 | 2009-09-03 |
CHEMBL1144460 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core. | 15582424 | 10.1016/j.bmcl.2004.10.022 | nan | Wang GT, Wang S, Gentles R, Sowin T, Maring CJ, Kempf DJ, Kati WM, Stoll V, Stewart KD, Laver G. | 2005 | 15 | 1 | 125 | 128 | PUBLICATION | (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-methoxycarbonyl]tetrahydrofuran-5-carboxylic acid (9) and (+/-)-(2R,3R,5R)-[2-(1'-S-acetamido-3'-methyl)butyl-3-(4'-imidazolyl)]tetrahydrofuran 5-carboxylic acid (14) were synthesized as inhibitors of influenza neuraminidase (NA). Both compounds 9 and 14 inhibit influenza NA A with an IC(50) of about 0.5 microM and NA B with an IC(50) of 1.0 microM. | 3 | 2 | 6 | CHEMBL_1 | 2009-09-03 |
CHEMBL2311450 | European journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis and antibacterial evaluation of novel 11,4″-disubstituted azithromycin analogs with greatly improved activity against erythromycin-resistant bacteria. | 23229056 | 10.1016/j.ejmech.2012.11.028 | nan | Li X, Ma S, Yan M, Wang Y, Ma S. | 2013 | 59 | nan | 209 | 217 | PUBLICATION | A series of novel 11,4″-disubstituted azithromycin analogs were synthesized and evaluated for their antibacterial activity. All the 11,4″-disubstituted analogs exhibited excellent activity (0.03-0.12 μg/ml) against erythromycin-susceptible Streptococcus pneumoniae, and significantly improved activity against three phenotypes of erythromycin-resistant S. pneumoniae compared with erythromycin A, clarithromycin or azithromycin. Among them, compounds 26-28 showed the most potent activity (0.25, 0.03 and 2 μg/ml) against S. pneumoniae expressing the erm gene, the mef gene and the erm and mef genes, respectively. In addition, compound 28 was the most effective (0.03 and 0.12 μg/ml) against erythromycin-susceptible S. pneumoniae and Staphylococcus aureus as well. It is noteworthy that the most active compounds described above possess the same terminal 3,5-dinitrophenyl groups on their C-4″ bisamide side chains. | 22 | 4 | 251 | CHEMBL_17 | 2013-08-29 |
CHEMBL1143512 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Antitubercular agents. Part 2: new thiolactomycin analogues active against Mycobacterium tuberculosis. | 15780635 | 10.1016/j.bmcl.2005.01.084 | nan | Kamal A, Shaik AA, Sinha R, Yadav JS, Arora SK. | 2005 | 15 | 7 | 1927 | 1929 | PUBLICATION | Structurally modified analogues of naturally occurring antibiotic thiolactomycin, substituted at 4-position of the thiolactone ring have been prepared and evaluated for their antitubercular activity. Some of the compounds have exhibited potential activity against Mycobacterium tuberculosis. | 25 | 3 | 125 | CHEMBL_1 | 2009-09-03 |
CHEMBL1143511 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Antitubercular agents. Part 1: synthesis of phthalimido- and naphthalimido-linked phenazines as new prototype antitubercular agents. | 15780634 | 10.1016/j.bmcl.2005.01.085 | nan | Kamal A, Hari Babu A, Venkata Ramana A, Sinha R, Yadav JS, Arora SK. | 2005 | 15 | 7 | 1923 | 1926 | PUBLICATION | The preparation and antitubercular properties of a series of phthalimido- and naphthalimido-linked phenazines are described. Some of these new compounds inhibited the growth of Mycobacterium tuberculosis ATCC 27294, Mycobacterium avium ATCC 49601, Mycobacterium intracellulare ATCC 13950 and some clinical isolates. | 9 | 3 | 45 | CHEMBL_1 | 2009-09-03 |
CHEMBL1123115 | Journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis and antiviral activity of 11-azapentacyclo[6.2.1.0.0.0]decane. | 2989519 | 10.1021/jm00383a022 | nan | Sacks SL, Scheffer JR, Teh CZ, Tse A. | 1985 | 28 | 6 | 819 | 821 | PUBLICATION | 11-Azapentacyclo[6.2.1.0.0.0]decane (6a) as well as its 6,7-dimethyl derivative 6b was synthesized by a novel, four-step sequence that holds promise for the construction of a variety of cage compounds with bridging nitrogen atoms. The hydrochloride salt of 6a was shown to possess no antiviral activity against either the influenza virus A/Victoria/3/75 or the herpes simplex viruses HSV-1 and HSV-2. | 1 | 2 | 2 | CHEMBL_1 | 2009-09-03 |
CHEMBL1759851 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Facile synthesis and stereochemical investigation of Mannich base derivatives: evaluation of antioxidant property and antituberculostic potency. | 21429744 | 10.1016/j.bmcl.2011.02.103 | nan | Parthiban P, Subalakshmi V, Balasubramanian K, Islam MN, Choi JS, Jeong YT. | 2011 | 21 | 8 | 2287 | 2296 | PUBLICATION | A mini-library of diversely substituted 2,4-diaryl-3-azabicyco[3.3.1]nonan-9-one O-methyloximes and their N-methyl analogs were synthesized by a non-laborious, modified and an optimized Mannich condensation in good yields. Both the ring N-methylation and oxime O-methylation were employed by various methods; of them, the usage of (t)BuOK was found to be the superior in terms of good yield in short time. Stereochemistry of all the synthesized compounds was unambiguously established by their NMR spectral ((1)H, (13)C, (1)H-(1)H COSY, (1)H-(13)C one and multiple bond COSY and NOESY) as well as single-crystal XRD studies. Irrespective of the nature and position of the substituents, all the synthesized oxime ethers of the bicyclic Mannich bases as well as their N-methyl analogs adopted the twin-chair conformation with equatorial orientations of all the substituents. All the synthesized oxime ethers were evaluated for their antioxidant property by DPPH radical scavenging method. According to the structure-activity correlations, compound 4y was found to be a lead molecule with the IC(50) of 0.187 mg/mL. Thus, the present study exploits the scope of finding more active analogs by further optimization with the incorporation of more electron enriched alkoxy/amino and/or phenolic groups on the heterocycle as well as oxime ether pharmacophore. Most of the synthesized molecules were screened for their antituberculostic potency against Mycobacterium tuberculosis H(37)Rv by zone of inhibition method. Of them, 4w/5d and 4x showed very promising inhibition zones of 21 and 23 mm, respectively, which leads to the optimization of 4x by introducing various substituents on the O-benzyl moiety to enhance the antituberculostic potency. | 37 | 2 | 93 | CHEMBL_12 | 2011-11-18 |
CHEMBL2046418 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: the hydrophobic side chain influences type A subtype selectivity. | 22677529 | 10.1016/j.bmc.2012.05.001 | nan | Li Y, Silamkoti A, Kolavi G, Mou L, Gulati S, Air GM, Brouillette WJ. | 2012 | 20 | 14 | 4582 | 4589 | PUBLICATION | Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that size and geometry of the C3-side chain are important for selectivity of inhibition against N1 versus N2 NA, important type A influenza variants that infect man, including the highly lethal avian influenza. | 11 | 5 | 34 | CHEMBL_15 | 2013-01-23 |
CHEMBL1938381 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Design, synthesis, and structure-activity relationship studies of conformationally restricted mutilin 14-carbamates. | 22209487 | 10.1016/j.bmcl.2011.12.063 | nan | Fu L, Liu X, Ling C, Cheng J, Guo X, He H, Ding S, Yang Y. | 2012 | 22 | 2 | 814 | 819 | PUBLICATION | We report herein the design, synthesis, and structure-activity relationship studies of conformationally restricted mutilin 14-carbamates based on the structure of SB-222734. The antibacterial activities of these newly synthesized compounds were also evaluated and compared with linezolid and retapamulin. Results showed that most of the target compounds exhibit good potency in inhibiting the growth of Gram-positive bacteria including Methicillin-susceptible Staphylococcus aureus MSSA (MIC: 0.0625-2μg/mL), Methicillin-resistant S. aureus MRSA (MIC: 0.0625-2μg/mL), Methicillin-susceptible Staphylococcus epidermidis MSSE (MIC: 0.0625-2μg/mL), Methicillin-resistant S. epidermidis MRSE (MIC: 0.0625-2μg/mL), and Streptococcus pneumonia (MIC: 0.0625-4μg/mL). In particular, three remarkable compounds of this series (12l, 12m, and 21l) exhibited comparable in vitro antibacterial profiles to that of retapamulin. | 38 | 3 | 214 | CHEMBL_14 | 2012-06-27 |
CHEMBL1125780 | Journal of medicinal chemistry. | 1 | Scientific Literature | Monovalent sialosides that bind tightly to influenza A virus. | 1920363 | 10.1021/jm00114a025 | nan | Toogood PL, Galliker PK, Glick GD, Knowles JR. | 1991 | 34 | 10 | 3138 | 3140 | PUBLICATION | nan | 14 | 1 | 14 | CHEMBL_1 | 2009-09-03 |
CHEMBL1759834 | European journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis, stereochemistry, antimicrobial evaluation and QSAR studies of 2,6-diaryltetrahydropyran-4-one thiosemicarbazones. | 21316819 | 10.1016/j.ejmech.2011.01.029 | nan | Umamatheswari S, Balaji B, Ramanathan M, Kabilan S. | 2011 | 46 | 4 | 1415 | 1424 | PUBLICATION | A series of 2,6-diaryltetrahydropyran-4-one thiosemicarbazones (11-27) were synthesized and characterized for evaluation of potential antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Bacillus subtilis and Klebsiella pneumonia and antifungal activity against Cryptococcus neoformans, Candida albicans, Rhizopus sp., Aspergillus niger and Aspergillus flavus were evaluated. Compounds 21 and 22 showed maximum inhibition potency at low concentration (6.25 μg/ml) against P. aeruginosa. For antifungal activity, 20 and 21 were effective against C. neoformans and 22-24 against C. albicans at minimum concentration. Further, the results of QSAR studies of these synthesized compounds indicated the importance of weakly polar component of surface area, hydrophobicity and ionization potential parameters in defining their antimicrobial activity. | 19 | 10 | 360 | CHEMBL_12 | 2011-11-18 |
CHEMBL1944546 | European journal of medicinal chemistry. | 1 | Scientific Literature | Structure-activity relationships of novel alkylides: 3-O-arylalkyl clarithromycin derivatives with improved antibacterial activities. | 22301216 | 10.1016/j.ejmech.2012.01.023 | nan | Liang JH, Li XL, Wang H, An K, Wang YY, Xu YC, Yao GW. | 2012 | 49 | nan | 289 | 303 | PUBLICATION | A series of novel alkylides, possessing 3-O-arylalkyl group instead of 3-O-cladinose, were designed, synthesized and evaluated for in vitro antibacterial activities. The increased potency clearly ranked by the order of 3-O-(3-aryl-2-propargyl), 3-O-(3-aryl-E-prop-2-enyl), 3-O-(3-aryl-propyl), and 3-O-(3-aryl-Z-prop-1-enyl) groups. Some alkylides, exemplified by 7a, 10a, 21, 22, 26, 27 and 33, showed improved activities against inducible MLS(B) resistance and efflux resistance compared to the second-generation macrolides. Among them, 26 possessed comparable activities against erythromycin-susceptible Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes (MICs of 0.016-0.5 μg/mL). Moreover, 26 displayed dramatically enhanced potency against both efflux resistant and inducibly MLS(B) resistant strains (MICs of 0.125-0.5 μg/mL) resistant to clarithromycin and azithromycin (MICs of 1- >254 μg/mL), independent of methicillin-susceptible and methicillin-resistant phenotypes. | 27 | 7 | 297 | CHEMBL_14 | 2012-06-27 |
CHEMBL2321764 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Synthesis and antibacterial activities of new piperidine substituted (5R)-[1,2,3]triazolylmethyl and (5R)-[(4-F-[1,2,3]triazolyl)methyl] oxazolidinones. | 23385213 | 10.1016/j.bmcl.2013.01.033 | nan | Shin HN, Seo SH, Choo H, Kuem G, Choi KI, Nam G. | 2013 | 23 | 5 | 1193 | 1196 | PUBLICATION | A novel series of 5(R)-[1,2,3]triazolylmethyl and (5R)-[(4-F-[1,2,3]triazolyl)methyl]oxazolidinones having various piperidine group were synthesized and evaluated antibacterial activity against clinically isolated resistant strains of Gram-positive and Gram-negative bacteria. The compound 12a having exo-cyanoethylidene group in the 4-position of piperidine ring was found to be two to threefold more potent than the linezolid against penicillin-resistant Staphylococcus pneumonia and Staphylococcus agalactiae, and also exhibited reduced MAO-B inhibitory activity. | 20 | 15 | 190 | CHEMBL_17 | 2013-08-29 |
CHEMBL2311278 | European journal of medicinal chemistry. | 1 | Scientific Literature | Novel fluorescent cephalosporins: synthesis, antimicrobial activity and photodynamic inactivation of antibiotic resistant bacteria. | 23220643 | 10.1016/j.ejmech.2012.11.019 | nan | Xiao JM, Feng L, Zhou LS, Gao HZ, Zhang YL, Yang KW. | 2013 | 59 | nan | 150 | 159 | PUBLICATION | Two novel fluorescent cephalosporins, TCA and TBCA, were synthesized and characterized by (1)H NMR, (13)C NMR, UV-vis, and fluorescence spectroscopies. Biological activity assays demonstrated that TCA inactivated a Klebsiella pneumonia strain that expressed extended-spectrum β-lactamases. Incubation of 6 μM TCA with K. pneumonia cultures resulted in cell death for 84% of the cells after 126 J/cm(2) of light irradiation. In vitro, TCA exhibited a MIC = 0.5 μg/mL with Staphylococcus aureus. Kinetic evaluation revealed that TCA and TBCA were substrates for B1 and B3 subclass metallo-β-lactamases. TBCA exhibited stronger binding affinities to the Gram-positive bacterial strains MRSA1, MRSA2, and S. aureus with value of 2.95-6.59 μM per 10(8) cells/mL. | 4 | 3 | 39 | CHEMBL_17 | 2013-08-29 |
CHEMBL1938247 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Synthesis and evaluation of inhibitors of bacterial drug efflux pumps of the major facilitator superfamily. | 22055717 | 10.1016/j.bmc.2011.10.011 | nan | Okandeji BO, Greenwald DM, Wroten J, Sello JK. | 2011 | 19 | 24 | 7679 | 7689 | PUBLICATION | Inhibitors of drug efflux pumps have great potential as pharmacological agents that restore the drug susceptibility of multidrug resistant bacterial pathogens. Most attention has been focused on the discovery of small molecules that inhibit the resistance nodulation division (RND) family drug efflux pumps in Gram-negative bacteria. The prototypical inhibitor of RND-family efflux pumps in Gram-negative bacteria is MC-207,110 (Phe-Arg-β-naphthylamide), a C-capped dipeptide. Here, we report that C-capped dipeptides inhibit two chloramphenicol-specific efflux pumps in Streptomyces coelicolor, a Gram-positive bacterium that is a relative of the human pathogen Mycobacterium tuberculosis. Diversity-oriented synthesis of a library of structurally related C-capped dipeptides via an Ugi four component reaction and screening of the resulting compounds resulted in the discovery of a compound that is threefold more potent as a suppressor of chloramphenicol resistance in S. coelicolor than MC-207,110. Since chloramphenicol resistance in S. coelicolor is mediated by major facilitator superfamily drug efflux pumps, our findings provide the first evidence that C-capped dipeptides can inhibit drug efflux pumps outside of the RND superfamily. | 22 | 2 | 58 | CHEMBL_14 | 2012-06-27 |
CHEMBL1955717 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Synthesis and in vitro study of novel neuraminidase inhibitors against avian influenza virus. | 22342267 | 10.1016/j.bmc.2012.01.026 | nan | Kongkamnerd J, Cappelletti L, Prandi A, Seneci P, Rungrotmongkol T, Jongaroonngamsang N, Rojsitthisak P, Frecer V, Milani A, Cattoli G, Terregino C, Capua I, Beneduce L, Gallotta A, Pengo P, Fassina G, Miertus S, De-Eknamkul W. | 2012 | 20 | 6 | 2152 | 2157 | PUBLICATION | Evidences of oseltamivir resistant influenza patients raised the need of novel neuraminidase inhibitors. In this study, five oseltamivir analogs PMC-31-PMC-36, synthesised according to the outcomes of a rational design analysis aimed to investigate the effects of substitution at the 5-amino and 4-amido groups of oseltamivir on its antiviral activity, were screened for their inhibition against neuraminidase N1 and N3. The enzymes used as models were from the avian influenza A H7N1 and H7N3 viruses. The neuraminidase inhibition assay was carried out by using recombinant species obtained from a baculovirus expression system and the fluorogenic substrate MUNANA. The assay was validated by using oseltamivir carboxylate as a reference inhibitor. Among the tested compounds, PMC-36 showed the highest inhibition on N1 with an IC(50) of 14.6±3.0nM (oseltamivir 25±4nM), while PMC-35 showed a significant inhibitory effect on N3 with an IC(50) of 0.1±0.03nM (oseltamivir 0.2±0.02nM). The analysis of the inhibitory properties of this panel of compounds allowed a preliminary assessment of a structure-activity relationship for the modification of the 4-amido and 5-amino groups of oseltamivir carboxylate. The substitution of the acetamido group in the oseltamivir structure with a 2-butenylamido moiety reduced the observed activity, while the introduction of a propenylamido group was well tolerated. Substitution of the free 5-amino group of oseltamivir carboxylate with an azide, decreased the activity against both N1 and N3. When these structural changes were both introduced, a dramatic reduction of activity was observed for both N1 and N3. The alkylation of the free 5-amino group in oseltamivir carboxylate introducing an isopropyl group seemed to increase the inhibitory effect for both N1 and N3 neuraminidases, displaying a more pronounced effect against N1. | 8 | 1 | 18 | CHEMBL_14 | 2012-06-27 |
CHEMBL2331438 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | An efficient domino reaction in ionic liquid: synthesis and biological evaluation of some pyrano- and thiopyrano-fused heterocycles. | 23414843 | 10.1016/j.bmcl.2013.01.079 | nan | Parmar NJ, Patel RA, Parmar BD, Talpada NP. | 2013 | 23 | 6 | 1656 | 1661 | PUBLICATION | An improved domino/Knoevenagel-hetero-Diels-Alder reaction of two new aldehyde substrates; 7-olefinoxy-coumarin-8-carbaldehyde and 2-alkensulfanyl-quinoline-3-carbaldehyde, with pyrazolones was studied in ionic liquid triethylammonium acetate (TEAA), affording a series of pyrazolopyran annulated-pyrano-fused coumarins, and thiopyrano-fused quinolones. Besides acting as catalyst, since no additional catalyst used, the ionic liquid TEAA also promised its easy recovery. In all new polyheterocycles, the cis-fusion of two pyranyl rings had been inferred from 2D NMR COSY and NOESY experiments. All are good antitubercular agents, as they are found active against Mycobacterium tuberculosis H37Rv, and antibacterial agents, as they are found active against three Gram-positive (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis) and three Gram-negative (Salmonella typhi, Vibrio cholerae, Escherichia coli) bacteria. | 42 | 10 | 375 | CHEMBL_17 | 2013-08-29 |
CHEMBL1926666 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Synthesis of novel 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds and their evaluation for tuberculostatic activity. | 22153872 | 10.1016/j.bmc.2011.11.020 | nan | Gobis K, Foks H, Bojanowski K, Augustynowicz-Kopeć E, Napiórkowska A. | 2012 | 20 | 1 | 137 | 144 | PUBLICATION | A series of novel 3-cyclohexylpropanoic acid derivatives and 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds (1-8) have been synthesized and evaluated for tuberculostatic activity. Compounds 1a, 1c, 1e and 1f bearing benzimidazole or benzimidazole-like systems showed the most potent tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 1.5 to 12.5μg/mL. More importantly 1a (6-chloro-2-(2-cyclohexylethyl)-4-nitro-1H-benzo[d]imidazole) and 1f (2-(2-cyclohexylethyl)-1H-imidazo[4,5-b]phenazine) appeared selective for M. tuberculosis as compared with eukaryotic cells (human fibroblasts), and other antimicrobial strains. These compounds may thus represent a novel, selective class of antitubercular agents. Additionally compound 1a stimulated type I collagen output by fibroblasts, in vitro. | 23 | 5 | 141 | CHEMBL_14 | 2012-06-27 |
CHEMBL2375319 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Design, synthesis and structure-activity relationships of 3,5-diaryl-1H-pyrazoles as inhibitors of arylamine N-acetyltransferase. | 23518278 | 10.1016/j.bmcl.2013.02.052 | nan | Fullam E, Talbot J, Abuhammed A, Westwood I, Davies SG, Russell AJ, Sim E. | 2013 | 23 | 9 | 2759 | 2764 | PUBLICATION | The synthesis and inhibitory potencies of a novel series of 3,5-diaryl-1H-pyrazoles as specific inhibitors of prokaryotic arylamine N-acetyltransferase enzymes is described. The series is based on hit compound 1 3,5-diaryl-1H-pyrazole identified from a high-throughout screen that has been carried out previously and found to inhibit the growth of Mycobacterium tuberculosis. | 16 | 2 | 36 | CHEMBL_18 | 2014-03-12 |
CHEMBL1155696 | Journal of natural products. | 1 | Scientific Literature | Enhanced cytotoxicity in a Z-photoisomer of a benzopyran derivative of propolis. | 10757720 | 10.1021/np990463m | nan | Hirota M, Matsuno T, Fujiwara T, Sugiyama H, Mineshita S. | 2000 | 63 | 3 | 366 | 370 | PUBLICATION | (Z)-2,2-Dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (1) was isolated from Brazilian propolis, together with the known benzopyran derivative, (E)-2, 2-dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (2). The structure was determined by spectroscopic analyses, which included 1D and 2D (1)H and (13)C NMR experiments, as well as MS, IR, and UV spectroscopy. Compound 2 rapidly changed to 1 under UV irradiation conditions (365 nm), and the reverse reaction was also observed. The ratio of 1 to 2 reached 2.3 when the reaction began from either 1 or 2, indicating a photostationary state. Compound 1 displayed an approximate 7-fold stronger cytotoxicity against human lung carcinoma cells (HLC-2) compared with 2. | 2 | 2 | 7 | CHEMBL_2 | 2009-11-30 |
CHEMBL1137688 | European journal of medicinal chemistry. | 1 | Scientific Literature | Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles. | 18617291 | 10.1016/j.ejmech.2008.05.009 | nan | Zhang D, Wang Z, Xu W, Sun F, Tang L, Wang J. | 2009 | 44 | 5 | 2202 | 2210 | PUBLICATION | A series of novel actinonin derivatives containing a benzimidazole heterocycle linked as amide isostere have been designed and synthesized. The structures of all the synthesized compounds were confirmed by analytical and spectroscopic methods. All the compounds were evaluated in vitro against Staphylococcus aureus, Klebsiella pneumoniae, and Sarcina lutea. Among them, compound 1a with unsubstituted benzimidazole ring exhibited potent antibacterial activities. | 8 | 3 | 24 | CHEMBL_2 | 2009-11-30 |
CHEMBL2146446 | ACS medicinal chemistry letters. | 1 | Scientific Literature | 3-Hydroxy-1-alkyl-2-methylpyridine-4(1H)-thiones: Inhibition of the Pseudomonas aeruginosa Virulence Factor LasB. | 23181168 | 10.1021/ml300128f | nan | Garner AL, Struss AK, Fullagar JL, Agrawal A, Moreno AY, Cohen SM, Janda KD. | 2012 | 3 | 8 | 668 | 672 | PUBLICATION | Bacterial resistance coupled to our current arsenal of antibiotics presents us with a growing threat to public health, thus warranting the exploration of alternative antibacterial strategies. In particular, the targeting of virulence factors has been regarded as a 'second generation' antibiotic approach. In Pseudomonas aeruginosa, a Zn(2+) metalloprotease virulence factor, LasB or P. aeruginosa elastase, has been implicated in the development of P. aeruginosa-related keratitis, pneumonia and burn infection. Moreover, the enzyme also plays a critical role in swarming and biofilm formation, both of which are processes that have been linked to antibiotic resistance. To further validate the importance of LasB in P. aeruginosa infection, we describe our efforts toward the discovery of non-peptidic small molecule inhibitors of LasB. Using identified compounds, we have confirmed the role that LasB plays in P. aeruginosa swarming and demonstrate the potential for LasB-targeted small molecules in studying antimicrobial resistant P. aeruginosa phenotypes. | 13 | 3 | 33 | CHEMBL_16 | 2013-05-07 |
CHEMBL2311457 | Journal of medicinal chemistry. | 1 | Scientific Literature | Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design. | 23362938 | 10.1021/jm301756m | nan | Teng M, Hilgers MT, Cunningham ML, Borchardt A, Locke JB, Abraham S, Haley G, Kwan BP, Hall C, Hough GW, Shaw KJ, Finn J. | 2013 | 56 | 4 | 1748 | 1760 | PUBLICATION | A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologues tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis. | 24 | 6 | 154 | CHEMBL_17 | 2013-08-29 |
CHEMBL1155773 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Effects of imipenem-cilastatin, ertapenem, piperacillin-tazobactam, and ceftriaxone treatments on persistence of intestinal colonization by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae strains in mice. | 17562802 | 10.1128/aac.00194-07 | nan | Pultz MJ, Donskey CJ. | 2007 | 51 | 8 | 3044 | 3045 | PUBLICATION | nan | 2 | 1 | 10 | CHEMBL_2 | 2009-11-30 |
CHEMBL2331078 | Journal of natural products. | 1 | Scientific Literature | Quantitative purity-activity relationships of natural products: the case of anti-tuberculosis active triterpenes from Oplopanax horridus. | 23356207 | 10.1021/np3007809 | nan | Qiu F, Cai G, Jaki BU, Lankin DC, Franzblau SG, Pauli GF. | 2013 | 76 | 3 | 413 | 419 | PUBLICATION | The present study provides an extension of the previously developed concept of purity-activity relationships (PARs) and enables the quantitative evaluation of the effects of multiple minor components on the bioactivity of residually complex natural products. The anti-tuberculosis active triterpenes from the Alaskan ethnobotanical Oplopanax horridus were selected as a case for the development of the quantitative PAR (QPAR) concept. The residual complexity of the purified triterpenes was initially evaluated by 1D- and 2D-NMR and identified as a combination of structurally related and unrelated impurities. Using a biochemometric approach, the qHNMR purity and anti-TB activity of successive chromatographic fractions of O. horridus triterpenes were correlated by linear regression analysis to generate a mathematical QPAR model. The results demonstrate that impurities, such as widely occurring monoglycerides, can have a profound impact on the observed antimycobacterial activity of triterpene-enriched fractions. The QPAR concept is shown to be capable of providing a quantitative assessment in situations where residually complex constitution contributes toward the biological activity of natural products. | 4 | 1 | 5 | CHEMBL_17 | 2013-08-29 |
CHEMBL2417551 | Journal of medicinal chemistry. | 1 | Scientific Literature | Structure-guided design of novel thiazolidine inhibitors of O-acetyl serine sulfhydrylase from Mycobacterium tuberculosis. | 23879381 | 10.1021/jm400710k | nan | Poyraz O, Jeankumar VU, Saxena S, Schnell R, Haraldsson M, Yogeeswari P, Sriram D, Schneider G. | 2013 | 56 | 16 | 6457 | 6466 | PUBLICATION | The cysteine biosynthetic pathway is absent in humans but essential in microbial pathogens, suggesting that it provides potential targets for the development of novel antibacterial compounds. CysK1 is a pyridoxalphosphate-dependent O-acetyl sulfhydrylase, which catalyzes the formation of l-cysteine from O-acetyl serine and hydrogen sulfide. Here we report nanomolar thiazolidine inhibitors of Mycobacterium tuberculosis CysK1 developed by rational inhibitor design. The thiazolidine compounds were discovered using the crystal structure of a CysK1-peptide inhibitor complex as template. Pharmacophore modeling and subsequent in vitro screening resulted in an initial hit compound 2 (IC50 of 103.8 nM), which was subsequently optimized by a combination of protein crystallography, modeling, and synthetic chemistry. Hit expansion of 2 by chemical synthesis led to improved thiazolidine inhibitors with an IC50 value of 19 nM for the best compound, a 150-fold higher potency than the natural peptide inhibitor (IC50 2.9 μM). | 100 | 2 | 183 | CHEMBL_18 | 2014-03-12 |
CHEMBL1138159 | Journal of medicinal chemistry. | 1 | Scientific Literature | Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase. | 16539372 | 10.1021/jm051273d | nan | Huai Q, Sun Y, Wang H, Macdonald D, Aspiotis R, Robinson H, Huang Z, Ke H. | 2006 | 49 | 6 | 1867 | 1873 | PUBLICATION | Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-, IC50=0.4 nM) and its enantiomer (-)-1 (L-, IC50=43 nM) and their cocrystal structures with PDE4D at 2.0 A resolution. Despite the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The weaker (-)-1 adopts an unfavorable conformation to preserve the pivotal interactions between the Mg-bound waters and the N-oxide of pyridine. These structures support a model in which inhibitors are anchored by the invariant glutamine at one end and the metal-pocket residues at another end. This model provides explanations for most of the observed structure-activity relationship and the metal ion dependency of the catechol-ether based inhibitors and should facilitate their further design. | 2 | 4 | 9 | CHEMBL_1 | 2009-09-03 |
CHEMBL1142210 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Plasmid-mediated KPC-2 in a Klebsiella pneumoniae isolate from China. | 17145797 | 10.1128/aac.01053-06 | nan | Wei ZQ, Du XX, Yu YS, Shen P, Chen YG, Li LJ. | 2007 | 51 | 2 | 763 | 765 | PUBLICATION | A carbapenem-resistant isolate of Klebsiella pneumoniae producing class A carbapenemase KPC-2 was identified in Zhejiang, China. The KPC-2 gene was located on an approximately 60-kb plasmid in a genetic environment partially different from that of blaKPC-2 in the isolates from the United States and Colombia. | 13 | 2 | 65 | CHEMBL_1 | 2009-09-03 |
CHEMBL1145575 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Design and synthesis of novel furoquinoline based inhibitors of multiple targets in the PI3K/Akt-mTOR pathway. | 18501601 | 10.1016/j.bmcl.2008.04.078 | nan | Lohar MV, Mundada R, Bhonde M, Padgaonkar A, Deore V, Yewalkar N, Bhatia D, Rathos M, Joshi K, Vishwakarma RA, Kumar S. | 2008 | 18 | 12 | 3603 | 3606 | PUBLICATION | We herein report the design and synthesis of furoquinoline based novel molecules (16-36) and their in vitro multiple targeted inhibitory potency against PI3K/Akt phosphorylation and mTOR using cell based and cell-free kinase assay. In particular, compound 23 in addition to PI3K-mTOR inhibitory potency, it has shown potent inhibition of hypoxia-induced accumulation of HIF-1alpha protein in U251-HRE cell line. The inhibitory activities of compound 23 were confirmed by Western blot analysis, using human non-small cell lung carcinoma H-460 cell line and glioblastoma U251 cell lines. | 24 | 5 | 102 | CHEMBL_1 | 2009-09-03 |
CHEMBL2202964 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Evaluation of sulfatase-directed quinone methide traps for proteomics. | 21570853 | 10.1016/j.bmc.2011.04.044 | nan | Lenger J, Schröder M, Ennemann EC, Müller B, Wong CH, Noll T, Dierks T, Hanson SR, Sewald N. | 2012 | 20 | 2 | 622 | 627 | PUBLICATION | Sulfatases hydrolytically cleave sulfate esters through a unique catalytic aldehyde, which is introduced by a posttranslational oxidation. To profile active sulfatases in health and disease, activity-based proteomic tools are needed. Herein, quinone methide (QM) traps directed against sulfatases are evaluated as activity-based proteomic probes (ABPPs). Starting from a p-fluoromethylphenyl sulfate scaffold, enzymatically generated QM-traps can inactivate bacterial aryl sulfatases from Pseudomonas aeruginosa and Klebsiella pneumoniae, and human steroid sulfatase. However, multiple enzyme-generated QMs form, diffuse, and non-specifically label purified enzyme. In complex proteomes, QM labeling is sulfatase-dependent but also non-specific. Thus, fluoromethylphenyl sulfates are poor ABPPs for sulfatases. | 3 | 4 | 23 | CHEMBL_16 | 2013-05-07 |
CHEMBL1138642 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | In vitro advanced antimycobacterial screening of cobalt(II) and copper(II) complexes of fluorinated isonicotinoylhydrazones. | 15501030 | 10.1016/j.bmcl.2004.09.052 | nan | Maccari R, Ottanà R, Bottari B, Rotondo E, Vigorita MG. | 2004 | 14 | 23 | 5731 | 5733 | PUBLICATION | The in vitro antimycobacterial activity of cobalt(II) and copper(II) complexes of some fluorinated isonicotinoylhydrazones was evaluated in a TB-infected macrophage model; all metalcomplexes exhibited excellent activity against Mycobacterium tuberculosis Erdman growing within macrophages, at concentrations much lower than in culture media. Moreover complexes 1b and 2a displayed EC(99) values lower than that of the parent-drug, isoniazid. In addition, all tested metalchelates significantly inhibited the growth of single-drug-resistant M. tuberculosis strains; complexes 1a and 2a also possessed moderate activity against Mycobacterium avium complex. | 7 | 1 | 71 | CHEMBL_1 | 2009-09-03 |
CHEMBL1141424 | Journal of natural products. | 1 | Scientific Literature | Antitubercular dihydroagarofuranoid sesquiterpenes from the roots of Microtropis fokienensis. | 17315960 | 10.1021/np060500r | nan | Chen JJ, Chou TH, Peng CF, Chen IS, Yang SZ. | 2007 | 70 | 2 | 202 | 205 | PUBLICATION | Four new dihydroagarofuranoid sesquiterpenes (1-4) and a new hydroxybenzylsalicylaldehyde, forkienin (5), together with nine known compounds have been isolated from the roots of Microtropis fokienensis. The structures of the new compounds were determined through analyses of physical data. Compounds 3, 4, 7, and 8 exhibited potent antitubercular activities (MICs < or = 26.0 microM) against Mycobacterium tuberculosis 90-221387 in vitro. | 15 | 1 | 15 | CHEMBL_1 | 2009-09-03 |
CHEMBL2040757 | European journal of medicinal chemistry. | 1 | Scientific Literature | New N-arylamino biquinoline derivatives: synthesis, antimicrobial, antituberculosis, and antimalarial evaluation. | 22652224 | 10.1016/j.ejmech.2012.05.004 | nan | Shah NM, Patel MP, Patel RG. | 2012 | 54 | nan | 239 | 247 | PUBLICATION | A new series of N-arylamino biquinoline derivatives 5a-x were synthesized by reaction of 2-chloro-3-formyl quinolines 2a-d with malononitrile and various enhydrazinoketones 4a-f in absolute ethanol. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against a representative panel of pathogenic strains and antituberculosis activity against Mycobacterium tuberculosis H37Rv. Compounds 5h and 5s exhibited excellent antibacterial activity and some of the compounds demonstrated moderate antituberculosis activities compared with the first line drugs. The compounds were evaluated in vitro for their activity against the growth of Plasmodium falciparum, the malaria causing parasite. Some of them showed antimalarial activity with IC(50) values as low as 0.005-0.009 μg/mL. | 33 | 10 | 292 | CHEMBL_15 | 2013-01-23 |
CHEMBL1149509 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Search of antitubercular activities in tetrahydroacridines: synthesis and biological evaluation. | 16870429 | 10.1016/j.bmcl.2006.07.025 | nan | Tripathi RP, Verma SS, Pandey J, Agarwal KC, Chaturvedi V, Manju YK, Srivastva AK, Gaikwad A, Sinha S. | 2006 | 16 | 19 | 5144 | 5147 | PUBLICATION | A series of 9-substituted tetrahydroacridines were synthesized by nucleophilic substitution of chloro group with different nucleophiles in 9-chlorotetrahydroacridine (2). The latter could be obtained by POCl(3) mediated cyclization of the intermediate enamine, which in turn, was prepared by acid catalyzed condensation of anthranilic acid and cyclohexanone. Most of the compounds on antitubercular evaluation against M. tuberculosis H37 Rv and H37 Ra strains exhibited potent activities with MIC 6.125-0.78 microg/mL comparable to the standard drugs. | 22 | 2 | 60 | CHEMBL_1 | 2009-09-03 |
CHEMBL2021893 | European journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis, structure-activity relationship and in vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives. | 22503208 | 10.1016/j.ejmech.2012.03.012 | nan | Liu YX, Xiao CL, Wang YX, Li YH, Yang YH, Li YB, Bi CW, Gao LM, Jiang JD, Song DQ. | 2012 | 52 | nan | 151 | 158 | PUBLICATION | Twenty-eight new 13-n-octylberberine derivatives were synthesized and evaluated for their activities against drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) strain H(37)Rv. Among these compounds, compound 16e was the most effective anti-tubercular agent with a MIC value of 0.125 μg/mL. Importantly, compound 16e exhibited more potent effect against rifampicin (RIF)- and isoniazid (INH)-resistant M. tuberculosis strains than both RIF and INH, suggesting a new mechanism of action. Therefore, it has been selected as a drug candidate for further investigation, or as a chemical probe for identifying protein target and studying tuberculosis biology. We consider 13-n-octylberberine analogs to be a promising novel class of antituberculars against multi-drug-resistant (MDR) strains of M. tuberculosis. | 39 | 1 | 69 | CHEMBL_15 | 2013-01-23 |
CHEMBL1811917 | Journal of medicinal chemistry. | 1 | Scientific Literature | Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design. | 21728378 | 10.1021/jm200443b | nan | Ilies M, Di Costanzo L, Dowling DP, Thorn KJ, Christianson DW. | 2011 | 54 | 15 | 5432 | 5443 | PUBLICATION | Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of α,α-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional α-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase. | 3 | 3 | 9 | CHEMBL_13 | 2012-02-21 |
CHEMBL1142074 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | In vitro activities of cloxyquin (5-chloroquinolin-8-ol) against Mycobacterium tuberculosis. | 17178795 | 10.1128/aac.01310-06 | nan | Hongmanee P, Rukseree K, Buabut B, Somsri B, Palittapongarnpim P. | 2007 | 51 | 3 | 1105 | 1106 | PUBLICATION | The in vitro activities of cloxyquin (5-chloroquinolin-8-ol) against 9 standard strains and 150 clinical isolates of Mycobacterium tuberculosis were studied. The MICs ranged from 0.062 to 0.25 microg/ml. The MIC(50) and MIC(90) were 0.125 and 0.25 microg/ml, respectively. These indicate that cloxyquin exhibited good antituberculosis activity, even for multidrug-resistant isolates. | 5 | 1 | 15 | CHEMBL_1 | 2009-09-03 |
CHEMBL1137114 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Antituberculous activity of some aryl semicarbazone derivatives. | 15225698 | 10.1016/j.bmcl.2004.05.060 | nan | Sriram D, Yogeeswari P, Thirumurugan R. | 2004 | 14 | 15 | 3923 | 3924 | PUBLICATION | During the course of our work on the synthesis and screening of new drugs for tuberculosis, we have identified N1-(4-acetamido phenyl)-N4-(2-nitro benzylidene) semicarbazone (1b), which inhibited in vitro Mycobacterium tuberculosis H(37)Rv; 100% inhibition at 1.56 microg/mL. This paper is first of its kind in which aryl semicarbazones are reported to possess antimycobacterials potency greater than p-aminosalicylic acid, ethionamide, ethambutol, ciprofloxacin and kanamycin. | 17 | 1 | 17 | CHEMBL_1 | 2009-09-03 |
CHEMBL2046287 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Conformation study of 2-arylbenzimidazoles as inhibitors of Chlamydia pneumoniae growth. | 22695128 | 10.1016/j.bmcl.2012.05.023 | nan | Siiskonen A, Keurulainen L, Salin O, Kiuru P, Pohjala L, Vuorela P, Yli-Kauhaluoma J. | 2012 | 22 | 14 | 4882 | 4886 | PUBLICATION | Chlamydia pneumoniae is a worldwide cause of various respiratory track diseases ranging from asymptomatic pharyngeal infection to severe, sometimes fatal pneumonia. We have previously identified 2-arylbenzimidazoles as highly active antichlamydial compounds. In this work the importance of conformational effects on the structure-activity relationship of these compounds was studied. To simplify calculations, properly substituted N-phenylbenzamides, or the corresponding heterocyclic compounds, and 2-arylbenzimidazoles were used as model compounds. They were energy minimized and the energy differences between certain conformations were calculated. The main finding was that the compounds which can more easily adopt a non-planar conformation show higher bioactivity. This finding can be utilized in designing new derivatives or in constructing a pharmacophore model. | 16 | 1 | 16 | CHEMBL_15 | 2013-01-23 |
CHEMBL1138866 | Journal of medicinal chemistry. | 1 | Scientific Literature | Antitubercular nucleosides that inhibit siderophore biosynthesis: SAR of the glycosyl domain. | 17181146 | 10.1021/jm061068d | nan | Somu RV, Wilson DJ, Bennett EM, Boshoff HI, Celia L, Beck BJ, Barry CE, Aldrich CC. | 2006 | 49 | 26 | 7623 | 7635 | PUBLICATION | Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a KIapp value of 2.3 nM and MIC99 values of 1.56 microM against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction. | 9 | 3 | 27 | CHEMBL_1 | 2009-09-03 |
CHEMBL1770122 | European journal of medicinal chemistry. | 1 | Scientific Literature | Synthesis, antibacterial and antimycobacterial activities of some new 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(aryl)-carbamoyl-1,4-dihydropyridines. | 21382653 | 10.1016/j.ejmech.2011.02.003 | nan | Sirisha K, Bikshapathi D, Achaiah G, Reddy VM. | 2011 | 46 | 5 | 1564 | 1571 | PUBLICATION | A novel class of 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(phenyl/substituted phenyl)-carbamoyl-1,4-dihydropyridines has been synthesized by simple, economical and eco-friendly, modified Hantzsch condensation reaction making use of N-arylacetoacetamides, aryl or heteroaryl aldehydes and ammonium acetate. The newly synthesized compounds were characterized by their spectral (IR, 1H NMR, Mass), elemental analyses data and evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 and antibacterial activity against different Gram +ve and Gram -ve bacteria. The preliminary screening results revealed that some of the compounds possess promising antimicrobial activity. Amongst the new series of compounds, 6m containing pyrrolyl and 4-methylphenyl groups and 6r possessing 2-pyridyl and 2-methylphenyl groups were found to exhibit a significant antitubercular activity (MIC=12.5-25 μg/mL) in comparison with the first line drug pyrazinamide. | 8 | 5 | 131 | CHEMBL_12 | 2011-11-18 |
CHEMBL1759889 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Susceptibility and mode of binding of the Mycobacterium tuberculosis cysteinyl transferase mycothiol ligase to tRNA synthetase inhibitors. | 21392992 | 10.1016/j.bmcl.2011.02.042 | nan | Gutierrez-Lugo MT, Bewley CA. | 2011 | 21 | 8 | 2480 | 2483 | PUBLICATION | The cysteinyl transferase mycothiol ligase, or MshC, catalyzes the fourth step in the biosynthesis of the small molecular weight thiol mycothiol. MshC is essential for growth of Mycobacterium tuberculosis. Two groups of known aminoacyl tRNA synthetase inhibitors were evaluated for inhibition of M. tuberculosis MshC including aminoacyl adenosine analogs and natural products. Using enzyme assays, isothermal titration calorimetry and NMR, we show that MshC is selectively inhibited by cysteinyl sulfamoyl adenosine, and that discrimination occurs at the amino acid moiety. | 7 | 1 | 11 | CHEMBL_12 | 2011-11-18 |
CHEMBL1128492 | Journal of medicinal chemistry. | 1 | Scientific Literature | Effect of lipophilicity at N-1 on activity of fluoroquinolones against mycobacteria. | 7636859 | 10.1021/jm00015a021 | nan | Renau TE, Sanchez JP, Shapiro MA, Dever JA, Gracheck SJ, Domagala JM. | 1995 | 38 | 15 | 2974 | 2977 | PUBLICATION | The dramatic increase in drug resistant Mycobacterium tuberculosis has caused a resurgence in research targeted toward these organisms. As part of a systematic study to optimize the quinolone antibacterials against mycobacteria, we have prepared a series of N-1-phenyl-substituted derivatives to explore the effect of increasing lipophilicity on potency at this position. The compounds, synthesized by the modification of a literature procedure, were evaluated for activity against Gram-negative and Gram-positive bacteria, Mycobacterium fortuitum and Mycobacterium smegmatis, and the results correlated with log P, pKa, and other attributes. The activity of the compounds against the rapidly growing, less hazardous organism M. fortuitum was used as a measure of M. tuberculosis activity. The results demonstrate that increasing lipophilic character by itself does not correlate with increased potency against mycobacteria. Rather, intrinsic activity against Gram-negative and/or Gram-positive bacteria is the governing factor for corresponding activity against mycobacteria. | 24 | 7 | 240 | CHEMBL_1 | 2009-09-03 |
CHEMBL1142073 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis. | 17178794 | 10.1128/aac.00898-06 | nan | Ibrahim M, Andries K, Lounis N, Chauffour A, Truffot-Pernot C, Jarlier V, Veziris N. | 2007 | 51 | 3 | 1011 | 1015 | PUBLICATION | In previous studies, the diarylquinoline R207910 (also known as TMC207) was demonstrated to have high bactericidal activity when combined with first- or second-line antituberculous drugs. Here we extend the evaluation of R207910 in the curative model of murine tuberculosis by assessing the activities of one-, two-, and three-drug combinations containing R207910 and isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or moxifloxacin (MXF) in the setting of a high initial bacillary load (7.2 log(10) CFU). Two months of treatment with the combinations R207910-PZA, R207910-PZA-INH, R207910-PZA-RIF, or R207910-PZA-MXF resulted in culture-negative lung homogenates in 70 to 100% of the mice, while mice treated with INH-RIF-PZA (the reference regimen) or RIF-MXF-PZA remained culture positive. Combinations including R207910 but not PZA (e.g., R207910-INH-RIF and R207910-MXF-RIF) were less active than R207910-PZA-containing regimens administered either alone or with the addition of INH, RIF, or MXF. These results reveal a synergistic interaction between R207910 and PZA. Three-drug combinations containing these two drugs and INH, RIF, or MXF have the potential to significantly shorten the treatment duration in patients, provided that these results can be confirmed in long-term experiments including periods of relapse. | 5 | 1 | 16 | CHEMBL_1 | 2009-09-03 |
CHEMBL1140684 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Phenylimidazole derivatives as new inhibitors of bacterial enoyl-ACP reductase FabK. | 17600706 | 10.1016/j.bmcl.2007.06.040 | nan | Kitagawa H, Ozawa T, Takahata S, Iida M. | 2007 | 17 | 17 | 4982 | 4986 | PUBLICATION | Novel FabK inhibitors with antibacterial activity against Streptococcus pneumoniae were synthesized and evaluated. Through SAR studies of our initial hit compound 2-(1H-benz[d]imidazol-2-ylthio)-N-(6-methoxycarbonylbenzo[d]thiazol-2-yl)acetamide, a series of novel phenylimidazole derivatives were discovered as potent FabK inhibitors. | 14 | 3 | 35 | CHEMBL_1 | 2009-09-03 |
CHEMBL1137371 | Journal of medicinal chemistry. | 1 | Scientific Literature | Pyrazolidine-3,5-diones and 5-hydroxy-1H-pyrazol-3(2H)-ones, inhibitors of UDP-N-acetylenolpyruvyl glucosamine reductase. | 17004716 | 10.1021/jm060499t | nan | Gilbert AM, Failli A, Shumsky J, Yang Y, Severin A, Singh G, Hu W, Keeney D, Petersen PJ, Katz AH. | 2006 | 49 | 20 | 6027 | 6036 | PUBLICATION | A series of pyrazolidine-3,5-dione and 5-hydroxy-1H-pyrazol-3(2H)-one inhibitors of Escherichia coli UDP-N-acetylenolpyruvyl glucosamine reductase (MurB) has been prepared. The 5-hydroxy-1H-pyrazol-3(2H)-ones show low micromolar IC(50) values versus E. coli MurB and submicromolar minimal inhibitory concentrations (MIC) against Staphylococcus aureus GC 1131, Enterococcus faecalis GC 2242, Streptococcus pneumoniae GC 1894, and E. coli GC 4560 imp, a strain with increased outer membrane permeability. None of these compounds show antimicrobial activity against Candida albicans, a marker of eukaryotic toxicity. Moreover, these compounds inhibit peptidoglycan biosynthesis, as assessed by measuring the amount of soluble peptidoglycan produced by Streptococcus epidermidis upon incubation with compounds. A partial least squares projection to latent structures analysis shows that improving MurB potency and MIC values correlate with increasing lipophilicity of the C-4 substituent of the 5-hydroxy-1H-pyrazol-3(2H)-one core. Docking studies using FLO and PharmDock produced several binding orientations for these molecules in the MurB active site. | 38 | 7 | 301 | CHEMBL_1 | 2009-09-03 |
CHEMBL1121752 | Journal of medicinal chemistry. | 1 | Scientific Literature | Cell-specific ligands for selective drug delivery to tissues and organs. | 7310815 | 10.1021/jm00144a004 | nan | Ponpipom MM, Bugianesi RL, Robbins JC, Doebber TW, Shen TY. | 1981 | 24 | 12 | 1388 | 1395 | PUBLICATION | Various numbers of D-mannose residues have been attached via spacer arms to lysine, dilysine, and oligolysine backbones. These D-mannosyl peptide analogues were found to be potent competitive inhibitors of the uptake of 125I-labeled D-mannose-bovine serum albumin conjugate by rat alveolar macrophages. The inhibitory potency of these synthetic ligands increased with increasing number of carbohydrate moieties. The chirality of the peptide backbone did not appear to play a major role in binding, whereas variations of the length and linkage of the spacer arm notably affected the inhibitory activities. The saccharide specificity of the macrophage receptor was demonstrated by the inactivity of the corresponding D-galactosyl peptide analogues. The L-fucosyl peptide derivative was only weakly active. The trimannosyldilysine ligand (KI = 3.9 microM) and its analogues are potentially useful in selective delivery of therapeutic agents to macrophages. | 12 | 1 | 22 | CHEMBL_1 | 2009-09-03 |
CHEMBL1147116 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Fluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin. | 17296740 | 10.1128/aac.00646-06 | nan | LaPlante KL, Rybak MJ, Tsuji B, Lodise TP, Kaatz GW. | 2007 | 51 | 4 | 1315 | 1320 | PUBLICATION | The potential for resistance development in Streptococcus pneumoniae secondary to exposure to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin at various levels was examined at high inoculum (10(8.5) to 10(9) log10 CFU/ml) over 96 h in an in vitro pharmacodynamic (PD) model using two fluoroquinolone-susceptible isolates. The pharmacokinetics of each drug was simulated to provide a range of free areas under the concentration-time curves (fAUC) that correlated with various fluoroquinolone doses. Potential first (parC and parE)- and second-step (gyrA and gyrB) mutations in isolates with raised MICs were identified by sequence analysis. PD models simulating fAUC/MICs of 51 and<or=60, 34 and 37, <or=82 and<or=86, and<or=24 for gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, respectively, against each isolate were associated with first-step parC (S52G, S79Y, and N91D) and second-step gyrA (S81Y and S114G) mutations. For each fluoroquinolone a delay of first- and second-step mutations was observed with increasingly higher fAUC/MIC ratios and recovery of topoisomerase mutations in S. pneumoniae was related to the fAUC/MIC exposure. Clinical doses of gatifloxacin, gemifloxacin, and moxifloxacin exceeded the fAUC/MIC resistance breakpoint against wild-type S. pneumoniae, whereas those of levofloxacin (500 and 750 mg) were associated with first- and second-step mutations. The exposure breakpoints for levofloxacin were significantly different (P<0.001) from those of the newer fluoroquinolones gatifloxacin, gemifloxacin, and moxifloxacin. Additionally, moxifloxacin breakpoints were significantly lower (P<0.002) than those of gatifloxacin. The order of resistance development determined from fAUC/MIC breakpoints was levofloxacin>gatifloxacin>moxifloxacin=gemifloxacin, which may be related to structural differences within the class. | 4 | 3 | 151 | CHEMBL_1 | 2009-09-03 |
CHEMBL1152997 | Antimicrobial agents and chemotherapy. | 1 | Scientific Literature | Prevalence of and molecular basis for tuberculosis drug resistance in the Republic of Georgia: validation of a QIAplex system for detection of drug resistance-related mutations. | 18070968 | 10.1128/aac.01124-07 | nan | Gegia M, Mdivani N, Mendes RE, Li H, Akhalaia M, Han J, Khechinashvili G, Tang YW. | 2008 | 52 | 2 | 725 | 729 | PUBLICATION | We developed a QIAplex system for the simultaneous detection of 24 Mycobacterium tuberculosis gene mutations responsible for resistance to isoniazid (INH), rifampin (RIF), streptomycin (STM), and ethambutol (EMB) in 196 M. tuberculosis isolates recovered in the Republic of Georgia. In comparison to phenotypic susceptibility tests, the QIAplex showed sensitivity and specificity of 85.4% and 96.1% for INH, 94.4% and 99.4% for RIF, 69.6% and 99.2% for STM, 50.0% and 98.8% for EBM, and 86.7% and 100.0% for multidrug resistance, respectively. The dominant resistance mutations revealed were a mutation in katG resulting in S315T (katG S315T), rpsL K43R, and rpoB S531L. Mutations katG S315G and S315T and rpoB S531L were detected with higher frequencies in pretreated patients than in naive patients (P < 0.05). Simultaneous detection of 24 common drug resistance-related mutations provides a molecular tool for studying and monitoring M. tuberculosis resistance mechanism and epidemiology. | 4 | 1 | 12 | CHEMBL_3 | 2010-04-16 |
CHEMBL1137764 | Bioorganic & medicinal chemistry. | 1 | Scientific Literature | Design, synthesis, antibacterial activity and physicochemical parameters of novel N-4-piperazinyl derivatives of norfloxacin. | 19419875 | 10.1016/j.bmc.2009.04.027 | nan | Abuo-Rahma Gel-D, Sarhan HA, Gad GF. | 2009 | 17 | 11 | 3879 | 3886 | PUBLICATION | We report herein the synthesis of some N-Mannich bases in addition to different N-4 substituents of norfloxacin. The antibacterial activities of the newly synthesized compounds were evaluated and correlated with their physicochemical properties. Results revealed that some of the tested compounds exhibited better inhibitory activities than the reference antibiotic norfloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus strains. Correlation results showed that there is no single physicochemical parameter that can determine the effect of N-4 piperazinyl group on the activity of these fluoroquinolones, where lipophilicity, molecular mass and electronic factors may influence the activity. | 11 | 5 | 314 | CHEMBL_2 | 2009-11-30 |
CHEMBL1122868 | Journal of medicinal chemistry. | 1 | Scientific Literature | New antiallergic pyrano [3,2-g]quinoline-2,8-dicarboxylic acids with potential for the topical treatment of asthma. | 2999403 | 10.1021/jm00150a014 | nan | Cairns H, Cox D, Gould KJ, Ingall AH, Suschitzky JL. | 1985 | 28 | 12 | 1832 | 1842 | PUBLICATION | A number of antiallergic pyranquinolinedicarboxylic acid derivatives with potential for the topical treatment of asthma have been synthesized. All the compounds have been evaluated against rat passive cutaneous anaphylaxis and in a dog hypotension screen. This is the first detailed description of the application of the latter screen for the identification of antiallergic agents. Two compounds, disodium 9-ethyl-6, 9-dihydro-4,6-dioxo-10-propyl-4H-pyrano [3,2-g]quinoline-2,8-dicarboxylate (86) and disodium 6-(methylamino)-4-oxo-10-propyl-4H-pyrano[3,2-g]-quinoline-2, 8-dicarboxylate (72), were selected and further evaluated for their ability to induce phosphorylation of a 78000 molecular weight protein associated with the rat peritoneal mast cell. Their ability to inhibit histamine release from these cells and from a mucosal mast cell preparation has also been evaluated. These compounds, nedocromil sodium (TILADE 86) and minocromil (the free acid of 72), are at present undergoing therapeutic evaluation. The rationale for the screening procedure and the relevance of the second carboxylic acid function of these dibasic acids to receptor binding are discussed. | 33 | 3 | 146 | CHEMBL_1 | 2009-09-03 |
CHEMBL1134120 | Bioorganic & medicinal chemistry letters. | 1 | Scientific Literature | Some 3-thioxo/alkylthio-1,2,4-triazoles with a substituted thiourea moiety as possible antimycobacterials. | 11425542 | 10.1016/s0960-894x(01)00283-9 | nan | Küçükgüzel I, Küçükgüzel SG, Rollas S, Kiraz M. | 2001 | 11 | 13 | 1703 | 1707 | PUBLICATION | A series of novel N-alkyl/aryl-N'-[4-(4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thione-5-yl)phenyl]thioureas 1-19 and three S-alkylated representatives of the former, N-alkyl/aryl-N'-[4-(3-aralkylthio-4-alkyl/aryl-4H-1,2,4-triazole-5-yl)phenyl]thioureas 20-22, were synthesized and tested for antimycobacterial activity against Mycobacterium tuberculosis H37Rv as well as Mycobacterium fortuitum ATCC 6841 which is a rapid growing opportunistic pathogen. Compounds 4 and 9-11 were found to possess the same MIC value with that of Tobramycin against M. fortuitum ATCC 6841 whereas 1-3 and 21 had positive response against M. tuberculosis H37Rv at varying degrees. Compound 21 was identified as the most potent derivative of the 1-22 series by an MIC value of 6.25 microg/mL and selectivity index of 1.6. | 24 | 4 | 86 | CHEMBL_1 | 2009-09-03 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.