Design, synthesis, and evaluation of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors.
Kim I, Song JH, Park CM, Jeong JW, Kim HR, Ha JR, No Z, Hyun YL, Cho YS, Sook Kang N, Jeon DJ.
Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC(50)<10nM).