Synthesis, biological activity, and SAR of antimycobacterial 9-aryl-, 9-arylsulfonyl-, and 9-benzyl-6-(2-furyl)purines.
Bakkestuen AK, Gundersen LL, Utenova BT.
9-Aryl-, 9-arylsulfonyl- and 9-benzyl-6-(2-furyl)purines were synthesized by N-alkylation or N-arylation of the purine followed by Stille coupling to introduce the furyl substituent in the 6-position and the compounds screened for activity against Mycobacterium tuberculosis. The 9-aryl- and 9-sulfonylarylpurines exhibited weak activity toward the bacteria, but 9-benzylpurines were good inhibitors especially those carrying electron-donating substituents on the phenyl ring. A chlorine atom in the purine 2-position further enhanced activity. The high antimycobacterial activity (MIC 0.39 microg/mL against M. tuberculosis), low toxicity against mammalian cells and activity inside macrophages found for 2-chloro-6-(2-furyl)-9-(4-methoxyphenylmethyl)-9H-purine makes this compound a highly interesting potential antituberculosis drug.