Synthesis, biological activity, and SAR of antimycobacterial 9-aryl-, 9-arylsulfonyl-, and 9-benzyl-6-(2-furyl)purines.
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.
Bakkestuen
Anne Kristin
AK
Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
Gundersen
Lise-Lotte
LL
Utenova
Bibigul T
BT
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002522:Chlorocebus aethiops; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014709:Vero Cells
C500168:2-chloro-6-(2-furyl)-9-(4-methoxyphenylmethyl)-9H-purine; D000995:Antitubercular Agents; D005663:Furans; D011687:Purines; D013450:Sulfones