Synthesis, biological activity, and SAR of antimycobacterial 9-aryl-, 9-arylsulfonyl-, and 9-benzyl-6-(2-furyl)purines. Journal of medicinal chemistry. [J Med Chem] Journal article | | Title | Synthesis, biological activity, and SAR of antimycobacterial 9-aryl-, 9-arylsulfonyl-, and 9-benzyl-6-(2-furyl)purines. | | Author(s) | Bakkestuen AK, Gundersen LL, Utenova BT | | Institution | Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway. | | Source | J Med Chem 2005 Apr 7; 48(7):2710-23. | | MeSH | Animals
Antitubercular Agents
Cercopithecus aethiops
Furans
In Vitro
Macrophages
Mice
Microbial Sensitivity Tests
Mycobacterium avium Complex
Mycobacterium tuberculosis
Purines
Research Support, Non-U.S. Gov't
Structure-Activity Relationship
Sulfones
Vero Cells
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15801862 |
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