Benzyl amide-ketoacid inhibitors of HIV-integrase.
Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. Previous reports have demonstrated that the diketoacid-based chemotype is a useful starting point for the design of inhibitors of this enzyme. In this study, one of the ketone groups is replaced by a benzylamide resulting in a new potent chemotype. A preliminary SAR study is carried out to investigate the substitution requirements on the phenyl ring and methylene group of the benzylamide.
Walker
Michael A
MA
Department of Medicinal Chemistry, Research and Development, Bristol-Myers Squibb, The Richard L Gelb Center for Pharmaceutical Research and Development, Wallingford, CT 06492, USA. michael.a.walker@bms.com
Johnson
Timothy
T
Naidu
B Narasimhulu
BN
Banville
Jacques
J
Remillard
Roger
R
Plamondon
Serge
S
Martel
Alain
A
Li
Chen
C
Torri
Albert
A
Samanta
Himadri
H
Lin
Zeyu
Z
Dicker
Ira
I
Krystal
Mark
M
Meanwell
Nicholas A
NA
D000577:Amides / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004583:Electrons; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D020128:Inhibitory Concentration 50; D019426:Integrases / Q000737:chemistry; D007651:Keto Acids / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D013329:Structure-Activity Relationship
D000577:Amides; D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D019428:HIV Integrase Inhibitors; D007651:Keto Acids; D019427:HIV Integrase; D019426:Integrases; D009584:Nitrogen