title: Benzyl amide-ketoacid inhibitors of HIV-integrase.
abstract: 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.
authors.affiliation: 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
authors.forename: Michael A
authors.initials: MA
authors.lastname: Walker
authors.forename: Timothy
authors.initials: T
authors.lastname: Johnson
authors.forename: B Narasimhulu
authors.initials: BN
authors.lastname: Naidu
authors.forename: Jacques
authors.initials: J
authors.lastname: Banville
authors.forename: Roger
authors.initials: R
authors.lastname: Remillard
authors.forename: Serge
authors.initials: S
authors.lastname: Plamondon
authors.forename: Alain
authors.initials: A
authors.lastname: Martel
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Albert
authors.initials: A
authors.lastname: Torri
authors.forename: Himadri
authors.initials: H
authors.lastname: Samanta
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Lin
authors.forename: Ira
authors.initials: I
authors.lastname: Dicker
authors.forename: Mark
authors.initials: M
authors.lastname: Krystal
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
mesh_terms: 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
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D019428:HIV Integrase Inhibitors; D007651:Keto Acids; D019427:HIV Integrase; D019426:Integrases; D009584:Nitrogen