title: 4,1-Benzoxazepinone analogues of efavirenz (Sustiva) as HIV-1 reverse transcriptase inhibitors.
abstract: A series of 4,1-benzoxazepinone analogues of efavirenz (Sustiva) as potent NNRTIs has been discovered. The cis-3-alkylbenzoxazepinones are more potent then the trans isomers and can be synthesized preferentially by a novel stereoselective cyclization. The best compounds are potent orally bioavailable inhibitors of both wild-type HIV-1 and its clinically relevant K103N mutant virus, but are highly protein-bound in human plasma.
authors.affiliation: DuPont Pharmaceuticals Company, Experimental Station, E336/141, PO Box 80336, Wilmington, DE 19880-0336, USA. cocuzza@dupontpharma.com
authors.forename: A J
authors.initials: AJ
authors.lastname: Cocuzza
authors.forename: D R
authors.initials: DR
authors.lastname: Chidester
authors.forename: B C
authors.initials: BC
authors.lastname: Cordova
authors.forename: R M
authors.initials: RM
authors.lastname: Klabe
authors.forename: S
authors.initials: S
authors.lastname: Jeffrey
authors.forename: S
authors.initials: S
authors.lastname: Diamond
authors.forename: C A
authors.initials: CA
authors.lastname: Weigelt
authors.forename: S S
authors.initials: SS
authors.lastname: Ko
authors.forename: L T
authors.initials: LT
authors.lastname: Bacheler
authors.forename: S K
authors.initials: SK
authors.lastname: Erickson-Viitanen
authors.forename: J D
authors.initials: JD
authors.lastname: Rodgers
mesh_terms: D000480:Alkynes; D000818:Animals; D048588:Benzoxazines; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D010078:Oxazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding; D011799:Quinazolines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D052999:Quinazolinones; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; C413505:DPC 961; D010078:Oxazines; D011799:Quinazolines; D052999:Quinazolinones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz