title: Synthesis and evaluation of analogs of Efavirenz (SUSTIVA) as HIV-1 reverse transcriptase inhibitors.
abstract: Efavirenz (SUSTIVA) is a potent non-nucleoside reverse transcriptase inhibitor. Due to the observation of breakthrough mutations of the reverse transcriptase enzyme during Efavirenz therapy, we sought to develop an optimized second generation series. To that end, SAR of the substituents on the aromatic ring was undertaken and the results are summarized here. The 5,6-difluoro (4f) and the 6-methoxy (4m) substituted benzoxazinones were determined to be equipotent, and as a result such substitution patterns will be incorporated in second generation scaffolds.
authors.affiliation: DuPont Pharmaceuticals Company, Experimental Station, Wilmington, DE, USA.
authors.forename: M
authors.initials: M
authors.lastname: Patel
authors.forename: S S
authors.initials: SS
authors.lastname: Ko
authors.forename: R J
authors.initials: RJ
authors.lastname: McHugh
authors.forename: J A
authors.initials: JA
authors.lastname: Markwalder
authors.forename: A S
authors.initials: AS
authors.lastname: Srivastava
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: Erickson-Viitanen
authors.forename: G L
authors.initials: GL
authors.lastname: Trainor
authors.forename: S P
authors.initials: SP
authors.lastname: Seitz
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D048588:Benzoxazines; D003521:Cyclopropanes; D015497:HIV-1; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz