title: Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic pyridobenzoxazepinones and dibenzoxazepinones.
abstract: Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)-ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as low as 19 nM. A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency. Substitution in the C-ring is generally neutral or detrimental to activity. Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted. Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.
authors.affiliation: Research and Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
authors.forename: J M
authors.initials: JM
authors.lastname: Klunder
authors.forename: K D
authors.initials: KD
authors.lastname: Hargrave
authors.forename: M
authors.initials: M
authors.lastname: West
authors.forename: E
authors.initials: E
authors.lastname: Cullen
authors.forename: K
authors.initials: K
authors.lastname: Pal
authors.forename: M L
authors.initials: ML
authors.lastname: Behnke
authors.forename: S R
authors.initials: SR
authors.lastname: Kapadia
authors.forename: D W
authors.initials: DW
authors.lastname: McNeil
authors.forename: J C
authors.initials: JC
authors.lastname: Wu
authors.forename: G C
authors.initials: GC
authors.lastname: Chow
mesh_terms: D003989:Dibenzoxazepines / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors
chemical_list: D003989:Dibenzoxazepines; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors