Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic pyridobenzoxazepinones and dibenzoxazepinones

J Med Chem. 1992 May 15;35(10):1887-97. doi: 10.1021/jm00088a027.


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.

MeSH terms

  • Dibenzoxazepines / chemistry
  • Dibenzoxazepines / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • HIV-1 / enzymology*
  • Recombinant Proteins / antagonists & inhibitors
  • Reverse Transcriptase Inhibitors*


  • Dibenzoxazepines
  • Enzyme Inhibitors
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors