Details

Autor(en) / Beteiligte

• Klunder, Janice M
• Hargrave, Karl D
• West, MaryAnn
• Cullen, Ernest
• Pal, Kollol
• Behnke, Mark L
• Kapadia, Suresh R
• McNeil, Daniel W
• Wu, Joe C
• Chow, Grace C
• Adams, Julian

Titel

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

Ist Teil von

• Journal of medicinal chemistry, 1992-05, Vol.35 (10), p.1887-1897

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

1992

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.