4,1-Benzoxazepinone analogues of efavirenz (Sustiva) as HIV-1 reverse transcriptase inhibitors.
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.
Cocuzza
A J
AJ
DuPont Pharmaceuticals Company, Experimental Station, E336/141, PO Box 80336, Wilmington, DE 19880-0336, USA. cocuzza@dupontpharma.com
Chidester
D R
DR
Cordova
B C
BC
Klabe
R M
RM
Jeffrey
S
S
Diamond
S
S
Weigelt
C A
CA
Ko
S S
SS
Bacheler
L T
LT
Erickson-Viitanen
S K
SK
Rodgers
J D
JD
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
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