Synthesis and evaluation of efavirenz (Sustiva) analogues as HIV-1 reverse transcriptase inhibitors: replacement of the cyclopropylacetylene side chain.
Two series of efavirenz analogues have been developed: one in which the cyclopropane ring has been replaced by small heterocycles and another in which the entire acetylenic side chain has been replaced by alkyloxy groups. Several members of both series show equivalent potency to efavirenz against both wild-type virus and the key K103N mutant.
Cocuzza
A J
AJ
DuPont Pharmaceuticals Company, Experimental Station, Wilmington, DE 19880-0336, USA. anthony.j.cocuzza@dupontpharma.com
Chidester
D R
DR
Cordova
B C
BC
Jeffrey
S
S
Parsons
R L
RL
Bacheler
L T
LT
Erickson-Viitanen
S
S
Trainor
G L
GL
Ko
S S
SS
D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D048588:Benzoxazines; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D009154:Mutation; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz