Tetrazole thioacetanilides: potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant.
A series of aryltetrazolylacetanilides was synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors on wild-type virus and on the clinically relevant K103N mutant strain. Extensive SAR investigation led to potent compounds, with nanomolar activity on K103N, and orally bioavailable in rats.
Muraglia
Ester
E
Department of Medicinal Chemistry, IRBM/MRL Rome, Via Pontina Km 30,600, 00040 Pomezia, Rome, Italy. Ester_Muraglia@merck.com
Kinzel
Olaf D
OD
Laufer
Ralph
R
Miller
Michael D
MD
Moyer
Gregory
G
Munshi
Vandna
V
Orvieto
Federica
F
Palumbi
Maria Cecilia
MC
Pescatore
Giovanna
G
Rowley
Michael
M
Williams
Peter D
PD
Summa
Vincenzo
V
D000083:Acetanilides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000083:Acetanilides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C039632:thioacetanilide