Scaffold hopping in the rational design of novel HIV-1 non-nucleoside reverse transcriptase inhibitors.
High-throughput screening hit 1 was identified as a potent, broad-spectrum, non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 replication. Analysis of the bound conformation of analogs of this inhibitor via molecular modeling and NMR contributed to the design of novel tertiary amide, carbamate, and thiocarbamate based NNRTIs.
O'Meara
Jeff A
JA
Boehringer Ingelheim (Canada) Ltd, Research and Development, 2100 Cunard Street, Laval, Que., Canada H7S 2G5. jomeara@lav.boehringer-ingelheim.com
Jakalian
Araz
A
LaPlante
Steven
S
Bonneau
Pierre R
PR
Coulombe
René
R
Faucher
Anne-Marie
AM
Guse
Ingrid
I
Landry
Serge
S
Racine
Jennifer
J
Simoneau
Bruno
B
Thavonekham
Bounkham
B
Yoakim
Christiane
C
D000577:Amides / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry; D015195:Drug Design; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects*
D000577:Amides; D019380:Anti-HIV Agents; D002219:Carbamates; D018894:Reverse Transcriptase Inhibitors; D013859:Thiocarbamates; D054303:HIV Reverse Transcriptase