1.
Bioorg Med Chem Lett
; 20(15): 4328-32, 2010 Aug 01.
Article
in English
| MEDLINE
| ID: mdl-20609585
ABSTRACT
Biaryl ethers were recently reported as potent NNRTIs. Herein, we disclose a detailed effort to modify the previously reported compound 1. We have designed and synthesized a series of novel pyrazole derivatives as a surrogate for pyrazolopyridine motif that were potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells.
Subject(s)
Anti-HIV Agents/chemistry , Ethers/chemistry , HIV Reverse Transcriptase/antagonists & inhibitors , Pyrazoles/chemistry , Pyridines/chemistry , Reverse Transcriptase Inhibitors/chemistry , Allosteric Regulation , Animals , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacokinetics , Dogs , Ethers/chemical synthesis , Ethers/pharmacokinetics , HIV Reverse Transcriptase/genetics , HIV Reverse Transcriptase/metabolism , Humans , Mutation , Pyrazoles/chemical synthesis , Pyrazoles/pharmacokinetics , Pyridines/chemical synthesis , Pyridines/pharmacokinetics , Rats , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/pharmacokinetics , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 18(9): 2959-66, 2008 May 01.
Article
in English
| MEDLINE
| ID: mdl-18396399
ABSTRACT
Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.