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Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5/CXCR4 HIV Entry and Reverse Transcriptase.

ABSTRACT: We report novel anti-HIV-1 agents with combined dual host-pathogen pharmacology. Lead compound 3, composed of a pyrazole-piperidine core, exhibits three concurrent mechanisms of action: (1) non-nucleoside reverse transcriptase inhibition, (2) CCR5-mediated M-tropic viral entry inhibition, and (3) CXCR4-based T-tropic viral entry inhibition that maintains native chemokine ligand binding. This discovery identifies important tool compounds for studying viral infectivity and prototype agents that block HIV-1 entry through dual chemokine receptor ligation.

SUBMITTER: Cox BD 

PROVIDER: S-EPMC4499816 | biostudies-other | 2015 Jul

REPOSITORIES: biostudies-other

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Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5/CXCR4 HIV Entry and Reverse Transcriptase.

Cox Bryan D BD   Prosser Anthony R AR   Sun Yongnian Y   Li Zhufang Z   Lee Sangil S   Huang Ming B MB   Bond Vincent C VC   Snyder James P JP   Krystal Mark M   Wilson Lawrence J LJ   Liotta Dennis C DC  

ACS medicinal chemistry letters 20150506 7

We report novel anti-HIV-1 agents with combined dual host-pathogen pharmacology. Lead compound 3, composed of a pyrazole-piperidine core, exhibits three concurrent mechanisms of action: (1) non-nucleoside reverse transcriptase inhibition, (2) CCR5-mediated M-tropic viral entry inhibition, and (3) CXCR4-based T-tropic viral entry inhibition that maintains native chemokine ligand binding. This discovery identifies important tool compounds for studying viral infectivity and prototype agents that bl  ...[more]