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Synthesis and Anti-HIV Profile of a Novel Tetrahydroindazolylbenzamide Derivative Obtained by Oxazolone Chemistry.

ABSTRACT: A new tetrahydroindazolylbenzamide derivative has been synthesized, characterized, and evaluated as HIV-inhibitor. The biological data revealed the ability to inhibit HIV proliferation with low cytotoxicity allowing for significant selectivity (EC₅₀ 2.77 ?M; CC₅₀ 118.7 ?M; SI = 68). The compound did not inhibit the viral integrase as demonstrated by in vitro studies. QPCR experiments showed that the block of viral replication occurred at early replication steps, prior to integration, profiling it as a late reverse transcription inhibitor. An efficient multistep strategy was adopted for the synthesis of the scaffold, consisting of a sequential ring-opening reaction of oxazol-5-(4H)-one with 1,3-diketone, followed by cyclocondensation with hydrazine and hydrolysis of the nitrile to the desired carboxamide.

SUBMITTER: Scala A

PROVIDER: S-EPMC6466547 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Synthesis and Anti-HIV Profile of a Novel Tetrahydroindazolylbenzamide Derivative Obtained by Oxazolone Chemistry.

Scala Angela A Piperno Anna A Micale Nicola N Christ Frauke F Debyser Zeger Z

ACS medicinal chemistry letters 20181215 4

A new tetrahydroindazolylbenzamide derivative has been synthesized, characterized, and evaluated as HIV-inhibitor. The biological data revealed the ability to inhibit HIV proliferation with low cytotoxicity allowing for significant selectivity (EC50 2.77 μM; CC50 118.7 μM; SI = 68). The compound did not inhibit the viral integrase as demonstrated by in vitro studies. QPCR experiments showed that the block of viral replication occurred at early replication steps, prio ...[more]

PMID: 30996769

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