5-Chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase

A series of highly potent, structurally novel, non-nucleoside RT inhibitors has been described. Low nanomolar concentrations of 5-chloro-3-(phenylsulfonyl)-indole-2-carboxamide (1) inhibit the HIV-1 RT enzyme in vitro and HTLVIIIb viral spread in MT-4 human T-lymphoid cells. Good oral bioavailabilit...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1993-04, Vol.36 (9), p.1291-1294
Main Authors: Williams, Theresa M, Ciccarone, Terrence M, MacTough, Suzanne C, Rooney, Clarence S, Balani, Suresh K, Condra, Jon H, Emini, Emilio A, Goldman, Mark E, Greenlee, William J
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Base Sequence
Biological Availability
Chemistry
Exact sciences and technology
Heterocyclic compounds
Heterocyclic compounds with only one n hetero atom and condensed derivatives
HIV - drug effects
HIV Reverse Transcriptase
HIV-1 - enzymology
human immunodeficiency virus
Indoles - chemistry
Indoles - pharmacokinetics
Indoles - pharmacology
Macaca mulatta
Molecular Sequence Data
Molecular Structure
Organic chemistry
Preparations and properties
Reverse Transcriptase Inhibitors
Sulfoxides - chemistry
Sulfoxides - pharmacokinetics
Sulfoxides - pharmacology
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Description
Summary:A series of highly potent, structurally novel, non-nucleoside RT inhibitors has been described. Low nanomolar concentrations of 5-chloro-3-(phenylsulfonyl)-indole-2-carboxamide (1) inhibit the HIV-1 RT enzyme in vitro and HTLVIIIb viral spread in MT-4 human T-lymphoid cells. Good oral bioavailability was observed in rhesus monkeys upon oral dosing of 1 as a suspension in methocel. When compared to other non-nucleoside inhibitors (e.g. 15-18), 1 possesses improved inhibitory potency with respect to the wild-type RT, as well as the K103N and Y181C mutant enzymes. Additional studies within this class of inhibitors are in progress.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00061a022