title: 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486-0004.
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: T M
authors.initials: TM
authors.lastname: Ciccarone
authors.forename: S C
authors.initials: SC
authors.lastname: MacTough
authors.forename: C S
authors.initials: CS
authors.lastname: Rooney
authors.forename: S K
authors.initials: SK
authors.lastname: Balani
authors.forename: J H
authors.initials: JH
authors.lastname: Condra
authors.forename: E A
authors.initials: EA
authors.lastname: Emini
authors.forename: M E
authors.initials: ME
authors.lastname: Goldman
authors.forename: W J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: L R
authors.initials: LR
authors.lastname: Kauffman
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001682:Biological Availability; D006678:HIV / Q000187:drug effects; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology*; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors; D013454:Sulfoxides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C081119:5-chloro-3-(phenylsulfonyl)indole-2-carboxamide; D000998:Antiviral Agents; D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; D013454:Sulfoxides; D054303:HIV Reverse Transcriptase