title: Selective non-nucleoside HIV-1 reverse transcriptase inhibitors. New 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds with anti-HIV-1 activity.
abstract: A series of substituted 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds 1-73 were synthesized and evaluated for their ability to inhibit reverse transcriptase (RT) of the human immune deficiency virus 1 (HIV-1) and replication of HIV-1 in MT2 cells. The antiviral activity of these compounds depends on the stereoselective configuration of the substituent in position 9b. Structure-activity studies were done within these series of compounds to determine the optimum substituents for antiviral activity. The most potent inhibitors were found in the class of 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones bearing a phenyl ring system in position 9b optionally substituted with one or two methyl groups or a chlorine atom in position 8. The most active analogues (R)-(+)-1, (R)-(+)-6, (R)-(+)-13, (R)-(+)-26, and (R)-(+)-53 inhibit the HIV-1 RT with an IC50 between 16 and 300 nM and an IC50 between 10 and 392 nM in MT2 cells, respectively.
authors.affiliation: Boehringer Mannheim GmbH, Chemical Research Department, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Mertens
authors.forename: H
authors.initials: H
authors.lastname: Zilch
authors.forename: B
authors.initials: B
authors.lastname: König
authors.forename: W
authors.initials: W
authors.lastname: Schäfer
authors.forename: T
authors.initials: T
authors.lastname: Poll
authors.forename: W
authors.initials: W
authors.lastname: Kampe
authors.forename: H
authors.initials: H
authors.lastname: Seidel
authors.forename: U
authors.initials: U
authors.lastname: Leser
authors.forename: H
authors.initials: H
authors.lastname: Leinert
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D054303:HIV Reverse Transcriptase; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D018894:Reverse Transcriptase Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; D054303:HIV Reverse Transcriptase