title: An approach to the stereo-controlled synthesis of polycyclic derivatives of l-4-thiazolidinecarboxylic acid active against HIV-1 integrase.
abstract: Herein, we describe a new strategy for the preparation of thiazolothiazepine-based inhibitors of human immunodeficiency virus type-1 integrase (IN). The present method allows facile preparation of the title compounds in a single enantiomeric form starting from l-4-thiazolidinecarboxylic acid. This method could be easily extended to the synthesis of several analogs derived from optically active cyclic aminoacids. We also present a putative model showing the interaction between l- and d-isomers of compound 1 in the IN active site. A sensibly lower IC(50) value was found for (-)-1 over racemic-1 in an anti-IN assay.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende (Cs), Italy.
authors.forename: F
authors.initials: F
authors.lastname: Aiello
authors.forename: A
authors.initials: A
authors.lastname: Brizzi
authors.forename: O
authors.initials: O
authors.lastname: De Grazia
authors.forename: A
authors.initials: A
authors.lastname: Garofalo
authors.forename: F
authors.initials: F
authors.lastname: Grande
authors.forename: M S
authors.initials: MS
authors.lastname: Sinicropi
authors.forename: R
authors.initials: R
authors.lastname: Dayam
authors.forename: N
authors.initials: N
authors.lastname: Neamati
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002264:Carboxylic Acids; D019428:HIV Integrase Inhibitors; D013844:Thiazoles; D019427:HIV Integrase; C514024:l-4-thiazolidinecarboxylic acid