An approach to the stereo-controlled synthesis of polycyclic derivatives of l-4-thiazolidinecarboxylic acid active against HIV-1 integrase.
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.
Aiello
F
F
Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende (Cs), Italy.
Brizzi
A
A
De Grazia
O
O
Garofalo
A
A
Grande
F
F
Sinicropi
M S
MS
Dayam
R
R
Neamati
N
N
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
D002264:Carboxylic Acids; D019428:HIV Integrase Inhibitors; D013844:Thiazoles; D019427:HIV Integrase; C514024:l-4-thiazolidinecarboxylic acid