An approach to the stereo-controlled synthesis of polycyclic derivatives of L-4-thiazolidinecarboxylic acid active against HIV-1 integrase

被引:2
作者
Aiello, F.
Brizzi, A.
De Grazia, O.
Garofalo, A. [1 ]
Grande, F.
Sinicropi, M. S.
Dayam, R.
Neamati, N.
机构
[1] Univ Calabria, Dipartimento Sci Farmaceut, I-87036 Arcavacata Di Rende, CS, Italy
[2] Univ Siena, Dipartimento Farmacochim Tecnol, I-53100 Siena, Italy
[3] Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA
关键词
HIV-1 integrase inhibitors; L-4-thiazolidinecarboxylic acid; thiazolothiazepines;
D O I
10.1016/j.ejmech.2006.03.032
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 I in the IN active site. A sensibly lower IC50 value was found for (-)-1 over racemic-1 in an anti-IN assay. (c) 2006 Elsevier SAS. All rights reserved.
引用
收藏
页码:914 / 917
页数:4
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