卡马西平新型水溶性亚磺酰胺前药的制备、表征及体内转化

Preparation, characterization and in vivo conversion of new water-soluble sulfenamide prodrugs of carbamazepine.

作者信息

Hemenway Jeffrey N, Nti-Addae Kwame, Guarino Victor R, Stella Valentino J

机构信息

Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, KS 66047, USA.

出版信息

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6629-32. doi: 10.1016/j.bmcl.2007.09.045. Epub 2007 Sep 15.

DOI:10.1016/j.bmcl.2007.09.045

PMID:17928225

Abstract

Improved synthetic methods are reported for the preparation of sulfenamide derivatives of carbamazepine (CBZ) for evaluation as prodrugs. These sulfenamide prodrugs were designed to rapidly release CBZ in vivo by cleavage of the sulfenamide bond by chemical reaction with glutathione and other sulfhydryl compounds. Physicochemical characterization and in vivo conversion of a new prodrug of CBZ was evaluated to further establish the proof of concept of the sulfenamide prodrug approach.

摘要

报道了用于制备卡马西平（CBZ）亚磺酰胺衍生物以评估其作为前药的改进合成方法。这些亚磺酰胺前药旨在通过与谷胱甘肽和其他巯基化合物发生化学反应裂解亚磺酰胺键，从而在体内快速释放CBZ。对一种新的CBZ前药进行了物理化学表征和体内转化评估，以进一步确立亚磺酰胺前药方法的概念验证。