Preparation of 6-Substituted Quinoxaline JSP-1 Inhibitors by Microwave Accelerated Nucleophilic Substitution 英文参考文献.docVIP

Molecules 2006, 11, 988-999 molecules ISSN 1420-3049 Full Paper Preparation of 6-Substituted Quinoxaline JSP-1 Inhibitors by Microwave Accelerated Nucleophilic Substitution Li Zhang 1, Beiying Qiu 2, Xin Li 1, Xin Wang 1, Jingya Li 2, Yongliang Zhang 1, Jian Liu 1, Jia Li 2 and Jingkang Shen 1,* 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P.R. China; E-mail: zhangli@ 2 The National Center for Drug Screening, 189 Guoshoujing Road, Shanghai 201203, P.R. China; E-mail: byqiu@, E-mail: jli@ * Author to whom correspondence should be addressed; E-mail: jkshen@ Received: 27 November 2006; in revised form: 17 December 2006 / Accepted: 18 December 2006 / Published: 21 December 2006 Abstract: A small library of 6-aminoquinoxalines has been prepared by nucleophilic substitution of 6-fluoroquinoxaline with amines and nitrogen-containing heterocycles under computer-controlled microwave irradiation. Some compounds were found to be potent inhibitors of JNK Stimulatory Phosphatase-1 (JSP-1) in an in vitro biological assay. Keywords: Microwave irradiation; nucleophilic substitution; 6-substituted quinoxalines; JSP-1. Introduction Quinoxalines are an important class of nitrogen-containing heterocycles with a variety of biological activities, specifically as AMPA/GlyN receptor antagonists [1-3], angiotensin II receptor antagonists [4-5], anticancer agents [6-9], antiinfection agents [10-11] and immunomodulating agents [12-13]. Through a high-throughput screening of our sample collection, an aminoquinoxaline derivative I (Figure 1) was found to show inhibitory activity towards JNK Stimulatory Phosphatase-1 (JSP-1) in an in vitro biological assay [14]. JSP-1, also known as VHX/MKPX [15] or JKAP [16], is a special  Molecules 2006, 11 989 member of the so-ca