title: The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives.
abstract: The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several compounds demonstrated highly efficacious immunosuppressive properties, especially compounds 2d, 2e, 2h and 2j, which were superior to MPA, while compounds 2k, 2m, 2n, 4c and 5d exhibited an equipotent inhibitory activity compared to MPA. Generally, it was obviously demonstrated that α,β-unsaturated amides proved more potent than the diamide and urea series. The present study provides a guide for further research on development of safe and effective immunosuppressive agents.
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.forename: Qing-He
authors.initials: QH
authors.lastname: Wang
authors.forename: Wen-Qian
authors.initials: WQ
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Shen-Peng
authors.initials: SP
authors.lastname: Tan
authors.forename: Mao-Sheng
authors.initials: MS
authors.lastname: Cheng
mesh_terms: D000577:Amides / Q000737:chemistry; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000577:Amides; D001572:Benzofurans; D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human