title: [Synthesis and immunosuppressive effects of novel phthalazine ketone derivatives].
abstract: A series of phthalazine ketone compounds were synthesized and the structures were confirmed by H NMR and HR-MS spectrum. All target compounds were obtained through 7 steps, including selective reduction, nitration, bromination, ring enlargement, reduction, Knoevenagel and acylated reaction. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and inhibitory activity of IMPDH type II in vitro, as well as their structure-activity relationship were assessed. Several compounds exhibited strong immunosuppressive properties, especially compounds 7f and 7h, with IC50 values of 0.093 micromol x L(-1) and 0.14 micromol x L(-1) respectively, which were superior to mycophenolic acid. The information obtained from the studies may be useful for further research on the immunosuppressive agents.
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
authors.forename: Qing-He
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Yang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
authors.forename: Bo-Jun
authors.initials: BJ
authors.lastname: Hao
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Liang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
authors.forename: Chong-Guo
authors.initials: CG
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
authors.forename: Mao-Sheng
authors.initials: MS
authors.lastname: Cheng
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D007168:IMP Dehydrogenase / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D010793:Phthalazines; D007168:IMP Dehydrogenase; C488212:IMPDH2, mouse