Synthesis and immunosuppressive effects of novel phthalazine ketone derivatives.
- Author:
Ya-Li WANG
1
;
Qing-He WANG
1
;
Hong-Guang YANG
1
;
Bo-Jun HAO
1
;
Guo-Dong LIANG
1
;
Chong-Guo JIANG
1
;
Mao-Sheng CHENG
1
Author Information
1. Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shengyang Pharmaceutical University, Shengyang 110016, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Proliferation;
drug effects;
Female;
IMP Dehydrogenase;
metabolism;
Immunosuppressive Agents;
chemical synthesis;
chemistry;
pharmacology;
Inhibitory Concentration 50;
Mice;
Mice, Inbred BALB C;
Phthalazines;
chemical synthesis;
chemistry;
pharmacology;
Spleen;
cytology;
Structure-Activity Relationship;
T-Lymphocytes;
drug effects
- From:
Acta Pharmaceutica Sinica
2013;48(10):1579-1584
- CountryChina
- Language:Chinese
-
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.
