Journal of Medicinal Chemistry p. 4013 - 4031 (2019)
Update date:2022-08-24
Topics:
Shi, Jing Bo
Chen, Liu Zeng
Wang, Bao Shi
Huang, Xin
Jiao, Ming Ming
Liu, Ming Ming
Tang, Wen Jian
Liu, Xin Hua
In order to discover novel anti-inflammatory agents for treatment of arthritis and based on preliminary structure-activity relationships, four series (A-D) of total 90 new pyrazolo[4,3-d]pyrimidine compounds were designed and synthesized. All the compounds have been tested for their anti-inflammatory activities by inhibiting of LPS-induced NO production. A clear structure-activity relationship has been concluded step by step, and finally 3,4,5-trimethoxystyryl-1H-pyrazolo[4,3-d]pyrimidine was found to be the most active scaffold. Among them, compound D27 was discovered as the most potent anti-inflammatory agent (IC50 = 3.17 μM) with low toxicity and strong inhibitory of NO release (IR = 90.4% at 10 μM). This compound also showed potent inhibition of iNOS with IC50 value of 1.12 μM. Preliminary mechanism studies indicated that it could interfere with the stability and formation of active dimeric iNOS. The anti-inflammatory effect of this compound was determined by adjuvant-induced arthritis in rat model. We believe these findings would further support the study of rational design of more efficient iNOS inhibitors in the future.
View Morewebsite:http://www.hybio.com.cn
Contact:+86 755 26588093
Address:No.9 Linkong West Street, Hengdian Street, Huangpi District, Wuhan City, China.
Contact:+8613400661290
Address:No 908,Kangwan Rd, Liuyang Economic
Zhejiang Sanmei Chemical Industry Co., Ltd
Contact:86-579-87633213
Address:Huchu Industrial Zone, Qingnian Rd., Wuyi County, Zhejiang Prov., China.
Anhui Sholon New Material Technology Co., Ltd.
website:http://www.sholonchem.com
Contact:+86-550-5261666
Address:4/F Block B, Beijing Chemical Building.No.520 Tianrun Road ,Science & Education Town Wujin District, Changzhou City Jiangsu Province
Anhui Redstar Pharmaceutical Corp., Ltd
Contact:+86-563-5120837
Address:Jingxian Industrial Development Zone, Anhui , China
Doi:10.1016/j.tet.2003.11.004
(2004)Doi:10.1246/bcsj.77.1395
(2004)Doi:10.1002/anie.202015703
(2021)Doi:10.1016/j.molstruc.2020.127860
(2020)Doi:10.1021/jo00216a047
(1985)Doi:10.1021/acs.inorgchem.5b01452
(2015)