炎症体
体内
药理学
磺酰脲
部分
生物利用度
化学
IC50型
分泌物
体外
药代动力学
口服活性
组合化学
生物化学
立体化学
医学
生物
受体
糖尿病
内分泌学
生物技术
作者
Sameer Agarwal,Santosh Sasane,Hardik Shah,Jignesh P. Pethani,Prashant Deshmukh,Vismit Vyas,Pravin S. Iyer,Harsh Bhavsar,Kasinath Viswanathan,Debdutta Bandyopadhyay,Poonam Giri,Jogeswar Mahapatra,Abhijit Chatterjee,Mukul Jain,Rajiv Sharma
标识
DOI:10.1021/acsmedchemlett.9b00433
摘要
NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases. In this study, rationally designed mimics of sulfonylurea moiety were investigated as NLRP3 inhibitors. Our results culminated into discovery of series of unprecedented N-cyano sulfoximineurea derivatives as potent NLRP3 inflammasome inhibitors. Compound 15 (IC50 = 7 nM) and analogues were found to be highly potent and selective NLRP3 inflammasome inhibitor with good pharmacokinetic profile. These effects translate in vivo, as 15, 29, and 34 significantly inhibit NLRP3 dependent IL-1β secretion in mice.
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