Discovery of Quinazolin-4(3H)-ones as NLRP3 Inflammasome Inhibitors: Computational Design, Metal-Free Synthesis, and in Vitro Biological Evaluation

被引：59

作者：

Abdullaha, Mohd ^{[1
,2
]}

Mohammed, Shabber ^{[1
,2
]}

Ali, Mehboob ^{[2
,3
]}

Kumar, Ajay ^{[2
,3
]}

Vishwakarma, Ram A. ^{[1
,2
]}

Bharate, Sandip B. ^{[1
,2
]}

机构：

[1] CSIR Indian Inst Integrat Med, Med Chem Div, Canal Rd, Jammu 180001, India

[2] CSIR Indian Inst Integrat Med, Acad Sci & Innovat Res, Canal Rd, Jammu 180001, India

[3] CSIR Indian Inst Integrat Med, PKPD Toxicol & Formulat Div, Canal Rd, Jammu 180001, India

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2019年 / 84卷 / 09期

关键词：

ONE-POT SYNTHESIS; QUINAZOLINE DERIVATIVES; OXIDATIVE SYNTHESIS; EFFICIENT SYNTHESIS; BENZYL ALCOHOLS; IONIC LIQUID; AMINATION; DISEASE; BOND; PHOSPHODIESTERASE;

D O I：

10.1021/acs.joc.9b00138

中图分类号：

O62 [有机化学];

学科分类号：

070303 [有机化学];

摘要：

NLRP3 inflammasome is an important therapeutic target for a number of human diseases. Herein, computationally designed series of quinazolin-4(3H)-ones were synthesized using iodine-catalyzed coupling of arylalkynes (or styrenes) with O-aminobenzamides. The key event in this transformation involves the oxidative cleavage of the C-C triple/double bond and the release of formaldehyde. The reaction relies on the C-N bond formation along with the C-C bond cleavage under metal-free conditions. The nitro-substituted quinazolin-4(3H)-one 2k inhibited NLRP3 inflammasome (IC50 5 mu M) via the suppression of IL-1 beta release from ATP-stimulated J774A.1 cells.

引用

收藏

页码：5129 / 5140

页数：12

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