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

相关论文

共 88 条

[51]

NLRP3 inflammasome and its inhibitors: a review [J].

Shao, Bo-Zong ;

Xu, Zhe-Qi ;

Han, Bin-Ze ;

Su, Ding-Feng ;

Liu, Chong .

FRONTIERS IN PHARMACOLOGY, 2015, 6

[52]

Oxidative synthesis of quinazolinones and benzothiadiazine 1,1-dioxides from 2-amino-benzamide and 2-aminobenzenesulfonamide with benzyl alcohols and aldehydes [J].

Sharif, Muhammad ;

Opalach, Julita ;

Langer, Peter ;

Beller, Matthias ;

Wu, Xiao-Feng .

RSC ADVANCES, 2014, 4 (01) :8-17

[53]

Bimetallic Cu-Mn-Catalyzed Synthesis of 2-Arylquinazolin-4(3H)-ones: Aqueous Ammonia as Source of a Ring Nitrogen Atom [J].

Sharma, Rohit ;

Vishwakarma, Ram A. ;

Bharate, Sandip B. .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2016, 2016 (31) :5227-5233

[54]

Estradiol inhibits NLRP3 inflammasome in fibroblast-like synoviocytes activated by lipopolysaccharide and adenosine triphosphate [J].

Shi, Jianfeng ;

Zhao, Weibo ;

Ying, Haijian ;

Zhang, Ying ;

Du, Juping ;

Chen, Shuaishuai ;

Li, Jun ;

Shen, Bo .

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, 2018, 21 (11) :2002-2010

[55]

CYCLIC-GMP PHOSPHODIESTERASE INHIBITORS .2. REQUIREMENT OF 6-SUBSTITUTION OF QUINAZOLINE DERIVATIVES FOR POTENT AND SELECTIVE INHIBITORY ACTIVITY [J].

TAKASE, Y ;

SAEKI, T ;

WATANABE, N ;

ADACHI, H ;

SOUDA, S ;

SAITO, I .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (13) :2106-2111

[56]

The NLRP3 Inflammasome in Alzheimer's Disease [J].

Tan, Meng-Shan ;

Yu, Jin-Tai ;

Jiang, Teng ;

Zhu, Xi-Chen ;

Tan, Lan .

MOLECULAR NEUROBIOLOGY, 2013, 48 (03) :875-882

[57]

Sildenafil (VIAGRA(TM)), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction [J].

Terrett, NK ;

Bell, AS ;

Brown, D ;

Ellis, P .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (15) :1819-1824

[58]

NLRP3 Inflammasome Activation in the Brain after Global Cerebral Ischemia and Regulation by 17β-Estradiol [J].

Thakkar, Roshni ;

Wang, Ruimin ;

Sareddy, Gangadhara ;

Wang, Jing ;

Thiruvaiyaru, Dharma ;

Vadlamudi, Ratna ;

Zhang, Quanguang ;

Brann, Darrell .

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2016, 2016

[59]

Selective autoxidation of benzylamines: application to the synthesis of some nitrogen heterocycles [J].

Thanh Binh Nguyen ;

Ermolenko, Ludmila ;

Al-Mourabit, Ali .

GREEN CHEMISTRY, 2013, 15 (10) :2713-2717

[60]

Metal-free one-pot synthesis of 1,3-diazaheterocyclic compounds via I2-mediated oxidative C-N bond formation [J].

Tian, Xianhai ;

Song, Lina ;

Li, Ertong ;

Wang, Qiang ;

Yu, Wenquan ;

Chang, Junbiao .

RSC ADVANCES, 2015, 5 (76) :62194-62201

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