Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets

DOI: 10.1248/cpb.43.1724

Source and publish data:

Chemical and Pharmaceutical Bulletin p. 1724 - 1733 (1995)

Update date:2022-09-26

Topics:

Authors:

Uno Uno

Ozeki Ozeki

Koga Koga

Chu Chu

Okada Okada

Tamura Tamura

Igawa Igawa

Unemi Unemi

Kido Kido

Nishi Nishi

Read Full Text PDF DownLoad Join now for total 90,000,000 free articles

Article abstract of DOI:10.1248/cpb.43.1724

A search for potent inhibitors of release of 12(S)- hydroxyeicosatetraenoic acid (12-HETE), which plays an important role in the pathogenesis of various circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5-tetrazolyl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)-quinolinone derivatives having an azole group in the side chain. Many 2(1H)-quinolinone derivatives were synthesized and tested in vitro for the inhibitory activity in human platelets. 3,4-Dihydro-6-[3-(1-o- tolylimidazol-2-yl)sulfinylpropoxy]-2(1H)-quinolinone (5k) was found to be one of the most potent inhibitors of 12-HETE release, being more potent than esculetin. In addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet adhesion in rats. Since 5k is racemic, the enantiomers were prepared and their potencies were compared in vitro and in vivo. (S)-(+)-5k had the best pharmacological profile and was selected as a candidate drug for further development. The structure-activity relationships are discussed.

Full text of DOI:10.1248/cpb.43.1724

NII-Electronic Library Service

Products guided by the article

Product name:2(1H)-Quinolinone, 3,4-dihydro-6-[3-[[1-(2-methylphenyl)-1H-imidazol-2-yl]thio]propoxy]-

Cas No:113857-31-1

R&D Labs maybe for 113857-31-1

Deltachem(QingDao)Co.,Ltd.

Contact:+8618766299236

Address:ROOM808, BUILDING2,NO.230 SHEN ZHEN ROAD, LAOSHAN DISTRICT
Shandong Jusage Technology Co.,Ltd.

Contact:86-13406130167

Address:No.20,North Ride No.9 Road, Guangrao Economic Development Zone, Shandong Province
Guangzhou Swan Chemical Co., Ltd.

Contact:+86-20-31075659

Address:NO.301, Hong ba fang investment BLDG 1,Guan chong village,Shiqi town,Panyu district,Guangzhou
Shenzhen Sunrising Industry Co., ltd.

Contact:+86 755 86571158 / 86571159 / 86571160

Address:2108 ZHENYE INT. BUSINESS CENTER,NO.3101-90 QIANHAI RD, NANSHAN,SHENZHEN, CHINA
Hefei TNJ chemical industry co.,ltd

website:https://www.tnjchem.com

Contact:+86-551-65418695

Address:B911 Xincheng Business Center, Qianshan Road, Hefei Anhui China

Relevant to this article

Stereoselective free-radical addition of secondary phosphine selenides to aromatic acetylenes

Doi:10.1016/j.jorganchem.2008.11.043
(2009)
Immobilization and chiral recognition of 3,5-dimethylphenylcarbamates of cellulose and amylose bearing 4-(trimethoxysilyl)phenylcarbamate groups

Doi:10.1002/chir.20722
(2010)
Chiral Synthesis via Organoboranes. 18. Selective Reductions. 43. Diisopinocampheylchloroborane as an Excellent Chiral Reducing Reagent for the Synthesis of Halo Alcohols of High Enantiomeric Purity. A Highly Enantioselective Synthesis of Both Optical Isomers of Tomoxetine, Fluoxetine, a

Doi:10.1021/jo00248a005
(1988)
Synthesis of 6- or 8-bromo flavonoids by regioselective mono-bromination and deprotection protocol from flavonoid alkyl ethers

Doi:10.1002/bkcs.10286
(2015)
N-(4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazin-1-yl)butyl) heterobiarylcarboxamides with functionalized linking chains as high affinity and enantioselective D3 receptor antagonists

Doi:10.1021/jm900095y
(2009)
Doi:10.1021/jo01102a603
(1958)

Article Doi