Improved synthesis of the PAR-1 thrombin receptor antagonist RWJ-58259

被引：0

作者：

Valdivielso, Angel M. ^{[1
]}

Teresa Garcia-Lopez, M. ^{[1
]}

Herranz, Rosario ^{[1
]}

机构：

[1] CSIC, Inst Quim Med, E-28006 Madrid, Spain

来源：

ARKIVOC | 2008年

关键词：

Peptidomimetics; heterocycles; alkylation; ureas; protease-activated receptor antagonists;

D O I：

暂无

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A significant improvement on the synthesis of the PAR-1 antagonist RWJ-58259 is described, which involves a base-related two-fold yield increase in the indazole N-alkylation, and an easier purification and a nine-fold yield increase in the urea formation, by using triphosgene/propylene oxide as urea coupling traceless reagents.

引用

收藏

页码：287 / 294

页数：8

相关论文

共 11 条

[1]

Andrade-Gordon P, 2001, J PHARMACOL EXP THER, V298, P34

[2]

ARORA P, 2007, THROMB RES, V120, pS75

[3] 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based potent and selective CCK1 receptor antagonists:: Structure-activity relationship studies on the substituent at N2-position [J].

Bartolomé-Nebreda, JM ;

Patiño-Molina, R ;

Martín-Martínez, M ;

Gómez-Monterrey, I ;

García-López, MT ;

González-Muñiz, R ;

Cenarruzabeitia, E ;

Latorre, M ;

Del Río, J ;

Herranz, R .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (13) :2219-2228

[4] Thrombin receptor (protease activated receptor-1) antagonists as potent antithrombotic agents with strong antiplatelet effects [J].

Chackalamannil, Samuel .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (18) :5389-5403

[5] Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? [J].

Chambers, R. C. .

BRITISH JOURNAL OF PHARMACOLOGY, 2008, 153 :S367-S378

[6]

Damiano BP, 2003, CARDIOVASC DRUG REV, V21, P313

[7] Blockade of the thrombin receptor protease-activated receptor-1 with a small-molecule antagonist prevents thrombus formation and vascular occlusion in nonhuman primates [J].

Derian, CK ;

Damiano, BP ;

Addo, MF ;

Darrow, AL ;

D'Andrea, MR ;

Nedelman, M ;

Zhang, HC ;

Maryanoff, BE ;

Andrade-Gordon, P .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 304 (02) :855-861

[8]

Maryanoff Bruce E., 2003, Current Medicinal Chemistry - Cardiovascular & Hematological Agents, V1, P13, DOI 10.2174/1568016033356724

[9] Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation [J].

Niessen, Frank ;

Schaffner, Florence ;

Furlan-Freguia, Christian ;

Pawlinski, Rafal ;

Bhattacharjee, Gourab ;

Chun, Jerold ;

Derian, Claudia K. ;

Andrade-Gordon, Patricia ;

Rosen, Hugh ;

Ruf, Wolfram .

NATURE, 2008, 452 (7187) :654-658

[10] Discovery and optimization of a novel series of thrombin receptor (PAR-1) antagonists: Potent, selective peptide mimetics based on indole and indazole templates [J].

Zhang, HC ;

Derian, CK ;

Andrade-Gordon, P ;

Hoekstra, WJ ;

McComsey, DF ;

White, KB ;

Poulter, BL ;

Addo, MF ;

Cheung, WM ;

Damiano, BP ;

Oksenberg, D ;

Reynolds, EE ;

Pandey, A ;

Scarborough, RM ;

Maryanoff, BE .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (07) :1021-1024