Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2

被引：43

作者：

Armer, RE

Ashton, MR

Boyd, EA

Brennan, CJ

Brookfield, FA

Gazi, L

Gyles, SL

Hay, PA

Hunter, MG

Middlemiss, D

Whittaker, M

Xue, LZ

Pettipher, R

机构：

[1] Oxagen Ltd, Abingdon OX14 4RY, Oxon, England

[2] Evotec OAI, Abingdon OX14 4RY, Oxon, England

[3] XaviaPharm, Bishops Stortford CM23 3NF, Herts, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 20期

关键词：

D O I：

10.1021/jm050519b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Prostaglandin D-2 (PGD(2)) acting at the CRTH2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells) has been linked with a variety of allergic and other inflammatory diseases. We describe a family of indole-1-sulfonyl-3-acetic acids that are potent and selective CRTH2 antagonists that possess good oral bioavailability. The compounds may serve as novel starting points for the development of treatments of inflammatory disease such as asthma, allergic rhinitis, and atopic dermatitis.

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页码：6174 / 6177

页数：4

相关论文

共 26 条

[1] Effects of prostaglandin D2, 15-deoxy-Δ12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats [J].

Almishri, W ;

Cossette, C ;

Rokach, J ;

Martin, JG ;

Hamid, Q ;

Powell, WS .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 313 (01) :64-69

[2]

BAUER PH, 2002, Patent No. 1170594

[3] PROSTAGLANDIN-D2 CAUSES ACCUMULATION OF EOSINOPHILS IN THE LUMEN OF THE DOG TRACHEA [J].

EMERY, DL ;

DJOKIC, TD ;

GRAF, PD ;

NADEL, JA .

JOURNAL OF APPLIED PHYSIOLOGY, 1989, 67 (03) :959-962

[4] Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice [J].

Fujitani, Y ;

Kanaoka, Y ;

Aritake, K ;

Uodome, N ;

Okazaki-Hatake, K ;

Urade, Y .

JOURNAL OF IMMUNOLOGY, 2002, 168 (01) :443-449

[5] Identification of a potent and selective synthetic agonist at the CRTH2 receptor [J].

Gervais, FG ;

Morello, JP ;

Beaulieu, C ;

Sawyer, N ;

Denis, D ;

Greig, G ;

Malebranche, AD ;

O'Neill, GP .

MOLECULAR PHARMACOLOGY, 2005, 67 (06) :1834-1839

[6] Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP [J].

Gervais, FG ;

Cruz, RPG ;

Chateauneuf, A ;

Gale, S ;

Sawyer, N ;

Nantel, F ;

Metters, KM ;

O'Neill, GP .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2001, 108 (06) :982-988

[7] THE BRONCHOCONSTRICTOR EFFECT OF INHALED PROSTAGLANDIN-D2 IN NORMAL AND ASTHMATIC MEN [J].

HARDY, CC ;

ROBINSON, C ;

TATTERSFIELD, AE ;

HOLGATE, ST .

NEW ENGLAND JOURNAL OF MEDICINE, 1984, 311 (04) :209-213

[8] Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2 [J].

Hata, AN ;

Lybrand, TP ;

Marnett, LJ ;

Breyer, RM .

MOLECULAR PHARMACOLOGY, 2005, 67 (03) :640-647

[9] Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2 [J].

Hirai, H ;

Tanaka, K ;

Yoshie, O ;

Ogawa, K ;

Kenmotsu, K ;

Takamori, Y ;

Ichimasa, M ;

Sugamura, K ;

Nakamura, M ;

Takano, S ;

Nagata, K .

JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 193 (02) :255-261

[10] Cutting edge:: Agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2 [J].

Hirai, H ;

Tanaka, K ;

Takano, S ;

Ichimasa, M ;

Nakamura, M ;

Nagata, K .

JOURNAL OF IMMUNOLOGY, 2002, 168 (03) :981-985