2,3-Diarylthiophenes as selective EP1 receptor antagonists

被引：31

作者：

Ducharme, Y ^{[1
]}

Blouin, M ^{[1
]}

Carrière, MC ^{[1
]}

Chateauneuf, A ^{[1
]}

Côté, B ^{[1
]}

Denis, D ^{[1
]}

Frenette, R ^{[1
]}

Greig, G ^{[1
]}

Kargman, S ^{[1
]}

Lamontagne, S ^{[1
]}

Martins, E ^{[1
]}

Nantel, F ^{[1
]}

O'Neill, G ^{[1
]}

Sawyer, N ^{[1
]}

Metters, KM ^{[1
]}

Friesen, RW ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 04期

关键词：

prostaglandin E-2; EP1 receptor antagonist;

D O I：

10.1016/j.bmcl.2004.12.005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and the EPI receptor binding affinity of 2,3-diarylthiophene derivatives are described. The evaluation of the structure-activity relationship (SAR) in this series led to the identification of compounds 4, 7, and 12a, which exhibit high affinity for the human EPI receptor and a selectivity greater than 100-fold against the EP2, EP3, EP4, DP, FP, and IP receptors and greater than 25-fold versus the TP receptor. These three antagonists present good pharmacokinetics in rats and significant differences in the way they are distributed in the brain. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1155 / 1160

页数：6

共 22 条

[1] The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs [J].

Abramovitz, M ;

Adam, M ;

Boie, Y ;

Carrière, MC ;

Denis, D ;

Godbout, C ;

Lamontagne, S ;

Rochette, C ;

Sawyer, N ;

Tremblay, NM ;

Belley, M ;

Gallant, M ;

Dufresne, C ;

Gareau, Y ;

Ruel, R ;

Juteau, H ;

Labelle, M ;

Ouimet, N ;

Metters, KM .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1483 (02) :285-293

[2]

Bath P.M, 1990, COMPREHENSIVE MED CH, VVolume 3, P643

[3] Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes [J].

Boie, Y ;

Stocco, R ;

Sawyer, N ;

Slipetz, DM ;

Ungrin, MD ;

Neuschäfer-Rube, F ;

Püschel, GP ;

Metters, KM ;

Abramovitz, M .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 340 (2-3) :227-241

[4]

COLEMAN RA, 1994, PHARMACOL REV, V46, P205

[5] Prostaglandins and leukotrienes: Advances in eicosanoid biology [J].

Funk, CD .

SCIENCE, 2001, 294 (5548) :1871-1875

[6] A prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) reduces hyperalgesia, allodynia, and c-fos gene expression in rats with chronic nerve constriction [J].

Kawahara, H ;

Sakamoto, A ;

Takeda, S ;

Onodera, H ;

Imaki, J ;

Ogawa, R .

ANESTHESIA AND ANALGESIA, 2001, 93 (04) :1012-1017

[7] Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP1 antagonist, on breast cancer development [J].

Kawamori, T ;

Uchiya, N ;

Nakatsugi, S ;

Watanabe, K ;

Ohuchida, S ;

Yamamoto, H ;

Maruyama, T ;

Kondo, K ;

Sugimura, T ;

Wakabayashi, K .

CARCINOGENESIS, 2001, 22 (12) :2001-2004

[8] Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells [J].

Kiriyama, M ;

Ushikubi, F ;

Kobayashi, T ;

Hirata, M ;

Sugimoto, Y ;

Narumiya, S .

BRITISH JOURNAL OF PHARMACOLOGY, 1997, 122 (02) :217-224

[9]

LACOMBE P, 2000, 220 ACS NAT M WASH A

[10] Prevention of diabetic nephropathy in rats by prostaglandin E receptor EP1-selective antagonist [J].

Makino, H ;

Tanaka, I ;

Mukoyama, M ;

Sugawara, A ;

Mori, K ;

Muro, S ;

Suganami, T ;

Yahata, K ;

Ishibashi, R ;

Ohuchida, S ;

Maruyama, T ;

Narumiya, S ;

Nakao, K .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2002, 13 (07) :1757-1765

← 1 2 3 →