3,4-Disubstituted indole acylsulfonamides: A novel series of potent and selective human EP3 receptor antagonists

被引：40

作者：

Zhou, Nian ^{[1
]}

Zeller, Wayne ^{[1
]}

Krohn, Michael ^{[1
]}

Anderson, Herb ^{[1
]}

Zhang, Jun ^{[1
]}

Onua, Emmanuel ^{[1
]}

Kiselyov, Alex S. ^{[1
]}

Ramirez, Jose ^{[2
]}

Halldorsdottir, Gulrun ^{[2
]}

Andresson, Porkell ^{[2
]}

Gurney, Mark E. ^{[2
]}

Singh, Jasbir ^{[1
]}

机构：

[1] deCODE Chem Inc, Dept Med Chem, Woodridge, IL 60517 USA

[2] deCODE Genet Inc, Reykjavik, Iceland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 01期

关键词：

Prostanoid receptor antagonists; EP3 receptor antagonists; Peri-substituted indoles; Acylsulfonamides; ANALOGS; PROSTAGLANDIN-E2; CYCLASE; CELLS;

D O I：

10.1016/j.bmcl.2008.11.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of potent and selective EP3 receptor antagonists are described. Utilizing a pharmacophore model developed for the EP3 receptor, a series of 3,4-disubstituted indoles were shown to be high affinity ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors and are potent antagonists in functional assays. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：123 / 126

页数：4

共 19 条

[11] Structure-activity relationship on the human EP3 prostanoid receptor by use of solid-support chemistry [J].

Juteau, H ;

Gareau, Y ;

Labelle, M ;

Lamontagne, S ;

Tremblay, N ;

Carrière, MC ;

Sawyer, N ;

Denis, D ;

Metters, KM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (05) :747-749

[12] Structure-activity relationship of cinnamic acylsulfonamide analogues on the human EP3 prostanoid receptor [J].

Juteau, HN ;

Gareau, Y ;

Labelle, M ;

Sturino, CF ;

Sawyer, N ;

Tremblay, N ;

Lamontagne, S ;

Carrière, MC ;

Denis, D ;

Metters, KM .

BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (08) :1977-1984

[13] Increased platelet sensitivity to collagen in individuals resistant to low-dose aspirin [J].

Kawasaki, T ;

Ozeki, Y ;

Igawa, T ;

Kambayashi, J .

STROKE, 2000, 31 (03) :591-595

[14] 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

[15] INTERACTION OF PROSTAGLANDIN-E2 AND BETA-ADRENERGIC CATECHOLAMINES IN THE REGULATION OF UTERINE SMOOTH-MUSCLE MOTILITY AND ADENYLATE-CYCLASE IN THE RAT [J].

KRALL, JF ;

BARRETT, JD ;

JAMGOTCHIAN, N ;

KORENMAN, SG .

JOURNAL OF ENDOCRINOLOGY, 1984, 102 (03) :329-336

[16] Prostaglandin E(2) both stimulates and inhibits adenyl cyclase on platelets: Comparison of effects on cloned EP4 and EP3 prostaglandin receptor subtypes [J].

Mao, GF ;

Jin, JG ;

Bastepe, M ;

OrtizVega, S ;

Ashby, B .

PROSTAGLANDINS, 1996, 52 (03) :175-185

[17]

OHIA SE, 1990, J PHARMACOL EXP THER, V255, P11

[18]

SINGH J, ACS CHEM BI IN PRESS

[19] Suppression of fever and hyperalgesic responses to the EP3-receptor agonist GR 63799X by EP3-receptor antisense in rats [J].

Xin, L ;

Geller, EB ;

Bastepe, M ;

Raffa, RB ;

Mao, GF ;

Ashby, B ;

Adler, MW .

JOURNAL OF THERMAL BIOLOGY, 2000, 25 (1-2) :77-79

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