3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 1: Discovery and exploration of the carboxyamide side chain

被引：12

作者：

Asada, Masaki ^{[1
]}

Obitsu, Tetsuo ^{[1
]}

Nagase, Toshihiko ^{[1
]}

Tanaka, Motoyuki ^{[1
]}

Yamaura, Yoshiyuki ^{[1
]}

Takizawa, Hiroya ^{[1
]}

Yoshikawa, Ken ^{[1
]}

Sato, Kazutoyo ^{[1
]}

Narita, Masami ^{[1
]}

Ohuchida, Shuichi ^{[1
]}

Nakai, Hisao ^{[1
]}

Toda, Masaaki ^{[1
]}

机构：

[1] Ono Pharmaceut Co Ltd, Minase Res Inst, Osaka 6188585, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 01期

关键词：

Prostaglandin; EP3; receptor; Antagonist; Serum albumin; Uterine contraction; PROSTANOID RECEPTOR; ACYLSULFONAMIDE ANALOGS; MICE LACKING; MYOMETRIUM; CELLS;

D O I：

10.1016/j.bmc.2009.11.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 3-(2-aminocarbonyl-4-phenoxymethylphenyl) propanoic acid analogs were synthesized and evaluated for their EP3 antagonist activity in the presence of additive serum albumin. Several compounds were biologically evaluated for their in vivo efficacy with respect to the PGE(2)-induced uterine contraction in pregnant rats as well as their pharmacokinetics. The discovery process of these potent and selective EP3 antagonists and their structure activity relationship are also presented. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：80 / 90

页数：11

共 22 条

[1] Discovery of a series of acrylic acids and their derivatives as chemical leads for selective EP3 receptor antagonists [J].

Asada, Masaki ;

Obitsu, Tetsuo ;

Nagase, Toshihiko ;

Sugimoto, Isamu ;

Yamaura, Yoshiyuki ;

Sato, Kazutoyo ;

Narita, Masami ;

Ohuchida, Shuichi ;

Nakai, Hisao ;

Toda, Masaaki .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (18) :6567-6582

[2] Structure-activity relationship studies on ortho-substituted cinnamic acids, a new class of selective EP3 antagonists [J].

Belley, M ;

Gallant, M ;

Roy, B ;

Houde, K ;

Lachance, N ;

Labelle, M ;

Trimble, LA ;

Chauret, N ;

Li, C ;

Sawyer, N ;

Tremblay, N ;

Lamontagne, S ;

Carrière, MC ;

Denis, D ;

Greig, GM ;

Slipetz, D ;

Metters, KM ;

Gordon, R ;

Chan, CC ;

Zamboni, RJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (03) :527-530

[3] Comparison between two classes of selective EP3 antagonists and their biological activities [J].

Belley, Michel ;

Chan, Chi Chung ;

Gareau, Yves ;

Gallant, Michel ;

Juteau, Helene ;

Houde, Karine ;

Lachance, Nicolas ;

Labelle, Marc ;

Sawyer, Nicole ;

Tremblay, Nathalie ;

Lamontagne, Sonia ;

Carriere, Marie-Claude ;

Denis, Danielle ;

Greig, Gillian M. ;

Slipetz, Deborah ;

Gordon, Robert ;

Chauret, Nathalie ;

Li, Chun ;

Zamboni, Robert J. ;

Metters, Kathleen M. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (21) :5639-5642

[4] PROSTANOID INHIBITION OF CANINE PARIETAL-CELLS - MEDIATION BY THE INHIBITORY GUANOSINE TRIPHOSPHATE-BINDING PROTEIN OF ADENYLATE-CYCLASE [J].

CHEN, MCY ;

AMIRIAN, DA ;

TOOMEY, M ;

SANDERS, MJ ;

SOLL, AH .

GASTROENTEROLOGY, 1988, 94 (05) :1121-1129

[5]

COLEMAN RA, 1994, PHARMACOL REV, V46, P205

[6] Structure-activity relationship of triaryl propionic acid analogues on the human EP3 prostanoid receptor [J].

Gallant, M ;

Belley, M ;

Carrière, MC ;

Chateauneuf, A ;

Denis, D ;

Lachance, N ;

Lamontagne, S ;

Metters, KM ;

Sawyer, N ;

Slipetz, D ;

Truchon, JF ;

Labelle, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (21) :3813-3816

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

Gallant, M ;

Carrière, MC ;

Chateauneuf, A ;

Denis, D ;

Gareau, Y ;

Godbout, C ;

Greig, G ;

Juteau, H ;

Lachance, N ;

Lacombe, P ;

Lamontagne, S ;

Metters, KM ;

Rochette, C ;

Ruel, R ;

Slipetz, D ;

Sawyer, N ;

Tremblay, N ;

Labelle, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (18) :2583-2586

[8] DIVERSE PROSTAGLANDIN RECEPTORS ACTIVATE DISTINCT SIGNAL TRANSDUCTION PATHWAYS IN RAT MYOMETRIUM [J].

GOUREAU, O ;

TANFIN, Z ;

MARC, S ;

HARBON, S .

AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (01) :C257-C265

[9] Vascular wall-produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors [J].

Gross, Sabrina ;

Tilly, Peggy ;

Hentsch, Didier ;

Vonesch, Jean-Luc ;

Fabre, Jean-Etienne .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (02) :311-320

[10] Discovery of novel aminothiadiazole amides as selective EP3 receptor antagonists [J].

Hilfiker, Mark A. ;

Wang, Ning ;

Hou, Xiaoping ;

Du, Zhimin ;

Pullen, Mark A. ;

Nord, Melanie ;

Nagilla, Rakesh ;

Fries, Harvey E. ;

Wu, Charlene W. ;

Sulpizio, Anthony C. ;

Jaworski, Jon-Paul ;

Morrow, Dwight ;

Edwards, Richard M. ;

Jin, Jian .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (15) :4292-4295

← 1 2 3 →