Discovery of novel thiourea derivatives as potent and selective β3-adrenergic receptor agonists

被引：13

作者：

Maruyama, Tatsuya ^{[1
]}

Seki, Norio ^{[1
]}

Onda, Kenichi ^{[1
]}

Suzuki, Takayuki ^{[1
]}

Kawazoe, Souichirou ^{[1
]}

Hayakawa, Masahiko ^{[1
]}

Matsui, Tetsuo ^{[1
]}

Takasu, Toshiyuki ^{[1
]}

Ohta, Mitsuaki ^{[1
]}

机构：

[1] Astellas Pharma Inc, Drug Discovery Res, Tsukuba, Ibaraki 3058585, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 15期

关键词：

beta 3-Adrenergic receptor; Agonist; Thiourea; Phenoxypropanolamine; Diabetes; BETA(3) ADRENERGIC-RECEPTOR; HUMAN DETRUSOR MUSCLE; BETA(3)-ADRENOCEPTOR AGONISTS; OBESITY; ADRENOCEPTOR; EXPRESSION; SUBTYPES; DRUGS;

D O I：

10.1016/j.bmc.2009.06.031

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：

In the search for potent and selective human beta 3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, we prepared a novel series of phenoxypropanolamine derivatives containing the thiourea moiety and evaluated their biological activities at human beta 3-, beta 2-, and beta 1-ARs. Among these compounds, 4-nitrophenylthiourea (18i) and 3-methoxyphenylthiourea (18k) derivatives were found to exhibit potent agonistic activity at the b3-AR, with EC(50) values of 0.10 and 0.16 mu M, respectively, and no agonistic activity for either the beta 1-or beta 2-AR. In addition, they showed significant hypoglycemic activity in a rodent diabetic model. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5510 / 5519

页数：10

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