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
收藏
页码：5510 / 5519
页数：10
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