Tetrahydroquinolines as a novel series of nonsteroidal selective androgen receptor modulators: Structural requirements for better physicochemical and biological properties

被引：14
|
作者：
Nagata, Naoya [1 ]
Miyakawa, Motonori [1 ]
Amano, Seiji [1 ]
Furuya, Kazuyuki [1 ]
Yamamoto, Noriko [1 ]
Nejishima, Hiroaki [1 ]
Inoguchi, Kiyoshi [1 ]
机构：
[1] Kaken Pharmaceut Co Ltd, Cent Res Labs, Yamashina Ku, Kyoto 6078042, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 21期
关键词：
THQ; Nonsteroidal SARM; Water solubility; Femoral BMD; Rat osteoporosis model; BONE; SARM;
D O I：
10.1016/j.bmcl.2011.08.118
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A rationally designed tetrahydroquinoline (1) for nonsteroidal selective androgen receptor modulators was modified for the exploration of promising compounds by Grieco three-component condensation using various dienophiles. Based on the in vitro effects and physicochemical properties of the synthesized compounds, compound 4c was selected for further study. Compound 4c increased the femoral bone mineral density as much as DHT, but it reduced the uterus effect compared with DHT in ovariectomized rats. Thus, compound 4c has desirable osteoanabolic effects with weak undesirable effects on the uterus in a female osteoporosis model. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6310 / 6313
页数：4
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