Nonpeptide αvβ3 antagonists.: Part 10:: In vitro and in vivo evaluation of a potent 7-methyl substituted tetrahydro-[1,8]naphthyridine derivative

被引：11

作者：

Breslin, MJ ^{[1
]}

Duggan, ME

Halczenko, W

Hartman, GD

Duong, LT

Fernandez-Metzler, C

Gentile, MA

Kimmel, DB

Leu, CT

Merkle, K

Prueksaritanont, T

Rodan, GA

Rodan, SB

Hutchinson, JH

机构：

[1] Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA

[2] Merck Res Labs, Dept Bone Biol & Osteoporosis Res, W Point, PA 19486 USA

[3] Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 17期

关键词：

D O I：

10.1016/j.bmcl.2004.06.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Subtle modifications were incorporated into the structure of clinical candidate 1. These changes were designed to maintain potency and selectivity while inducing changes in physical properties leading to improved pharmacokinetics in three species. This approach led to the identification of 4 as a potent, selective alpha(v)beta(3) receptor antagonist that was selected for clinical development based on an improved PK profile and efficacy demonstrated in an in vivo model of bone turnover. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4515 / 4518

页数：4

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