Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists

被引：21

作者：

Didiuk, Mary T. ^{[1
]}

Griffith, David A. ^{[1
]}

Benbow, John W. ^{[1
]}

Liu, Kevin K. C. ^{[1
]}

Walker, Daniel P. ^{[1
]}

Bi, F. Christopher ^{[1
]}

Morris, Joel ^{[1
]}

Guzman-Perez, Angel ^{[1
]}

Gao, Hua ^{[1
]}

Bechle, Bruce M. ^{[1
]}

Kelley, Ryan M. ^{[1
]}

Yang, Xiaojing ^{[1
]}

Dirico, Kenneth ^{[1
]}

Ahmed, Syed ^{[1
]}

Hungerford, William ^{[1
]}

DiBrinno, Joseph ^{[1
]}

Zawistoski, Michael P. ^{[1
]}

Bagley, Scott W. ^{[1
]}

Li, Jianke ^{[1
]}

Zeng, Yuan ^{[1
]}

Santucci, Stephanie ^{[1
]}

Oliver, Robert ^{[1
]}

Corbett, Matthew ^{[1
]}

Olson, Thanh ^{[1
]}

Chen, Chiliu ^{[1
]}

Li, Mei ^{[1
]}

Paralkar, Vishwas M. ^{[1
]}

Riccardi, Keith A. ^{[1
]}

Healy, David R. ^{[1
]}

Kalgutkar, Amit S. ^{[1
]}

Maurer, Tristan S. ^{[1
]}

Nguyen, Hang T. ^{[1
]}

Frederick, Kosea S. ^{[1
]}

机构：

[1] Pfizer Inc, Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 16期

关键词：

Osteoporosis; Human parathyroid hormone; Calcium receptor antagonists; Pharmacokinetics; SAR exploration; PARATHYROID-HORMONE SECRETION; NONSPECIFIC-BINDING; OSTEOPOROSIS; BONE; RATS; MICROSOMES; DISCOVERY;

D O I：

10.1016/j.bmcl.2009.07.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis and structure-activity relationship (SAR) studies on 5-trifluoromethylpyrido[4,3-d] pyrimidin-4(3H)-ones, a novel class of calcium receptor antagonists is described with particular emphasis on optimization of the pharmacokinetic/pharmacodynamic parameters required for a short duration of action compound. Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4555 / 4559

页数：5

共 21 条

[1] Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Parathyroid Hormone-Calcium Homeostasis in Rats and Humans [J].