Iminopyrimidinones: A novel pharmacophore for the development of orally active renin inhibitors

被引：6

作者：

McKittrick, Brian A. ^{[1
]}

Caldwell, John P. ^{[1
]}

Bara, Thomas ^{[1
]}

Boykow, George ^{[3
]}

Chintala, Madhu ^{[3
]}

Clader, John ^{[1
]}

Czarniecki, Michael ^{[1
]}

Courneya, Brandy ^{[6
]}

Duffy, Ruth ^{[3
]}

Fleming, Linda

Giessert, Rachel ^{[6
]}

Greenlee, William J. ^{[1
]}

Heap, Charles

Hong, Liwu ^{[1
]}

Huang, Ying ^{[1
]}

Iserloh, Ulrich ^{[1
]}

Josien, Hubert ^{[1
]}

Khan, Tanweer ^{[1
]}

Korfmacher, Walter ^{[4
]}

Liang, Xian ^{[1
]}

Mazzola, Robert ^{[1
]}

Mitra, Soumya ^{[6
]}

Moore, Kristina ^{[3
]}

Orth, Peter ^{[2
]}

Rajagopalan, Murali ^{[1
]}

Roy, Sudipta ^{[6
]}

Sakwa, Samuel ^{[6
]}

Strickland, Corey ^{[2
]}

Vaccaro, Henry ^{[1
]}

Voigt, Johannes ^{[2
]}

Wang, Hongwu ^{[2
]}

Wong, Jesse ^{[1
]}

Zhang, Rumin ^{[5
]}

Zych, Andrew ^{[6
]}

机构：

[1] Merck Res Labs, Discovery Chem, Kenilworth, NJ 07033 USA

[2] Merck Res Labs, Struct Chem, Kenilworth, NJ 07033 USA

[3] Merck Res Labs, Cardiovasc Pharmacol, Kenilworth, NJ 07033 USA

[4] Merck Res Labs, Pharmacokinet Pharmacodynam & Metab, Kenilworth, NJ 07033 USA

[5] Merck Res Labs, Biochem & Biophys, Kenilworth, NJ 07033 USA

[6] Albany Mol Res Inc, Dept Med Chem, Albany, NY 12203 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 07期

关键词：

Renin inhibitors; BACE1; Hypertension; Structure-based drug design; Enzyme inhibitors; STRUCTURE-BASED DESIGN; BACE1; INHIBITORS; TRANSGENIC RATS; DRUG DISCOVERY; HYPERTENSION; ALISKIREN; POTENT; MANAGEMENT; VTP-27999; PART;

D O I：

10.1016/j.bmcl.2015.02.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The development of renin inhibitors with favorable oral pharmacokinetic profiles has been a longstanding challenge for the pharmaceutical industry. As part of our work to identify inhibitors of BACE1, we have previously developed iminopyrimidinones as a novel pharmacophore for aspartyl protease inhibition. In this letter we describe how we modified substitution around this pharmacophore to develop a potent, selective and orally active renin inhibitor. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：1592 / 1596

页数：5

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