Imidazopyridyl compounds as aldosterone synthase inhibitors

Brent R Whitehead; Michael M-C Lo; Amjad Ali; Min K Park; Scott B Hoyt; Yusheng Xiong; Jiaqiang Cai; Emma Carswell; Andrew Cooke; John MacLean; Paul Ratcliffe; John Robinson; D Jonathan Bennett; Joseph A Clemas; Tom Wisniewski; Mary Struthers; Doris Cully; Douglas J MacNeil

doi:10.1016/j.bmcl.2016.12.003

Imidazopyridyl compounds as aldosterone synthase inhibitors

Bioorg Med Chem Lett. 2017 Jan 15;27(2):143-146. doi: 10.1016/j.bmcl.2016.12.003. Epub 2016 Dec 2.

Authors

Brent R Whitehead¹, Michael M-C Lo², Amjad Ali², Min K Park², Scott B Hoyt², Yusheng Xiong², Jiaqiang Cai³, Emma Carswell³, Andrew Cooke³, John MacLean³, Paul Ratcliffe³, John Robinson³, D Jonathan Bennett³, Joseph A Clemas², Tom Wisniewski², Mary Struthers², Doris Cully², Douglas J MacNeil²

Affiliations

¹ MRL, Rahway, NJ 07065, USA. Electronic address: brent.whitehead@merck.com.
² MRL, Rahway, NJ 07065, USA.
³ MRL, Newhouse, Lanarkshire ML1 5SH, United Kingdom.

PMID: 27979595
DOI: 10.1016/j.bmcl.2016.12.003

Abstract

The inhibition of aldosterone synthase (CYP11B2) may be an effective treatment of hypertension and heart failure, among other ailments. Previously reported benzimidazole CYP11B2 inhibitors led the way for bioisosteric imidazopyridines that are both potent and selective over CYP11B1.

Keywords: Aldosterone; CYP11B2; Heart failure; Hypertension; Imidazopyridine.

MeSH terms

Animals
Cricetulus
Cytochrome P-450 CYP11B2 / antagonists & inhibitors*
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry
Imidazoles / pharmacokinetics
Imidazoles / pharmacology*
Macaca mulatta
Male
Microsomes, Liver / metabolism
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacokinetics
Pyridines / pharmacology*
Rats, Wistar
Steroid 11-beta-Hydroxylase / antagonists & inhibitors
Structure-Activity Relationship

Substances

Imidazoles
Pyridines
Cytochrome P-450 CYP11B2
Steroid 11-beta-Hydroxylase