Diphenylpyridylethanamine (DPPE)-based aminoheterocycles as cholesteryl ester transfer protein inhibitors

Yufeng Wang; Wu Yang; Heather J Finlay; Lalgudi S Harikrishnan; Ji Jiang; Muthoni G Kamau; Katy Van Kirk; David S Nirschl; David S Taylor; Alice Ye A Chen; Xiaohong Yin; Paul G Sleph; Richard Z Yang; Christine S Huang; Leonard P Adam; R Michael Lawrence; Ruth R Wexler; Mark E Salvati

doi:10.1016/j.bmcl.2013.12.088

Diphenylpyridylethanamine (DPPE)-based aminoheterocycles as cholesteryl ester transfer protein inhibitors

Bioorg Med Chem Lett. 2014 Feb 1;24(3):860-4. doi: 10.1016/j.bmcl.2013.12.088. Epub 2014 Jan 6.

Authors

Yufeng Wang¹, Wu Yang², Heather J Finlay², Lalgudi S Harikrishnan², Ji Jiang², Muthoni G Kamau², Katy Van Kirk², David S Nirschl³, David S Taylor⁴, Alice Ye A Chen⁴, Xiaohong Yin⁴, Paul G Sleph⁴, Richard Z Yang⁴, Christine S Huang⁵, Leonard P Adam⁴, R Michael Lawrence², Ruth R Wexler², Mark E Salvati²

Affiliations

¹ Department of Chemistry, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08543-4000, USA. Electronic address: yufeng.wang@bms.com.
² Department of Chemistry, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08543-4000, USA.
³ Synthesis & Analysis Technology Team, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08543-4000, USA.
⁴ Department of Biology, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08543-4000, USA.
⁵ Department of Preclinical Candidate Optimization, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08543-4000, USA.

PMID: 24424134
DOI: 10.1016/j.bmcl.2013.12.088

Abstract

A series of diphenylpyridylethanamine-based inhibitors of cholesteryl ester transfer protein with aminoheterocycles appended onto the N-terminus of the chemotype were explored as urea mimetics. Potent compounds were discovered and were further optimized to improve metabolic stability and PXR transactivation profile.

Keywords: CETP.

MeSH terms

Biomimetics
Biphenyl Compounds / chemical synthesis
Biphenyl Compounds / chemistry
Biphenyl Compounds / pharmacology
Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
Drug Stability
Ethylamines / chemical synthesis
Ethylamines / chemistry
Ethylamines / pharmacology
Heterocyclic Compounds / chemical synthesis*
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology*
Humans
Inhibitory Concentration 50
Molecular Structure
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacology
Structure-Activity Relationship
Urea / chemistry

Substances

Biphenyl Compounds
CETP protein, human
Cholesterol Ester Transfer Proteins
Ethylamines
Heterocyclic Compounds
Pyridines
diphenyl
Urea