Identification and characterization of amino-piperidinequinolones and quinazolinones as MCHr1 antagonists

Christopher Blackburn; Matthew J LaMarche; James Brown; Jennifer Lee Che; Courtney A Cullis; Sujen Lai; Martin Maguire; Thomas Marsilje; Bradley Geddes; Elizabeth Govek; Vivek Kadambi; Colleen Doherty; Brian Dayton; Sevan Brodjian; Kennan C Marsh; Christine A Collins; Philip R Kym

doi:10.1016/j.bmcl.2006.02.044

Identification and characterization of amino-piperidinequinolones and quinazolinones as MCHr1 antagonists

Bioorg Med Chem Lett. 2006 May 15;16(10):2621-7. doi: 10.1016/j.bmcl.2006.02.044. Epub 2006 Mar 9.

Authors

Christopher Blackburn¹, Matthew J LaMarche, James Brown, Jennifer Lee Che, Courtney A Cullis, Sujen Lai, Martin Maguire, Thomas Marsilje, Bradley Geddes, Elizabeth Govek, Vivek Kadambi, Colleen Doherty, Brian Dayton, Sevan Brodjian, Kennan C Marsh, Christine A Collins, Philip R Kym

Affiliation

¹ Millennium Pharmaceuticals, Inc., 40 Landsdowne St. Cambridge, MA 02139, USA. chris.blackburn@mpi.com

PMID: 16524729
DOI: 10.1016/j.bmcl.2006.02.044

Abstract

Several potent, functionally active MCHr1 antagonists derived from quinolin-2(1H)-ones and quinazoline-2(1H)-ones have been synthesized and evaluated. Pyridylmethyl substitution at the quinolone 1-position results in derivatives with low-nM binding potency and good selectivity with respect to hERG binding.

MeSH terms

Animals
Mice
Quinazolines / chemistry*
Quinazolines / pharmacokinetics
Quinazolines / pharmacology*
Quinolones / chemistry*
Quinolones / pharmacokinetics
Quinolones / pharmacology*
Receptors, Pituitary Hormone / antagonists & inhibitors*

Substances

Quinazolines
Quinolones
Receptors, Pituitary Hormone
melanin-concentrating hormone receptor