Pyridine containing M(1) positive allosteric modulators with reduced plasma protein binding

Scott D Kuduk; Christina N Di Marco; Victoria Cofre; Daniel R Pitts; William J Ray; Lei Ma; Marion Wittmann; Matthew A Seager; Kenneth Koeplinger; Chuck D Thompson; George D Hartman; Mark T Bilodeau

doi:10.1016/j.bmcl.2009.11.059

Pyridine containing M(1) positive allosteric modulators with reduced plasma protein binding

Bioorg Med Chem Lett. 2010 Jan 15;20(2):657-61. doi: 10.1016/j.bmcl.2009.11.059. Epub 2009 Dec 2.

Authors

Scott D Kuduk¹, Christina N Di Marco, Victoria Cofre, Daniel R Pitts, William J Ray, Lei Ma, Marion Wittmann, Matthew A Seager, Kenneth Koeplinger, Chuck D Thompson, George D Hartman, Mark T Bilodeau

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. scott_d_kuduk@merck.com

PMID: 19962304
DOI: 10.1016/j.bmcl.2009.11.059

Abstract

Incorporation of pyridines and diazines into the biphenyl region of quinolone carboxylic acid derived M(1) positive allosteric modulators was investigated as a means of lowering plasma protein binding to enhance CNS exposure.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Allosteric Regulation
Animals
Blood Proteins / chemistry*
Blood Proteins / metabolism
Humans
Protein Binding
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Rats
Receptor, Muscarinic M1 / antagonists & inhibitors*
Receptor, Muscarinic M1 / metabolism
Structure-Activity Relationship

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Blood Proteins
Pyridines
Receptor, Muscarinic M1