Heterocyclic fused pyridone carboxylic acid M(1) positive allosteric modulators

Scott D Kuduk; Christina N Di Marco; Ronald K Chang; William J Ray; Lei Ma; Marion Wittmann; Matthew A Seager; Kenneth A Koeplinger; Charles D Thompson; George D Hartman; Mark T Bilodeau

doi:10.1016/j.bmcl.2010.02.096

Heterocyclic fused pyridone carboxylic acid M(1) positive allosteric modulators

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2533-7. doi: 10.1016/j.bmcl.2010.02.096. Epub 2010 Mar 3.

Authors

Scott D Kuduk¹, Christina N Di Marco, Ronald K Chang, William J Ray, Lei Ma, Marion Wittmann, Matthew A Seager, Kenneth A Koeplinger, Charles D Thompson, George D Hartman, Mark T Bilodeau

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486, USA. [email protected]

PMID: 20303264
DOI: 10.1016/j.bmcl.2010.02.096

Abstract

The phenyl ring in a series of quinolone carboxylic acid M(1) positive allosteric modulators was replaced with a variety of heterocycles in order to reduce protein plasma binding and enhance CNS exposure.

MeSH terms

Allosteric Regulation
Animals
Blood Proteins / chemistry
Carboxylic Acids / chemistry
Carboxylic Acids / pharmacokinetics
Carboxylic Acids / pharmacology*
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacokinetics
Heterocyclic Compounds / pharmacology*
Humans
Pyridones / chemistry*
Rats

Substances

Blood Proteins
Carboxylic Acids
Heterocyclic Compounds
Pyridones