N-heterocyclic derived M1 positive allosteric modulators

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

doi:10.1016/j.bmcl.2010.01.013

N-heterocyclic derived M1 positive allosteric modulators

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1334-7. doi: 10.1016/j.bmcl.2010.01.013. Epub 2010 Jan 11.

Authors

Scott D Kuduk¹, Christina N Di Marco, Victoria Cofre, Daniel R Pitts, William J Ray, Lei Ma, Marion Wittmann, Lone Veng, Matthew A Seager, Kenneth Koeplinger, Charles 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. [email protected]

PMID: 20097564
DOI: 10.1016/j.bmcl.2010.01.013

Abstract

Replacement of a phenyl ring with N-linked heterocycles in a series of quinolone carboxylic acid M1 positive allosteric modulators was investigated. In particular, a pyrazole derivative exhibited improvements in potency, free fraction, and CNS exposure.

MeSH terms

Allosteric Regulation
Animals
CHO Cells
Carboxylic Acids / chemical synthesis*
Carboxylic Acids / chemistry
Carboxylic Acids / pharmacology
Cell Line
Cricetinae
Cricetulus
Heterocyclic Compounds / chemical synthesis*
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology
Humans
Molecular Structure
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology
Rats
Structure-Activity Relationship

Substances

Carboxylic Acids
Heterocyclic Compounds
Pyrazoles
Quinolines