Parallel synthesis of N-biaryl quinolone carboxylic acids as selective M(1) positive allosteric modulators

Feng V Yang; William D Shipe; Jaime L Bunda; M Brad Nolt; David D Wisnoski; Zhijian Zhao; James C Barrow; William J Ray; Lei Ma; Marion Wittmann; Matthew A Seager; Kenneth A Koeplinger; George D Hartman; Craig W Lindsley

doi:10.1016/j.bmcl.2009.11.100

Parallel synthesis of N-biaryl quinolone carboxylic acids as selective M(1) positive allosteric modulators

Bioorg Med Chem Lett. 2010 Jan 15;20(2):531-6. doi: 10.1016/j.bmcl.2009.11.100. Epub 2009 Nov 24.

Authors

Feng V Yang¹, William D Shipe, Jaime L Bunda, M Brad Nolt, David D Wisnoski, Zhijian Zhao, James C Barrow, William J Ray, Lei Ma, Marion Wittmann, Matthew A Seager, Kenneth A Koeplinger, George D Hartman, Craig W Lindsley

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.

PMID: 20004574
DOI: 10.1016/j.bmcl.2009.11.100

Abstract

An iterative analog library synthesis approach was employed in the exploration of a quinolone carboxylic acid series of selective M(1) positive allosteric modulators, and strategies for improving potency and plasma free fraction were identified.

MeSH terms

Allosteric Regulation
Animals
Blood Proteins / chemistry
Blood Proteins / metabolism
Carboxylic Acids / chemical synthesis*
Carboxylic Acids / chemistry
Carboxylic Acids / pharmacology
Humans
Protein Binding
Quinolines / chemistry*
Rats
Receptor, Muscarinic M1 / metabolism*
Small Molecule Libraries

Substances

Blood Proteins
Carboxylic Acids
Quinolines
Receptor, Muscarinic M1
Small Molecule Libraries