Fused heterocyclic M1 positive allosteric modulators

Scott D Kuduk; Christina N Di Marco; Victoria Cofre; 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.2010.10.028

Fused heterocyclic M1 positive allosteric modulators

Bioorg Med Chem Lett. 2011 May 1;21(9):2769-72. doi: 10.1016/j.bmcl.2010.10.028. Epub 2010 Oct 16.

Authors

Scott D Kuduk¹, Christina N Di Marco, Victoria Cofre, 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, PO Box 4, West Point, PA 19486, USA. [email protected]

PMID: 21055928
DOI: 10.1016/j.bmcl.2010.10.028

Abstract

Fused aromatics such as naphthalene were identified as highly potent and CNS penetrant M(1) positive allosteric modulators during an SAR study to replace the phenyl B-ring linkage.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / blood
ATP Binding Cassette Transporter, Subfamily B, Member 1 / cerebrospinal fluid
Allosteric Regulation / drug effects
Animals
Carboxylic Acids / chemistry
Carboxylic Acids / pharmacology
Humans
Molecular Structure
Naphthols / chemistry*
Naphthols / pharmacology
Quinolones / chemistry
Quinolones / pharmacology
Rats
Receptor, Muscarinic M1 / metabolism*
Structure-Activity Relationship

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Carboxylic Acids
Naphthols
Quinolones
Receptor, Muscarinic M1