title: N-heterocyclic derived M1 positive allosteric modulators.
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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. scott_d_kuduk@merck.com
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kuduk
authors.forename: Christina N
authors.initials: CN
authors.lastname: Di Marco
authors.forename: Victoria
authors.initials: V
authors.lastname: Cofre
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Pitts
authors.forename: William J
authors.initials: WJ
authors.lastname: Ray
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Marion
authors.initials: M
authors.lastname: Wittmann
authors.forename: Lone
authors.initials: L
authors.lastname: Veng
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Seager
authors.forename: Kenneth
authors.initials: K
authors.lastname: Koeplinger
authors.forename: Charles D
authors.initials: CD
authors.lastname: Thompson
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bilodeau
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D006571:Heterocyclic Compounds; D011720:Pyrazoles; D011804:Quinolines