N-heterocyclic derived M1 positive allosteric modulators.
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.
Kuduk
Scott D
SD
Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. scott_d_kuduk@merck.com
Di Marco
Christina N
CN
Cofre
Victoria
V
Pitts
Daniel R
DR
Ray
William J
WJ
Ma
Lei
L
Wittmann
Marion
M
Veng
Lone
L
Seager
Matthew A
MA
Koeplinger
Kenneth
K
Thompson
Charles D
CD
Hartman
George D
GD
Bilodeau
Mark T
MT
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
D002264:Carboxylic Acids; D006571:Heterocyclic Compounds; D011720:Pyrazoles; D011804:Quinolines