Parallel synthesis of N-biaryl quinolone carboxylic acids as selective M(1) positive allosteric modulators.
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.
Yang
Feng V
FV
Department of Medicinal Chemistry, Merck Research Laboratories, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Shipe
William D
WD
Bunda
Jaime L
JL
Nolt
M Brad
MB
Wisnoski
David D
DD
Zhao
Zhijian
Z
Barrow
James C
JC
Ray
William J
WJ
Ma
Lei
L
Wittmann
Marion
M
Seager
Matthew A
MA
Koeplinger
Kenneth A
KA
Hartman
George D
GD
Lindsley
Craig W
CW
D000494:Allosteric Regulation; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry*; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D054852:Small Molecule Libraries
D001798:Blood Proteins; D002264:Carboxylic Acids; D011804:Quinolines; D043643:Receptor, Muscarinic M1; D054852:Small Molecule Libraries