Pyridine containing M(1) positive allosteric modulators with reduced plasma protein binding.
Incorporation of pyridines and diazines into the biphenyl region of quinolone carboxylic acid derived M(1) positive allosteric modulators was investigated as a means of lowering plasma protein binding to enhance 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
Seager
Matthew A
MA
Seager
Matthew
M
Koeplinger
Kenneth
K
Thompson
Chuck D
CD
Hartman
George D
GD
Bilodeau
Mark T
MT
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001798:Blood Proteins; D011725:Pyridines; D043643:Receptor, Muscarinic M1