Identification of a methoxynaphthalene scaffold as a core replacement in quinolizidinone amide M(1) positive allosteric modulators.
A series of methoxynaphthalene amides were prepared and evaluated as alternatives to quinolizidinone amide M1 positive allosteric modulators. A methoxy group was optimal for M1 activity and addressed key P-gp issues present in the aforementioned quinolizidinone amide series.
Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. Electronic address: scott_d_kuduk@merck.com.
Scott D
SD
Kuduk
Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Christina N
CN
Di Marco
Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Jonathan R
JR
Saffold
Department of Alzheimer's Research, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
William J
WJ
Ray
Department of Alzheimer's Research, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Lei
L
Ma
Department of Alzheimer's Research, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Marion
M
Wittmann
Department of Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Kenneth A
KA
Koeplinger
Department of Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Charles D
CD
Thompson
Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
George D
GD
Hartman
Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Mark T
MT
Bilodeau
Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Douglas C
DC
Beshore
D000494:Allosteric Regulation; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D051379:Mice; D009281:Naphthalenes / Q000737:chemistry*; D011485:Protein Binding; D054837:Quinolizidines / Q000737:chemistry*; D043643:Receptor, Muscarinic M1 / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000577:Amides; D009281:Naphthalenes; D054837:Quinolizidines; D043643:Receptor, Muscarinic M1; C031721:naphthalene
Allosteric modulator; Alzheimer’s disease; M(1); Muscarinic; P-glycoprotein