Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor.

Hao, Junliang; Beck, James P; Schaus, John M; Krushinski, Joseph H; Chen, Qi; Beadle, Christopher D; Vidal, Paloma; Reinhard, Matthew R; Dressman, Bruce A; Massey, Steven M; Boulet, Serge L; Cohen, Michael P; Watson, Brian M; Tupper, David; Gardinier, Kevin M; Myers, Jason; Johansson, Anette M; Richardson, Jeffery; Richards, Daniel S; Hembre, Erik J; Remick, David M; Coates, David A; Bhardwaj, Rajni M; Diseroad, Benjamin A; Bender, David; Stephenson, Greg; Wolfangel, Craig D; Diaz, Nuria; Getman, Brian G; Wang, Xu-Shan; Heinz, Beverly A; Cramer, Jeff W; Zhou, Xin; Maren, Deanna L; Falcone, Julie F; Wright, Rebecca A; Mitchell, Stephen N; Carter, Guy; Yang, Charles R; Bruns, Robert F; Svensson, Kjell A

Hao, Junliang; Beck, James P; Schaus, John M; Krushinski, Joseph H; Chen, Qi; Beadle, Christopher D; Vidal, Paloma; Reinhard, Matthew R; Dressman, Bruce A; Massey, Steven M; Boulet, Serge L; Cohen, Michael P; Watson, Brian M; Tupper, David; Gardinier, Kevin M; Myers, Jason; Johansson, Anette M; Richardson, Jeffery; Richards, Daniel S; Hembre, Erik J; Remick, David M; Coates, David A; Bhardwaj, Rajni M; Diseroad, Benjamin A; Bender, David; Stephenson, Greg; Wolfangel, Craig D; Diaz, Nuria; Getman, Brian G; Wang, Xu-Shan; Heinz, Beverly A; Cramer, Jeff W; Zhou, Xin; Maren, Deanna L; Falcone, Julie F; Wright, Rebecca A; Mitchell, Stephen N; Carter, Guy; Yang, Charles R; Bruns, Robert F; Svensson, Kjell A.

Affiliation

Richards DS; AMRI UK Ltd , Erl Wood Manor, Sunninghill Road , Windlesham , Surrey , GU20 6PH , United Kingdom.

J Med Chem ; 62(19): 8711-8732, 2019 10 10.

Article in En | MEDLINE | ID: mdl-31532644

Subject(s)

Isoquinolines/pharmacology; Receptors, Dopamine D1/agonists; Acetylcholine/metabolism; Administration, Oral; Allosteric Regulation/drug effects; Animals; Binding Sites; Crystallography, X-Ray; Cyclic AMP/metabolism; HEK293 Cells; Half-Life; Humans; Isoquinolines/chemistry; Isoquinolines/pharmacokinetics; Kidney/drug effects; Kidney/metabolism; Locomotion/drug effects; Mice; Molecular Conformation; Protein Isoforms/agonists; Protein Isoforms/metabolism; Rats; Receptors, Dopamine D1/metabolism; Small Molecule Libraries/chemistry; Small Molecule Libraries/metabolism; Small Molecule Libraries/pharmacology; Structure-Activity Relationship

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Full text: 1 Database: MEDLINE Main subject: Receptors, Dopamine D1 / Isoquinolines Limits: Animals / Humans Language: En Year: 2019 Type: Article

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Full text: 1 Database: MEDLINE Main subject: Receptors, Dopamine D1 / Isoquinolines Limits: Animals / Humans Language: En Year: 2019 Type: Article