Pyrazoloquinolines as PDE10A inhibitors: Discovery of a tool compound

A series of pyrazoloquinolines, possessing (hetero)arylhydroxymethyl substituents at the quinoline C-4 position were evaluated as PDE10A inhibitors. Among these, methylpyrimidyl analogue 15 was identified as having good rodent and monkey exposure, and a MED of 10mg/kg in an in vivo model.

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Published in	Bioorganic & medicinal chemistry letters Vol. 22; no. 3; pp. 1335 - 1339
Main Authors	McElroy, William T., Tan, Zheng, Basu, Kallol, Yang, Shu-Wei, Smotryski, Jennifer, Ho, Ginny D., Tulshian, Deen, Greenlee, William J., Mullins, Deborra, Guzzi, Mario, Zhang, Xiaoping, Bleickardt, Carina, Hodgson, Robert
Format	Journal Article
Language	English
Published	Amsterdam Elsevier Ltd 01.02.2012 Elsevier
Subjects	Animals Biological and medical sciences chemistry Drug Discovery Enzyme Activation - drug effects Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacokinetics Enzyme Inhibitors - pharmacology Haplorhini Hepatocytes - drug effects Hepatocytes - metabolism Inhibitory Concentration 50 Medical sciences Molecular Structure monkeys PDE10A Pharmacology. Drug treatments Phosphodiesterase inhibitor Phosphoric Diester Hydrolases - metabolism Pyrazolones - chemical synthesis Pyrazolones - chemistry Pyrazolones - pharmacokinetics Pyrazolones - pharmacology quinoline Quinolines Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacokinetics Quinolines - pharmacology Rats rodents Schizophrenia Phosphodiesterase inhibitor Schizophrenia PDE10A Psychosis
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Abstract	A series of pyrazoloquinolines, possessing (hetero)arylhydroxymethyl substituents at the quinoline C-4 position were evaluated as PDE10A inhibitors. Among these, methylpyrimidyl analogue 15 was identified as having good rodent and monkey exposure, and a MED of 10mg/kg in an in vivo model.
AbstractList	A series of pyrazoloquinolines, possessing (hetero)arylhydroxymethyl substituents at the quinoline C-4 position were evaluated as PDE10A inhibitors. Among these, methylpyrimidyl analogue 15 was identified as having good rodent and monkey exposure, and a MED of 10mg/kg in an in vivo model. A series of pyrazoloquinolines, possessing (hetero)arylhydroxymethyl substituents at the quinoline C-4 position were evaluated as PDE10A inhibitors. Among these, methylpyrimidyl analogue 15 was identified as having good rodent and monkey exposure, and a MED of 10 mg/kg in an in vivo model.
Author	Tan, Zheng Tulshian, Deen Yang, Shu-Wei Zhang, Xiaoping Ho, Ginny D. Hodgson, Robert McElroy, William T. Guzzi, Mario Basu, Kallol Mullins, Deborra Bleickardt, Carina Greenlee, William J. Smotryski, Jennifer
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SubjectTerms	Animals Biological and medical sciences chemistry Drug Discovery Enzyme Activation - drug effects Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacokinetics Enzyme Inhibitors - pharmacology Haplorhini Hepatocytes - drug effects Hepatocytes - metabolism Inhibitory Concentration 50 Medical sciences Molecular Structure monkeys PDE10A Pharmacology. Drug treatments Phosphodiesterase inhibitor Phosphoric Diester Hydrolases - metabolism Pyrazolones - chemical synthesis Pyrazolones - chemistry Pyrazolones - pharmacokinetics Pyrazolones - pharmacology quinoline Quinolines Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacokinetics Quinolines - pharmacology Rats rodents Schizophrenia
Title	Pyrazoloquinolines as PDE10A inhibitors: Discovery of a tool compound
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