Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis

Journal of Medicinal Chemistry

Volumn 58, Issue 19, 2015, Pages 7888-7894

  Shipe, William D ^a   Sharik, Steven S ^a,b   Barrow, James C ^a,c   McGaughey, Georgia B ^a,d   Theberge, Cory R ^a,e   Uslaner, Jason M ^a   Yan, Youwei ^a   Renger, John J ^a   Smith, Sean M ^a   Coleman, Paul J ^a   Cox, Christopher D ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Exelon Nuclear   (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VERTEX PHARMACEUTICALS   (United States)

^e UNIVERSITY OF NEW ENGLAND   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 CHLORO N [(2,4 DIMETHYLTHIAZOL 5 YL)METHYL] 5 METHYL 2 [3 (QUINOLIN 2 YL)PROPOXY]PYRIMIDIN 4 AMINE; CHLOROPYRIMIDINE; DICHLOROPYRIMIDINE; DIHYDROXYPYRIMIDINE; DIZOCILPINE; PHOSPHODIESTERASE 10A INHIBITOR; PHOSPHODIESTERASE INHIBITOR; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; DIZOCILPINE MALEATE; PDE10A PROTEIN, HUMAN; PHOSPHODIESTERASE;

ARTICLE; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; HIGH THROUGHPUT SCREENING; HYDROGEN BOND; IN VIVO STUDY; MOLECULAR DOCKING; MOLECULAR WEIGHT; PLASMA CLEARANCE; PROCESS OPTIMIZATION; PSYCHOMOTOR ACTIVITY; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SCHIZOPHRENIA; ANIMAL; CHEMISTRY; DISEASE MODEL; DRUG DEVELOPMENT; HUMAN; MALE; METABOLISM; PRECLINICAL STUDY; PROCEDURES; STRUCTURE ACTIVITY RELATION; SYNTHESIS; WISTAR RAT; X RAY CRYSTALLOGRAPHY;

ANIMALS; CHEMISTRY TECHNIQUES, SYNTHETIC; CRYSTALLOGRAPHY, X-RAY; DISEASE MODELS, ANIMAL; DIZOCILPINE MALEATE; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS; MALE; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PYRIMIDINES; RATS, WISTAR; SCHIZOPHRENIA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84943743884     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00983     Document Type: Article

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