Discovery of 1-[2-Fluoro-4-(1 H -pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1 H -pyrazol-5-yl)pyridazin-4(1 H)-one (TAK-063), a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor

Journal of Medicinal Chemistry

Volumn 57, Issue 22, 2014, Pages 9627-9643

  Kunitomo, Jun ^a   Yoshikawa, Masato ^a   Fushimi, Makoto ^a   Kawada, Akira ^a   Quinn, John F ^b,c   Oki, Hideyuki ^a   Kokubo, Hironori ^a   Kondo, Mitsuyo ^a   Nakashima, Kosuke ^a   Kamiguchi, Naomi ^a   Suzuki, Kazunori ^a   Kimura, Haruhide ^a   Taniguchi, Takahiko ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b ALBANY MOLECULAR RESEARCH INC   (United States)

^c NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2 CHLOROPHENYL) 3 (1 PHENYL 1H PYRAZOL 5 YL)PYRIDAZIN 4 (1H) ONE; 1 (2 FLUOROPHENYL) 3 (1 PHENYL 1H PYRAZOL 5 YL)PYRIDAZIN 4 (1H) ONE; 1 (2 METHYLPHENYL) 3 (1 PHENYL 1H PYRAZOL 5 YL)PYRIDAZIN 4(1H) ONE; 1 PHENYL 3 (1 PHENYL 1H PYRAZOL 5 YL)PYRIDAZIN 4(1H) ONE; 1 [2 FLUORO 4 (1H PYRAZOL 1 YL)PHENYL] 5 METHOXY 3 (1 PHENYL 1H PYRAZOL 5 YL)PYRIDAZIN 4(1H) ONE; 3 (1 PHENYL 1H 1,2,4 TRIAZOL 5 YL) 1 [3 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4 (1H) ONE; 3 (1 PHENYL 1H PYRAZOL 5 YL) 1 [2 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4(1H) ONE; 3 (2 CHLOROPYRIDIN 3 YL) 1 [3 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4(1H) ONE; 3 (2 PHENYL 1H IMIDAZOL 1 YL) 1 [3 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4 (1H) ONE; 3 (2 PHENYL 3 FURYL) 1 [3 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4(1H) ONE; 3 (2 PHENYLPYRIDIN 3 YL) 1 [3 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4(1H) ONE; 3 AMINO 1 [3 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4(1H) ONE; 3 BROMO 1 [3 (TRIFLUOROMETHYL)PHENYL]PYRIDAZIN 4(1H) ONE; 3 [(2 CHLOROPHENYL)HYDRAZONO]PENTANE 2,4 DIONE; 3 [(2 FLUOROPHENYL)HYDRAZONO]PENTANE 2,4 DIONE; 3 [(2 METHYLPHENYL)HYDRAZONO]PENTANE 2,4 DIONE; 3 [[2 (TRIFLUOROMETHYL)PHENYL]HYDRAZONO]PENTANE 2,4 DIONE; 4 OXO 1 [3 (TRIFLUOROMETHYL)PHENYL] 1,4 DIHYDROPYRIDAZINE 3 CARBOXAMIDE; 4 OXO 1 [3 (TRIFLUOROMETHYL)PHENYL] 1,4 DIHYDROPYRIDAZINE 3 CARBOXYLIC ACID; CYCLIC AMP; CYCLIC GMP; METHYL 3 OXO 2 [[3 (TRIFLUOROMETHYL)PHENYL]HYDRAZONO] BUTANOATE; METHYL 4 OXO 1 [3 (TRIFLUOROMETHYL)PHENYL] 1,4 DIHYDROPYRIDAZINE 3 CARBOXYLATE; N [(DIMETHYLAMINO)METHYLENE] 4 OXO 1 [3 (TRIFLUOROMETHYL)PHENYL] 1,4 DIHYDROPYRIDAZINE 3 CARBOXAMIDE; PHENCYCLIDINE; PHOSPHODIESTERASE; PHOSPHODIESTERASE 10A; PHOSPHODIESTERASE INHIBITOR; PYRIDAZINONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; 1-(2-FLUORO-4-(1H-PYRAZOL-1-YL)PHENYL)-5-METHOXY-3-(1-PHENYL-1H-PYRAZOL-5-YL)PYRIDAZIN-4(1H)-ONE; PDE10A PROTEIN, HUMAN; PDE10A PROTEIN, MOUSE; PYRAZOLE DERIVATIVE; PYRIDAZINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; CRYSTAL STRUCTURE; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DESIGN; DRUG IDENTIFICATION; DRUG PENETRATION; DRUG POTENCY; DRUG STRUCTURE; GENE EXPRESSION SYSTEM; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; HYPERACTIVITY; IC50; MALE; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; SAMPLE; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; TRANSCYTOSIS; X RAY DIFFRACTION; ANIMAL; BRAIN; C57BL MOUSE; CHEMISTRY; DRUG EFFECTS; INSTITUTE FOR CANCER RESEARCH MOUSE; LIVER MICROSOME; METABOLISM; MOVEMENT (PHYSIOLOGY); PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

ADMINISTRATION, ORAL; ANIMALS; BRAIN; CRYSTALLOGRAPHY, X-RAY; CYCLIC GMP; DRUG DESIGN; HUMANS; INHIBITORY CONCENTRATION 50; MALE; MICE; MICE, INBRED C57BL; MICE, INBRED ICR; MICROSOMES, LIVER; MOVEMENT; PHENCYCLIDINE; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PROTEIN CONFORMATION; PYRAZOLES; PYRIDAZINES;

EID: 84913580991     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5013648     Document Type: Article

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