Synthesis and SAR study of novel tricyclic pyrazoles as potent phosphodiesterase 10A inhibitors

European Journal of Medicinal Chemistry

Volumn 84, Issue , 2014, Pages 181-193

  Dore, Antonio ^a   Asproni, Battistina ^a   Scampuddu, Alessia ^a   Pinna, Gerard Aime ^a   Christoffersen, Claus Tornby ^b   Langgård, Morten ^b   Kehler, Jan ^b  

^a UNIVERSITY OF SASSARI   (Italy)

^b H LUNDBECK A S   (Denmark)

Author keywords

PDE10A inhibition; Structure activity relationships; Tricyclic pyrazoles

Indexed keywords

(2 METHYLPYRAZOLO[5,1 A]ISOQUINOLIN 5 YL)METHANOL; (2 METHYLPYRAZOLO[5,1 F][1,6]NAPHTHYRIDIN 5 YL)METHANOL; (9 METHYLPYRAZOLO[5,1 A][2,7]NAPHTHYRIDIN 6 YL)METHANOL; 2 (METHOXYMETHYL) 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 2 METHYL 5 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 A]ISOQUINOLINE; 2 METHYL 5 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 A]ISOQUINOLINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 A][2,6]NAPHTHYRIDINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL]PYRAZOLO[5,1 A]ISOQUINOLINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; 2 METHYLPYRAZOLO[5,1 A]ISOQUINOLINE 5 CARBALDEHYDE; 2 METHYLPYRAZOLO[5,1 F][1,6]NAPHTHYRIDIN 5 CARBALDEHYDE; 2 [4 [1 METHYL 4 (4 PYRIDINYL) 3 PYRAZOLYL]PHENOXYMETHYL]QUINOLINE; 5 (HYDROXYMETHYL)PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; 5 (METHOXYMETHYL) 2 METHYLPYRAZOLO[5,1 A]ISOQUINOLINE; 5 (METHOXYMETHYL) 2 METHYLPYRAZOLO[5,1 A][2,6]NAPHTHYRIDINE; 5 (METHOXYMETHYL) 2 METHYLPYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL] 2 (TRIFLUOROMWTHYL)PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; 6 (METHOXYMETHYL) 9 METHYLPYRAZOLO[5,1 A][2,7]NAPHTHYRIDINE; 9 METHYL 6 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 A][2,7]NAPHTHYRIDINE; 9 METHYL 6 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 A][2,7]NAPHTHYRIDINE; 9 METHYL 6 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL]PYRAZOLO[5,1 A][2,7]NAPHTHYRIDINE 2 CARBOXYLATE; ETHYL 5 (METHOXYMETHYL)PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; ETHYL 5 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; ETHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; PHOSPHODIESTERASE INHIBITOR; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; 2 (3 METHOXYPROP 1 YN 1 YL)BENZALDEHYDE; 2 (3 METHOXYPROP 1 YN YL)NICOTINALDEHYDE; 2 METHYL 5 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)VINYL] PYRAZOLO[5,1 A]ISOQUINOLINE; 2 METHYL 5 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)VINYL] PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL] PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL] PYRAZOLO[5,1 A]ISOQUINOLINE; 2 METHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL] PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE; 3 (3 METHOXYPROP 1 YN 1 YL)ISONICOTINALDEHYDE; 4 (3 METHOXYPROP 1 YN YL)NICOTINALDEHYDE; 5 (METHOXYMETHYL)PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; 5 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)VINYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)ETHYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; 9 METHYL 6 [2 (1 METHYL 1H BENZO[D]IMIDAZOL 2 YL)VINYL] PYRAZOLO[5,1 A][2,7]NAPHTHYRIDINE; 9 METHYL 6 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL] PYRAZOLO[5,1 A][2,7]NAPHTHYRIDINE; ETHYL 5 (HYDROXYMETHYL)PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; ETHYL 5 [2 (1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)VINYL]PYRAZOLO[5,1 F][1,6]NAPHTHYRIDINE 2 CARBOXYLATE; NAPHTHYRIDINE DERIVATIVE; [(1 METHYL 4 PHENYL 1H IMIDAZOL 2 YL)METHYL] TRIPHENYLPHOSPHONIUM CHLORIDE; PDE10A PROTEIN, HUMAN; PHOSPHODIESTERASE;

ANIMAL TISSUE; AROMATIZATION; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG HYDROLYSIS; DRUG PENETRATION; DRUG POTENCY; DRUG SCREENING; DRUG STABILITY; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME INHIBITION; HUMAN; HUMAN TISSUE; IC 50; LIVER MICROSOME; MOLECULAR DOCKING; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; SONOGASHIRA REACTION; STRUCTURE ACTIVITY RELATION; WITTIG REACTION; ALKYLATION; CATALYSIS; HALOGENATION; MASS SPECTROMETRY; MICROWAVE IRRADIATION; ROOM TEMPERATURE; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; ENZYMOLOGY; METABOLISM; SYNTHESIS;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MICROSOMES, LIVER; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PYRAZOLES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84904196928     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.07.020     Document Type: Article

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