Discovery of a novel series of orally active nociceptin/orphanin FQ (NOP) receptor antagonists based on a dihydrospiro(piperidine-4,7′-thieno[2,3- C ]pyran) scaffold

Journal of Medicinal Chemistry

Volumn 57, Issue 8, 2014, Pages 3418-3429

  Toledo, Miguel A ^a   Pedregal, Concepción ^a   Lafuente, Celia ^a   Diaz, Nuria ^a   Martinez Grau, Maria Angeles ^a   Jiménez, Alma ^a   Benito, Ana ^a   Torrado, Alicia ^a   Mateos, Carlos ^a   Joshi, Elizabeth M ^b   Kahl, Steven D ^b   Rash, Karen S ^b   Mudra, Daniel R ^b   Barth, Vanessa N ^b   Shaw, David B ^b   McKinzie, David ^b   Witkin, Jeffrey M ^b   Statnick, Michael A ^b  

^a ELI LILLY AND COMPANY   (Spain)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 [4 [[2 CHLORO 4,4 DIFLUOROSPIRO(5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1' YL]METHYL] 3 METHYLPYRAZOL 1 YL] 3 FLUOROPHENYL] N,N DIMETHYLMETHANAMINE LEVO TARTRATE; 1 [2 [4 [[2 CHLORO 4,4 DIFLUOROSPIRO(5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1' YL]METHYL] 3 METHYLPYRAZOL 1 YL] 3 PYRIDYL] N.N DIMETHYLMETHANAMINE LEVO TARTRATE; 1 [2 [4 [[2 CHLOROSPIRO(4,5 DIHYDROTHIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1' YL]METHYL] 3 METHYLPYRAZOL 1 YL] 3 FLUOROPHENYL N.N DIMETHYLMETHANAMINE LEVO TARTRATE; 1 [3 FLUORO 2 [4 [[2 FLUOROSPIRO(4,5 DIHYDROTHIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1' YL]METHYL] 3 METHYLPYRAZOL 1 YL]PHENYL] N,N DIMETHYLMETHANAMINE LEVO TARTRATE; 1' [[1 (2,6 DIFLUOROPHENYL) 3 METHYLPYRAZOL 4 YL]METHYL] 2 FLUOROSPIRO[4,5 DIHYDROTHIENO[2,3 C]PYRAN 7,4' PIPERIDINE] LEVO TARTRATE; 2 CHLORO 1' [[1 (2,6 DIFLUOROPHENYL) 3 METHYLPYRAZOL 4 YL]METHYL] 4,4 DIFLUOROSPIRO[5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE LEVO TARTRATE; 2 CHLORO 1' [[1 [3 (METHOXYMETHYL) 2 PYRIDYL] 3 METHYLPYRAZOL 4 YL]METHYL]SPIRO[4,5 DIHYDROTHIENO[2,3 C]PYRAN 7,4' PIPERIDINE] LEVO TARTRATE; 2 CHLORO 4,4 DIFLUORO 1' [[1 (3 FLUORO 2 PYRIDYL) 3 METHYLPYRAZOL 4 YL]MEHTYL]SPIRO[5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE LEVO TARTRATE; 2 CHLORO 4,4 DIFLUORO 1' [[1 [3 (1H IMIDAZOL 2 YL) 2 PYRIDYL] 3 METHYLPYRAZOL 4 YL]METHYL]SPIRO[5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE]; 2 CHLORO 4,4 DIFLUORO 1' [[1 [3 (METHOXYMETHYL) 2 PYRIDYL] 3 METHYLPYRAZOL 4 YL]METHYL]SPIRO[5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE] LEVO TARTARTE; 2 FLUORO 1' [[1 (3 FLUORO 2 PYRIDYL) 3 METHYLPYRAZOL 4 YL]METHYL]SPIRO[4,5 DIHYDROTHIENO[2,3 C]PYRAN 7,4' PIPERIDINE LEVO TARTRATE; 2 FLUORO 1' [[1 [3 (METHOXYMETHYL) 2 PYRIDYL] 3 METHYLPYRAZOL 4 YL]METHYL]SPIRO[4,5 DIHYDROTHIENO[2,3 C]PYRAN 7,4' PIPERIDINE LEVO TARTRATE; 3 FLUORO 2 [4 [(2 FLUOROSPIRO[4,5 DIHYDROTHIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1' YL]METHYLPYRAZOL 1 YL]BENZAMIDE LEVO TARTRATE; DELTA OPIATE RECEPTOR; KAPPA OPIATE RECEPTOR; MU OPIATE RECEPTOR; NOCICEPTIN; NOCICEPTIN RECEPTOR; PIPERIDINE DERIVATIVE; PYRAN DERIVATIVE; UNCLASSIFIED DRUG; [2 [4 [[2 CHLORO 4,4 DIFLUOROSPIRO(5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1 YL]METHYL] 3 METHYLPYRAZOL 1 YL] 3 PYRIDYL]METHANOL LEVO TARTRATE; [2 [4 [[2 CHLORO 4,4 DIFLUOROSPIRO(5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1' YL]METHYL 3 METHYLPYRAZOL 1 YL] 3 FLUOROPHENYL] N METHYLMETHANAMINE LEVO TARTRATE; [2 [4 [[2 CHLORO 4,4 DIFLUOROSPIRO(5H THIENO[2,3 C]PYRAN 7,4' PIPERIDINE) 1' YL]METHYL] 3 METHYLPYRAZOL 1 YL] 3 FLUOROPHENYL]METHANOL LEVO TARTRATE;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG SELECTIVITY; DRUG SYNTHESIS; HYPOTHERMIA; IN VITRO STUDY; IN VIVO STUDY; MALE; NONHUMAN; RAT; RECEPTOR BINDING; RECEPTOR OCCUPANCY; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; DRUG DISCOVERY; MALE; PYRANS; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, OPIOID; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84899502466     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500117r     Document Type: Article

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