Discovery and optimization of 1,3,4-trisubstituted-pyrazolone derivatives as novel, potent, and nonsteroidal farnesoid X receptor (FXR) selective antagonists

Journal of Medicinal Chemistry

Volumn 55, Issue 16, 2012, Pages 7037-7053

  Huang, Huang ^a   Yu, Ying ^a   Gao, Zhenting ^a   Zhang, Yong ^c   Li, Chenjing ^b   Xu, Xing ^b   Jin, Hui ^a   Yan, Wenzhong ^a   Ma, Ruoqun ^a   Zhu, Jin ^a   Shen, Xu ^a,b   Jiang, Hualiang ^a,b   Chen, Lili ^b   Li, Jian ^a  

^a EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^c ZUNYI MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3,5 BIS(TRIFLUOROMETHYL)PHENYL] 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 1H PYRAZOL 5(4H) ONE; 3 [4 (3,4 DIHYDROXYBENZYLIDENE) 3 METHYL 5 OXO 4,5 DIHYDRO 1H PYRAZOL 1 YL]BENZOIC ACID; 3 [4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 5 OXO 4,5 DIHYDRO 1H PYRAZOL 1 YL]BENZOIC ACID; 3 [4 (4 HYDROXY 3 METHOXYBENZYLIDENE) 3 METHYL 5 OXO 4,5 DIHYDRO 1H PYRAZOL 1 YL]BENZOIC ACID; 3 [4 (4 ISOPROPOXY 3 METHOXYBENZYLIDENE) 3 METHYL 5 OXO 4,5 DIHYDRO 1H PYRAZOL 1 YL]BENZOIC ACID; 3 [4 [3 METHOXY 4 (PENTYLOXY)BENZYLIDENE] 3 METHYL 5 OXO 4,5 DIHYDRO 1H PYRAZOL 1 YL]BENZOIC ACID; 3 [4 [4 (BENZYLOXY) 3 METHOXYBENZYLIDENE] 3 METHYL 5 OXO 4,5 DIHYDRO 1H PYRAZOL 1 YL]BENZOIC ACID; 3 METHYL 4 [(5 METHYLTHIOPHEN 2 YL)METHYLENE] 1 (3 NITROPHENYL) 1H PYRAZOL 5(4H) ONE; 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 1 (2 FLUOROPHENYL) 3 METHYL 1H PYRAZOL 5(4H) ONE; 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 1 (3 NITROPHENYL)PYRAZOL 5(4H) ONE; 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 1 (4 NITROPHENYL) 1H PYRAZOL 5(4H) ONE; 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 1 [3 (TRIFLUOROMETHYL)PHENYL] 1H PYRAZOL 5(4H) ONE; 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 1 [4 (TRIFLUOROMETHYL)PHENYL] 1H PYRAZOL 5(4H) ONE; 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 1 PERFLUOROPHENYL 1H PYRAZOL 5(4H) ONE; 4 (4 ETHOXY 3 METHOXYBENZYLIDENE) 3 METHYL 1 PHENYL 1H PYRAZOL 5(4H) ONE; 4 (4 HYDROXY 3 METHOXYBENZYLIDENE) 1 (3 NITROPHENYL) 3 PHENYL 1H PYRAZOL 5(4H) ONE; 4 (4 HYDROXY 3 METHOXYBENZYLIDENE) 3 ISOPROPYL 1 (3 NITROPHENYL) 1H PYRAZOL 5(4H) ONE; 4 [(4 METHOXYNAPHTHALEN 1 YL)METHYLENE] 3 METHYL 1 (3 NITROPHENYL) 1H PYRAZOL 5(4H) ONE; 4 [1 (4 CHLOROPHENYL)ETHYLIDEN 1 YL] 3 METHYL 1 (4 NITROPHENYL) 1H PYRAZOL 5(4H) ONE; 4 BENZYLIDENE 3 METHYL 1 PHENYL 1H PYRAZOLIDINYL 5(4H) KETONE; ANTILIPEMIC AGENT; CHENODEOXYCHOLIC ACID; CHOLESTEROL; FARNESOID X RECEPTOR; FARNESOID X RECEPTOR ANTAGONIST; GUGGULSTERONE; PYRAZOLONE DERIVATIVE; RECEPTOR BLOCKING AGENT; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CELL LEVEL; CELL STRAIN HEPG2; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL LIVER LEVEL; CONTROLLED STUDY; DRUG DESIGN; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG SYNTHESIS; FLUORESCENCE ANALYSIS; HUMAN; HUMAN CELL; HYPERCHOLESTEROLEMIA; LIPID LIVER LEVEL; MALE; MOUSE; NONHUMAN; RECEPTOR BLOCKING; STRUCTURE ACTIVITY RELATION; TRANSCRIPTION REGULATION; TRIACYLGLYCEROL BLOOD LEVEL;

ANIMALS; ANTICHOLESTEREMIC AGENTS; BENZYLIDENE COMPOUNDS; BIOLOGICAL AVAILABILITY; CHENODEOXYCHOLIC ACID; CHOLESTEROL; DATABASES, CHEMICAL; HEK293 CELLS; HEP G2 CELLS; HUMANS; LIVER; MALE; MICE; MICE, INBRED C57BL; MODELS, MOLECULAR; PYRAZOLES; PYRAZOLONES; RATS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SOLUBILITY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTION, GENETIC; TRANSCRIPTIONAL ACTIVATION; TRIGLYCERIDES;

EID: 84866903943     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3002718     Document Type: Article

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