Discovery of triazolone derivatives as novel, potent stearoyl-CoA desaturase-1 (SCD1) inhibitors

Bioorganic and Medicinal Chemistry

Volumn 23, Issue 3, 2015, Pages 455-465

  Sun, Shaoyi ^a   Zhang, Zaihui ^a   Pokrovskaia, Natalia ^a   Chowdhury, Sultan ^a   Jia, Qi ^a   Chang, Elaine ^a   Khakh, Kuldip ^a   Kwan, Rainbow ^a   McLaren, David G ^a   Radomski, Chris C ^a   Ratkay, Leslie G ^a   Fu, Jianmin ^a   Dales, Natalie A ^b   Winther, Michael D ^a  

^a Xenon Pharmaceuticals Inc   (Canada)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

Desaturation index; Pyrazolyltriazolone; Stearoyl CoA desaturase; Thiazolytriazolone

Indexed keywords

2 [1 (3,5 DIFLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (OXAZOL 2 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (OXAZOL 4 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (PIPERIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE TRIFLUOROACETIC ACID SALT; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (PYRIDIN 2 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (THIAZOL 2 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N [(1 METHYL 1H IMIDAZOL 4 YL)METHYL]THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N [(2 METHYLTHIAZOL 5 YL)METHYL]THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N [(3 METHYL 1H PYRAZOL 5 YL)METHYL]THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N [(5 METHYLPYRAZIN 2 YL)METHYL]THIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYLTHIAZOLE 5 CARBOXAMIDE; 2 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) Y] 4 METHYL N [[6 (TRIFLUOROMETHYL)PYRIDIN 3 YL]METHYL]THIAZOLE 5 CARBOXAMIDE; 2 [1 (CYCLOPROPYLMETHYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 [(2,2 DIFLUOROCYCLOPROPYL)METHYL] 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 [1 (4 FLUOROPHENYL)ETHYL] 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) Y] 4 METHYL N (PYRIDIN 2 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 2 [1 [2 (4 FLUOROPHENOXY)ETHYL] 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] 4 METHYL N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 3 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] N (OXAZOL 4 YLMETHYL) 1H PYRAZOLE 5 CARBOXAMIDE; 3 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] N (PYRIDIN 2 YLMETHYL) 1H PYRAZOLE 5 CARBOXAMIDE; 3 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] N (PYRIDIN 4 YLMETHYL) 1H PYRAZOLE 5 CARBOXAMIDE; 3 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) YL] N [(1 METHYL 1H PYRAZOL 4 YL)METHYL] 1H PYRAZOLE 5 CARBOXAMIDE; 3 [1 (4 FLUOROBENZYL) 5 OXO 1H 1,2,4 TRIAZOL 4 (5H) Y] N (PYRIDIN 3 YLMETHYL) 1H PYRAZOLE 5 CARBOXAMIDE; 4 METHYL 2 [5 OXO 1 (4,4,4 TRIFLUOROBUTYL) 1H 1,2,4 TRIAZOL 4 (5H) YL] N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 4 METHYL 2 [5 OXO 1 [4 (TRIFLUOROMETHYL)BENZYL] 1H 1,2,4 TRIAZO 4 (5H) YL] N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 4 METHYL 2 [5 OXO 1 [4 (TRIFLUOROMETHYL)BENZYL] 1H 1,2,4 TRIAZOL 4 (5H) YL] N (PYRIDIN 2 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; 4 METHYL 2 [5 OXO 1 [[5 (TRIFLUOROMETHYL)FURAN 2 YL]METHYL] 1H 1,2,4 TRIAZOL 4 (5H) YL] N (PYRIDIN 3 YLMETHYL)THIAZOLE 5 CARBOXAMIDE; ACYL COENZYME A DESATURASE; ENZYME INHIBITOR; TRIAZOLONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; TRIAZOLE DERIVATIVE;

ALKYLATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CLINICAL EFFECTIVENESS; DESATURATION INDEX; DOSE RESPONSE; DRUG DETERMINATION; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG PENETRATION; DRUG POTENCY; DRUG SAFETY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRY SKIN; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; EYE REDNESS; FEMALE; HAIR LOSS; HUMAN; HUMAN CELL; HYDROGENOLYSIS; IN VITRO STUDY; IN VIVO STUDY; LEWIS RAT; LIVER MICROSOME; METABOLIC PARAMETERS; MOUSE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; HEPG2 CELL LINE; LIPID METABOLISM; METABOLIC DISEASES;

RATTUS;

ANIMALS; DRUG DISCOVERY; HEP G2 CELLS; HUMANS; LIPID METABOLISM; METABOLIC DISEASES; MICE; RATS; RATS, INBRED LEW; STEAROYL-COA DESATURASE; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 84921368779     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.12.014     Document Type: Article

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