Structure-activity relationship studies and discovery of a potent transient receptor potential vanilloid (TRPV1) antagonist 4-[3-chloro-5-[(1 S)-1,2-dihydroxyethyl]-2-pyridyl]-N-[5-(trifluoromethyl)-2-pyridyl]-3, 6-dihydro-2 H-pyridine-1-carboxamide (V116517) as a clinical candidate for pain management

Journal of Medicinal Chemistry

Volumn 57, Issue 15, 2014, Pages 6781-6794

  Tafesse, Laykea ^a   Kanemasa, Toshiyuki ^b   Kurose, Noriyuki ^b   Yu, Jianming ^a   Asaki, Toshiyuki ^b   Wu, Gang ^a   Iwamoto, Yuka ^b   Yamaguchi, Yoshitaka ^b   Ni, Chiyou ^a   Engel, John ^a   Tsuno, Naoki ^b   Patel, Aniket ^a   Zhou, Xiaoming ^a   Shintani, Takuya ^b   Brown, Kevin ^a   Hasegawa, Tsuyoshi ^b   Shet, Manjunath ^a   Iso, Yasuyoshi ^b   Kato, Akira ^b   Kyle, Donald J ^a  

^a Purdue Pharma Discovery Research   (United States)

^b SHIONOGI AND CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 (3 CHLORO 1',2',3',6' TETRAHYDRO [2,4']BIPYRIDINYL 5 YL)ETHANE 1,2 DIOL; 1 (5,6 DICHLOROPYRIDIN 3 YL)ETHANE 1,2 DIOL; 2 [3 CHLORO 1' [(4 (TRIFLUOROMETHYL)PHENYL)CARBAMOYL] 1',2',3',6' TETRAHYDRO (2,4' BIPYRIDIN) 5 YL] ACETIC ACID; 2,3 DICHLORO 5 VINYLPYRIDINE; 3 CHLORO 1' [[4 (TRIFLUOROMETHYL)PHENYL]CARBOMOYL] 1',2' 3',6' TETRAHYDRO (2,4' BIPYRIDINE) 5 CARBOXYLIC ACID; 3 CHLORO 1',2',3',6' TETRAHYDRO(2,4' BIPYRIDINE); 3 CHLORO 5 (1,2 DIHYDROXYETHYL) 3',6' DIHYDRO 2'H [2,4'] BIPYRIDINYL 1' CARBOXYLIC ACID TERT BUTYL ESTER; 3 CHLORO 5 (1,2 DIHYDROXYETHYL) N [4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CABOXAMIDE; 3 CHLORO 5 (CYANOMETHYL) N [4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2H) CARBOXAMIDE; 3 CHLORO 5 (HYDROXYETHYL) N [4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2H) CARBOXAMIDE; 3 CHLORO 5 (HYDROXYMETHYL) N [4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2H) CARBOXAMIDE; 3 CHLORO 5 (METHYLSULFONAMIDOMETHYL) N [4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2H) CARBOXAMIDE; 3 CHLORO 5 [(DIETHYLAMINO)METHYL] N [4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 CHLORO N [2 (DIMETHYLAMINO) 4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 CHLORO N [2 METHOXY 4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 CHLORO N [3 (DIMETHYLAMINO) 4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 CHLORO N [3 METHOXY 4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 CHLORO N [4 (DIETHYLAMINO)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 CHLORO N [4 (TRIFLUOROMETHOXY)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 CHLORO N [4 (TRIFLUOROMETHYL)PHENYL] 3',6' DIHYDRO (2,4' BIPYRIDINE) 1' (2'H)CARBOXAMIDE; 3 FLUORO 4 (HYDROXYMETHYL) N [4 (TRIFLUOROMETHYL)PHENYL] 3'6 DIHYDRO (2,4' BIPYRIDINE) 1' (2'H) CARBOXAMIDE; 3 FLUORO 4 [(DIMETHYLAMINOMETHYL)] N [4 (TRIFLUOROMETHYL) PHENYL] 3'6 DIHYDRO (2,4' BIPYRIDINE) 1' (2'H) CARBOXAMIDE; 4 [3 CHLORO 5 (1,2 DIHYDROXYETHYL)PYRIDIN 2 YL] N [5 (TRIFLUOROMETHYL)PYRIDIN 2 YL] 3',6' DIHYDROPYRIDINE 1'(2'H)CARBOXAMIDE; 4 [3 CHLORO 5 [1,2 DIHYDROXYETHYL] 2 PYRIDYL] N [5 (TRIFLUOROMETHYL) 2 PYRIDYL] 3,6 DIHYDRO 2H PYRIDINE 1 CARBOXAMIDE; CAPSAICIN; TERT BUTYL 3 CHLORO 5',6' DIHYDRO(2,4' BIPYRIDINE) 1' (2'H)CARBOXYLATE; UNCLASSIFIED DRUG; V 116517; VANILLOID RECEPTOR 1 ANTAGONIST; 4-(3-CHLORO-5-(1,2-DIHYDROXYETHYL)-2-PYRIDYL)-N-(5-(TRIFLUOROMETHYL)-2-PYRIDYL)-3,6-DIHYDRO-2H-PYRIDINE-1-CARBOXAMIDE; AMINOPYRIDINE DERIVATIVE; ANALGESIC AGENT; CALCIUM; FREUND ADJUVANT; TRPV1 PROTEIN, HUMAN; VANILLOID RECEPTOR;

ANALGESIA; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; BODY TEMPERATURE; BODY TEMPERATURE DISORDER; CALCIUM TRANSPORT; CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DEVELOPMENT; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG SCREENING; FEMALE; HUMAN; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; REPEATED DRUG DOSE; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; CHO CELL LINE; CRICETULUS; CYTOLOGY; DRUG EFFECTS; METABOLISM; PAIN; PH; PHYSIOLOGY; SENSORY NERVE CELL; SPINAL GANGLION; SPRAGUE DAWLEY RAT; STEREOISOMERISM;

AMINOPYRIDINES; ANALGESICS; ANIMALS; BODY TEMPERATURE; CALCIUM; CAPSAICIN; CHO CELLS; CRICETULUS; FREUND'S ADJUVANT; GANGLIA, SPINAL; HUMANS; HYDROGEN-ION CONCENTRATION; MALE; PAIN; RATS, SPRAGUE-DAWLEY; SENSORY RECEPTOR CELLS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRPV CATION CHANNELS;

EID: 84906074794     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500818a     Document Type: Article

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