Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (a-1165442): A temperature-neutral transient receptor potential vanilloid-1 (trpv1) antagonist with analgesic efficacy

Journal of Medicinal Chemistry

Volumn 57, Issue 17, 2014, Pages 7412-7424

  Voight, Eric A ^a   Gomtsyan, Arthur R ^a   Daanen, Jerome F ^a   Perner, Richard J ^a   Schmidt, Robert G ^a   Bayburt, Erol K ^a   Didomenico, Stanley ^a   McDonald, Heath A ^a   Puttfarcken, Pamela S ^a   Chen, Jun ^a   Neelands, Torben R ^a   Bianchi, Bruce R ^a   Han, Ping ^a   Reilly, Regina M ^a   Franklin, Pamela H ^a   Segreti, Jason A ^a   Nelson, Richard A ^a   Su, Zhi ^a   King, Andrew J ^a   Polakowski, James S ^a   Baker, Scott J ^a   Gauvin, Donna M ^a   Lewis, Lageisha R ^a   Mikusa, Joseph P ^a   Joshi, Shailen K ^a   Faltynek, Connie R ^a   Kym, Philip R ^a   Kort, Michael E ^a   more..

^a ABBVIE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2,2 DIETHYL 6 FLUOROCHROMAN 4 YL) 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 (2,2 DIETHYL 6 FLUOROCHROMAN 4 YL) 3 (ISOQUINOLIN 5 YL)UREA; 1 (2,2 DIETHYL 8 FLUOROCHROMAN 4 YL) 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 (2,2 DIMETHYLCHROMAN 4 YL) 3 (ISOQUINOLIN 5 YL)UREA; 1 (7 FLUORO 2,2 DIMETHYLCHROMAN 4 YL) 3 (1 METHYL 1H INDAZOL 4 YL)UREA; 1 (7 FLUORO 2,2 DIMETHYLCHROMAN 4 YL) 3 (1H INDAZOL 4 YL)UREA; 1 (7 FLUORO 2,2 DIMETHYLCHROMAN 4 YL) 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 (7 FLUORO 2,2 DIMETHYLCHROMAN 4 YL) 3 (7 HYDROXY 5,6,7,8 TETRAHYDRONAPHTHALEN 1 YL)UREA; 1 (7 FLUORO 2,2 DIMETHYLCHROMAN 4 YL) 3 (ISOQUINOLIN 5 YL)UREA; 1 (7 TRIFLUOROMETHOXY 2,2 DIMETHYLCHROMAN 4 YL) 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 (7 TRIFLUOROMETHOXY 2,2 DIMETHYLCHROMAN 4 YL) 3 (ISOQUINOLIN 5 YL)UREA; 1 (7 TRIFLUOROMETHYLL 2,2 DIMETHYLCHROMAN 4 YL) 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 (7,8 DIFLUORO 2,2 DIMETHYLCHROMAN 4 YL) 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 [6 FLUORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 [7 CHLORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 [7 CHLORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (3,6 DIMETHYLISOQUINOLIN 5 YL)UREA; 1 [7 CHLORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (3,8 DIMETHYLISOQUINOLIN 5 YL)UREA; 1 [7 CHLORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (6 FLUORO 3 METHYLISOQUINOLIN 5 YL)UREA; 1 [7 CHLORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (7 FLUORO 3 METHYLISOQUINOLIN 5 YL)UREA; 1 [7 CHLORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (CHLORO 3 METHYLISOQUINOLIN 5 YL)UREA; 1 [7 CHLORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 [3 METHYL 7 (TRIFLUOROMETHYL)ISOQUINOLIN 5 YL]UREA; 1 [7 CYCLOPROPYL 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 [7 FLUORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 [8 FLUORO 2,2 BIS(FLUOROMETHYL)CHROMAN 4 YL] 3 (3 METHYLISOQUINOLIN 5 YL)UREA; 1 [8 FLUORO 2,2 DIMETHYL 7 (TRIFLUOROMETHYL)CHROMAN 4 YL] 3 (3 METHYLISOQUINOLIN 5 YL)UREA; ANALGESIC AGENT; CAPSAICIN; UNCLASSIFIED DRUG; UREA DERIVATIVE; VANILLOID RECEPTOR 1 ANTAGONIST; 1-(7-CHLORO-2,2-BIS(FLUOROMETHYL)CHROMAN-4-YL)-3-(3-METHYLISOQUINOLIN-5-YL)UREA; ISOQUINOLINE DERIVATIVE; TRPV1 PROTEIN, HUMAN; UREA; VANILLOID RECEPTOR;

ANALGESIC ACTIVITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; CONTROLLED STUDY; CORE TEMPERATURE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG SELECTIVITY; DRUG SYNTHESIS; ELIMINATION HALF-LIFE; EMBRYO; HEK293 CELL LINE; HUMAN; HUMAN CELL; HYPERTHERMIA; IC50; IN VITRO STUDY; INTRINSIC CLEARANCE; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; OSTEOARTHRITIS; OSTEOARTHRITIS PAIN; PLASMA PROTEIN BINDING; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; TRANSCRIPTION INITIATION; VOLUME OF DISTRIBUTION AT STEADY-STATE; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; BODY TEMPERATURE; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; DOG; DOSE RESPONSE; DRUG DEVELOPMENT; DRUG EFFECTS; METABOLIC CLEARANCE RATE; METABOLISM; PHYSIOLOGY;

ANALGESICS; ANIMALS; AREA UNDER CURVE; BODY TEMPERATURE; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; HEK293 CELLS; HUMANS; ISOQUINOLINES; METABOLIC CLEARANCE RATE; MODELS, CHEMICAL; MOLECULAR STRUCTURE; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; TRPV CATION CHANNELS; UREA;

EID: 84907164364     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500916t     Document Type: Article

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