Discovery of trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxamido) phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid: An orally active, selective very late antigen-4 antagonist

Journal of Medicinal Chemistry

Volumn 52, Issue 24, 2009, Pages 7974-7992

  Muro, Fumihito ^a   Iimura, Shin ^a   Sugimoto, Yuuichi ^a   Yoneda, Yoshiyuki ^a   Chiba, Jun ^a   Watanabe, Toshiyuki ^a   Setoguchi, Masaki ^a   Iigou, Yutaka ^a   Matsumoto, Keiko ^a   Satoh, Atsushi ^a   Takayama, Gensuke ^a   Taira, Tomoe ^a   Yokoyama, Mika ^a   Takashi, Tohru ^a   Nakayama, Atsushi ^a   Machinaga, Nobuo ^a  

^a DAIICHI SANKYO CO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

4 [1 [[2 (3 FLUORO 2 METHYLPHENYLAMINO) 7 FLUORO 6 BENZOXAZOLYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (4 FLUORO 2 METHYLPHENYLAMINO) 7 FLUORO 6 BENZOXAZOLYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (5 FLUORO 2 METHYLPHENYLAMINO) 7 FLUORO 6 BENZOXAZOLYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2,5 DICHLORO 4 (1 METHYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]HYDROXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2,5 DICHLORO 4 (1 METHYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]METHOXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (1 ETHYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (1 INDOLINYLCARBOXAMIDO)]PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (1 ISOPROPYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (1 ISOQUINOLINYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (1 METHYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (6 FLUORO 2 BENZOXAZOLYL)AMINOPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]1 CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 [2 (4 METHYLBENZOXAZOLYL)]AMINOPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 [2 (5 FLUOROBENZOXAZOLYL)]AMINOPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 [2 (7 FLUOROBENZOXAZOLYL)]AMINOPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[4 (2 BENZOXAZOLYL)AMINO 3 CHLOROPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[4 (3 BENZO[D]ISOTHIAZOLYLCARBOXAMIDO) 3 CHLOROPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[4 (3 BENZO[D]ISOTHIAZOLYLCARBOXAMIDO) 5 CHLORO 2 FLUOROPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[4 (3 BENZO[D]ISOXAZOLECARBOXAMIDO) 5 CHLORO 2 FLUOROPHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[5 CHLORO 2 FLUORO 4 (1 INDOLINYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[5 CHLORO 2 FLUORO 4 (1 ISOQUINOLINYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[5 CHLORO 2 FLUORO 4 (1 METHYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[5 CHLORO 2 FLUORO 4 (1 METHYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]HYDROXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[5 CHLORO 2 FLUORO 4 (1 METHYL 3 INDOLYLCARBOXAMIDO)PHENYL]ACETYL]PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[5 CHLORO 2 FLUORO 4 (3 INDAZOLYLCARBOXAMIDO)PHENYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (2 METHYLPHENYL)AMINO 6 BENZOXAZOYL]ACETYL]FLUOROPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [FLUORO 1 [[2 (2 METHYLBENZYL) 6 BENZOXAZOLYL]ACETYL]PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; ANTIINFLAMMATORY AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASTHMA; CONTROLLED STUDY; DISTRIBUTION VOLUME; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; EXPERIMENTAL DOG; EXPERIMENTAL GUINEA PIG; EXPERIMENTAL MONKEY; FEMALE; IC 50; LIPOPHILICITY; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; RAT;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; CHO CELLS; CRICETINAE; CRICETULUS; CYCLOHEXANECARBOXYLIC ACIDS; DOGS; GUINEA PIGS; HAPLORHINI; HUMANS; INDOLES; INTEGRIN ALPHA4BETA1; MICE; PYRROLIDINES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 73249123942     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm901154c     Document Type: Article

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