Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6- benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist

Bioorganic and Medicinal Chemistry

Volumn 20, Issue 3, 2012, Pages 1201-1212

  Setoguchi, Masaki ^a   Iimura, Shin ^a   Sugimoto, Yuuichi ^a   Yoneda, Yoshiyuki ^a   Chiba, Jun ^a   Watanabe, Toshiyuki ^a   Muro, Fumihito ^a   Iigo, Yutaka ^a   Takayama, Gensuke ^a   Yokoyama, Mika ^a   Taira, Tomoe ^a   Aonuma, Misato ^a   Takashi, Tohru ^a   Nakayama, Atsushi ^a   MacHinaga, Nobuo ^a  

^a DAIICHI SANKYO CO   (Japan)

Author keywords

Asthma; Eosinophil infiltration; Integrin; VLA 4

Indexed keywords

2 PHENYL 6 BENZOXAZOLYLACETIC ACID; 4 [1 [(2 PHENYL 6 BENZOXAZOLYL)ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (1 ISOQUINOLINYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (1 METHYL 3 INDOYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (1 NAPHTHYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (4 QUINOLINYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (5 CHLORO 1 METHYL 3 INDOYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (5 FLUORO 1 METHYL 3 INDOYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 (6 FLUORO 1 METHYL 3 INDOYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[2 [1 METHYL 3 (1H PYRROLO[2,3 B]PYRIDINYL)] 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (4 CHLORO 2 BENZOTHIAZOLYL) AMINOPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (5 FLUORO 1 METHYL 3 INDOYL) 7 FLUORO 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (5 FLUORO 2 BENZOTHIAZOLYL)AMINOPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (6 CHLORO 2 BENZOTHIAZOLYL) AMINOPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (6 FLUORO 2 BENZOTHIAZOLYL) AMINOPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[3 CHLORO 4 (6 METHYL 2 BENZOTHIAZOLYL) AMINOPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[4 (2 BENZOTHIAZOLYL)AMINO 3 CHLOROPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[4 (2 BENZOTHIAZOLYL)AMINO 5 CHLORO 2 FLUOROPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[5 CHLORO 2 FLUORO 4 (5 FLUORO 2 BENZOTHIAZOLYL)AMINOPHENYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (1 METHYL 3 INDOYL) 6 BENZOXAZOLYL]ACETYL] FLUORO PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 6 FLUORO 1 METHYLINDOLE 3 CARBALDEHYDE; [2 (1 METHYL 3 INDOLYL) 6 BENZOXAZOLYL]ACETIC ACID; [2 (6 FLUORO 1 METHYL 3 INDOLYL) 6 BENZOXAZOLYL]ACETIC ACID; ANTIBODY; ASCARIS ANTIGEN; BENZOXAZOLE DERIVATIVE; MOUSE ALPHA4 ANTIBODY; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERY LATE ACTIVATION ANTIGEN 4;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; BRONCHITIS; CELL INFILTRATION; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME MODIFICATION; EOSINOPHIL; HUMAN; HUMAN CELL; IN VITRO STUDY; LUNG LAVAGE; NONHUMAN; RAT;

ADMINISTRATION, ORAL; ANIMALS; ASTHMA; BRONCHI; BRONCHOALVEOLAR LAVAGE; CELL LINE; CYCLOHEXANECARBOXYLIC ACIDS; EOSINOPHILS; FEMALE; HUMANS; INTEGRIN ALPHA4BETA1; MICE; MICE, INBRED BALB C; STRUCTURE-ACTIVITY RELATIONSHIP;

ASCARIS; MURINAE;

EID: 84862798348     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2011.12.045     Document Type: Article

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