A novel, potent, and orally active VLA-4 antagonist with good aqueous solubility: Trans-4-[1-[[2-(5-Fluoro-2-methylphenylamino)-7-fluoro-6- benzoxazolyl]acetyl]-(5S)-[methoxy(methyl)amino]methyl-(2S)-pyrrolidinylmethoxy] cyclohexanecarboxylic acid

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 1, 2013, Pages 42-61

  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

Aqueous solubility; Asthma; Eosinophil infiltration; VLA 4

Indexed keywords

4 [1 [[2 (5 FLUORO 2 METHYLPHENYLAMINO) 7 FLUORO 6 BENZOXAZOLYL]ACETYL] [METHOXY(METHYL)AMINO]METHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]HYDROXYMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL] [METHOXY(METHYL)AMINO]METHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]FLUOROMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHYLTHIOMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [ETHOXYMETHYL 1 [[7 FLUORO 2 (2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; 4 [ETHOXYMETHYL 1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLIC ACID; ETHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL](1 ISOXAZOLIDINYLMETHYL)PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; ETHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL](3 METHOXYAZETIDINYLMETHYL)PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; ETHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL](4 MORPHOLINYL)METHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; ETHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHANESULFONYLMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; ETHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; HUMAN SERUM ALBUMIN; METHYL 4 [1 [[7 FLUORO 2 (2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]DIMETHYLANIMOMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]FLUOROMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHYLTHIOMETHYLPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [ACETOXYMETHYL 1 [[7 FLUORO 2 (7 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]PYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [ETHOXYMETHYL 1 [[7 FLUORO 2 (5 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; METHYL 4 [ETHOXYMETHYL 1 [[7 FLUORO 2 (7 FLUORO 2 METHYLPHENYLAMINO) 6 BENZOXAZOLYL]ACETYL]METHOXYPYRROLIDINYLMETHOXY]CYCLOHEXANECARBOXYLATE; NEW DRUG; PYRROLIDINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERY LATE ACTIVATION ANTIGEN 4;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AQUEOUS SOLUTION; ARTICLE; ASTHMA; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG POTENCY; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HYDROPHILICITY; IC 50; IN VITRO STUDY; LIPOPHILICITY; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION; TRANS ISOMER;

ADMINISTRATION, ORAL; ANIMALS; ANTI-INFLAMMATORY AGENTS; ASTHMA; BIOLOGICAL AVAILABILITY; BRONCHI; CELL LINE; CYCLOHEXANECARBOXYLIC ACIDS; EOSINOPHILS; FEMALE; HAPLORHINI; HUMANS; INTEGRIN ALPHA4BETA1; MICE; MICE, INBRED BALB C; PYRROLIDINES; SOLUBILITY; WATER;

MURINAE;

EID: 84870944501     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.11.003     Document Type: Article

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