[5-chloro-2-fluoro-4-(5-fluoro-2-benzothiazolyl)aminophenyl]acetic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: [5-chloro-2-fluoro-4-(5-fluoro-2-benzothiazolyl)aminophenyl]acetic acid
• 英文别名: (5-chloro-4-(5-fluoro-2-benzothiazolyl)amino-2-fluorophenyl)acetic acid；[5-chloro-4-(5-fluoro-2-benzothiazolyl)amino-2-fluorophenyl]acetic acid；2-[5-chloro-2-fluoro-4-[(5-fluoro-1,3-benzothiazol-2-yl)amino]phenyl]acetic acid
• 化学式: C₁₅H₉ClF₂N₂O₂S
• 分子量: 354.764
• InChiKey: BAHIENOOSXYQHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  90.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [5-chloro-2-fluoro-4-(5-fluoro-2-benzothiazolyl)aminophenyl]acetic acid 在 甲醇 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 trans-4-[1-[[5-chloro-2-fluoro-4-(5-fluoro-2-benzothiazolyl)aminophenyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid
  参考文献：
  名称：

  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

  摘要：

  For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido) phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido) phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15 mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse alpha(4) antibody (R1-2). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.045
• 作为产物：
  描述：

  2-溴-5-氟苯并噻唑 在 4-甲基苯磺酸吡啶 、 sodium hydroxide 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 25.0h， 生成 [5-chloro-2-fluoro-4-(5-fluoro-2-benzothiazolyl)aminophenyl]acetic acid
  参考文献：
  名称：

  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

  摘要：

  For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido) phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido) phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15 mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse alpha(4) antibody (R1-2). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.045

文献信息

• [EN] VLA-4 INHIBITOR<br/>[FR] INHIBITEUR DE VLA-4
  申请人：DAIICHI SEIYAKU CO

  公开号：WO2005121135A1

  公开（公告）日：2005-12-22

  A compound which selectively inhibits bonding between a ligand and α4β1 integrin (VLA-4); a process for producing the compound; and a medicine containing the compound. The compound is one represented by, e.g., the formula (I) or a salt thereof. Also provided is a preventive and/or therapeutic agent which contains the compound or salt as a major component and is effective against diseases attributable to cell adhesion, such as, e.g., inflammatory reaction, autoimmune disease, cancer metastasis, bronchial asthma, nasal obstruction, diabetes, arthritis, psoriasis, multiple sclerosis, inflammatory intestinal disease, and rejection reaction in transplantation. (In the formula, Y1 represents arylene, etc.; V1 represents aryl, etc.; and R11 to R14 each represents H, OH, halogeno, etc.)

  一种选择性抑制配体与α4β1整合素（VLA-4）结合的化合物；一种生产该化合物的方法；以及含有该化合物的药物。该化合物可由例如式（I）或其盐所代表。还提供了一种预防和/或治疗剂，其含有该化合物或盐作为主要成分，并对由细胞粘附引起的疾病具有有效性，例如炎症反应、自身免疫疾病、癌症转移、支气管哮喘、鼻塞、糖尿病、关节炎、牛皮癣、多发性硬化、炎症性肠道疾病和移植排斥反应等（在该式中，Y1代表芳基等；V1代表芳基等；R11至R14分别代表H、OH、卤素等）。
• Vla-4 inhibitors
  申请人：——

  公开号：US20040110945A1

  公开（公告）日：2004-06-10

  The present invention relates to a compound represented by the following formula (I): 1 (wherein, W represents W A —A 1 —W B — (in which, W A is substituted or unsubstituted aryl, etc., A 1 is —NR 1 —, single bond, —C(O)—, etc., and W B is substituted or unsubstituted arylene, etc.), R is single bond, —NH—, —OCH 2 —, alkenylene, etc., X is —C(O)—, —CH 2 —, etc., and M is, for example, the following formula: 2 (in which, R 11 , R 12 and R 13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R 14 is hydrogen or lower alkyl, Y represents —CH 2 —O—, etc., Z is substituted or unsubstituted arylene, etc., A 2 is single bond, etc, and R 10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.

  本发明涉及以下式(I)所表示的化合物：1（其中，W代表WA-A1-WB-（其中，WA是取代或未取代的芳基等，A1是-NR1-，单键，-C（O）-等，WB是取代或未取代的芳烃基等），R是单键，-NH-，-OCH2-，烯烃基等，X是-C（O）-，-CH2-等，M是例如以下公式：2（其中，R11，R12和R13分别独立地代表氢，羟基，氨基，卤素等，R14是氢或低级烷基，Y代表-CH2-O-等，Z是取代或未取代的芳烃基等，A2是单键等，而R10是羟基或低级烷氧基），或其盐；以及含有该化合物的药物。该化合物或其盐选择性地抑制细胞黏附分子与VAL-4的结合，并表现出高的生物利用度，因此可用作预防和/或治疗炎症性疾病、自身免疫性疾病、转移、支气管哮喘、鼻窦狭窄、糖尿病等。
• Vla-4 Inhibitor
  申请人：Yoneda Yoshiyuki

  公开号：US20070232601A1

  公开（公告）日：2007-10-04

  An object of the present invention is to provide a compound which selectively inhibits binding of a ligand and α4β1 integrin (VLA-4), a process for producing the compound, and a medicament containing the compound. A compound represented by the formula (I) etc. or a salt thereof, a process for producing the compound or a salt thereof, a medicament containing the compound or a salt thereof, as well as a preventive and/or a therapeutic agent for a disease caused by cell adhesion, for example, inflammatory reaction, autoimmune disease, cancer metastasis, bronchial asthma, nasal obstruction, diabetes, arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease and rejection reaction at transplantation, containing the compound or a salt thereof as a primary component. [wherein Y 1 represents a divalent aryl group etc., V 1 represents an aryl group etc., and R 11 to R 14 represent H, OH or a halogen atom etc.]

  本发明的目的是提供一种化合物，其能够选择性地抑制配体和α4β1整合素（VLA-4）的结合，以及制备该化合物的方法和含有该化合物的药物。该化合物由式（I）等或其盐表示，制备该化合物或其盐的方法，含有该化合物或其盐的药物，以及作为细胞黏附引起的疾病的预防和/或治疗剂，例如炎症反应、自身免疫疾病、癌症转移、支气管哮喘、鼻塞、糖尿病、关节炎、牛皮癣、多发性硬化症、炎症性肠病和移植排斥反应，其中该化合物或其盐为主要成分。[其中，Y1表示双价芳基等，V1表示芳基等，R11至R14表示H、OH或卤素原子等]
• VLA-4 INHIBITORS
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1346982B1

  公开（公告）日：2011-09-14
• US7157487B2
  申请人：——

  公开号：US7157487B2

  公开（公告）日：2007-01-02