4-(3-fluoro-2-methylphenyl)butyl 4-methylbenzenesulfonate | 1232862-54-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-fluoro-2-methylphenyl)butyl 4-methylbenzenesulfonate
• 英文别名: 4-(3-Fluoro-2-methylphenyl)butyl 4-methylbenzenesulfonate
• CAS: 1232862-54-2
• 化学式: C₁₈H₂₁FO₃S
• 分子量: 336.427
• InChiKey: IKZOZOZJFNRXEF-UHFFFAOYSA-N

物化性质

• 沸点：
  472.4±33.0 °C(Predicted)
• 密度：
  1.182±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl 4,4′-{4-fluoro-7-[(4-hydroxyphenyl)ethynyl]-2-methyl-1H-indole-1,3-diyl}dibutanoate 、 4-(3-fluoro-2-methylphenyl)butyl 4-methylbenzenesulfonate 在 水 、 caesium carbonate 、 sodium hydroxide 作用下， 以 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 4,4’-[4-fluoro-7-(2-{4-[4-(3-fluoro-2-methylphenyl)butoxy]phenyl}ethynyl)-2-methyl-1H-indole-1,3-diyl]dibutanoic acid
  参考文献：
  名称：

  Discovery of Gemilukast (ONO-6950), a Dual CysLT₁ and CysLT₂ Antagonist As a Therapeutic Agent for Asthma

  摘要：

  An orally active dual CysLT(1) and CysLT(2) antagonist possessing a distinctive structure which consists of triple bond and dicarboxylic acid moieties is described. Gemilukast (ONO-6950) was generated via isomerization of the core indole and the incorporation of a triple bond into a lead compound. Gemilukast exhibited antagonist activities with IC50 values of 1.7 and 25 nM against human CysLT(1) and human CysLT(2), respectively, and potent efficacy at an oral dose of 0.1 mg/kg given 24 h before LTD4 challenge in a CysLT(1)-dependent guinea pig asthmatic model. In addition, gemilukast dose-dependently reduced LTC4-induced bronchoconstriction in both CysLT(1)- and CysLT(2)-dependent guinea pig asthmatic models, and it reduced antigen-induced constriction of isolated human bronchi. Gemilukast is currently being evaluated in phase II trials for the treatment of asthma.

  DOI：

  10.1021/acs.jmedchem.5b00741
• 作为产物：
  描述：

  2-溴-6-氟甲苯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 氢气 、 三甲胺盐酸盐 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 6.5h， 生成 4-(3-fluoro-2-methylphenyl)butyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Discovery of Gemilukast (ONO-6950), a Dual CysLT₁ and CysLT₂ Antagonist As a Therapeutic Agent for Asthma

  摘要：

  An orally active dual CysLT(1) and CysLT(2) antagonist possessing a distinctive structure which consists of triple bond and dicarboxylic acid moieties is described. Gemilukast (ONO-6950) was generated via isomerization of the core indole and the incorporation of a triple bond into a lead compound. Gemilukast exhibited antagonist activities with IC50 values of 1.7 and 25 nM against human CysLT(1) and human CysLT(2), respectively, and potent efficacy at an oral dose of 0.1 mg/kg given 24 h before LTD4 challenge in a CysLT(1)-dependent guinea pig asthmatic model. In addition, gemilukast dose-dependently reduced LTC4-induced bronchoconstriction in both CysLT(1)- and CysLT(2)-dependent guinea pig asthmatic models, and it reduced antigen-induced constriction of isolated human bronchi. Gemilukast is currently being evaluated in phase II trials for the treatment of asthma.

  DOI：

  10.1021/acs.jmedchem.5b00741
• 作为试剂：
  描述：

  diethyl 4,4′-{4-fluoro-7-[(4-hydroxyphenyl)ethynyl]-2-methyl-1H-indole-1,3-diyl}dibutanoate 、 4-(3-fluoro-2-methylphenyl)butyl 4-methylbenzenesulfonate 在 4-(3-fluoro-2-methylphenyl)butyl 4-methylbenzenesulfonate 作用下， 生成
  参考文献：
  名称：

  J. Med. Chem. 2015, 58, 6093-6113

  摘要：

  DOI：

文献信息

• ETHYNYLINDOLE COMPOUNDS
  申请人：OHMOTO Kazuyuki

  公开号：US20100160647A1

  公开（公告）日：2010-06-24

  As a compound having a potent oral activity and a long-lasting cysLT 1 /cysLT 2 receptor antagonistic activity, the compound of the formula (I): which exhibits potent antagonistic activity against the cysLT 1 /cysLT 2 receptor, and have long-lasting effects even in case of oral administration, and therefore is useful as an oral agent for preventing and/or treating a variety of diseases, for example, respiratory disease (for example, asthma (bronchial asthma, etc.), chronic obstructive pulmonary disease (COPD), pulmonary emphysema, chronic bronchitis, pneumonia (interstitial pneumonia, etc.), severe acute respiratory syndrome (SARS), acute respiratory distress syndrome (ARDS), apnea syndrome, allergic rhinitis, sinusitis (acute sinusitis, chronic sinusitis, etc.), pulmonary fibrosis, coughing (chronic coughing, etc.), and the like) was developed.

  作为一种具有强效口服活性和长效cysLT1/cysLT2受体拮抗活性的化合物，具有公式(I)的化合物表现出对cysLT1/cysLT2受体的强效拮抗活性，并且即使口服后也具有长效作用，因此可用作口服药剂预防和/或治疗各种疾病，例如呼吸道疾病（例如哮喘（支气管哮喘等）、慢性阻塞性肺病（COPD）、肺气肿、慢性支气管炎、肺炎（间质性肺炎等）、严重急性呼吸综合征（SARS）、急性呼吸窘迫综合征（ARDS）、呼吸暂停综合征、过敏性鼻炎、鼻窦炎（急性鼻窦炎、慢性鼻窦炎等）、肺纤维化、咳嗽（慢性咳嗽等）等）。
• Ethynylindole compounds
  申请人：ONO Pharmaceuticals, Co., Ltd.

  公开号：US08115014B2

  公开（公告）日：2012-02-14

  As a compound having a potent oral activity and a long-lasting cysLT1/cysLT2 receptor antagonistic activity, the compound of the formula (I): which exhibits potent antagonistic activity against the cysLT1/cysLT2 receptor, and have long-lasting effects even in case of oral administration, and therefore is useful as an oral agent for preventing and/or treating a variety of diseases, for example, respiratory disease (for example, asthma (bronchial asthma, etc.), chronic obstructive pulmonary disease (COPD), pulmonary emphysema, chronic bronchitis, pneumonia (interstitial pneumonia, etc.), severe acute respiratory syndrome (SARS), acute respiratory distress syndrome (ARDS), apnea syndrome, allergic rhinitis, sinusitis (acute sinusitis, chronic sinusitis, etc.), pulmonary fibrosis, coughing (chronic coughing, etc.), and the like) was developed.

  作为一种具有强效口服活性和长效cysLT1 / cysLT2受体拮抗活性的化合物，公式（I）的化合物表现出对cysLT1 / cysLT2受体的强效拮抗活性，并且即使口服也具有长效作用，因此可用作口服药物，用于预防和/或治疗各种疾病，例如呼吸系统疾病（例如哮喘（支气管哮喘等），慢性阻塞性肺疾病（COPD），肺气肿，慢性支气管炎，肺炎（间质性肺炎等），严重急性呼吸综合征（SARS），急性呼吸窘迫综合征（ARDS），呼吸暂停综合征，过敏性鼻炎，鼻窦炎（急性鼻窦炎，慢性鼻窦炎等），肺纤维化，咳嗽（慢性咳嗽等）等。
• US8115014B2
  申请人：——

  公开号：US8115014B2

  公开（公告）日：2012-02-14
• Discovery of Gemilukast (ONO-6950), a Dual CysLT₁ and CysLT₂ Antagonist As a Therapeutic Agent for Asthma
  作者：Satoshi Itadani、Kentaro Yashiro、Yoshiyuki Aratani、Tetsuya Sekiguchi、Atsushi Kinoshita、Hideki Moriguchi、Nobukazu Ohta、Shinya Takahashi、Akiharu Ishida、Yohei Tajima、Katsuya Hisaichi、Masaki Ima、Junya Ueda、Hiromu Egashira、Tomohiko Sekioka、Michiaki Kadode、Yasuo Yonetomi、Takafumi Nakao、Atsuto Inoue、Hiroaki Nomura、Tetsuya Kitamine、Manabu Fujita、Takeshi Nabe、Yoshiyuki Yamaura、Naoya Matsumura、Akira Imagawa、Yoshisuke Nakayama、Jun Takeuchi、Kazuyuki Ohmoto

  DOI：10.1021/acs.jmedchem.5b00741

  日期：2015.8.13

  An orally active dual CysLT(1) and CysLT(2) antagonist possessing a distinctive structure which consists of triple bond and dicarboxylic acid moieties is described. Gemilukast (ONO-6950) was generated via isomerization of the core indole and the incorporation of a triple bond into a lead compound. Gemilukast exhibited antagonist activities with IC50 values of 1.7 and 25 nM against human CysLT(1) and human CysLT(2), respectively, and potent efficacy at an oral dose of 0.1 mg/kg given 24 h before LTD4 challenge in a CysLT(1)-dependent guinea pig asthmatic model. In addition, gemilukast dose-dependently reduced LTC4-induced bronchoconstriction in both CysLT(1)- and CysLT(2)-dependent guinea pig asthmatic models, and it reduced antigen-induced constriction of isolated human bronchi. Gemilukast is currently being evaluated in phase II trials for the treatment of asthma.
• J. Med. Chem. 2015, 58, 6093-6113
  作者：

  DOI：——

  日期：——