diethyl 4,4'-(7-{[4-(acetyloxy)phenyl]ethynyl}-2-methyl-1H-indole-1,3-diyl)dibutanoate | 1232860-68-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: diethyl 4,4'-(7-{[4-(acetyloxy)phenyl]ethynyl}-2-methyl-1H-indole-1,3-diyl)dibutanoate
• 英文别名: Ethyl 4-[7-[2-(4-acetyloxyphenyl)ethynyl]-1-(4-ethoxy-4-oxobutyl)-2-methylindol-3-yl]butanoate
• CAS: 1232860-68-2
• 化学式: C₃₁H₃₅NO₆
• 分子量: 517.622
• InChiKey: KEPSHVLXQDWIJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  83.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl 4,4'-(7-{[4-(acetyloxy)phenyl]ethynyl}-2-methyl-1H-indole-1,3-diyl)dibutanoate 在 水 、 potassium carbonate 、 caesium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 4,4′-[7-({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：

  丁二酸单乙酯酰氯 在 aluminum (III) chloride 、 sodium tetrahydroborate 、 三氟化硼乙醚 、 (Bis(tri-tert-butylphosphine)palladium⁽⁰⁾) 、 caesium carbonate 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.5h， 生成 diethyl 4,4'-(7-{[4-(acetyloxy)phenyl]ethynyl}-2-methyl-1H-indole-1,3-diyl)dibutanoate
  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

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）。
• CRYSTALLINE FORMS OF 4, 4'- [4-FLUORO-7-( ETHYNYL)-2-METHYL-1H-INDOLE-1,3-DIYL] DIBUTANOIC ACID, 4,4'-[2-METHYL-7-( ETHYNYL)-1H-INDOLE-1, 3-DIYL] DIBUTANOIC ACID, AND 4,4'-[4-FLUORO-2-METHYL-7- ( ETHYNYL)-1H-INDOLE-1, 3-DIYL] DIBUTANOIC ACID
  申请人：Takeuchi Jun

  公开号：US20130090482A1

  公开（公告）日：2013-04-11

  The present invention provides type C crystal of compound I, type B crystal of compound II, or type C crystal of compound III set forth in this specification.

  本发明提供了本规范中所述的化合物I的C型晶体，化合物II的B型晶体，或化合物III的C型晶体。
• NOVEL CRYSTALLINE FORMS OF 4,4'-[4-FLUORO-7-({4-[4-(3-FLUORO-2-METHYLPHENYL)BUTOXY]PHENYL}ETHYNYL)-2-METHYL-1H-INDOLE-1,3-DIYL]DIBUTANOIC ACID, 4,4'-[2-METHYL-7-({4-[4-(PENTAFLUOROPHENYL)BUTOXY]PHENYL}ETHYNYL)-1H-INDOLE-1,3-DIYL]DIBUTANOIC ACID, AND 4,4'-[4-FLUORO-2-METHYL-7-({4-[4-(2,3,4,6-TETRAFLUOROPHENYL)BUTOXY]PHENYL}ETHYNYL)-1H-INDOLE-1,3-DIYL]DIBUTANOIC ACID
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP2583964A1

  公开（公告）日：2013-04-24

  The present invention provides type C crystal of compound I, type B crystal of compound II, or type C crystal of compound III set forth in this specification.

  本发明提供了本说明书所述化合物 I 的 C 型晶体、化合物 II 的 B 型晶体或化合物 III 的 C 型晶体。
• Ethynylindole compounds
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP2206698B1

  公开（公告）日：2012-07-18
• NEW CRYSTALLINE FORMS OF 4,4'-[4-FLUORO-7-({4-[4-(3-FLUORO-2-METHYLPHENYL)BUTOXY]PHENYL}ETHYNYL)-2-METHYL-1H-INDOLE-1,3-DIYL]DIBUTANOIC ACID
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP2583964B1

  公开（公告）日：2016-03-23