4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid | 866613-86-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid
• 英文别名: 4-bromo-3-methyl-5-propoxythiophene-2-carboxylic acid
• CAS: 866613-86-7
• 化学式: C₉H₁₁BrO₃S
• 分子量: 279.155
• InChiKey: VWFVJVPPXXCWAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  74.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid 、 N-[3-(8-aza-bicyclo[3.2.1]oct-3-yl)-4-fluoro-benzyl]-2,2,2-trifluoro-acetamide hydrochloride 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-{3-[8-(4-bromo-3-methyl-5-propoxy-thiophene-2-carbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-fluoro-benzyl}-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  A β-tryptase inhibitor with a tropanylamide scaffold to improve in vitro stability and to lower hERG channel binding affinity

  摘要：

  Tropanylamide was investigated as a possible scaffold for beta-tryptase inhibitors with a basic benzylamine P1 group and a substituted thiophene P4 group. Comparing to piperidinylamide, the tropanylamide scaffold is much more rigid, which presents less opportunity for the inhibitor to bind with off-target proteins, such as cytochrome P450, SSAO, and hERG potassium channel. The proposed binding mode was further confirmed by an in-house X-ray structure through co-crystallization. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.127
• 作为产物：
  描述：

  4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid methyl ester 在 lithium hydroxide 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以80.5%的产率得到4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid
  参考文献：
  名称：

  [EN] [4-(5-AMINOMETHYL-2-FLUORO-PHENYL)-PIPERIDIN-1-YL]-(4-BROMO-3-METHYL-5-PROPOXY-THIOPHEN-2-YL)-METHANONE HYDROCHLORIDE AS AN INHIBITOR OF MAST CELL TRYPTASE
  [FR] [4-(5-AMINOMETHYL-2-FLUORO-PHENYL)-PIPERIDIN-1-YL]-(4-BROMO-3-METHYL-5-PROPOXY-THIOPHEN-2-YL)-METHANONE HYDROCHLORURE TENANT LIEU D'INHIBITEUR DE LA MASTOCYTE TRYPTASE

  摘要：

  本发明涉及到式I的化合物，或者该化合物的前药、药学上可接受的盐或溶剂。此外，本发明涉及一种药物组合物，包括式I的化合物的药学有效量和药学上可接受的载体。此外，本发明涉及将式I的化合物用作色氨酸蛋白酶抑制剂的用途，包括将该化合物引入含有色氨酸蛋白酶的组合物中。此外，本发明还涉及将式I的化合物用于治疗患有或患有需要改善色氨酸蛋白酶抑制剂的生理状况的患者的用途，包括向患者施用权利要求1中的化合物的治疗有效量。本发明还涉及制备式I的化合物。

  公开号：

  WO2005097780A1

文献信息

• [EN] [4-(5-AMINOMETHYL-2-FLUORO-PHENYL)-PIPERIDIN-1-YL]-(4-BROMO-3-METHYL-5-PROPOXY-THIOPHEN-2-YL)-METHANONE HYDROCHLORIDE AS AN INHIBITOR OF MAST CELL TRYPTASE<br/>[FR] [4-(5-AMINOMETHYL-2-FLUORO-PHENYL)-PIPERIDIN-1-YL]-(4-BROMO-3-METHYL-5-PROPOXY-THIOPHEN-2-YL)-METHANONE HYDROCHLORURE TENANT LIEU D'INHIBITEUR DE LA MASTOCYTE TRYPTASE
  申请人：AVENTIS PHARMA INC

  公开号：WO2005097780A1

  公开（公告）日：2005-10-20

  The present invention extends to the compound of formula I, or a prodrug, pharmaceutically acceptable salt, or solvate of said compound. Furthermore, the present invention is directed to a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula I, and a pharmaceutically acceptable carrier. Furthermore, the present invention is directed to the use of a compound of formula I as an inhibitor of tryptase, comprising introducing the compound into a composition comprising tryptase. In addition, the present invention is directed to the use of a compound of formula I for treating a patient suffering from, or subject to, a physiological condition in need of amelioration of an inhibitor of tryptase comprising administering to the patient a therapeutically effective amount of the compound of Claim 1. The present invention is directed also to the preparation of a compound of formula I.

  本发明涉及到式I的化合物，或者该化合物的前药、药学上可接受的盐或溶剂。此外，本发明涉及一种药物组合物，包括式I的化合物的药学有效量和药学上可接受的载体。此外，本发明涉及将式I的化合物用作色氨酸蛋白酶抑制剂的用途，包括将该化合物引入含有色氨酸蛋白酶的组合物中。此外，本发明还涉及将式I的化合物用于治疗患有或患有需要改善色氨酸蛋白酶抑制剂的生理状况的患者的用途，包括向患者施用权利要求1中的化合物的治疗有效量。本发明还涉及制备式I的化合物。
• [EN] TROPINONE BENZYLAMINES AS BETA-TRYPTASE INHIBITORS<br/>[FR] BENZYLAMINES DE TROPINONE UTILISÉS COMME INHIBITEURS DE LA BÊTA-TRYPTASE
  申请人：SANOFI SA

  公开号：WO2011087652A1

  公开（公告）日：2011-07-21

  The present invention discloses and claims a series of substituted tropinone benzylamines of formula (I). More specifically, the compounds of this invention are inhibitors of β-tryptase and are, therefore, useful as pharmaceutical agents. Additionally, this invention also discloses methods of preparation of substituted tropinone benzylamines.

  本发明公开并要求一系列取代托品酮苄胺的公式（I）化合物。更具体地说，本发明的化合物是β-tryptase的抑制剂，因此可用作药物制剂。此外，本发明还公开了取代托品酮苄胺的制备方法。
• [EN] SYNTHESIS OF (4-FLUORO-3-PIPERIDIN-4-YL-BENZYL)-CARBAMIC ACID TERT-BUTYL ESTER AND INTERMEDIATES THEREOF<br/>[FR] SYNTHÈSE DE L'ESTER TERT-BUTYLIQUE DE L'ACIDE (4-FLUORO-3-PIPÉRIDIN-4-YL-BENZYL)-CARBAMIQUE ET INTERMÉDIAIRES CORRESPONDANTS
  申请人：SANOFI AVENTIS US LLC

  公开号：WO2011037947A1

  公开（公告）日：2011-03-31

  The present invention is an improved method for the preparation of 4-fluoro-3-piperidin-4-yl-benzyl)-carbamic acid tert-butyl ester, compound of formula I. The invention is directed to a method of synthesis for the compound of formula I in three steps, comprising formation of 5-((tert-butoxycarbonyl)aminomethyl)-2-fluorobenzeneboronic acid (compound 11), reaction of compound 11 under Suzuki coupling conditions to yield (4-fluoro-2-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester and selective hydrogenation of the aforementioned product under hydrogenation conditions yields compound I. The invention is also directed to the intermediates 5-((tert-Butoxycarbonyl)amino-methyl)-2-fluorobenzeneboronic acid (compound 11), and (4-fluoro-2-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester (compound 13).

  该发明是一种改进的制备4-氟-3-哌啶-4-基苄基)氨基甲酸叔丁酯（化合物I）的方法。该发明涉及一种合成化合物I的三步方法，包括形成5-((叔丁氧羰基)氨甲基)-2-氟苯硼酸（化合物11），将化合物11在铜促进的Suzuki偶联条件下反应，得到(4-氟-2-吡啶-4-基苄基)氨基甲酸叔丁酯，并在氢化条件下选择性氢化上述产物得到化合物I。该发明还涉及中间体5-((叔丁氧羰基)氨基甲基)-2-氟苯硼酸（化合物11）和(4-氟-2-吡啶-4-基苄基)氨基甲酸叔丁酯（化合物13）。
• [4-(5-Aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone hydrochloride as an inhibitor of mast cell tryptase
  申请人：Gao Zhongli

  公开号：US20070142435A1

  公开（公告）日：2007-06-21

  The present invention extends to the compound of formula I: or a prodrug, pharmaceutically acceptable salt, or solvate of said compound. Furthermore, the present invention is directed to a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula I, and a pharmaceutically acceptable carrier. Furthermore, the present invention is directed to the use of a compound of formula I as an inhibitor of tryptase, comprising introducing the compound into a composition comprising tryptase. In addition, the present invention is directed to the use of a compound of formula I for treating a patient suffering from, or subject to, a physiological condition in need of amelioration of an inhibitor of tryptase comprising administering to the patient a therapeutically effective amount of the compound of claim 1 The present invention is directed also to the preparation of a compound of formula I.

  本发明涉及化合物I的化合物：或者其前药、药学上可接受的盐或溶剂。此外，本发明涉及一种药物组合物，包括药学有效量的化合物I和药学上可接受的载体。此外，本发明涉及使用化合物I作为组成三胺酸酶抑制剂的用途，包括将化合物引入包含三胺酸酶的组成物中。此外，本发明还涉及使用化合物I治疗患有或受到需要改善三胺酸酶抑制剂的生理状况的患者，包括向患者施用化合物的治疗有效量。本发明还涉及制备化合物I的方法。
• SYNTHESIS OF (4-FLUORO-3-PIPERIDIN-4-YL-BENZYL)-CARBAMIC ACID TERT-BUTYL ESTER AND INTERMEDIATES THEREOF
  申请人：CHOY Nakyen

  公开号：US20120184745A1

  公开（公告）日：2012-07-19

  The present invention is an improved method for the preparation of 4-fluoro-3-piperidin-4-yl-benzyl)-carbamic acid tert-butyl ester, compound of formula I. The invention is directed to a method of synthesis for the compound of formula I in three steps, comprising formation of 5-((tert-butoxycarbonyl)aminomethyl)-2-fluorobenzeneboronic acid (compound 11), reaction of compound 11 under Suzuki coupling conditions to yield (4-fluoro-2-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester and selective hydrogenation of the aforementioned product under hydrogenation conditions yields compound I. The invention is also directed to the intermediates 5-((tert-butoxycarbonyl)amino-methyl)-2-fluorobenzeneboronic acid (compound 11), and (4-fluoro-2-pyridin-4-yl-benzyl)-carbamic acid tert-butyl ester (compound 13).

  本发明是一种改进的制备4-氟-3-哌啶-4-基苯甲酸叔丁酯（化合物I）的方法。该发明涉及一种由三步合成化合物I的方法，包括形成5-（（叔丁氧羰基）氨甲基）-2-氟苯硼酸（化合物11），在Suzuki偶联条件下反应化合物11以得到（4-氟-2-吡啶-4-基苯甲酸叔丁酯），并在氢化条件下选择性氢化上述产物得到化合物I。该发明还涉及中间体5-（（叔丁氧羰基）氨甲基）-2-氟苯硼酸（化合物11）和（4-氟-2-吡啶-4-基苯甲酸叔丁酯）（化合物13）。