ethyl 2-(5-hydroxy-1H-benzoimidazol-2-yl)propionate | 214782-11-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: ethyl 2-(5-hydroxy-1H-benzoimidazol-2-yl)propionate
• 英文别名: ethyl 2-(6-hydroxy-1H-benzimidazol-2-yl)propanoate
• CAS: 214782-11-3
• 化学式: C₁₂H₁₄N₂O₃
• 分子量: 234.255
• InChiKey: DZRBCCOSFPYSPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-(5-hydroxy-1H-benzoimidazol-2-yl)propionate 、 4-amino-N-[2-(2-methoxyphenoxy)ethyl]-3-methylaminobenzamide 在 氮气 、 乙醚 、 acetonitrile-water 作用下， 以 N,N-二甲基丙烯基脲 为溶剂， 反应 2.0h， 以to provide 2-[1-(5-hydroxy-1H-benzoimidazol-2-yl)ethyl]-N-[2-(2-methoxyphenoxy)ethyl]-3-methyl-3H-benzoimidazole-5-carboxamide (40 mg, 13% yield) as a light pink solid的产率得到2-[1-(5-hydroxy-1H-benzoimidazol-2-yl)ethyl]-N-[2-(2-methoxyphenoxy)ethyl]-3-methyl-3H-benzoimidazole-5-carboxamide
  参考文献：
  名称：

  Novel compounds and compositions for treating diseases asociated with protease activity

  摘要：

  本文描述了一种新的化合物、组合物和方法，对于预防和治疗由肥大细胞介导的炎症性疾病具有有效作用。这些化合物、组合物和方法对于预防和治疗与呼吸道相关的炎症性疾病，如哮喘和过敏性鼻炎，以及其他类型的免疫介导性炎症性疾病，如类风湿性关节炎、结膜炎和炎症性肠病、各种皮肤病以及某些病毒性疾病具有有效作用。这些化合物包括肥大细胞蛋白酶组胺酶的有效和选择性抑制剂。治疗这些疾病的组合物包括口服、吸入、局部和静脉制剂，以及包含这些制剂的设备。

  公开号：

  US20010053779A1
• 作为产物：
  描述：

  ethyl 2-(N-ethoxyamidino)propionate 、 3,4-二氨基苯酚 在 乙酸乙酯 、 碳酸氢钠 、 Brine 、 magnesium sulfate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以to provide ethyl 2-(5-hydroxy-1H-benzoimidazol-2-yl)propionate (6.3 g, 91% yield) as a dark solid的产率得到ethyl 2-(5-hydroxy-1H-benzoimidazol-2-yl)propionate
  参考文献：
  名称：

  Novel compounds and compositions for treating diseases asociated with protease activity

  摘要：

  本文描述了一种新的化合物、组合物和方法，对于预防和治疗由肥大细胞介导的炎症性疾病具有有效作用。这些化合物、组合物和方法对于预防和治疗与呼吸道相关的炎症性疾病，如哮喘和过敏性鼻炎，以及其他类型的免疫介导性炎症性疾病，如类风湿性关节炎、结膜炎和炎症性肠病、各种皮肤病以及某些病毒性疾病具有有效作用。这些化合物包括肥大细胞蛋白酶组胺酶的有效和选择性抑制剂。治疗这些疾病的组合物包括口服、吸入、局部和静脉制剂，以及包含这些制剂的设备。

  公开号：

  US20010053779A1

文献信息

• Novel compounds and compositions for treating diseases asociated with protease activity
  申请人：——

  公开号：US20010053779A1

  公开（公告）日：2001-12-20

  Novel compounds, compositions and methods effective for the prevention and treatment of mast-cell mediated inflammatory disorders are described. The compounds, compositions and methods are effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, as well as other types of immunomediated inflammatory disorders, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various dermatological conditions, as well as certain viral conditions. The compounds comprise potent and selective inhibitors of the mast cell protease tryptase. The compositions for treating these conditions include oral, inhalant, topical and parenteral preparations as well as devices comprising such preparations.

  描述了用于预防和治疗由肥大细胞介导的炎症性疾病的新化合物、组合物和方法。这些化合物、组合物和方法对预防和治疗与呼吸道相关的炎症性疾病（如哮喘和过敏性鼻炎）以及其他类型的免疫介导性炎症性疾病（如类风湿关节炎、结膜炎和炎症性肠病、各种皮肤病症以及某些病毒性疾病）有效。这些化合物包括对肥大细胞蛋白酶组胺酶的有效和选择性抑制剂。用于治疗这些疾病的组合物包括口服、吸入、局部和静脉制剂，以及包含这些制剂的装置。
• COMPOUNDS AND COMPOSITIONS FOR TREATING DISEASES ASSOCIATED WITH SERINE PROTEASE, PARTICULARLY TRYPTASE, ACTIVITY
  申请人：AXYS PHARMACEUTICALS, INC.

  公开号：EP1019382A1

  公开（公告）日：2000-07-19
• US6562854B2
  申请人：——

  公开号：US6562854B2

  公开（公告）日：2003-05-13
• [EN] COMPOUNDS AND COMPOSITIONS FOR TREATING DISEASES ASSOCIATED WITH SERINE PROTEASE, PARTICULARLY TRYPTASE, ACTIVITY<br/>[FR] COMPOSES ET COMPOSITIONS POUR TRAITEMENT DE MALADIES ASSOCIEES A UNE SERINE PROTEASE, EN PARTICULIER UNE ACTIVITE DE TRYPTASE
  申请人：AXYS PHARMACEUTICALS CORPORATION

  公开号：WO1998045275A1

  公开（公告）日：1998-10-15

  (EN) Novel compounds, compositions and methods effective for the prevention and treatment of mast-cell mediated inflammatory disorders are described. A preferred aspect of the invention are compounds of Formula (II) in which: the dashed lines independently represent optional bonds; each R2 independently is (C1-6)alkyl, (C1-6)alkyloxy, halo or hydroxy; each R3 independently is (C1-6)alkyl, (C1-6)alkyloxy, halo or hydroxy; X3 is -C(O)- or -CR7R8-, X8 is -CH(R1)n1- or -C(R1)n1=, wherein R1 is amino(N1-4)azolidinyl, amino(N1-4)azolyl, (N1-4)azolidinyl, (N1-4)azolyl, -NHC(NH)NR9R9, -C(NR9)R9, -C(NH)NHR10, -C(NH)NR10R10 or -(CR11R11)yNH2, or X8 is -N= or -NH(R1)n1-, wherein R1 is -C(NR9)R9, -C(NH)NHR10 or -C(NH)NR10R10, wherein each R9 independently is hydrogen or (C1-6)alkyl and each R10 independently is (C1-6)alkyl; and X9 is -CH(R4)- or -C(R4)=, wherein R4 is -R12, -OR12, -N(R13)R12, -SR12, -S(O)R12, -S(O)2R12, -S(O)2OR12, -S(O)2N(R13)R12, -N(R13)S(O)2R12, -C(O)R12, -C(O)OR12, -C(O)N(R13)R12, -N(R13)C(O)R12, -OC(O)N(R13)R12, -N(R13)C(O)OR12, -(CH2)n4N(R13)C(O)N(R13)R12, -OP(O)(OR13)OR12 or -C(O)N(R14)CH(COOH)R12, or X9 is -N= or -N(R4)-, wherein R4 is -C(O)R12, -C(O)OR12, -C(O)N(R13)R12, -OC(O)N(R13)R12 or -C(O)N(R14)CH(COOH)R12, wherein R12, R13 and R14 are as defined in the Summary of the Invention; R5 is hydrogen or (C1-4)alkyl, R6 is hydrogen or (C1-4¿) alkyl, which alkyl optionally is substituted with one to two substituents independently selected from (C¿1-4)alkyloxy, hydroxy and sulfo, R7 is hydrogen or methyl and R8 is hydrogen, methyl or hydroxy. The compounds, compositions and methods are effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, as well as other types of immunomediated inflammatory disorders, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various dermatological conditions, as well as certain viral conditions. The compounds comprise potent and selective inhibitors of the mast cell protease tryptase. The compositions for treating these conditions include oral, inhalant, topical and parenteral preparations as well as devices comprising such preparations.(FR) La présente invention concerne de nouveaux composés, des compositions et des procédés efficaces dans la prévention et le traitement de désordres inflammatoires à médiation mastocytaire. Selon un mode préféré de réalisation de l'invention, les composés sont représentés par la formule (II) dans laquelle les lignes en pointillé représentent des liaisons facultatives; chaque R2 représente indépendamment (C1-6)alkyle, (C1-6)alkyloxy, halo ou hydroxy; chaque R3 représente indépendamment (C1-6)alkyle, (C1-6)alkyloxy, halo ou hydroxy; X3 représente -C(O)- ou CR7R8-, X8 représente -CH(R1)n1- ou -C(R1)n1=, dans laquelle R1 représente amino(N1-4)azolidinyl, amino(N1-4)azolyl, (N1-4)azolidinyl, (N1-4)azolyl, -NHC(NH)NR9R9, -C(NR9)R9, -C(NH)NHR10, -C(NH)NR10R10 ou -(CR11R11)yNH2, ou X8 représente -N= ou -NH(R1)n1-, dans laquelle R1 représente -C(NR9)R9, -C(NH)NRH10 ou -C(NH)NR10R10, dans laquelle R9 représente indépendamment hydrogène ou (C1-6)alkyle et chaque R10 représente indépendamment (C1-6)alkyle; et X9 représente -CH(R4)- ou -C(R4)=, dans laquelle R4 représente -R12, -OR12, -N(R13)R12, -SR12, -S(O)R12, -S(O)2R12, -S(O)2O R12, -S(O)2N(R13)R12, -N(R13)S(O)2R12, -C(O)R12, -C(O)OR12, -C(O)N(R13)R12, -N(R13)C(O)R12, -OC(O)N(R13)R12, -N(R13)C(O)OR12, -(CH2)n4N(R13)C(O)NR13)R12, -OP(O)(OR13)OR12 ou -C(O)N(R14)CH(COOH)R12, ou X9 représente -N= ou -N(R4)-, dans laquelle R4 représente -C(O)R12, -C(O)OR12 ou -C(O)N(R13)R12, ou -C(O)N(R14)CH(COOH)R12, dans laquelle R12, R13 et R14 sont tels que définis dans la description de l'invention; R5 représente hydrogène ou (C1-4)alkyle, R6 représente hydrogène ou (C1-4)alkyle, lequel alkyle est éventuellement substitué par un ou deux substituants sélectionnés indépendamment dans le groupe (C1-4)alkyloxy, hydroxy et sulfo, R7 représente hydrogène ou méthyle ou hydroxy. Les composés, les compositions et les procédés sont efficaces dans la prévention, et le traitement de maladies inflammatoires associées à l'appareil respiratoire telles que l'asthme et les rhinites allergiques ainsi que d'autres types de désordres inflammatoires à immunomédiation tels que la polyarthrite rhumatoïde, la conjonctivite, une maladie intestinale inflammatoire, et différents états dermatologiques ainsi que certains états viraux. Les composés comprennent des inhibiteurs sélectifs et puissants de la tryptase protéase mastocytaire. Les compositions permettant de traiter ces états comprennent des préparations parentales, topiques, orales, et pour inhalation ainsi que des dispositifs comprenant ces préparations.
• Compositions comprising a substituted benzimidazole useful for treating immunomediated inflammatory disorders
  申请人：Axys Pharmaceuticals, Inc.

  公开号：US20030212120A1

  公开（公告）日：2003-11-13

  Novel compounds, compositions and methods effective for the prevention and treatment of mast-cell mediated inflammatory disorders are described. The compounds, compositions and methods are effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis, as well as other types of immunomediated inflammatory disorders, such as rheumatoid arthritis, conjunctivitis and inflammatory bowel disease, various dermatological conditions, as well as certain viral conditions. The compounds comprise potent and selective inhibitors of the mast cell protease tryptase. The compositions for treating these conditions include oral, inhalant, topical and parenteral preparations as well as devices comprising such preparations.

  本发明描述了一种新型化合物、组合物和方法，用于预防和治疗由肥大细胞介导的炎症性疾病。这些化合物、组合物和方法对预防和治疗呼吸道相关的炎症性疾病，如哮喘和过敏性鼻炎，以及其他类型的免疫介导的炎症性疾病，如类风湿性关节炎、结膜炎和炎症性肠病、各种皮肤病和某些病毒性疾病均有效。这些化合物包括强效和选择性的肥大细胞蛋白酶酶抑制剂。治疗这些疾病的组合物包括口服、吸入、局部和静脉制剂，以及包含这些制剂的装置。