trans-1-acetyl-4-benzyloxy-L-proline | 182964-78-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: trans-1-acetyl-4-benzyloxy-L-proline
• 英文别名: (4R)-1-Acetyl-4-(benzyloxy)-L-proline；(2S,4R)-1-acetyl-4-phenylmethoxypyrrolidine-2-carboxylic acid
• CAS: 182964-78-9
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: AMYCNQOGXKPGLM-OLZOCXBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-1-acetyl-4-benzyloxy-L-proline 在 氢氟酸 、 戴斯-马丁氧化剂 、 苯甲醚 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 RWJ-56423
  参考文献：
  名称：

  Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-Based Transition-State Analogue Containing a Benzothiazole Ketone

  摘要：

  Inhibitors of human mast cell tryptase (EC 3.4.21.59) have therapeutic potential for treating allergic or inflammatory disorders. We have investigated transition-state mimetics possessing a heterocycle-activated ketone group and identified in particular benzothiazole ketone (2S)-6 (RWJ-56423) as a potent, reversible, low-molecular-weight tryptase inhibitor with a K-i value of 10 nM. A single-crystal X-ray analysis of the sulfate salt of (2S)-6 confirmed the stereochemistry. Analogues 12 and 15-17 are also potent tryptase inhibitors. Although RWJ-56423 potently inhibits trypsin (K-i = 8.1 nM), it is selective vs other serine proteases, such as kallikrein, plasmin, and thrombin. We obtained an X-ray structure of (2S)-6 complexed with bovine trypsin (1.9-Angstrom resolution), which depicts inter alia a hemiketal involving Ser-189, and hydrogen bonds with His-57 and Gln-192. Aerosol administration of 6 (2R,2S; RWJ-58643) to allergic sheep effectively antagonized antigen-induced asthmatic responses, with 70-75% blockade of the early response and complete ablation of the late response and airway hyperresponsiveness.

  DOI：

  10.1021/jm030050p
• 作为产物：
  描述：

  (2S,4R)-N-BOC-4-苄氧基-2-吡咯烷甲酸甲酯 在 吡啶 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 trans-1-acetyl-4-benzyloxy-L-proline
  参考文献：
  名称：

  O-benzyl hydroxyproline as a bioisostere for Phe-Pro: Novel dipeptide thrombin inhibitors

  摘要：

  A series of analogs were prepared based on the known thrombin inhibitor PPACK, in which the D-Phe-ho dipeptide has been replaced by trans-4-O-benzyl hydroxyproline. One of these analogs is a more potent inhibitor of thrombin, and is more selective, than PPACK itself. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00404-0

文献信息

• Process for preparing peptidyl heterocyclic ketone derivatives
  申请人：Breslav Michael

  公开号：US20050059607A1

  公开（公告）日：2005-03-17

  The present invention relates to novel processes for the preparation of peptidyl heterocyclic ketones of the general formula (I) wherein all variables are as herein defined. The present invention further relates to novel pharmaceutical salts and processes for their preparation. The peptidyl heterocyclic ketones of formula (I) are potent and selective inhibitors of tryptase, useful for the treatment and prevention of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis.

  本发明涉及一种新型方法，用于制备一般公式（I）中的肽杂环酮，其中所有变量如本文所定义。本发明还涉及新型药用盐和其制备方法。公式（I）中的肽杂环酮是三肽酶的强效和选择性抑制剂，可用于治疗和预防与呼吸道相关的炎症性疾病，如哮喘和过敏性鼻炎。
• [EN] PEPTIDYL HETEROCYCLIC KETONES USEFUL AS TRYPTASE INHIBITORS<br/>[FR] PEPTIDYLCETONES HETEROCYCLIQUES INHIBITRICES DE LA TRYPTASE
  申请人：ORTHO MCNEIL PHARM INC

  公开号：WO2000044733A1

  公开（公告）日：2000-08-03

  The present invention relates to a series of peptidyl heterocyclic ketones which are inflammatory cell serine protease inhibitors and their compositions and methods for the prevention and treatment of a variety of immunomediated inflammatory disorders. More particularly, these compounds are potent and selective inhibitors of tryptase and are therefore effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis.

  本发明涉及一系列肽基杂环酮，它们是炎症细胞丝氨酸蛋白酶抑制剂及其组合物和预防和治疗各种免疫介导的炎症性疾病的方法。更具体地说，这些化合物是强效和选择性的替普汀酶抑制剂，因此对于预防和治疗与呼吸道有关的炎症性疾病，如哮喘和过敏性鼻炎，具有有效性。
• [EN] PEPTIDYL HETEROCYCLIC KETONE DERIVATIVES AND PREPARATION PROCESSES<br/>[FR] DERIVES CETONES HETEROCYCLIQUES PEPTIDYLIQUES ET PROCEDES DE DE PREPARATION
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005023804A1

  公开（公告）日：2005-03-17

  The present invention relates to novel processes for the preparation of peptidyl heterocyclic ketones of the general formula (I) wherein all variables are as herein defined. The present invention further relates to novel pharmaceutical salts and processes for their preparation. The peptidyl heterocyclic ketones of formula (I) are potent and selective inhibitors of tryptase, useful for the treatment and prevention of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis.

  本发明涉及一种制备通式（I）中所有变量如此定义的肽杂环酮的新工艺。本发明还涉及新的药物盐及其制备工艺。通式（I）中的肽杂环酮是一种有效且选择性的胰蛋白酶抑制剂，可用于治疗和预防与呼吸道有关的炎症性疾病，如哮喘和过敏性鼻炎。
• Peptidyl heterocyclic ketones useful as tryptase inhibitors
  申请人：——

  公开号：US20030008829A1

  公开（公告）日：2003-01-09

  The present invention relates to a series of peptidyl heterocyclic ketones which are inflammatory cell serine protease inhibitors and their compositions and methods for the prevention and treatment of a variety of immunomediated inflammatory disorders. More particularly, these compounds are potent and selective inhibitors of tryptase and are therefore effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis.

  本发明涉及一系列肽杂环酮，它们是炎症细胞丝氨酸蛋白酶抑制剂及其组合物和用于预防和治疗各种免疫介导的炎症性疾病的方法。更具体地说，这些化合物是强效且选择性的组胺酶抑制剂，因此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，非常有效。
• J. Med. Chem. 2003, 46, 3865-3876
  作者：

  DOI：——

  日期：——