Ethyl 4(S)-amino-2,2-difluoro-3(R)-hydroxy-5-phenylpentanoate hydrochloride

• 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: Ethyl 4(S)-amino-2,2-difluoro-3(R)-hydroxy-5-phenylpentanoate hydrochloride
• 英文别名: ethyl (3R,4S)-4-amino-2,2-difluoro-3-hydroxy-5-phenylpentanoate;hydrochloride
• 化学式: C₁₃H₁₇F₂NO₃*ClH
• 分子量: 309.741
• InChiKey: KFQDKBFMPAKLHC-VZXYPILPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.54
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  72.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 4(S)-amino-2,2-difluoro-3(R)-hydroxy-5-phenylpentanoate hydrochloride 在 palladium on activated charcoal 吡啶 、 盐酸 、 sodium hydroxide 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 戴斯-马丁氧化剂 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-(4-{[(S)-1-((S)-2-tert-Butoxycarbonylamino-4-carboxy-butyryl)-pyrrolidine-2-carbonyl]-amino}-2,2-difluoro-3-oxo-5-phenyl-pentanoylamino)-naphthalene-1-carboxylic acid
  参考文献：
  名称：

  Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu AT P3 site

  摘要：

  Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = >100 mu M). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00132-2
• 作为产物：
  描述：

  ethyl 5-phenyl-4(S)-[(N-tert-butoxycarbonyl)amino]-2,2-difluoro-3(R)-hydroxypentanoate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 Ethyl 4(S)-amino-2,2-difluoro-3(R)-hydroxy-5-phenylpentanoate hydrochloride
  参考文献：
  名称：

  Heterocyclic amide compounds and pharmaceutical use of the same

  摘要：

  式(I)的杂环酰胺化合物##STR1##，其中每个符号如规范中定义的那样，其药理学上可接受的盐，其药物组合物和其药用。本发明的杂环酰胺化合物及其药理学上可接受的盐对哺乳动物包括人类的胰蛋白酶组具有优越的抑制活性，并可经口或经肠外途径给药。因此，它们可用作胰蛋白酶抑制剂，并可有效预防和治疗由胰蛋白酶引起的各种疾病，如由II型血管紧张素引起的疾病。

  公开号：

  US05948785A1

文献信息

• Heterocyclic amide compounds and pharmaceutical use of the same
  申请人：The Green Cross Corporation

  公开号：US05948785A1

  公开（公告）日：1999-09-07

  Heterocyclic amide compounds of the formula (I) ##STR1## wherein each symbol is as defined in the specification, pharmacologically acceptable salts thereof, pharmaceutical compositions thereof and pharmaceutical use thereof. The heterocyclic amide compounds and pharmacologically acceptable salts thereof of the present invention have superior inhibitory activity against chymase groups in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be effective for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.

  式(I)的杂环酰胺化合物##STR1##，其中每个符号如规范中定义的那样，其药理学上可接受的盐，其药物组合物和其药用。本发明的杂环酰胺化合物及其药理学上可接受的盐对哺乳动物包括人类的胰蛋白酶组具有优越的抑制活性，并可经口或经肠外途径给药。因此，它们可用作胰蛋白酶抑制剂，并可有效预防和治疗由胰蛋白酶引起的各种疾病，如由II型血管紧张素引起的疾病。
• HETEROCYCLIC AMIDE COMPOUNDS AND MEDICINAL USE OF THE SAME
  申请人：THE GREEN CROSS CORPORATION

  公开号：EP0826671A1

  公开（公告）日：1998-03-04

  Heterocyclic amide compounds of the formula (I) wherein each symbol is as defined in the specification, pharmacologically acceptable salts thereof, pharmaceutical compositions thereof and pharmaceutical use thereof. The heterocyclic amide compounds and pharmacologically acceptable salts thereof of the present invention have superior inhibitory activity against chymase groups in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be effective for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.

  式 (I) 的杂环酰胺化合物 其中各符号如说明书中所定义，其药理上可接受的盐、其药物组合物和其药物用途。本发明的杂环酰胺化合物及其药理学上可接受的盐类对哺乳动物（包括人类）的糜蛋白酶基团具有优异的抑制活性，并且可以口服或肠外给药。因此，它们可作为糜蛋白酶抑制剂，有效预防和治疗由糜蛋白酶引起的各种疾病，如血管紧张素 II 引起的疾病。
• US5948785A
  申请人：——

  公开号：US5948785A

  公开（公告）日：1999-09-07
• Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu AT P3 site
  作者：Masahiro Eda、Atsuyuki Ashimori、Fumihiko Akahoshi、Takuya Yoshimura、Yoshihisa Inoue、Chikara Fukaya、Masahide Nakajima、Hajime Fukuyama、Teruaki Imada、Norifumi Nakamura

  DOI：10.1016/s0960-894x(98)00132-2

  日期：1998.4

  Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = >100 mu M). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions, (C) 1998 Elsevier Science Ltd. All rights reserved.