ethyl 4-benzyl-4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxybutylate | 130405-00-4

• 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-benzyl-4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxybutylate
• 英文别名: 4-Benzyloxycarbonylamino-2,2-difluoro-3-hydroxy-5-phenyl-pentanoic acid,ethyl ester；ethyl 4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxy-5-phenylpentanoate；ethyl 2,2-difluoro-3-hydroxy-5-phenyl-4-(phenylmethoxycarbonylamino)pentanoate
• CAS: 130405-00-4
• 化学式: C₂₁H₂₃F₂NO₅
• 分子量: 407.414
• InChiKey: NEMYKFORFGJGBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 4-benzyl-4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxybutylate 生成 4-Benzyloxycarbonylamino-2,2-difluoro-3-hydroxy-5-phenyl-pentanamide
  参考文献：
  名称：

  SCHIRLIN, D.;BALTZER, S.;ALTENBERGER, J. M., TETRAHEDRON LETT., 29,(1988) N 30, C. 3687-3690

  摘要：

  DOI：
• 作为产物：
  描述：

  二氟溴乙酸乙酯 、 rac-2-(benzyloxycarbonylamino)-3-phenylpropanal 在 锌 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以82%的产率得到ethyl 4-benzyl-4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxybutylate
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and Pharmacokinetic Profiles of Nonpeptidic Difluoromethylene Ketones as Novel Inhibitors of Human Chymase

  摘要：

  Potent human chymase inhibitors with high enzymatic selectivity and satisfactory metabolic stability were obtained by replacing the Val-Pro (P-3-P-2) dipeptide portion of the previously described inhibitor 1 with a nonpeptidic pyrimidinone skeleton. The potency of the novel compounds was further enhanced by the introduction of carbamoyl-substituted difluoromethylene ketone moieties. The most potent chymase inhibitor of the newly created series was 2u (Y-40018), which had a K-i of 2.62 nM. Compound 2u possessed high selectivity for human chymase since it lacked significant activity toward other representative human proteolytic enzymes. Moreover its strict specificity for human chymase suggested that 2u strongly inhibited human and canine chymases but not rat and mouse ones. Pharmacokinetic studies in rats and dogs indicated that 2u was absorbed rapidly after oral administration and had satisfactory bioavailability in these experimental animal species (rat, 17%; dog, 32%). In conclusion, 2u is a novel, potent, and orally active chymase inhibitor which would prove very useful in revealing the precise roles of the latter in various pathophysiological processes.

  DOI：

  10.1021/jm000497n

文献信息

• Analog of peptidase substrates
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05114927A1

  公开（公告）日：1992-05-19

  This invention relates to novel analogs of certain peptidase substrates in which the nitrogen atom of the scissile amide bond has been replaced with a difluoromethylene moiety and in which the carbonyl moiety of its adjacent amide bond has been replaced with a terminal amine function, said novel analogs having the property of inhibiting renin and which are useful in the treatment of hypertension.

  这项发明涉及某些肽酶底物的新型类似物，其中可切割酰胺键的氮原子已被二氟甲亚甲基取代，并且其相邻酰胺键的羰基部分已被末端胺基取代，这些新型类似物具有抑制肾素的特性，并可用于治疗高血压。
• Novel peptidase inhibitors
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0356595A1

  公开（公告）日：1990-03-07

  This invention relates to analogs of peptidase substrates in which the nitrogen atom of the scissile amide bond of a partial retropeptide analog of the substrate has been replaced by a difluoromethylene moiety. These peptidase substrate analogs provide specific enzyme inhibitors for a variety of proteases, the inhibition of which exert valuable pharmacological activities and therefore have useful physiological consequences in a variety of disease states.

  这项发明涉及肽酶底物的类似物，其中底物的部分反肽类似物的可切割酰胺键的氮原子被二氟甲亚甲基取代。这些肽酶底物类似物提供了各种蛋白酶的特异性酶抑制剂，这些蛋白酶的抑制对多种蛋白酶具有有用的药理活性，因此在多种疾病状态下具有有用的生理后果。
• IgE antibody production inhibitors and autoimmune diseases inhibitors
  申请人：Welfide Corporation

  公开号：US06528514B1

  公开（公告）日：2003-03-04

  The present invention relates to an IgE antibody production inhibitor and an autoimmune disease suppressant containing a heterocyclic amide compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient wherein R represents a hydrogen atom, alkyl, —CHO, —COOH, etc.; R5, R6 and R7 represent each hydrogen, alkyl, aryl, etc.; M represents a carbon atom or a nitrogen atom; Y represents aryl, etc.; and Z represents hydrogen, alkyl, aryl, etc.

  本发明涉及一种IgE抗体产生抑制剂和一种自身免疫疾病抑制剂，其包含下述一般式（1）所表示的杂环酰胺化合物或其药学上可接受的盐作为活性成分，其中R表示氢原子、烷基、-CHO、-COOH等；R5、R6和R7分别表示氢、烷基、芳基等；M表示碳原子或氮原子；Y表示芳基等；Z表示氢、烷基、芳基等。
• IgE ANTIBODY PRODUCTION INHIBITORS AND AUTOIMMUNE DISEASES INHIBITORS
  申请人：Welfide Corporation

  公开号：EP1062949A1

  公开（公告）日：2000-12-27

  The present invention relates to an IgE antibody production inhibitor and an autoimmune disease suppressant containing a heterocyclic amide compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient wherein R represents a hydrogen atom, alkyl, -CHO, -COOH, etc.; R5, R6 and R7 represent each hydrogen, alkyl, aryl, etc.; M represents a carbon atom or a nitrogen atom; Y represents aryl, etc.; and Z represents hydrogen, alkyl, aryl, etc.

  本发明涉及一种 IgE 抗体产生抑制剂和一种自身免疫性疾病抑制剂，其活性成分含有下 列通式 (1) 所代表的杂环酰胺化合物或其药学上可接受的盐 其中 R 代表氢原子、烷基、-CHO、-COOH 等；R5、R6 和 R7 分别代表氢、烷基、芳基等；M 代表碳原子或氮原子；Y 代表芳基等；Z 代表氢、烷基、芳基等。
• US6528514B1
  申请人：——

  公开号：US6528514B1

  公开（公告）日：2003-03-04