S-1-phenyl-5-tetrazolyl N-(L-prolylmethyl)-N-isopropylcarbamate hydrochloride | 102284-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: S-1-phenyl-5-tetrazolyl N-(L-prolylmethyl)-N-isopropylcarbamate hydrochloride
• 英文别名: 1-Phenyl-5-tetrazolyl N-(L-prolylmethyl)-N-isopropylthiocarbamate Hydrochloride；S-(1-phenyltetrazol-5-yl) N-[2-oxo-2-[(2S)-pyrrolidin-2-yl]ethyl]-N-propan-2-ylcarbamothioate;hydrochloride
• CAS: 102284-56-0
• 化学式: C₁₇H₂₂N₆O₂S*ClH
• 分子量: 410.928
• InChiKey: AIPDIGVAARNHQC-UQKRIMTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  、 S-1-phenyl-5-tetrazolyl N-(L-prolylmethyl)-N-isopropylcarbamate hydrochloride 在 牛血清白蛋白 作用下， 以 四氢呋喃 为溶剂， 生成 S-1-phenyl-5-tetrazolyl N-<(methoxysuccinyl)-L-alanyl-L-alanyl-L-prolylmethyl>-N-isopropylcarbamate
  参考文献：
  名称：

  Peptidyl carbamates incorporating amino acid isosteres as novel elastase inhibitors

  摘要：

  The design and synthesis of 13 novel peptidyl carbamates are described. When tested for inhibitory activity toward porcine pancreatic elastase, trypsin, and chymotrypsin, six compounds were found to specifically inhibit elastase without affecting the other two serine proteases. All the active inhibitors had an amino acid isostere at the P1 position. Kinetic studies indicated that the inhibition was competitive with Ki values ranging from 4.23 X 10(-5) to 2.4 X 10(-6) M. The degree of inhibition was found to be dependent on the specificity of the peptide chain for the extended subsites on the enzyme as well as on the nature of P1'. Preliminary work on one inhibitor indicates that the inhibition is reversible and proceeds via the rapid formation of a strong enzyme-inhibitor complex, followed by slow acylation of the serine residue on the active site of the enzyme. Peptidyl carbamates represent a novel class of elastase inhibitors.

  DOI：

  10.1021/jm00158a025
• 作为产物：
  描述：

  S-(1-Phenyl-5-tetrazolyl) chlorothioformate 在 盐酸 、 甲酸 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 S-1-phenyl-5-tetrazolyl N-(L-prolylmethyl)-N-isopropylcarbamate hydrochloride
  参考文献：
  名称：

  Peptidyl carbamates incorporating amino acid isosteres as novel elastase inhibitors

  摘要：

  The design and synthesis of 13 novel peptidyl carbamates are described. When tested for inhibitory activity toward porcine pancreatic elastase, trypsin, and chymotrypsin, six compounds were found to specifically inhibit elastase without affecting the other two serine proteases. All the active inhibitors had an amino acid isostere at the P1 position. Kinetic studies indicated that the inhibition was competitive with Ki values ranging from 4.23 X 10(-5) to 2.4 X 10(-6) M. The degree of inhibition was found to be dependent on the specificity of the peptide chain for the extended subsites on the enzyme as well as on the nature of P1'. Preliminary work on one inhibitor indicates that the inhibition is reversible and proceeds via the rapid formation of a strong enzyme-inhibitor complex, followed by slow acylation of the serine residue on the active site of the enzyme. Peptidyl carbamates represent a novel class of elastase inhibitors.

  DOI：

  10.1021/jm00158a025

文献信息

• Human leukocyte elastase inhibitors and methods for producing and using same
  申请人：UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION

  公开号：EP0367514A2

  公开（公告）日：1990-05-09

  Compounds selected from the group consisting of a compound of the formula and a compound of the formula wherein x is 1 or 2. Y is carbobenzoxy or benzoyl, and XR is have use as elastase enzyme inhibitors. Particularly potent are the L-proline diastereomers. Elastase Enzyme inhibitory compositions comprise a carrier and an elastase enzyme inhibiting amount of the compounds of the invention. A method of selectively inhibiting the enzyme elastase in an animal or a human in need of such treatment comprises administering to the animal or human an enzyme elastase inhibiting amount of one of the compounds of the invention or a composition thereof. A method of reducing corneal scarring or fibroblast proliferation comprises applying to an area of a subject's eye afflicted with the condition a corneal scar- fibroblast proliferation-reducing amount of a free or polymer- bound HLE inhibitory agent under conditions and for a period of time effective to attain the desired effect. A method of reducing neovascularization of corneal scar tissue comprises applying to an area of a subject's eye afflicted with the condition a neovascularization-inhibitory amount of a free or polymer-bound HLE inhibitory agent under conditions and for a period of time effective to attain the desired effect.

  选自以下组别的化合物： 式化合物 和式化合物 其中 x 是 1 或 2 Y 是羧基苯氧基或苯甲酰基，以及 XR 是 可用作弹性蛋白酶抑制剂。特别有效的是 L-脯氨酸非对映异构体。 弹性蛋白酶抑制剂组合物包括载体和本发明化合物的弹性蛋白酶抑制剂。 一种选择性抑制需要此类治疗的动物或人体内的弹性蛋白酶的方法，包括向动物或人施用本发明化合物之一或其组合物的弹性蛋白酶抑制剂。 一种减少角膜瘢痕或成纤维细胞增生的方法，包括在有效达到预期效果的条件下和时间内，向受试者眼部受该症状困扰的区域施用可减少角膜瘢痕-成纤维细胞增生的游离或聚合物结合的HLE抑制剂。一种减少角膜瘢痕组织新生血管的方法，包括在有效达到预期效果的条件下和有效达到预期效果的时间内，将一定量的游离的或与聚合物结合的HLE抑制剂施用到受试者眼睛的一个区域。
• EP0396709A4
  申请人：——

  公开号：EP0396709A4

  公开（公告）日：1991-05-22
• HUMAN LEUKOCYTE ELASTASE INHIBITORS AND METHODS OF PRODUCING AND USING SAME
  申请人：UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION

  公开号：EP0396709A1

  公开（公告）日：1990-11-14
• US4643991A
  申请人：——

  公开号：US4643991A

  公开（公告）日：1987-02-17
• US5008245A
  申请人：——

  公开号：US5008245A

  公开（公告）日：1991-04-16