p-nitrophenyl N-(succinyl-L-alanyl-L-alanyl-L-prolylmethyl)-N-isopropyl carbamate | 958819-90-4

• 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: p-nitrophenyl N-(succinyl-L-alanyl-L-alanyl-L-prolylmethyl)-N-isopropyl carbamate
• 英文别名: 4-Nitrophenyl N-(succinyl-alanyl-alanyl-prolylmethyl)-N-isopropylcarbamate；(4-nitrophenyl) N-[1-[(2S)-1-[(2S)-2-[[(2S)-2-aminopropanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]-2,5-dioxocyclopentyl]-N-propan-2-ylcarbamate
• CAS: 958819-90-4
• 化学式: C₂₆H₃₃N₅O₉
• 分子量: 559.576
• InChiKey: DMPXNIKPTPJOGJ-BXWFABGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  202
• 氢给体数：
  2
• 氢受体数：
  10

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。
• Elastase inhibiting polymers and methods to produce them
  申请人：Digenis, George Alexander

  公开号：EP0368449A2

  公开（公告）日：1990-05-16

  A polymer of the formula P-(L-R)q wherein P is a polymer comprising at least one unit of the formula (AmBn), wherein (AmBn) is substantially nonbiodegradable and has an average molecular weight of about 1,000 to 500,000 daltons, m and n may be the same or different and are about 5 to 3,000, and A and B may be the same or different and at least one of A and B is capable of covalently binding to one of L and R, R is a compound selected from the group consisting of a compound C of the formula wherein X is oxygen or sulfur, R′ is selected from the group consisting of straight and secondary branch-chained (C₁-C₄) alkyl, (C₂-C₃) alkenyl, 4) alkynyl, (C₃-C₆) cycloalkyl, and benzyl, and is selected from the group consisting of substituted and unsubstituted phenyl, wherein the substituents are selected from the group consisting of nitro, and penta-fluoro, benzyl, CH₂CF₂CF₂CF₃, 1-lower alkyl tetrazolyl, 1-phenyltetrazolyl, 2-thioxo3-thiazolidinyl-, pyridyl and benzothiazolyl, provided that when R² is pnitrophenyl R′ is other than tert-butyl, benzyl or cyclohexyl, and when X is sulfur R² is other than benzyl; a compound D of the formula: wherein X is 0 or S, R² is selected from the group consisting of phenyl, nitrophenyl, fluorophenyl, - CH₂CF₂CF₂CF₃, 1 -lower alkyltetrazolyl 1 -phenyltetrazolyl, benzyl, 2-thioxo-3- thiazolidinyl, pyridyl and benzothiazolyl, and R′ is selected from the group consisting of straight or secondary branch chained (C₁-C₄) alkyl, (C₂-C₃) alkenyl, (C₂-C₄) alkynyl, (C₃-C₆) cycloalkyl, and benzyl, provided that when R² is p - nitropheny 1 R′ is other than tertiary-butyl, benzyl or cyclohexyl, and when X is sulfur R² is other than benzyl; and a compound E of the formula wherein Z is -O-Suc-Ala-Ala each said R being covalently bound to L or to one of A and B, L is selected from the group consisting of a covalent bond and a linker group which is covalently bound to R and one of A and B, and g is about 1 to m+n. Pharmaceutical compositions and methods of inhibiting the enzyme elastase and increasing the biological half-life and/or potency in terms of inhibitory activity of the enzyme elastase of peptide compounds are also provided.

  式中的聚合物 P-(L-R)q 其中 P 是至少包含一个式（AmBn）单元的聚合物，其中（AmBn）基本上不可生物降解，平均分子量约为 1,000 至 500,000 道尔顿，m 和 n 可以相同或不同，约为 5 至 3,000 道尔顿，A 和 B 可以相同或不同，且 A 和 B 中至少有一个能与 L 和 R 中的一个共价结合，R 是选自由以下组成的组的化合物 式中的化合物 C 其中 X 是氧或硫，R′选自直链和仲支链的（C₁-C₄）烷基、（C₂-C₃）烯基、4）炔基、（C₃-C₆）环烷基和苄基组成的组，并选自取代和未取代的苯基组成的组，其中取代基选自硝基、和五氟、苄基、CH₂CF₂CF₂CF₃、1-低烷基四唑基、1-苯基四唑基、2-硫酮-3-噻唑烷基、吡啶基和苯并噻唑基、但当 R² 为对硝基苯基时，R′不是叔丁基、苄基或环己基，当 X 为硫时，R² 不是苄基； 式中的化合物 D： 其中 X 是 0 或 S，R² 选自苯基、硝基苯基、氟苯基、-CH₂CF₂CF₂CF₃、1-低级烷基四唑基 1-苯基四唑基、苄基、2-硫酮-3-噻唑烷基、吡啶基和苯并噻唑基组成的组、和 R′选自直链或仲支链（C₁-C₄）烷基、（C₂-C₃）烯基、（C₂-C₄）炔基、（C₃-C₆）环烷基和苄基组成的组、和苄基，条件是当 R² 是对硝基苯 1 时，R′不是叔丁基、苄基或环己基；当 X 是硫时，R² 不是苄基；和 式中化合物 E 其中 Z 是-O-Suc-Ala-Ala，每个所述 R 与 L 或 A 和 B 之一共价结合，L 选自共价键和与 R 及 A 和 B 之一共价结合的连接基团组成的组，且 g 约为 1 至 m+n。 还提供了抑制弹性蛋白酶的药物组合物和方法，以及增加多肽化合物的生物半衰期和/或抑制弹性蛋白酶活性的有效性的药物组合物和方法。
• 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
• ELASTASE INHIBITING POLYMERS AND METHODS
  申请人：UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION

  公开号：EP0403605A1

  公开（公告）日：1990-12-27