N-Benzyloxycarbonyl-L-valyl-L-prolyl-L-valinal | 95501-78-3

• 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: N-Benzyloxycarbonyl-L-valyl-L-prolyl-L-valinal
• 英文别名: Cbz-Val-Pro-Val-H；{(S)-1-[(S)-2-((S)-1-Formyl-2-methyl-propylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid benzyl ester；benzyl N-[(2S)-3-methyl-1-[(2S)-2-[[(2S)-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxobutan-2-yl]carbamate
• CAS: 95501-78-3
• 化学式: C₂₃H₃₃N₃O₅
• 分子量: 431.532
• InChiKey: GCMAQTFFEHYZIW-AABGKKOBSA-N

物化性质

• 沸点：
  660.0±55.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-Benzyloxycarbonyl-L-valyl-L-prolyl-L-valinal 在 palladium on activated charcoal 水 、 氢气 、 戴斯-马丁氧化剂 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 乙酰氯 、 叔丁醇 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 氯仿 为溶剂， 25.0~60.0 ℃ 、344.73 kPa 条件下， 反应 62.5h， 生成
  参考文献：
  名称：

  Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl .alpha.-ketobenzoxazoles

  摘要：

  A series of peptidyl alpha-ketobenzoxazoles were synthesized and evaluated for their in vitro and in vivo inhibition of human neutrophil elastase (HNE). These compounds inhibit HNE by forming both a covalent bond between the ketone carbonyl carbon atom and the hydroxyl group of Ser-195 and a hydrogen bond between the benzoxazole nitrogen atom and His-57. Appending to the parent benzoxazole ring a variety of substituents which spanned a range of physicochemical properties had only a modest effect on in, vitro potency (K-i = 3-0.4 nM). This apparent lack of a significant effect is believed to result from the fact that any increased ketone carbonyl activation by the ring substituent is counter balanced by a corresponding decrease in the hydrogen-bonding ability of the benzoxazole nitrogen atom. In contrast to the results in vitro, maximizing in vive activity was critically dependent upon the choice of the benzoxazole ring substituent. Several substituted peptidyl alpha-ketobenzoxazoles effectively inhibited HNE-induced lung injury when administered intratracheally 24 h prior to the enzyme.

  DOI：

  10.1021/jm00020a011
• 作为产物：
  描述：

  N-Benzyloxycarbonyl-L-valyl-L-prolyl-L-valinal diethylacetal 在 对甲苯磺酸 作用下， 以 乙酸乙酯 、 丙酮 为溶剂， 生成 N-Benzyloxycarbonyl-L-valyl-L-prolyl-L-valinal
  参考文献：
  名称：

  Proline derivatives

  摘要：

  公式为: ##STR1## 其中R.sup.1到R.sup.11具有定义的值，以及它们的酸盐和碱盐，以及醛基的平衡加合物；其制备方法；制备所述脯氨酸衍生物的药物组合物；以及制备所述脯氨酸衍生物的中间体。这些脯氨酸衍生物是人类白细胞弹性蛋白酶抑制剂，例如在治疗肺气肿中有用。

  公开号：

  US04596789A1

文献信息

• A practical method for the combinatorial synthesis of peptide aldehydes
  作者：Beverley J. Hall、John D. Sutherland

  DOI：10.1016/s0040-4039(98)01374-4

  日期：1998.9

  A practical strategy for solid phase synthesis of peptide aldehydes is described. An olefin linker is constructed using Wittig chemistry, after peptide synthesis ozonolytic treatment of the linker and subsequent workup with dimethyl sulphide results in facile isolation of peptide aldehydes. The principle is demonstrated by synthesis of a 3×3×3 array of 27 tripeptide aldehydes.

  描述了一种固相合成肽醛的实用策略。在肽合成，连接子的臭氧分解处理和随后用二甲基硫的后处理后，可以容易地分离出肽醛，然后使用Wittig化学方法构建了一个烯烃连接子。通过合成27个三肽醛的3×3×3阵列证明了该原理。
• Design, synthesis, and kinetic evaluation of a unique class of elastase inhibitors, the peptidyl .alpha.-ketobenzoxazoles, and the x-ray crystal structure of the covalent complex between porcine pancreatic elastase and Ac-Ala-Pro-Val-2-benzoxazole
  作者：Philip D. Edwards、Edgar F. Meyer、J. Vijayalakshmi、Paul A. Tuthill、Donald A. Andisik、Bruce Gomes、Anne Strimpler

  DOI：10.1021/ja00031a046

  日期：1992.2

  2 are potent, competitive, reversible inhibitors or the serine proteinases HLE and PPE. These inhibitors were designed to inactivate the enzyme by interacting with both the serine hydroxyl group and the histidine imidazole ring or the catalytic triad. The X-ray crystal structure determination of 2 bound to PPE confirms the covalent attachment or the inhibitor's carbonyl carbon atom to the hydroxyl group

  肽基 α-酮苯并恶唑 1 和 2 是有效的、竞争性的、可逆的抑制剂或丝氨酸蛋白酶 HLE 和 PPE。这些抑制剂旨在通过与丝氨酸羟基和组氨酸咪唑环或催化三联体相互作用来使酶失活。与 PPE 结合的 2 的 X 射线晶体结构测定证实了与羟基或活性位点 Ser-195 的共价连接或抑制剂的羰基碳原子。氮原子或苯并恶唑环参与与 His-57 的氢键相互作用
• Selected difluoro derivatives
  申请人：ICI AMERICAS INC.

  公开号：EP0204571A2

  公开（公告）日：1986-12-10

  The invention discloses a series of difluoroketone mono. di- and tri-peptide derivatives of the formula la, Ib and Ic:- and salts thereof where appropriate, and wherein the radicals are defined hereafter in the specification. The derivatives are useful in inhibiting the action of human leukocyte elastase. There are also disclosed methods and intermediates for the manufacture of, and pharmaceutical compositions comprising, the said derivatives.

  本发明公开了一系列二氟酮类单肽、二肽和三肽衍生物，其式分别为 la、Ib 和 Ic：-- 二氟酮类单肽、二肽和三肽衍生物 及其适当的盐类，其中基团在下文说明书中定义。这些衍生物可用于抑制人白细胞弹性蛋白酶的作用。还公开了制造上述衍生物的方法和中间体，以及包含上述衍生物的药物组合物。
• Difluoroketo compounds
  申请人：ICI AMERICAS INC.

  公开号：EP0249349A1

  公开（公告）日：1987-12-16

  The invention relates to selected difluoro compounds of formulae la, 1b and Ic (set out hereinafter) which are useful as inhibitors of human leukocyte elastase.

  本发明涉及可用作人类白细胞弹性蛋白酶抑制剂的式 la、1b 和 Ic（如下所述）的特定二氟化合物。
• Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency
  作者：Philip D. Edwards、Donald J. Wolanin、Donald W. Andisik、Matthew W. Davis

  DOI：10.1021/jm00001a013

  日期：1995.1

  A series of peptidyl alpha-ketoheterocycles were synthesized and evaluated for their in vitro inhibition of human neutrophil elastase (HNE). Several heterocycles, including oxazoline and benzoxazole, afforded extremely potent inhibitors of HNE (1p-r) with nanomolar to subnanomolar K-i values. The structure-activity relationships revealed that for compounds with a K-i < 1000 nM potency tends to be positively correlated with the sigma(I) value of the heterocycle. Furthermore, the results in this study support the hypothesis that, in the covalent enzyme-inhibitor adduct, the azole nitrogen atom of the inhibitor heterocycle participates in a hydrogen-bonding interaction with the active-site His-57.