4-[N'-[(4-Chlorophenyl)sulfonyl]ureido]benzoic acid | 119411-33-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[N'-[(4-Chlorophenyl)sulfonyl]ureido]benzoic acid
• 英文别名: 4-[(4-Chlorophenyl)sulfonylcarbamoylamino]benzoic acid
• CAS: 119411-33-5
• 化学式: C₁₄H₁₁ClN₂O₅S
• 分子量: 354.771
• InChiKey: OYPCLRJPZNDFGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[N'-[(4-Chlorophenyl)sulfonyl]ureido]benzoic acid 、 (1S)-L-valyl-N-<1-<(2-benzoxazolyl)hydroxymethyl>-2-methylpropyl>-L-prolinamide 在 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 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 (2S)-N-[(2S)-1-(1,3-benzoxazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]-1-[(2S)-2-[[4-[(4-chlorophenyl)sulfonylcarbamoylamino]benzoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxamide
  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：

  对氨基苯甲酸 、 对氯苯磺酰异氰酸酯 以 四氢呋喃 为溶剂， 生成 4-[N'-[(4-Chlorophenyl)sulfonyl]ureido]benzoic acid
  参考文献：
  名称：

  Substituted peptide derivatives

  摘要：

  该发明提供了一系列新颖的肽衍生物，其化学式为Ia、Ib和Ic（以下列出），以及其药学上可接受的盐，其中基团A、R1、R2和R4-R9的含义如下规范中所定义。化合物Ia、Ib和Ic是人类白细胞弹性蛋白酶的抑制剂。该发明还提供了含有化合物Ia、Ib或Ic或其药学上可接受的盐的药物组合物，以及用于制备化合物Ia、Ib和Ic的工艺和中间体。

  公开号：

  EP0276101A3

文献信息

• Peptidic human leukocyte elastase (HLE) inhibitors
  申请人：ZENECA INC.

  公开号：EP0291234A2

  公开（公告）日：1988-11-17

  The invention provides a series of novel heterocyclic ketones of formula I (set out hereinafter) and pharmaceutically acceptable base-addition salts thereof, in which the values of R4, L, A, X and Q have the meanings defined in the following specification. The compounds of formula I are inhibitors of human leukocytic elastase. The invention also provides pharmaceutical compositions containing a compound of formula I, or a pharmaceutically acceptable base-addition salt thereof, and processes and intermediates for the manufacture of compounds of formula I.

  本发明提供了一系列新颖的式 I 杂环酮类化合物（如下所述）及其药学上可接受的碱加成盐，其中 R4、L、A、X 和 Q 的值具有以下说明书中定义的含义。式 I 的化合物是人白细胞弹性蛋白酶的抑制剂。本发明还提供了含有式 I 化合物或其药学上可接受的碱加成盐的药物组合物，以及制造式 I 化合物的工艺和中间体。
• US5164371A
  申请人：——

  公开号：US5164371A

  公开（公告）日：1992-11-17
• Substituted peptide derivatives
  申请人：ICI AMERICAS INC.

  公开号：EP0276101A3

  公开（公告）日：1989-11-23

  The invention provides a series of novel substituted peptide derivatives of the formulae la, Ib and Ic (set out hereinafter) and pharmaceutically acceptable salts thereof, in which the radicals A, R1, R2 and R4-R9 have the meanings defined in the following specification. The compounds of formulae la, Ib, and Ic are inhbitors of human leukocytic elastase. The invention also provides pharmaceutical compositions containing a compound of formula la, Ib or Ic, or a pharmaceutically acceptable salt thereof and processes and intermediates for the manufacture of compounds of formulae la, Ib, and Ic.

  该发明提供了一系列新颖的肽衍生物，其化学式为Ia、Ib和Ic（以下列出），以及其药学上可接受的盐，其中基团A、R1、R2和R4-R9的含义如下规范中所定义。化合物Ia、Ib和Ic是人类白细胞弹性蛋白酶的抑制剂。该发明还提供了含有化合物Ia、Ib或Ic或其药学上可接受的盐的药物组合物，以及用于制备化合物Ia、Ib和Ic的工艺和中间体。
• Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl .alpha.-ketobenzoxazoles
  作者：Philip D. Edwards、Mark A. Zottola、Matthew Davis、Joseph Williams、Paul A. Tuthill

  DOI：10.1021/jm00020a011

  日期：1995.9

  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.