4-<(phenylsulfonamido)carbonyl>benzoic acid | 118271-07-1

• 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-<(phenylsulfonamido)carbonyl>benzoic acid
• 英文别名: 4-(Phenylsulfonylaminocarbonyl)benzoic acid；4-phenylsulfonamidocarbonyl-benzoic acid；4-(Benzenesulfonylcarbamoyl)benzoic acid
• CAS: 118271-07-1
• 化学式: C₁₄H₁₁NO₅S
• 分子量: 305.311
• InChiKey: DDOAZZPGLWMEAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 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：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-<(phenylsulfonamido)carbonyl>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 4-N-(benzenesulfonyl)-1-N-[(2S)-1-[(2S)-2-[[(2S)-1-(1,3-benzoxazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]benzene-1,4-dicarboxamide
  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：

  4-(Phenylsulfonylaminocarbonyl)benzoic acid t-butyl ester 在 三氟乙酸 作用下， 以 水 为溶剂， 生成 4-<(phenylsulfonamido)carbonyl>benzoic acid
  参考文献：
  名称：

  Selected difluoro derivatives

  摘要：

  该发明披露了一系列二氟酮、单肽、二肽和三肽衍生物的化学式Ia、Ib和Ic：______________________________________（见示例后的页面上的化学式）Ia（见示例后的页面上的化学式）Ib（见示例后的页面上的化学式）Ic______________________________________PAL及其适当的盐，其中这些基团在规范中有定义。这些衍生物在抑制人白细胞弹性蛋白酶的作用方面是有用的。还公开了制造这些衍生物的方法和中间体，以及包括这些衍生物的药物组合物。

  公开号：

  US04880780A1

文献信息

• Aryloxy and arylacyloxy methyl ketones as thiol protease inhibitors
  申请人：SANDOZ LTD.

  公开号：EP0272671A2

  公开（公告）日：1988-06-29

  Thiol protease inhibitors are disclosed having the formula: or an optical isomer thereof, or a pharmaceutically acceptable salt thereof, wherein: n is 0 or 1; m is 0, 1 or 2; X is H or an N-protecting group; each Y is independently an optionally protected α-amino acid residue; R is an optionally protected α-amino acid side chain that is H or CH₃ or that is bonded to the α-carbon atom to which it is attached by a methylene, methine or phenyl radical; and Rʹ is optionally substituted aryl.

  已公开的硫醇蛋白酶抑制剂具有以下式子：或其光学异构体，或其药学上可接受的盐，其中：n为0或1；m为0、1或2；X为H或N-保护基团；每个Y独立地为任选保护的α-氨基酸残基；R为任选保护的α-氨基酸侧链，该侧链为H或CH₃，或通过亚甲基、甲基或苯基与所连接的α-碳原子键合；以及Rʹ为任选取代的芳基。
• 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。
• In vivo Inhibition of Cathepsin B by Peptidyl (Acyloxy)methyl Ketones
  作者：Bonnie M. Wagner、Roger A. Smith、Peter J. Coles、Leslie J. Copp、Michael J. Ernest、Allen Krantz

  DOI：10.1021/jm00038a012

  日期：1994.6

  Peptidyl (acyloxy)methyl ketones, previously established as potent irreversible inhibitors of the cysteine proteinase cathepsin B in vitro, were investigated and optimized for their inhibitory activity in vivo. Incorporation of polar or charged functional groups in the inhibitor structure afforded effective cathepsin B inhibition, following dosing to rats. The most effective inhibitor, Z-Phe-Lys-CH2OCO-(2,4,6-Me(3))Ph (8), was found to give ED(50) values of 18 mg/kg po (orally) and 5.0 mg/kg ip (intraperitoneally) at 4-5 h postdose, and 2.4 mg/kg sc (subcutaneously) at 24 h postdose, for liver cathepsin B inhibition (measured ex vivo). The subcutaneous route of administration of (acyloxy)methyl ketone 8 also provided potent cathepsin B inhibition in certain peripheral tissues (e.g., ED(50) 1.0 mg/kg for skeletal muscle, 0.1 mg/kg for heart). These investigations demonstrate that peptidyl (acyloxy)methyl ketones such as 8 have promise as tools for the characterization of in vivo biochemical processes and as therapeutic agents.
• US4880780A
  申请人：——

  公开号：US4880780A

  公开（公告）日：1989-11-14
• US5055451A
  申请人：——

  公开号：US5055451A

  公开（公告）日：1991-10-08