(S)-2-Benzenesulfonylamino-3-(4-hydroxy-phenyl)-propionic acid | 168974-61-6

• 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: (S)-2-Benzenesulfonylamino-3-(4-hydroxy-phenyl)-propionic acid
• 英文别名: N-(Phenylsulfonyl)-L-tyrosine；(2S)-2-(benzenesulfonamido)-3-(4-hydroxyphenyl)propanoic acid
• CAS: 168974-61-6
• 化学式: C₁₅H₁₅NO₅S
• 分子量: 321.354
• InChiKey: QRRXWQYXIGYIDW-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-Benzenesulfonylamino-3-(4-hydroxy-phenyl)-propionic acid 在 氯化亚砜 、 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Abdel-Ghaffar; Mpango; Ismail, Bollettino Chimico Farmaceutico, 2002, vol. 141, # 5, p. 389 - 393

  摘要：

  DOI：
• 作为产物：
  描述：

  L-酪氨酸甲酯盐酸盐 在 氢氧化钾 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 (S)-2-Benzenesulfonylamino-3-(4-hydroxy-phenyl)-propionic acid
  参考文献：
  名称：

  Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A

  摘要：

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

  DOI：

  10.1021/jm960581w

文献信息

• AROMATIC SULFONAMIDE DERIVATIVES, THEIR USE AS ENZYME INHIBITORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：PHARNO-WEDROPHARM GmbH

  公开号：EP0602028B1

  公开（公告）日：1996-01-17
• US5663174A
  申请人：——

  公开号：US5663174A

  公开（公告）日：1997-09-02
• [EN] AROMATIC SULFONAMIDE DERIVATIVES, THEIR USE AS ENZYME INHIBITORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：PHARNO-WEDROPHARM GMBH

  公开号：WO1993005014A1

  公开（公告）日：1993-03-18

  (EN) Aromatic sulfonamide derivatives, particularly benzene-sulfonamide, 4-fluorobenzenesulfonamide, 5-chloro-1-naphthalenesulfonamide and 5-isoquinolinesulfonamide derivatives are provided that inhibit Ca2+-dependent enzymes and proteins such as Phospholipase A2, protein kinases such as Protein Kinase C, and inhibit membrane fusion, thereby being a valuable drug for the treatment of inflammation, arthritis, infarction, nephritis and many other types of tissue injury.(FR) Des dérivés aromatiques de sulfamide, particulièrement de sulfamide benzénique, sulfamide fluoro-benzénique-4, sulfamide chloro 5-naphtalénique-1 et sulfamide isoquinoline-5 sont décrits. Ils inhibent les enzymes dépendantes du Ca2+ et les protéines telles que les phospholipases A2, les protéines kinases telles que la protéine kinase C, et inhibent la fusion de membranes, étant ainsi des médicaments précieux pour le traitement des inflammations, des arthrites, des infarctus, des néphrites et de beaucoup d'autres lésions des tissus.
• Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A
  作者：Jean M. Defauw、Marcia M. Murphy、G. Erik Jagdmann、Hong Hu、John W. Lampe、Sean P. Hollinshead、Thomas J. Mitchell、Heidi M. Crane、Julia M. Heerding、José S. Mendoza、Jefferson E. Davis、James W. Darges、Frederick R. Hubbard、Steven E. Hall

  DOI：10.1021/jm960581w

  日期：1996.1.1

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.
• Abdel-Ghaffar; Mpango; Ismail, Bollettino Chimico Farmaceutico, 2002, vol. 141, # 5, p. 389 - 393
  作者：Abdel-Ghaffar、Mpango、Ismail、Nanyonga

  DOI：——

  日期：——