(2S)-6-amino-2-[(4-methylphenyl)sulfonylamino]-N-(4-nitrophenyl)hexanamide;hydrochloride | 103892-20-2

• 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: (2S)-6-amino-2-[(4-methylphenyl)sulfonylamino]-N-(4-nitrophenyl)hexanamide;hydrochloride
• CAS: 103892-20-2
• 化学式: C₁₉H₂₄N₄O₅S*ClH
• 分子量: 456.95
• InChiKey: GJOYCOZDGCKYSM-FERBBOLQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.74
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  NΕ-苄氧羰基-NΑ-甲苯磺酰基-L-赖氨酸 在 氢溴酸 、 溶剂黄146 、 三氯化磷 作用下， 以 吡啶 为溶剂， 反应 4.17h， 生成 (2S)-6-amino-2-[(4-methylphenyl)sulfonylamino]-N-(4-nitrophenyl)hexanamide;hydrochloride
  参考文献：
  名称：

  Synthesis of active center-directed peptide inhibitors of plasmin.

  摘要：

  活性中心导向的纤溶酶肽抑制剂是基于纤溶酶特定底物的结构设计的，并通过常规溶液法合成。对其对纤溶酶的作用进行了研究，并考察了结构-活性关系。D-Ile-Phe-Lys-BZA（4-苯甲酰阿尼林）抑制了纤溶酶对S-2251和纤维蛋白的活性（IC50：分别为0.069mM和0.18mM），但D-Ile-Phe-Lys-BPP（4-苯基哌啶酰胺）没有抑制作用。然而，D-Ile-Phe-Lys-BZA被纤溶酶降解，释放出苯甲酰苯胺，表明这种类型的肽抑制剂对纤溶酶并不稳定。研究发现，Tos-Lys-pNA没有被纤溶酶降解，并且抑制了纤溶酶对纤维蛋白、小肽底物和纤维蛋白原的活性，通过选择性地阻断纤溶酶的活性中心。为了获得有效且稳定的纤溶酶抑制剂，建议以Tos-Lys-pNA和特定底物D-Ile-Phe-Lys-pNA的结构为参考进行设计。

  DOI：

  10.1248/cpb.36.1289

文献信息

• Lysin derivative and proteinase inhibitor
  申请人：Okamoto, Shosuke

  公开号：EP0183271A2

  公开（公告）日：1986-06-04

  A lysine derivative having the general formula: A-Y-Lys- B (L-form) (A) wherein A represents or wherein X and X' independently represent hydrogen, halogen, alkyl, cycloalkyl, alkoxy, aryloxy, dialkylamino, alkylcarbonyl amino, arylcarbonyl amino, and n, is an integer of 3 to 6, n2 is an integer of 1 to 3, and n3 is an integer of 0 to 3; Y represents S02 or CO; -Lys- represents B represents NR1R2, NZW, or tetrahydroquinolyl, wherein R' and R2 independently represents hydrogen provided that both R' and R2 cannot be hydrogen at the same time; alkyl substituted with carboxyl, alkoxycarbonyl, phenyl, hydroxyphenyl, or benzoyl; cycloalkyl which may be substituted with arylcarbonyl; cycloalkyl-alkyl which may be substituted with carboxyl, arylcarbonyl, or aralkyloxycar- bonyi; phenyl which may be substituted with halogen, nitro, cyano, trifluoromethyl, alkyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, phenylalkyl which may be further substituted with dialkylamino, alkylcarbonyl, phenylalkenyl which may be further substituted with dialkylamino, phenoxy, pheny-Icarbonyl which may be further substituted with an amino, dialkylamino, alkoxycarbonyl, or nitro group, pyridylmethyl, phenyl hydroxyalkyl, alkylsulfonyl, or alkoxycarbonyl alkylcarbonyl, coumaryl which may be substituted with alkyl; quinolyl; adamantyl; norbornyl; or tetrahydronaphthyl; and W is hydrogen; hydroxyl; carboxyl; aminocarbonyl; alkyl; alkoxy carbonyl; phenyl; phenylalkyl which may be substituted with dialkylamino; or phenylcarbonyl which may be substituted with alkoxycarbonyl; or tetrahydroquinolyl; andor the pharmaceutically acceptable salt thereof. This lysine derivative is effective as a proteinase inhibitor.

  具有以下通式的赖氨酸衍生物A-Y-Lys- B（L-形式） (A) 其中 A 代表 或 其中X和X'独立地代表氢、卤素、烷基、环烷基、烷氧基、芳氧基、二烷基氨基、烷基羰基氨基、芳基羰基氨基，n为3至6的整数，n2为1至3的整数，n3为0至3的整数；Y代表S02或CO；-Lys-代表 B 代表 NR1R2、NZW 或四氢喹啉基，其中 R' 和 R2 独立地代表氢，但 R' 和 R2 不能同时为氢；被羧基、烷氧羰基、苯基、羟基苯基或苯甲酰基取代的烷基；可被芳基羰基取代的环烷基；可被羧基、芳基羰基或芳氧基羰基取代的环烷基-烷基；可被卤素、硝基、氰基、三氟甲基、烷基、烷氧基、烷氧羰基、烷氧羰基烷基、可进一步被二烷基氨基取代的苯基烷基、烷基羰基、可进一步被二烷基氨基取代的苯基烯基取代的苯基、可进一步被氨基、二烷基氨基、烷氧羰基或硝基取代的苯氧基、苯基羰基、吡啶甲基、苯基羟烷基、烷基磺酰基或烷氧羰基烷基羰基、可被烷基取代的香豆素基；喹啉基；金刚烷基；降冰片基；或四氢萘基；以及 W 是氢；羟基；羧基；氨基羰基；烷基；烷氧基羰基；苯基；可被二烷基氨基取代的苯基烷基；或可被烷氧基羰基取代的苯基羰基；或四氢喹啉基；以及或其药学上可接受的盐。这种赖氨酸衍生物是有效的蛋白酶抑制剂。
• OKADA, YOSHIO;TSUDA, YUKO;TENO, NAOKI;WANAKA, KEIKO;BOHGAKI, MIYAKO;HIJIK+, CHEM. AND PHARM. BULL., 36,(1988) N 4, 1289-1297
  作者：OKADA, YOSHIO、TSUDA, YUKO、TENO, NAOKI、WANAKA, KEIKO、BOHGAKI, MIYAKO、HIJIK+

  DOI：——

  日期：——
• Synthesis of active center-directed peptide inhibitors of plasmin.
  作者：YOSHIO OKADA、YUKO TSUDA、NAOKI TENO、KEIKO WANAKA、MIYAKO BOHGAKI、AKIKO HIJIKATA-OKUNOMIYA、TAKETOSHI NAITO、SHOSUKE OKAMOTO

  DOI：10.1248/cpb.36.1289

  日期：——

  Active center-directed peptide inhibitors of plasmin were designed based on the structure of specific substrates of plasmin and synthesized by a conventional solution method. Their effects on plasmin were examined and the structure-activity relationship was studied. D-Ile-Phe-Lys-BZA (4-benzoylanilide) inhibited plasmin activities toward S-2251 and fibrin (IC50 : 0.069mM and 0.18mM respectively) but D-Ile-Phe-Lys-BPP (4-benzylpiperidine amide) was not inhibitory. However D-Ile-Phe-Lys-BZA was cleaved by plasmin to release benzoylaniline, indicating that this type of peptide inhibitor is not stable to plasmin. It was found that Tos-Lys-pNA was not cleaved by palsmin and inhibited plasmin activity toward not only fibrin but also amall peptide substrates and fibrinogen by blocking the active center of plasmin with some selectivity. In order to obtain potent and stable inhibitors of plasmin, it is recommended to design them with reference to the structures of Tos-Lys-pNA and the specific substrate, D-Ile-Phe-Lys-pNA.

  活性中心导向的纤溶酶肽抑制剂是基于纤溶酶特定底物的结构设计的，并通过常规溶液法合成。对其对纤溶酶的作用进行了研究，并考察了结构-活性关系。D-Ile-Phe-Lys-BZA（4-苯甲酰阿尼林）抑制了纤溶酶对S-2251和纤维蛋白的活性（IC50：分别为0.069mM和0.18mM），但D-Ile-Phe-Lys-BPP（4-苯基哌啶酰胺）没有抑制作用。然而，D-Ile-Phe-Lys-BZA被纤溶酶降解，释放出苯甲酰苯胺，表明这种类型的肽抑制剂对纤溶酶并不稳定。研究发现，Tos-Lys-pNA没有被纤溶酶降解，并且抑制了纤溶酶对纤维蛋白、小肽底物和纤维蛋白原的活性，通过选择性地阻断纤溶酶的活性中心。为了获得有效且稳定的纤溶酶抑制剂，建议以Tos-Lys-pNA和特定底物D-Ile-Phe-Lys-pNA的结构为参考进行设计。