(2S)-N4-hydroxy-N1-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-isobutylsuccinamide | 142880-37-3

• 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: (2S)-N4-hydroxy-N1-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-isobutylsuccinamide
• 英文别名: (S)-N*4*-Hydroxy-N*1*-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide；(2S)-N'-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
• CAS: 142880-37-3
• 化学式: C₂₀H₂₈N₄O₄
• 分子量: 388.467
• InChiKey: NITYDPDXAAFEIT-GUYCJALGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  123
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-L-色氨酸 在 盐酸 、 氢氧化钾 、 盐酸羟胺 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 32.0h， 生成 (2S)-N4-hydroxy-N1-[(1S)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxoethyl]-2-isobutylsuccinamide
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study

  摘要：

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

  DOI：

  10.1021/jm970494j

文献信息

• REMEDIES FOR DISEASES DUE TO STENOTIC LESIONS OF BLOOD VESSEL
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1275385A1

  公开（公告）日：2003-01-15

  An agent for treating and/or preventing diseases due to a constrictive vascular lesion, which comprises, as an active ingredient, a hydroxamic acid derivative represented by formula (I): (wherein R1 represents a hydrogen atom, C1-8 alkyl, or C1-8 alkyl substituted with -OR2; and R2 represents a hydrogen atom, C1-8 alkyl, benzyl, or C1-8 alkyl substituted with C1-8 alkoxy) having a matrix metalloproteinase inhibitory activity, or a nontoxic salt thereof.

  一种用于治疗和/或预防因血管收缩性病变引起的疾病的制剂，其活性成分包括由式(I)代表的羟肟酸衍生物： (其中 R1 代表氢原子、C1-8 烷基或被 -OR2 取代的 C1-8 烷基；R2 代表氢原子、C1-8 烷基、苄基或被 C1-8 烷氧基取代的 C1-8 烷基）具有基质金属蛋白酶抑制活性，或其无毒盐。
• Remedies for diseases due to stenotic lesions of blood vessel
  申请人：——

  公开号：US20040068015A1

  公开（公告）日：2004-04-08

  An agent for treating and/or preventing diseases due to a constrictive vascular lesion, which comprises, as an active ingredient, a hydroxamic acid derivative represented by formula (I): 1 (wherein R 1 represents a hydrogen atom, C1-8 alkyl, or C1-8 alkyl substituted with —OR 2 ; and R 2 represents a hydrogen atom, C1-8 alkyl, benzyl, or C1-8 alkyl substituted with C1-8 alkoxy) having a matrix metalloproteinase inhibitory activity, or a nontoxic salt thereof.

  一种用于治疗和/或预防因血管收缩病变引起的疾病的制剂，其活性成分包括由式 (I) 所代表的羟肟酸衍生物： 1 (其中 R 1 代表氢原子、C1-8 烷基或被 -OR 取代的 C1-8 烷基 2 和 R 2 代表氢原子、C1-8 烷基、苄基或被 C1-8 烷氧基取代的 C1-8 烷基）具有基质金属蛋白酶抑制活性，或其无毒盐。
• REGULATION OF DIFFERENTIATION INTO DOPAMINERGIC NEURONS BY METALLOPROTEASE
  申请人：Korea University Research and Business Foundation

  公开号：US20160040126A1

  公开（公告）日：2016-02-11

  The present invention relates to a method for regulating the differentiation of neural stem cells or neural progenitor cells into dopaminergic neural cells, the method comprising increasing or inhibiting the activity of ADAM17 and/or ADAM10 in neural stem cells or neural progenitor cells, and to the use of an activator or inhibitor of ADMA17 and/or ADAM10. The method and composition according to the invention can regulate the activity of ADAM17 and/or ADAM10 in neural stem cells or neural progenitor cells to increase dopaminergic neural cells in the midbrain area, and thereby providing the effect of treating diseases induced by the death of dopaminergic neural cells such as Parkinson's disease. In addition, the method and composition according to the invention can inhibit the activity of ADAM17 and/or ADAM10, and thereby improving effect of treating diseases such as tumor. Thus, the present invention is very useful.
• Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study
  作者：Daniel E. Levy、France Lapierre、Weisheng Liang、Wenqing Ye、Christopher W. Lange、Xiaoyuan Li、Damian Grobelny、Marie Casabonne、David Tyrrell、Kevin Holme、Alex Nadzan、Richard E. Galardy

  DOI：10.1021/jm970494j

  日期：1998.1.1

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.