2-amino-N-(cyanomethyl)-4-methylpentanamide | 45012-57-5

• 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: 2-amino-N-(cyanomethyl)-4-methylpentanamide
• 英文别名: Leu-Gly-nitril
• CAS: 45012-57-5
• 化学式: C₈H₁₅N₃O
• 分子量: 169.227
• InChiKey: GQHJCLXWRQHKPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-N-(cyanomethyl)-4-methylpentanamide 在 copper(l) chloride 作用下， 以 甲醇 为溶剂， 生成 5-amino-3-isobutyl-3,6-dihydropyrazin-2(1H)-one hydrochloride
  参考文献：
  名称：

  (+)-Cinereain 和 (−)-Janoxepin 通过片段偶联/Retro-Claisen 重排级联的全合成

  摘要：

  (+)-cinereain 和 (-)-janoxepin 的全合成，这两种真菌环三肽具有复杂的杂环核心和有趣的植物毒性和抗疟活性，已经以高度收敛的方式实现。在关键步骤中，由片段偶联（环缩合）引发的单锅级联随后是自发的逆克莱森重排，得到 2,5-二氢氧杂庚啶融合杂三环产物。

  DOI：

  10.1002/anie.202212855
• 作为产物：
  描述：

  Boc-DL-Leu-OH 在 N-甲基吗啉 、 水 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 18.25h， 生成 2-amino-N-(cyanomethyl)-4-methylpentanamide
  参考文献：
  名称：

  (+)-Cinereain 和 (−)-Janoxepin 通过片段偶联/Retro-Claisen 重排级联的全合成

  摘要：

  (+)-cinereain 和 (-)-janoxepin 的全合成，这两种真菌环三肽具有复杂的杂环核心和有趣的植物毒性和抗疟活性，已经以高度收敛的方式实现。在关键步骤中，由片段偶联（环缩合）引发的单锅级联随后是自发的逆克莱森重排，得到 2,5-二氢氧杂庚啶融合杂三环产物。

  DOI：

  10.1002/anie.202212855

文献信息

• Studies on Hepatic Agents. I. Synthesis of Aminoacyl (and Hydroxyacyl) Aminoacetonitriles
  作者：SEIGO SUZUE、TUTOMU IRIKURA

  DOI：10.1248/cpb.16.1417

  日期：——

  For the purpose of elucidating the structural relationship between lathyrism and inhibition of necrosis induced by CCl4 in the liver of the rat, many compounds related to aminoacetonitrile were synthesized. N-Aminoacylaminoacetonitriles (VIII, XIV) were synthesized from phthaloylaminoacylaminoacetonitriles. VIII were converted to 2-hydroxyimino-5-oxopiperazine derivatives (XV) and 5-oxo-2-thio-piperazines (XX). Preparations of N-(N-acylaminoacyl) aminoacetonitriles were also described. Further, N-α-hydroxyacylaminoacetonitriles were prepared from chloralides of α-hydroxyacids with aminoacetonitrile. In addition, XV (R=H) was converted to 2-acetamino-5-acetoxypyrazine by treatment with acetic anhydride.

  为了阐明贻贝症与四氯化碳诱导的大鼠肝脏坏死抑制之间的结构关系，合成了许多与氨基乙腈相关的化合物。N-氨基酰氨基乙腈（VIII，XIV）是从邻苯二甲酰氨基酰氨基乙腈合成的。VIII被转化为2-羟基亚胺-5-氧杂哌嗪衍生物（XV）和5-氧-2-硫杂哌嗪（XX）。还描述了N-(N-酰氨基酰)氨基乙腈的制备。此外，N-α-羟基酰氨基乙腈是由α-羟基酸的氯化物与氨基乙腈反应制备的。此外，通过用醋酸无水物处理，XV（R=H）被转化为2-乙酰氨基-5-乙酰氧基吡唑。
• Novel compounds and compositions as protease inhibitors
  申请人：AXYS PHARMACEUTICALS, INC.

  公开号：US20020086996A1

  公开（公告）日：2002-07-04

  The present invention relates to novel N-cyanomethyl amides which are cysteine protease inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

  本发明涉及一种新颖的N-氰甲基酰胺，它们是半胱氨酸蛋白酶抑制剂，以及它们的药用盐和N-氧化物，它们作为治疗剂的用途以及它们的制备方法。
• Dipeptide derivatives
  申请人：——

  公开号：US20040110806A1

  公开（公告）日：2004-06-10

  N-terminal substituted dipeptide nitriles as defined are useful as inhibitors of cysteine cathepsins, e.g. cathepsins B, K, L and S, and can be used for the treatment of cysteine cathepsin dependent diseases and conditions, including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis, tumors (especially tumor invasion and tumor metastasis), coronary disease, atherosclerosis (including atherosclerotic plaque rupture and destabilization). Particular dipeptide nitriles are compounds of formula I, or physiologically-acceptable and -cleavable esters or a salts thereof 1 wherein: the symbols are as defined. In particular it has been found that by appropriate choice of groups R, R 2 , R 3 , R 4 , R 5 , X 1 , Y and L, the relative selectivity of the compounds as inhibitors of the various cysteine cathepsin types, e.g. cathepsins B, K, L and S may be altered, e.g. to obtain inhibitors which selectively inhibit a particular cathepsin type or combination of cathepsin types.

  N-末端取代的二肽硝基化合物可作为半胱氨酸蛋白酶的抑制剂，例如半胱氨酸蛋白酶B、K、L和S，并可用于治疗半胱氨酸蛋白酶依赖性疾病和病况，包括炎症、类风湿性关节炎、骨关节炎、骨质疏松症、肿瘤（尤其是肿瘤侵袭和转移）、冠心病、动脉粥样硬化（包括动脉粥样硬化斑块破裂和不稳定性）。特定的二肽硝基化合物是公式I的化合物，或其生理上可接受和可分解酯或其盐，其中：符号的定义如上所述。特别是，通过适当选择R、R2、R3、R4、R5、X1、Y和L基团，可以改变化合物作为不同半胱氨酸蛋白酶类型的抑制剂的相对选择性，例如获得选择性抑制特定半胱氨酸蛋白酶类型或半胱氨酸蛋白酶类型组合的抑制剂。
• Cyanomethyl derivatives as cysteine protease inhibitors
  申请人：Graupe Michael

  公开号：US20060122184A1

  公开（公告）日：2006-06-08

  The present invention is directed to cyanomethyl derivatives that are inhibitors of cysteine protease, in particular, cathepsin B, K, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

  本发明涉及氰甲基衍生物，其是半胱氨酸蛋白酶的抑制剂，特别是对于B、K、F和S型的卡特普辛，因此可用于治疗由这些蛋白酶介导的疾病。本发明还涉及包含这些化合物的制药组合物和其制备过程。
• Dipeptide nitriles
  申请人：——

  公开号：US20040029814A1

  公开（公告）日：2004-02-12

  N-terminal substituted dipeptide nitrites as defined are useful as inhibitors of cysteine cathepsins, e.g. cathepsins B, K, L and S, and can be used for the treatment of cysteine cathepsin dependent diseases and conditions, including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis, tumors (especially tumor invasion and tumor metastasis), coronary disease, atherosclerosis (including atherosclerotic plaque rupture and destabilization). Particular dipeptide nitrites are compounds of formula I, or physiologically-acceptable and -cleavable esters or a salts thereof 1 wherein: the symbols are as defined. In particular it has been found that by appropriate choice of groups R, R 2 , R 3 , R 4 , R 5 , X 1 , Y and L, the relative selectivity of the compounds as inhibitors of the various cysteine cathepsin types, e.g. cathepsins B, K, L and S may be altered, e.g. to obtain inhibitors which selectively inhibit a particular cathepsin type or combination of cathepsin types.

  N-末端取代二肽硝酸盐可作为半胱氨酸蛋白酶的抑制剂，例如半胱氨酸蛋白酶B、K、L和S，并可用于治疗半胱氨酸蛋白酶依赖性疾病和病况，包括炎症、类风湿性关节炎、骨关节炎、骨质疏松症、肿瘤（尤其是肿瘤侵袭和转移）、冠心病、动脉粥样硬化（包括动脉粥样硬化斑块破裂和不稳定）。特定的二肽硝酸盐是化合物I的化合物，或其生理可接受和可分解的酯或盐。其中：符号如定义。特别是通过适当选择R、R2、R3、R4、R5、X1、Y和L的基团，可以改变化合物作为各种半胱氨酸蛋白酶类型的抑制剂的相对选择性，例如半胱氨酸蛋白酶B、K、L和S，以获得选择性抑制特定半胱氨酸蛋白酶类型或半胱氨酸蛋白酶类型组合的抑制剂。