N-甲基-L-组氨酸甲酯单盐酸盐 | 118384-75-1

• 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
• 中文名称: N-甲基-L-组氨酸甲酯单盐酸盐
• 英文名称: Nα-methyl-L-histidine methyl ester dihydrochloride
• 英文别名: (S)-N-methylhistidine methylester dihydrochloride；H-His(N^α-Me)-OMe*2HCl；N-Methyl-L-Histidine methyl ester dihydrochloride；N-Me-His-Ome HCl；methyl (2S)-3-(1H-imidazol-5-yl)-2-(methylamino)propanoate;hydrochloride
• CAS: 118384-75-1
• 化学式: C₈H₁₃N₃O₂*2ClH
• 分子量: 256.132
• InChiKey: WMEMVRNBUHETIW-FJXQXJEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.13
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-甲基-L-组氨酸甲酯单盐酸盐 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 生成 N-t-Boc-L-Phe-L-His(N^α-Me)-OH
  参考文献：
  名称：

  Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bond

  摘要：

  The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Replacement of the scissile bond with the phosphinic analogue of Leu10-Val11 (1b) gave the most potent inhibitors, having IC50 = 7.5 x 10(-8) M for H-Pro-His-Pro-Phe-His-(1b)-Ile-His-Lys-OH and IC50 = 1.0 x 10(-7) M for Z-Arg-Arg-Pro-Phe-His-(1b)-Ile-His-NH2. The shorter phosphonic acid sequence Z-Pro-Phe-His-(1d) retained biological activity with an IC50 = 6.4 x 10(-6) M.

  DOI：

  10.1021/jm00127a041
• 作为产物：
  描述：

  N-甲基-L-组氨酸 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 N-甲基-L-组氨酸甲酯单盐酸盐
  参考文献：
  名称：

  Renin inhibitors containing statine or derivatives thereof

  摘要：

  本发明揭示了一系列包含statine或其衍生物（例如，aminostatine，cyclostatine）的新型肽和多肽衍生物，用于抑制酶肾素的血管紧张素原裂解作用。特别感兴趣的是具有N-末端序列-Pro-Phe-His-Sta-Lys的化合物，其中末端脯氨酸氮原子与氨基保护酰基团结合，或具有N-末端序列-R-Phe-His-Sta-Lys-的化合物，其中R代表氨基保护酰基团。

  公开号：

  US04749687A1

文献信息

• Novel 5-amino-4-hydroxyvaleryl derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US04727060A1

  公开（公告）日：1988-02-23

  Compounds of the formula ##STR1## in which R.sub.1 represents hydrogen or acyl, A represents an optionally N-alkylated .alpha.-amino acid residue which is bonded N-terminally to R.sub.1 and C-terminally to the group --NR.sub.2 --, R.sub.2 represents hydrogen or lower alkyl, R.sub.3 represents hydrogen, lower alkyl, optionally etherified or esterified hydroxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl-lower alkyl, tricycloalkyl-lower alkyl, aryl or aryl-lower alkyl, R.sub.4 represents hydroxy or etherified or esterified hydroxy, R.sub.5 represents lower alkyl having 2 or more carbon atoms, optionally etherified or esterified hydroxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, tricycloalkyl, tricycloalkyl-lower alkyl, aryl, aryl-lower alkyl, optionally substituted carbamoyl, optionally substituted amino, optionally substituted hydroxy or optionally substituted mercapto and R.sub.6 represents substituted amino, and salts of such compounds having salt-forming groups inhibit the blood pressure-increasing action of the enzyme renin and can be used as antihypertensives.

  式为##STR1##的化合物，其中R.sub.1代表氢或酰基，A代表一个可选的N-烷基化的α-氨基酸残基，其N-末端与R.sub.1和C-末端与--NR.sub.2--基团连接，R.sub.2代表氢或较低的烷基，R.sub.3代表氢、较低烷基、可选地醚化或酯化的羟基较低烷基、环烷基、环烷基较低烷基、双环烷基较低烷基、三环烷基较低烷基、芳基或芳基较低烷基，R.sub.4代表羟基或醚化或酯化的羟基，R.sub.5代表具有2个或更多碳原子的较低烷基、可选地醚化或酯化的羟基较低烷基、环烷基、环烷基较低烷基、双环烷基、双环烷基较低烷基、三环烷基、三环烷基较低烷基、芳基、芳基较低烷基、可选地取代的氨基甲酰基、可选地取代的氨基、可选地取代的羟基或可选地取代的巯基，R.sub.6代表取代的氨基，以及具有形成盐的基团的这类化合物的盐，抑制肾素酶增加血压的作用，可用作降压药。
• Studies on cyclic dipeptides, II. Methylated modifications ofcyclo-[Phe-His]
  作者：C. R. Noe、A. Weigand、S. Pirker、P. Liepert

  DOI：10.1007/bf00807896

  日期：1997.3

  Synthesis of seven new cyclic dipeptides and their conformational analysis based on H-1 NMR spectra is reported as well as their application as models to elucidate the mechanism of cyclic dipeptide catalysis in enantioselective mandelonitrile formation. Further evidence is presented to support the view that a highly ordered supramolecular complex of dipeptides acts as catalyst.
• Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bond
  作者：Mark C. Allen、Walter Fuhrer、Brian Tuck、Roy Wade、Jeanette M. Wood

  DOI：10.1021/jm00127a041

  日期：1989.7

  The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Replacement of the scissile bond with the phosphinic analogue of Leu10-Val11 (1b) gave the most potent inhibitors, having IC50 = 7.5 x 10(-8) M for H-Pro-His-Pro-Phe-His-(1b)-Ile-His-Lys-OH and IC50 = 1.0 x 10(-7) M for Z-Arg-Arg-Pro-Phe-His-(1b)-Ile-His-NH2. The shorter phosphonic acid sequence Z-Pro-Phe-His-(1d) retained biological activity with an IC50 = 6.4 x 10(-6) M.
• Renin inhibitors containing statine or derivatives thereof
  申请人：Pfizer Inc.

  公开号：US04749687A1

  公开（公告）日：1988-06-07

  A series of novel peptide and polypeptide derivatives containing statine or derivatives thereof (e.g., aminostatine, cyclostatine) are disclosed that are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin. Of particular interest are compounds possessing the N-terminal sequence -Pro-Phe-His-Sta-Lys with the terminal proline nitrogen bonded to an amino-protecting acyl moiety or compounds possessing the N-terminal sequence -R-Phe-His-Sta-Lys- wherein R represents an amino protecting acyl group.

  本发明揭示了一系列包含statine或其衍生物（例如，aminostatine，cyclostatine）的新型肽和多肽衍生物，用于抑制酶肾素的血管紧张素原裂解作用。特别感兴趣的是具有N-末端序列-Pro-Phe-His-Sta-Lys的化合物，其中末端脯氨酸氮原子与氨基保护酰基团结合，或具有N-末端序列-R-Phe-His-Sta-Lys-的化合物，其中R代表氨基保护酰基团。