2-amino>-3-methylbutyl>phosphinyl>acetic acid methyl ester | 120609-57-6

• 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: 2-amino>-3-methylbutyl>phosphinyl>acetic acid methyl ester
• 英文别名: 2-[hydroxy(1(R)-{N-[(benzyloxycarbonyl)-(3S,4S)-statyl-L-alanyl]amino}-3-methylbutyl)phosphinyl]acetic acid methyl ester；[(1R)-1-[[(2S)-2-[[(3S,4S)-3-hydroxy-6-methyl-4-(phenylmethoxycarbonylamino)heptanoyl]amino]propanoyl]amino]-3-methylbutyl]-(2-methoxy-2-oxoethyl)phosphinic acid
• CAS: 120609-57-6
• 化学式: C₂₇H₄₄N₃O₉P
• 分子量: 585.635
• InChiKey: AIEAGDFQOOOLNG-NRTAZHGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  40.0
• 可旋转键数：
  16.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  180.36
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  2-amino>-3-methylbutyl>phosphinyl>acetic acid methyl ester 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、110.31 kPa 条件下， 反应 41.0h， 生成 2-amino>-3-methylbutyl>phosphinyl>acetic acid methyl ester
  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：

  methyl 2-phosphinyl>acetate 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、110.31 kPa 条件下， 反应 82.0h， 生成 2-amino>-3-methylbutyl>phosphinyl>acetic acid methyl ester
  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

文献信息

• ALLEN, MARK C.;FUHRER, WALTER;TUCK, BRIAN;WADE, ROY;WOOD, JEANETTE M., J. MED. CHEM., 32,(1989) N, C. 1652-1661
  作者：ALLEN, MARK C.、FUHRER, WALTER、TUCK, BRIAN、WADE, ROY、WOOD, JEANETTE M.

  DOI：——

  日期：——