N-t-Boc-L-Phe-L-His(N^α-Me)-OMe | 105137-29-9

• 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: N-t-Boc-L-Phe-L-His(N^α-Me)-OMe
• 英文别名: Boc-Phe-N(Me)His-OMe；methyl (2S)-3-(1H-imidazol-5-yl)-2-[methyl-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoate
• CAS: 105137-29-9
• 化学式: C₂₂H₃₀N₄O₅
• 分子量: 430.504
• InChiKey: HCVIBJJCQOBKTB-ROUUACIJSA-N

物化性质

• 沸点：
  658.2±55.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-t-Boc-L-Phe-L-His(N^α-Me)-OMe 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 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 41.0h， 生成 2(R,S)-<α-methyl)>amino>-3-methylbutyl>phosphinyl>methyl>-3-methylbutanoyl-L-isoleucyl-L-histidine amide
  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：

  BOC-L-苯丙氨酸 、 N-甲基-L-组氨酸甲酯单盐酸盐 在 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 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 以60%的产率得到N-t-Boc-L-Phe-L-His(N^α-Me)-OMe
  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

• Novel amino acid derivatives possessing renin-inhibitory activities
  申请人：Japan Tobacco Inc.

  公开号：EP0396065A1

  公开（公告）日：1990-11-07

  An amino acid derivative of the general formula: wherein R1 is wherein, R10 is a lower alkyl group and R" is (wherein R111 is a lower alkyl group and n is an integer of 1 to 5) or a lower alkyl group which may be substituted by hydroxy group or methoxyethoxymethoxy group, or R'° and R" are combinedly together with the adjacent nitrogen atom; R12 is a hydrogen atom, CnH2n+1-O-CO- (n is as defined above) or R'3 is a lower alkyl group which may be substituted by substituent(s) selected from HOOC-(H2C)n-O-, R12- NH- (n and R12 are as defined above) and pyridyl group; X is -CH2-, -O- or -NH- and Y is -O- or -NH-; wherein (wherein Z is -0-, -S-, -S(O)-. -S(O)2-, -CH2-, -CH(OH)-, or and a and b are independently an integer of 1 to 4 and the total of a and b is not more than 5) ; R2 is an aralkyl group which may be substituted by lower alkyl group(s); R3 is a hydrogen atom or a lower alkyl group; R4 is a lower alkyl group; and A is hydroxy group and B is a hydrogen atom, or A and B are carbonyl group combinedly together with the adjacent carbon atom, a pharmaceutically acceptable acid addition salt or an ester thereof is described. The compounds of the invention possess inhibitory activities against renin and are useful as an antihypertensive agent.

  通用公式的氨基酸衍生物： 其中R1为 其中，R10为较低的烷基基团，R"为 （其中R111为较低的烷基基团，n为1至5的整数）或者可以被羟基或甲氧乙氧甲氧基取代的较低烷基基团，或者R'°和R"与相邻的氮原子 结合在一起； R12为氢原子，CnH2n+1-O-CO-（n如上定义）或者 R'3为可以被HOOC-(H2C)n-O-、R12-NH-（n和R12如上定义）和吡啶基取代的较低烷基基团； X为-CH2-、-O-或-NH-，Y为-O-或-NH-；其中 （其中Z为-0-、-S-、-S(O)-、-S(O)2-、-CH2-、-CH(OH)-， 或 a和b分别独立为1至4的整数，且a和b的总和不超过5）； R2为可以被较低烷基基团取代的芳基烷基基团； R3为氢原子或较低烷基基团； R4为较低烷基基团； A为羟基，B为氢原子，或者A和B与相邻的碳原子结合在一起，描述了一种药学上可接受的酸盐或其酯。本发明的化合物具有对肾素的抑制活性，并可用作降压药。
• 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：——
• 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.