N-t-Boc-L-Phe-L-His(N^α-Me)-OH | 112228-27-0

• 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)-OH
• 英文别名: Boc-Phe-N(Me)His-OH；(2S)-3-(1H-imidazol-5-yl)-2-[methyl-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoic acid
• CAS: 112228-27-0
• 化学式: C₂₁H₂₈N₄O₅
• 分子量: 416.477
• InChiKey: BJKSHZPLLOIDEH-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  125
• 氢给体数：
  3
• 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)-OH 、 [2-[[(2S)-1-[[(2S)-1-amino-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]-3-methylbutyl]-[(1R)-1-amino-3-methylbutyl]phosphinic acid 以7%的产率得到
  参考文献：
  名称：

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

  摘要：

  DOI：
• 作为产物：
  描述：

  N-t-Boc-L-Phe-L-His(N^α-Me)-OMe 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以54%的产率得到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

文献信息

• Peptidartige Aminosäurederivate
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0310918A2

  公开（公告）日：1989-04-12

  Verbindung der Formel worin R1, R2, R3, R4 und A die in Anspruch 1 angegebene Bedeutung haben, sowie pharmazeutisch verwendbare Salze davon besitzen Renin-inhibierende Eigenschaften und können demnach in Form pharmazeutischer Präparate als Arzneimittel verwendet werden. Sie können nach an sich bekannten Methoden hergestellt werden.

  式中的化合物 其中 R1、R2、R3、R4 和 A 具有权利要求 1 中给出的含义，其药用盐具有抑制肾素的特性，因此可以以药物制剂的形式用作药物。它们可以通过本身已知的方法制备。
• Renin inhibiting dipeptides, their preparation and compositions containing them
  申请人：GLAXO GROUP LIMITED

  公开号：EP0320204A2

  公开（公告）日：1989-06-14

  There are described new compounds of formula (1) wherein R¹ represents an acyl group; X¹ represents phenylalanine or p-methoxyphenyl­alanine bonded N-terminally to R¹ and C-terminally to X²; X² represents histidine or N-methylhistidine bonded N-terminally to X¹ and C-terminally to the group -NH-; R² represents a C₄₋₆ cycloalkyl group; R³ represents a group CHR⁶R⁷ (where R⁶ is a hydrogen atom or a hydroxyl group and R⁷ is a pyridinyl ring); X³ represents a C₂₋₆ alkylene chain optionally substituted by one or more C₁₋₄ alkyl groups; R⁴ and R⁵, which may be the same or different, each independently represent a hydrogen atom or a C₁₋₄ alkyl group, or NR⁴R⁵ may form a 5- or 6- membered polymethylenimine ring; and salts and solvates thereof. The new compounds have been found to exhibit activity as renin inhibitors, combining good duration of action with significant oral potency. Compositions containing the compounds of formula (1) and processes for preparing the compounds are also described.

  所述新化合物为式(1) 其中 R¹ 代表酰基 X¹ 代表苯丙氨酸或对甲氧基苯丙氨酸，N-端与 R¹ 键合，C-端与 X² 键合； X² 代表组氨酸或 N-甲基组氨酸，其 N 端与 X¹ 键合，C 端与基团 -NH- 键合； R² 代表 C₄₋₆环烷基； R³ 代表基团 CHR⁶R⁷（其中 R⁶ 是氢原子或羟基，R⁷ 是吡啶基环）； X³ 代表任选被一个或多个 C₁₋₄ 烷基取代的 C₂₋₆ 亚烷基链； R⁴和R⁵可以相同或不同，各自独立地代表一个氢原子或一个C₁₋₄烷基，或者NR⁴R⁵可以形成一个5-或6-成员的聚亚甲基亚胺环； 及其盐和溶剂。 研究发现，这些新化合物具有肾素抑制剂的活性，同时具有良好的作用持续时间和显著的口服效力。 此外，还描述了含有式（1）化合物的组合物以及制备这些化合物的工艺。
• 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：——
• US5250517A
  申请人：——

  公开号：US5250517A

  公开（公告）日：1993-10-05
• 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.