N^α-(tert-butyloxycarbonyl)-N^α-methyl-N^im-tosyl-L-histidine | 103372-35-6

• 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: N^α-(tert-butyloxycarbonyl)-N^α-methyl-N^im-tosyl-L-histidine
• 英文别名: Boc-N(Me)His(1-Tos)-OH；(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-[1-(4-methylphenyl)sulfonylimidazol-4-yl]propanoic acid
• CAS: 103372-35-6
• 化学式: C₁₉H₂₅N₃O₆S
• 分子量: 423.49
• InChiKey: IIQNJQPKUVYPMV-INIZCTEOSA-N

物化性质

• 沸点：
  615.2±65.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N^α-(tert-butyloxycarbonyl)-N^α-methyl-N^im-tosyl-L-histidine 在 diethylphosphoryl cyanide 、 氰基磷酸二乙酯 、 1-羟基苯并三唑 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 地替吉仑
  参考文献：
  名称：

  设计和合成具有延长的体内作用时间的有效的特异性肾素抑制剂。

  摘要：

  对含有主链Cα-甲基和Nα-甲基修饰的肽进行结构活性分析导致发现了具有高代谢稳定性的有效肾素抑制剂。在体外，Boc-Pro-Phe-Nα-MeHis-Leupsi- [CHOHCH2] Val-Ile-Amp（XII）是人血浆肾素的有效抑制剂，IC50为0.26 nM。它是其他天冬氨酸蛋白酶（如猪胃蛋白酶或牛组织蛋白酶D）的弱得多的抑制剂（IC50 = 6 microM）。已表明它不会被大鼠肝匀浆制剂降解。在体内，它抑制了血浆血浆肾素的活性并降低了呋塞米治疗的食蟹猴的血压。静脉注射5 mg / kg时，明显的降压反应持续3个小时以上。

  DOI：

  10.1021/jm00160a049
• 作为产物：
  描述：

  N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以72%的产率得到N^α-(tert-butyloxycarbonyl)-N^α-methyl-N^im-tosyl-L-histidine
  参考文献：
  名称：

  设计和合成具有延长的体内作用时间的有效的特异性肾素抑制剂。

  摘要：

  对含有主链Cα-甲基和Nα-甲基修饰的肽进行结构活性分析导致发现了具有高代谢稳定性的有效肾素抑制剂。在体外，Boc-Pro-Phe-Nα-MeHis-Leupsi- [CHOHCH2] Val-Ile-Amp（XII）是人血浆肾素的有效抑制剂，IC50为0.26 nM。它是其他天冬氨酸蛋白酶（如猪胃蛋白酶或牛组织蛋白酶D）的弱得多的抑制剂（IC50 = 6 microM）。已表明它不会被大鼠肝匀浆制剂降解。在体内，它抑制了血浆血浆肾素的活性并降低了呋塞米治疗的食蟹猴的血压。静脉注射5 mg / kg时，明显的降压反应持续3个小时以上。

  DOI：

  10.1021/jm00160a049

文献信息

• Renin inhibitors. Dipeptide analogs of angiotensinogen utilizing a structurally modified phenylalanine residue to impart proteolytic stability
  作者：Jacob J. Plattner、Patrick A. Marcotte、Hollis D. Kleinert、Herman H. Stein、Jonathan Greer、Giorgio Bolis、Anthony K. L. Fung、Barbara A. Bopp、Jay R. Luly

  DOI：10.1021/jm00120a006

  日期：1988.12

  A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine residue, compounds with varying degrees of renin inhibitory potency and chymotrypsin susceptibility were obtained. Selected analogues from this group were examined in vivo for both their hypotensive effects and metabolic patterns.
• The effects of N-methylation on the enantioselectivity of catalysis by cyclo[(R)-His-(R)-Phe]
  作者：Jason C. Thoen、Mark A. Lipton

  DOI：10.1016/s0957-4166(97)00573-9

  日期：1997.12

  The cyclic dipeptide cyclo[(R)-His-(R)-Phe] 1 has been known since 1981 to catalyze the enantioselective formation of cyanohydrins from aldehydes and HCN. Although 1 has proved to be very effective in the production of optically active cyanohydrins, the precise structure of its catalytically active form remains unresolved. Two derivatives, in which the two amides in 1 were independently N-methylated, were synthesized as probes of the structural and functional requirements for catalysis by 1. Both derivatives were far more soluble in organic solvents and were found to catalyze the formation of racemic cyanohydrin, but differed greatly in their turnover rates. Mixtures of the two derivatives with each other and with 1 were also examined as hydrocyanation catalysts. Only the mixtures containing 1 demonstrated any enantioselectivity, but did not appear any more competent as catalysts than reduced quantities of 1. From these data, it is concluded that both amide bonds are essential for effective catalysis by 1, but that the amide containing the His N-alpha appears to be involved in interactions with the substrate while the other amide plays a structural role, possibly for self-associative hydrogen bonding. (C) 1997 Published by Elsevier Science Ltd. All rights reserved.
• Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo
  作者：Suvit Thaisrivongs、Donald T. Pals、Douglas W. Harris、Warren M. Kati、Steve R. Turner

  DOI：10.1021/jm00160a049

  日期：1986.10

  A structure-activity analysis of peptides containing backbone C alpha-methyl and N alpha-methyl modifications led to the discovery of potent renin inhibitors with high metabolic stability. In vitro, Boc-Pro-Phe-N alpha-MeHis-Leu psi-[CHOHCH2]Val-Ile-Amp (XII) is a potent inhibitor of human plasma renin with IC50 of 0.26 nM. It is a much weaker inhibitor of other aspartic proteases such as porcine pepsin

  对含有主链Cα-甲基和Nα-甲基修饰的肽进行结构活性分析导致发现了具有高代谢稳定性的有效肾素抑制剂。在体外，Boc-Pro-Phe-Nα-MeHis-Leupsi- [CHOHCH2] Val-Ile-Amp（XII）是人血浆肾素的有效抑制剂，IC50为0.26 nM。它是其他天冬氨酸蛋白酶（如猪胃蛋白酶或牛组织蛋白酶D）的弱得多的抑制剂（IC50 = 6 microM）。已表明它不会被大鼠肝匀浆制剂降解。在体内，它抑制了血浆血浆肾素的活性并降低了呋塞米治疗的食蟹猴的血压。静脉注射5 mg / kg时，明显的降压反应持续3个小时以上。