N^α,N^im-ditritylhistidine | 74853-62-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N^α,N^im-ditritylhistidine
• 英文别名: Trt-His(Trt)-OH；(2S)-2-(tritylamino)-3-(1-tritylimidazol-4-yl)propanoic acid
• CAS: 74853-62-6
• 化学式: C₄₄H₃₇N₃O₂
• 分子量: 639.797
• InChiKey: FFVVHORODDZQPF-RWYGWLOXSA-N

物化性质

• 沸点：
  773.7±60.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N^α,N^im-ditritylhistidine 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 (2S,4S,5S)-5-[(S)-2-[(S)-2-Benzyl-3-(2-methyl-propane-2-sulfonyl)-propionylamino]-3-(1H-imidazol-4-yl)-propionylamino]-6-cyclohexyl-4-hydroxy-2-isopropyl-hexanoic acid butylamide
  参考文献：
  名称：

  Synthesis and biological activity of some transition-state inhibitors of human renin

  摘要：

  A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu (OH)/Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (CHa /(OH)/Val) was prepared. A structure-activity study with Boc-Phe-His-Leu (OH)/Val-Ile-His-NH2 (8a) as starting material led to N-[(2S)-2-[(tert-butylsulfonyl)methyl]-3-phenylpropionyl]-His-Cha (OH)/ Val- NHC4H9-n (8i) which has the length of a tetrapeptide and contains only one natural amino acid. Compound 8i had an IC50 of 2 x 10(-9) M against human renin and showed high enzyme specificity; IC50 values against the related aspartic proteinases pepsin and cathepsin D were (8 x 10(-6) and 3 x 10(-6) M, respectively). In salt-depleted marmosets, 8i inhibited plasma renin activity PRA and lowered blood pressure for up to 2 h after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00117a027
• 作为产物：
  描述：

  以 甲醇 为溶剂， 生成 N^α,N^im-ditritylhistidine
  参考文献：
  名称：

  Improved methods of obtaining Nim-trityl-substituted histidine derivatives

  摘要：

  DOI：

  10.1007/bf00580461

文献信息

• Renin inhibitors containing a pyridyl amino diol derived C-terminus
  作者：Holger Heitsch、Rainer Henning、Heinz Werner Kleemann、Wolfgang Linz、Wolf Ulrich Nickel、Dieter Ruppert、Hansjoerg Urbach、Adalbert Wagner

  DOI：10.1021/jm00071a009

  日期：1993.9

  the concept of transition-state analogs, a series of nonpeptide renin inhibitors with the new (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-(2-pyridyl)hexane moiety at the C-terminal functionality were synthesized and evaluated for inhibition of renin both in vitro and in vivo. All compounds exhibited potencies in the nanomolar or even subnanomolar range when tested versus human renin in vitro. Selected

  基于过渡态类似物的概念，一系列具有新的（2S，3R，4S）-2-氨基-1-环己基-3,4-二羟基-6-（2-吡啶基）己烷部分的非肽肾素抑制剂合成了在C-末端的C末端功能，并在体外和体内评估了对肾素的抑制。当与人肾素进行体外测试时，所有化合物均显示出纳摩尔或什至亚纳摩尔范围的效力。在麻醉的，钠缺乏的恒河猴中评估选定的抑制剂，并在十二指肠内给予2 mg / kg的剂量后，平均动脉血压（MAP）明显降低。含有氨基哌啶基琥珀酸衍生的N端的化合物38（S 2864）是该系列中最有希望的成员。38种抑制人肾素的IC50为0.38 nM，不影响其他人天冬氨酸蛋白酶，
• Amiard et al., Bulletin de la Societe Chimique de France, 1955, p. 191
  作者：Amiard et al.

  DOI：——

  日期：——
• WO2007/9944
  申请人：——

  公开号：——

  公开（公告）日：——
• Barlos, Kleomenis; Mamos, Petros; Papaioannou, Dionysios, Liebigs Annalen der Chemie, 1987, p. 1025 - 1030
  作者：Barlos, Kleomenis、Mamos, Petros、Papaioannou, Dionysios、Patrianakou, Stella、Sanida, Chariklia、Schaefer, Wolfram

  DOI：——

  日期：——
• Synth�se de laL-histidyl-L-ph�nylalanyl-L-arginyl-L-tryptophanyl-glycyl-?-CBO-L-lysyl-L-prolyl-L-valylamide
  作者：R. A. Boissonnas、St. Guttmann、R. L. Huguenin、P.-A. Jaquenoud、Ed. Sandrin

  DOI：10.1002/hlca.19580410641

  日期：——

  AbstractTrityl‐glycyl‐ϵ‐CBO‐L‐lysine is condensed with L‐prolyl‐L‐valine methyl ester and, after amidification and splitting of the trityl group, glycyl‐ϵ‐CBO‐L‐lysyl‐L‐prolyl‐L‐valylamide is obtained. This is condensed with ditrityl‐L‐histidyl‐L‐phenylalanyl‐L‐arginyl‐L‐tryptophane prepared by condensation of ditrityl‐L‐histidyl‐L‐phenylalanine with L‐arginyl‐L‐tryptophane methyl ester and saponification. Dicyclohexyl‐carbodiimide is used as a condensing agent. After splitting off the trityl groups, the final octapeptide, L‐histidyl‐L‐phenylalanyl‐L‐arginyl‐L‐tryptophanyl‐glycyl‐ϵ‐CBO‐L‐lysyl‐L‐prolyl‐L‐valylamide is shown to be optically pure by leucine‐aminopeptidase digestion.