氨甲酸,(2-环己基-1-甲酰基乙基)-,苯基甲基酯,(S)- | 105852-47-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 氨甲酸,(2-环己基-1-甲酰基乙基)-,苯基甲基酯,(S)-
• 英文名称: 2-<(benzyloxycarbonyl)amino>-3-cyclohexyl-(2S)-propionaldehyde
• 英文别名: N-benzyloxycarbonyl-L-cyclohexylalaninal；N-Cbz-L-cyclohexylalanal；2(S)-(Benzyloxycarbonyl)amino-3-cyclohexylpropanal；2(S)-benzyloxycarbonylamino-3-cyclohexyl-propanal；2(S)-benzyloxycarbonylamino-3-cyclohexylpropanal；N-benzyloxycarbonyl-3-cyclohexylalaninal；benzyl N-[(2S)-1-cyclohexyl-3-oxopropan-2-yl]carbamate
• CAS: 105852-47-9
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: MQHGQTHXEFNQFV-INIZCTEOSA-N

物化性质

• 沸点：
  442.5±38.0 °C(Predicted)
• 密度：
  1.095±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  氨甲酸,(2-环己基-1-甲酰基乙基)-,苯基甲基酯,(S)- 生成 4-benzyloxycarbonylamino-5-cyclohexyl-2,2-difluoro-3-hydroxypentanoic acid ethyl ester
  参考文献：
  名称：

  MERRELL, DOW;SCHIRLIN, DANIEL;PELTON, JOHN TOM;TARNUS, CELINE;JUNG, MICHE+

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-3-cyclohexyl-L-alanine ethyl ester 在 盐酸 、 聚合甲醛 、 sodium acetate 、 二异丁基氢化铝 作用下， 以 四氢呋喃 为溶剂， 反应 3.33h， 生成 氨甲酸,(2-环己基-1-甲酰基乙基)-,苯基甲基酯,(S)-
  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

文献信息

• Renin Inhibitors. I. Synthesis and Structure-Activity Relationships of Transition-State Inhibitors Containing Homostatine Analogues at the Scissile Bond.
  作者：Shugo ATSUUMI、Masato NAKANO、Yutaka KOIKE、Seiichi TANAKA、Kenji MATSUYAMA、Makiko NAKANO、Hajime MORISHIMA

  DOI：10.1248/cpb.40.364

  日期：——

  The synthesis and structure-activity relationships of transition-state renin inhibitors containing the homostatine analogues at the scissile bond are described. These inhibitors incorporate the amino acid side chains corresponding to positions 7-12 (P4-P2') of angiotensinogen. Ethyl, 2-hydroxyethyl and 3-hydroxypropyl groups at position 2 of the homostatine analogues (P1') are more effective for increasing potency than the isopropyl group. A combination of residues at P1, P3 and P4 is important for potency and this result auggests that S1, S3 and S4 form a huge hydrophobic core together in renin.

  描述了含有在切割键处的同胺酸类似物的过渡态肾素抑制剂的合成及其结构-活性关系。这些抑制剂包含了与血管紧张素原第7-12位（P4-P2'）相对应的氨基酸侧链。在同胺酸类似物的第2位（P1'）上的乙基、2-羟乙基和3-羟丙基比异丙基更有效地增加了效力。P1、P3和P4位点的氨基酸残基组合对效力很重要，结果表明S1、S3和S4在肾素中共同形成了一个巨大的疏水核心。
• Dipeptide isosteres. 2. Synthesis of hydroxyethylene dipeptide isostere diastereomers from a common γ-lactone intermediate. Preparation of renin and HIV-1 protease inhibitor transition state mimics.
  作者：William R. Baker、John K. Pratt

  DOI：10.1016/s0040-4020(01)81896-2

  日期：1993.1

  A general strategy for the synthesis of the hydroxyethylene dipeptide isostere diastereomers C or D has been developed. The syntheses proceeded through a common γ-lactone intermediate A or B. The C(3α) γ-lactone diastereomer A was prepared from the N-Cbz protected α-amino aldehyde and 2-(2-isopropylpropen-2-yl)trimethylsilane in five steps. The C(3β) γ-lactone diastereomer B was obtained by kinetic

  已经开发了合成羟乙烯二肽等排非对映异构体C或D的一般策略。合成过程通过常见的γ-内酯中间体A或B进行。由N-Cbz保护的α-氨基醛和2-（2-异丙基丙烯-2-基）三甲基硅烷分五个步骤制备C（3α）γ-内酯非对映异构体A。C（3β）γ-内酯非对映异构体B是通过使用丙二酸酯衍生物对内酯烯醇酯进行动态质子化而获得的。
• Novel peptidase inhibitors
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0356595A1

  公开（公告）日：1990-03-07

  This invention relates to analogs of peptidase substrates in which the nitrogen atom of the scissile amide bond of a partial retropeptide analog of the substrate has been replaced by a difluoromethylene moiety. These peptidase substrate analogs provide specific enzyme inhibitors for a variety of proteases, the inhibition of which exert valuable pharmacological activities and therefore have useful physiological consequences in a variety of disease states.

  这项发明涉及肽酶底物的类似物，其中底物的部分反肽类似物的可切割酰胺键的氮原子被二氟甲亚甲基取代。这些肽酶底物类似物提供了各种蛋白酶的特异性酶抑制剂，这些蛋白酶的抑制对多种蛋白酶具有有用的药理活性，因此在多种疾病状态下具有有用的生理后果。
• Fluorine-containing organozinc reagents. IV.
  作者：Robert W Lang、Bruno Schaub

  DOI：10.1016/0040-4039(88)85053-6

  日期：1988.1

  Chlorodifluoroacetic acid has shown to be a promising starting material for Reformatskii-type syntheses of fluorine-containing molecules and thus, it offers an attractive extension to what is known from rather expensive bromodifluoroacetic acid.

  氯二氟乙酸已被证明是用于含氟分子的Reformatskii型合成的有前途的原料，因此，它提供了对相当昂贵的溴代二氟乙酸所具有的吸引力的扩展。
• Analog of peptidase substrates
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05114927A1

  公开（公告）日：1992-05-19

  This invention relates to novel analogs of certain peptidase substrates in which the nitrogen atom of the scissile amide bond has been replaced with a difluoromethylene moiety and in which the carbonyl moiety of its adjacent amide bond has been replaced with a terminal amine function, said novel analogs having the property of inhibiting renin and which are useful in the treatment of hypertension.

  本发明涉及某些肽酶底物的新型类似物，其中剪切酰胺键的氮原子已被二氟甲基基团取代，并且其相邻酰胺键的羰基基团已被末端胺基取代，这些新型类似物具有抑制肾素的性质，并且在治疗高血压方面是有用的。