ethyl 4(S)-<(tert-butyloxycarbonyl)amino>-5-(cyclohexylmethyl)-2,2-difluoro-3(S)-hydroxypentanoate | 103420-29-7

• 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: ethyl 4(S)-<(tert-butyloxycarbonyl)amino>-5-(cyclohexylmethyl)-2,2-difluoro-3(S)-hydroxypentanoate
• 英文别名: ethyl 4(S)-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-2,2-difluoro-3(S)-hydroxypentanoate；ethyl 4(S)-[(tert-butyloxycarbonyl)amino]-5-(cyclohexylmethyl)-2,2-difluoro-3(S)-hydroxypentanoate；ethyl (3S,4S)-5-cyclohexyl-2,2-difluoro-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 103420-29-7
• 化学式: C₁₈H₃₁F₂NO₅
• 分子量: 379.445
• InChiKey: YTRKCQUAWRUHJW-KBPBESRZSA-N

物化性质

• 沸点：
  500.4±50.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 4(S)-<(tert-butyloxycarbonyl)amino>-5-(cyclohexylmethyl)-2,2-difluoro-3(S)-hydroxypentanoate 生成 ethyl 2-[(4S,5S)-4-(cyclohexylmethyl)-2-oxo-1,3-oxazolidin-5-yl]-2,2-difluoroacetate
  参考文献：
  名称：

  SHAM, HING L.;REMPEL, CHERYL A.;STEIN, HERMAN;COHEN, JEROME, J. CHEM. SOC. CHEM. COMMUN.,(1990) N3, C. 904-905

  摘要：

  DOI：
• 作为产物：
  描述：

  S-(-)-2-N-BOC-3-环己基-1-丙醇 在 草酰氯 、 二甲基亚砜 、 锌 作用下， 生成 ethyl 4(S)-<(tert-butyloxycarbonyl)amino>-5-(cyclohexylmethyl)-2,2-difluoro-3(S)-hydroxypentanoate
  参考文献：
  名称：

  新型二肽模拟物6（S）-氨基-7-环己基-4,4-二氟-3（R），5（R）-二羟基-2-甲基庚烷的合成

  摘要：

  通过Boc- L-环己基丙氨醇（Boc =叔丁氧羰基）合成的新型二肽模拟物（1）掺入二肽序列已产生非常有效的肾素抑制剂。

  DOI：

  10.1039/c39900000904

文献信息

• Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone, and related analogs
  作者：Suvit Thaisrivongs、Donald T. Pals、Warren M. Kati、Steve R. Turner、Lisa M. Thomasco、William Watt

  DOI：10.1021/jm00160a048

  日期：1986.10

  Peptides that contain difluorostatine and difluorostatone residues have been shown to be potent inhibitors of the aspartyl protease renin. The readily hydrated fluoro ketone is proposed to mimic the tetrahedral intermediate that forms during the enzyme-catalyzed hydrolysis of a peptidic bond. It is suggested that the sp3-hybridized ketal acts as a transition-state analogue renin inhibitor. The fluoro

  已显示含有二氟他汀和二氟他酮残基的肽是天冬氨酰蛋白酶肾素的有效抑制剂。提议将易水合的氟代酮模拟在肽催化的酶催化水解过程中形成的四面体中间体。建议将sp3杂化的缩酮用作过渡态类似物肾素抑制剂。氟代酮显示出比相应的非氟代酮更有效的抑制剂，后者是伪底物。P1位点上更多的亲脂性侧链可以增强二氟他汀类似物的抑制能力，但这在二氟他酮系列中无法得到证实。另外，对于含二氟他酮的肽已经显示出高的肾素特异性。
• Difluorocyclostatine containing polypeptides
  申请人：PFIZER INC.

  公开号：EP0222523A2

  公开（公告）日：1987-05-20

  Polypeptides and derivatives thereof containing 2,2-difluorocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.

  含有 2,2-二氟环司他丁的多肽及其衍生物可用于抑制肾素酶的血管紧张素原分解作用。
• Design and synthesis of potent, selective, and orally active fluorine-containing renin inhibitors
  作者：Annette M. Doherty、Ila Sircar、Brian E. Kornberg、John Quin、R. Thomas Winters、James S. Kaltenbronn、Michael D. Taylor、Brian L. Batley、Stephen R. Rapundalo

  DOI：10.1021/jm00079a001

  日期：1992.1

  A series of primate renin inhibitors containing difluorocarbinol and difluoroketone groups at the P1-P1' position have been synthesized and studied both in vitro and in vivo. In vitro, the compounds were evaluated as inhibitors of monkey renin and the closely related aspartic proteinase, cathepsin D (bovine), as a measure of enzyme selectivity. Interestingly, the difluoroketone derivatives showed greatly reduced selectivity compared with the corresponding alcohols. However, selectivity could be enhanced by judicious choice of other substituents. Sites influencing selectivity, included not only P2, Which is well-known to strongly affect selectivity, but also the P4, P1-P1', and P2' sites. These results make possible the design of inhibitors with a greater selectivity for either renin versus cathepsin D. In vivo several of the compounds in the difluoroketone series have shown good oral activity in the salt depleted normotensive cynomolgus monkey model.
• HOOVER, D. J.
  作者：HOOVER, D. J.

  DOI：——

  日期：——
• [EN] DIFLUOROCYCLOSTATINE CONTAINING POLYPEPTIDES
  申请人：PFIZER INC.

  公开号：WO1987002675A1

  公开（公告）日：1987-05-07

  (EN) Polypeptides and derivatives thereof containing 2,2-difluorocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.(FR) Sont décrits des polypeptides et leurs dérivés contenant 2,2-difluorocyclostatine, lesquels sont utiles pour inhiber l'action de clivage sur l'angiotensinogène de la rénine enzymatique.