<3R-<3R*,6S*,7(S*)>>-<2--2-oxo-1-(phenylmethyl)ethyl>carbamic acid 1,1-dimethylethyl ester | 111437-65-1

• 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: <3R-<3R*,6S*,7(S*)>>-<2--2-oxo-1-(phenylmethyl)ethyl>carbamic acid 1,1-dimethylethyl ester
• 英文别名: tert-butyl N-[(2S)-1-[(3R,6S)-3-(hydroxymethyl)-6-methyl-5-oxo-1,4,7-oxadiazecan-7-yl]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 111437-65-1
• 化学式: C₂₃H₃₅N₃O₆
• 分子量: 449.547
• InChiKey: HRXFTRKIGGOFAF-UHOSZYNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.24
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  117.2
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  <3R-<3R*,6S*,7(S*)>>-<2--2-oxo-1-(phenylmethyl)ethyl>carbamic acid 1,1-dimethylethyl ester 在 palladium on activated charcoal 草酰氯 、 氢气 、 sodium acetate 、 sodium cyanoborohydride 、 二甲基亚砜 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.67h， 生成 (S)-2-{[(3R,6S)-7-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionyl)-6-methyl-5-oxo-[1,4,7]oxadiazecan-3-ylmethyl]-amino}-3-methyl-butyric acid
  参考文献：
  名称：

  Renin inhibitors. Design and synthesis of a new class of conformationally restricted analogs of angiotensinogen

  摘要：

  Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, 12, and 14, based upon a linear hexapeptide inhibitor with a reduced amide replacing the scissile bond at the active site. When tested, the 14-membered-ring compound was as potent an inhibitor of human renin as the parent while the 12-membered-ring compound was 6-fold more potent than the parent against mouse renin. However, the 10-membered-ring compound was inactive against both renins. The lack of potency of the 10-membered compound was explained by using NMR and molecular modeling techniques. It forms another conformation in solution that is inconsistent with binding at the active site. The cyclic compounds did not inhibit either pepsin or cathepsin D significantly. The cyclic modification rendered these inhibitors significantly resistant to cleavage by chymotrypsin and thus prevented loss of activity by this enzyme. Thus, the goals of enhanced inhibitory potency, high specificity, and metabolic stability were achieved in the series of compounds.

  DOI：

  10.1021/jm00397a003
• 作为产物：
  描述：

  (2S)-2-[3-[(2S)-3-(methoxymethoxy)-2-(phenylmethoxycarbonylamino)propoxy]propyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid 在 palladium on activated charcoal 盐酸 、 氢气 、 4-吡咯烷基吡啶 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 乙醇 、 乙酸乙酯 为溶剂， 反应 8.5h， 生成 <3R-<3R*,6S*,7(S*)>>-<2--2-oxo-1-(phenylmethyl)ethyl>carbamic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Renin inhibitors. Design and synthesis of a new class of conformationally restricted analogs of angiotensinogen

  摘要：

  Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, 12, and 14, based upon a linear hexapeptide inhibitor with a reduced amide replacing the scissile bond at the active site. When tested, the 14-membered-ring compound was as potent an inhibitor of human renin as the parent while the 12-membered-ring compound was 6-fold more potent than the parent against mouse renin. However, the 10-membered-ring compound was inactive against both renins. The lack of potency of the 10-membered compound was explained by using NMR and molecular modeling techniques. It forms another conformation in solution that is inconsistent with binding at the active site. The cyclic compounds did not inhibit either pepsin or cathepsin D significantly. The cyclic modification rendered these inhibitors significantly resistant to cleavage by chymotrypsin and thus prevented loss of activity by this enzyme. Thus, the goals of enhanced inhibitory potency, high specificity, and metabolic stability were achieved in the series of compounds.

  DOI：

  10.1021/jm00397a003

文献信息

• SHAM, HING L.;BOLIS, GIORGIO;STEIN, HERMAN H.;FESIK, STEPHEN W.;MARCOTTE,+, J. MED. CHEM., 31,(1988) N 2, 284-295
  作者：SHAM, HING L.、BOLIS, GIORGIO、STEIN, HERMAN H.、FESIK, STEPHEN W.、MARCOTTE,+

  DOI：——

  日期：——