ethyl 10(S)-<(benzyloxycarbonyl)amino>-8,12,14-trioxapentadeca-2,4-dienoate | 111437-72-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 10(S)-<(benzyloxycarbonyl)amino>-8,12,14-trioxapentadeca-2,4-dienoate
• CAS: 111437-72-0
• 化学式: C₂₂H₃₁NO₇
• 分子量: 421.491
• InChiKey: JTOTXRVPGHJYRY-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  30.0
• 可旋转键数：
  15.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  92.32
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 10(S)-<(benzyloxycarbonyl)amino>-8,12,14-trioxapentadeca-2,4-dienoate 在 palladium on activated charcoal 盐酸 、 lithium hydroxide 、 草酰氯 、 1-(benzyloxy)pyrrolidine-2,5-dione 、 氢气 、 sodium acetate 、 二异丁基氢化铝 、 sodium cyanoborohydride 、 4-吡咯烷基吡啶 、 二甲基亚砜 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 氯仿 、 乙酸乙酯 为溶剂， 反应 25.67h， 生成 (S)-2-{[(3R,6S)-7-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionyl)-6-methyl-5-oxo-1-oxa-4,7-diaza-cyclotetradec-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：

  N-苄氧羰基-L-丝氨酸 在 9-borabicyclo[3.3.1]nonane dimer 、 草酰氯 、 sodium hydride 、 二异丁基氢化铝 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 9.75h， 生成 ethyl 10(S)-<(benzyloxycarbonyl)amino>-8,12,14-trioxapentadeca-2,4-dienoate
  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