N-[1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]-2(R)-(cyclopropylmethyl)-3(S),5(S)-dihydroxy-3,5-O-isopropylidene-6-phenylhexanamide | 220588-94-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-[1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]-2(R)-(cyclopropylmethyl)-3(S),5(S)-dihydroxy-3,5-O-isopropylidene-6-phenylhexanamide
• CAS: 220588-94-3
• 化学式: C₃₃H₅₃NO₅
• 分子量: 543.788
• InChiKey: QCZJWUKSOIYJOV-WOVUZPOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.78
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  88.02
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-[1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]-2(R)-(cyclopropylmethyl)-3(S),5(S)-dihydroxy-3,5-O-isopropylidene-6-phenylhexanamide 在 Amberlite IR-120 (H⁺) 作用下， 以 甲醇 、 水 为溶剂， 以100%的产率得到N-[1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]-2(R)-(cyclopropylmethyl)-3(S),5(S)-dihydroxy-6-phenylhexanamide
  参考文献：
  名称：

  Novel small renin inhibitors containing 4,5- or 3,5-dihydroxy-2-substituted-6-phenylhexanamide replacements at the P2P3 sites

  摘要：

  Renin inhibitors containing a 4,5- or a 3,5-dihydroxy-2-substituted-6-phenylhexanamide fragment at the P-2- P-3 Sites have been prepared and evaluated. The four possible diastereomeric diols of the two series of inhibitors were synthesized to determine the optimal configuration of the carbinol centers for these replacements. The most potent inhibitors of each series, 1a and 2c have a molecular weight of only 503 and IC50 values of 23 and 20 nM in a human plasma renin assay at pH 6.0. Their very low aqueous solubility limited their further evaluation. The efficacy of these P-2-P-3 replacements is a result of their ability to maintain the important hydrogen-bonds with the enzyme. Due to conformational differences with the dipeptide, adjustment at the P-2 Side chain was required. These 4,5- and 3,5-dihydroxyhexanamide segments could be seen as novel N-terminal dipeptide replacements. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)80011-4
• 作为产物：
  描述：

  3-[2(R)-(cyclopropylmethyl)-1,3-dioxobutyl]-4(S)-(phenylmethyl)-2-oxazolidinone 在 lithium hydroxide 、 双氧水 、 四氯化钛 、 二异丁基氢化铝 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 N-[1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]-2(R)-(cyclopropylmethyl)-3(S),5(S)-dihydroxy-3,5-O-isopropylidene-6-phenylhexanamide
  参考文献：
  名称：

  Novel small renin inhibitors containing 4,5- or 3,5-dihydroxy-2-substituted-6-phenylhexanamide replacements at the P2P3 sites

  摘要：

  Renin inhibitors containing a 4,5- or a 3,5-dihydroxy-2-substituted-6-phenylhexanamide fragment at the P-2- P-3 Sites have been prepared and evaluated. The four possible diastereomeric diols of the two series of inhibitors were synthesized to determine the optimal configuration of the carbinol centers for these replacements. The most potent inhibitors of each series, 1a and 2c have a molecular weight of only 503 and IC50 values of 23 and 20 nM in a human plasma renin assay at pH 6.0. Their very low aqueous solubility limited their further evaluation. The efficacy of these P-2-P-3 replacements is a result of their ability to maintain the important hydrogen-bonds with the enzyme. Due to conformational differences with the dipeptide, adjustment at the P-2 Side chain was required. These 4,5- and 3,5-dihydroxyhexanamide segments could be seen as novel N-terminal dipeptide replacements. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)80011-4