(3R,4S,7S)-4-(cyclohexylmethyl)-7-<-L-phenylalanyl>amino>-3-hydroxy-2,6,10-trioxo-1-oxa-5,9-diazacyclotridecane | 134848-67-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3R,4S,7S)-4-(cyclohexylmethyl)-7-<-L-phenylalanyl>amino>-3-hydroxy-2,6,10-trioxo-1-oxa-5,9-diazacyclotridecane
• 英文别名: [1-(4-Cyclohexylmethyl-3-hydroxy-2,6,10-trioxo-1-oxa-5,9-diaza-cyclotridec-7-ylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-1-[[(3R,4S,7S)-4-(cyclohexylmethyl)-3-hydroxy-2,6,10-trioxo-1-oxa-5,9-diazacyclotridec-7-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 134848-67-2
• 化学式: C₃₁H₄₆N₄O₈
• 分子量: 602.728
• InChiKey: KEHJFSADHYLALA-JAYJDBRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  172
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-oxo-4-(phenylmethoxy)butyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-<<(2S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-3-<<(phenylmethoxy)carbonyl>amino>propanoyl>amino>butanoate 在 palladium on activated charcoal 叠氮磷酸二苯酯 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 16.0h， 生成 (3R,4S,7S)-4-(cyclohexylmethyl)-7-<-L-phenylalanyl>amino>-3-hydroxy-2,6,10-trioxo-1-oxa-5,9-diazacyclotridecane
  参考文献：
  名称：

  Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors

  摘要：

  Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65-mu-M, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.

  DOI：

  10.1021/jm00113a005

文献信息

• Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors
  作者：Ann E. Weber、Thomas A. Halgren、John J. Doyle、Robert J. Lynch、Peter K. S. Siegl、William H. Parsons、William J. Greenlee、Arthur A. Patchett

  DOI：10.1021/jm00113a005

  日期：1991.9

  Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65-mu-M, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.