(3S,12R,13S)-13-(cyclohexylmethyl)-3-<-L-phenylalanyl>amino>-12-hydroxy-2,6,11-trioxo-1,7-diazacyclotridecane ethylene glycol ketal | 134848-69-4

• 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: (3S,12R,13S)-13-(cyclohexylmethyl)-3-<-L-phenylalanyl>amino>-12-hydroxy-2,6,11-trioxo-1,7-diazacyclotridecane ethylene glycol ketal
• 英文别名: [1-(7-Cyclohexylmethyl-6-hydroxy-9,13-dioxo-1,4-dioxa-8,14-diaza-spiro[4.12]heptadec-10-ylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-1-[[(13S,16S,17R)-16-(cyclohexylmethyl)-17-hydroxy-10,14-dioxo-1,4-dioxa-9,15-diazaspiro[4.12]heptadecan-13-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 134848-69-4
• 化学式: C₃₄H₅₂N₄O₈
• 分子量: 644.809
• InChiKey: WZKOVMBSHSOODL-PFWSVGDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  164
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3S,12R,13S)-13-(cyclohexylmethyl)-3-<-L-phenylalanyl>amino>-12-hydroxy-2,6,11-trioxo-1,7-diazacyclotridecane ethylene glycol ketal 在 碳酸氢钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 (3S,12R,13S)-13-(cyclohexylmethyl)-3-<-L-phenylalanyl>amino>-12-hydroxy-2,6,11-trioxo-1,7-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
• 作为产物：
  描述：

  N-叔丁氧羰基-L-谷氨酸 5-苄酯 在 palladium on activated charcoal 1-Hydrobenzotriazole monohydrate 、 叠氮磷酸二苯酯 、 氢气 、 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 ℃ 、275.79 kPa 条件下， 反应 16.0h， 生成 (3S,12R,13S)-13-(cyclohexylmethyl)-3-<-L-phenylalanyl>amino>-12-hydroxy-2,6,11-trioxo-1,7-diazacyclotridecane ethylene glycol ketal
  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