(3S,11S,12R,13S)-13-(cyclohexylmethyl)-11,12-dihydroxy-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2,6-dioxo-1,7-diazacyclotridecane | 134848-88-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: (3S,11S,12R,13S)-13-(cyclohexylmethyl)-11,12-dihydroxy-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2,6-dioxo-1,7-diazacyclotridecane
• 英文别名: tert-butyl N-[(3S,11S,12R,13S)-13-(cyclohexylmethyl)-11,12-dihydroxy-2,6-dioxo-1,7-diazacyclotridec-3-yl]carbamate
• CAS: 134848-88-7
• 化学式: C₂₃H₄₁N₃O₆
• 分子量: 455.595
• InChiKey: QBGBPLHOTZDWPR-CGBFIWBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  32.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  136.99
• 氢给体数：
  5.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (3S,11S,12R,13S)-13-(cyclohexylmethyl)-11,12-dihydroxy-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2,6-dioxo-1,7-diazacyclotridecane 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (3S,11S,12R,13S)-3-Amino-13-cyclohexylmethyl-11,12-dihydroxy-1,7-diaza-cyclotridecane-2,6-dione
  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 叠氮磷酸二苯酯 、 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 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,11S,12R,13S)-13-(cyclohexylmethyl)-11,12-dihydroxy-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2,6-dioxo-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