(2S,3R,4S)-7-azido-1-cyclohexyl-3,4-dihydroxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>heptane | 134848-86-5

• 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: (2S,3R,4S)-7-azido-1-cyclohexyl-3,4-dihydroxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>heptane
• 英文别名: tert-butyl N-[(2S,3R,4S)-7-azido-1-cyclohexyl-3,4-dihydroxyheptan-2-yl]carbamate
• CAS: 134848-86-5
• 化学式: C₁₈H₃₄N₄O₄
• 分子量: 370.492
• InChiKey: VBQQIWOSEVNEQU-HRCADAONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  93.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S)-7-azido-1-cyclohexyl-3,4-dihydroxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>heptane 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 、 三氟乙酸 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
• 作为产物：
  描述：

  (4S,5R)-4-(cyclohexylmethyl)-5-<2-(3-hydroxypropyl)-1,3-dioxolan-2-yl>-2-oxazolidinone 在 盐酸 、 barium dihydroxide 、 sodium tetrahydroborate 、 叠氮化锂 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 (2S,3R,4S)-7-azido-1-cyclohexyl-3,4-dihydroxy-2-<<(1,1-dimethylethoxy)carbonyl>amino>heptane
  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

• Cyclic renin inhibitors
  申请人：MERCK & CO. INC.

  公开号：EP0432974A1

  公开（公告）日：1991-06-19

  Compounds of the formuia : are disclosed. These compounds inhibit the angiotensinogen-cleaving action of the natural proteolytic enzyme, renin, and are useful in treating, preventing or managing renin-associated hypertension, hyperaldosteronism, congestive heart failure, and glaucoma.

  的化合物： 的化合物。这些化合物能抑制天然蛋白分解酶肾素的血管紧张素原分解作用，可用于治疗、预防或控制肾素相关性高血压、高醛固酮症、充血性心力衰竭和青光眼。
• US5254682A
  申请人：——

  公开号：US5254682A

  公开（公告）日：1993-10-19
• 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.