(3S)-5-[(1S,3S)-1-azido-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-4-methylpentyl]-3-propan-2-yloxolan-2-one | 1227379-44-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3S)-5-[(1S,3S)-1-azido-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-4-methylpentyl]-3-propan-2-yloxolan-2-one
• CAS: 1227379-44-3
• 化学式: C₂₅H₃₉N₃O₅
• 分子量: 461.602
• InChiKey: YTRPFWMXDNQTCX-FYHRMECFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  68.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-azido-2,2-dimethylpropan-1-amine hydrochloride 、 (3S)-5-[(1S,3S)-1-azido-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-4-methylpentyl]-3-propan-2-yloxolan-2-one 在 2-羟基吡啶 、 三乙胺 作用下， 以63.1%的产率得到(2S,4S,5S,7S)-5-azido-N-(3-azido-2,2-dimethylpropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-2-propan-2-ylnonanamide
  参考文献：
  名称：

  Synthesis, biological evaluation and docking studies of octane-carboxamide based renin inhibitors with extended segments toward S3′ site of renin

  摘要：

  Eighteen octane-carboxamide based renin inhibitors with extended segments for mimicking P3' unit of angiotensinogen have been synthesized. The biological evaluation identified novel renin inhibitors with more potent activity than aliskiren. Molecular docking studies showed that the extended amide-tails matched the P3' position of angiotensinogen and exerted interactions with the S3' site of renin. An unexpected pi-pi stacking interaction was observed during docking study for compound 9r, which could be a reasonable explanation for the outstanding potency of this compound. Further study is in progress to reveal a feasibility for developing novel renin inhibitors based on the possible non-classical interactions between the ligands and the new subsite of renin. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.059

文献信息

• Organic Compounds
  申请人：Maibaum Juergen Klaus

  公开号：US20090076062A1

  公开（公告）日：2009-03-19

  Disclosed are δ-amino-γ-hydroxy-ω-aryl-alkanoic acid amide compounds of formula (I) and the salts thereof, having renin-inhibiting properties. Also disclosed are pharmaceutical compositions comprising these compounds and methods of administering them for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, cardiomyopathy postinfarction, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, raised intra-ocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, alzheimers, dementia, anxiety states and cognitive disorders.

  揭示了具有抑制肾素作用的δ-氨基-γ-羟基-ω-芳基-烷酸酰胺化合物的化学式(I)及其盐。还揭示了包括这些化合物的药物组合物以及用于治疗高血压、动脉粥样硬化、不稳定性冠状动脉综合征、充血性心力衰竭、心肌肥大、心脏纤维化、心肌梗死后心肌病、不稳定性冠状动脉综合征、舒张功能障碍、慢性肾病、肝纤维化、糖尿病并发症（如肾病、血管病和神经病变）、冠状血管疾病、血管成形术后再狭窄、眼内压升高、青光眼、异常血管生长、高醛固酮症、认知障碍、阿尔茨海默病、痴呆症、焦虑状态和认知障碍的治疗方法。
• AMIDE INHIBITORS OF RENIN
  申请人：Gant Thomas G.

  公开号：US20100124550A1

  公开（公告）日：2010-05-20

  The present invention relates to new amide inhibitors of renin, pharmaceutical compositions thereof, and methods of use thereof

  本发明涉及新的肾素酶抑制剂酰胺、其药物组成以及使用方法。
• Synthesis, biological evaluation and docking studies of octane-carboxamide based renin inhibitors with extended segments toward S3′ site of renin
  作者：Yong Wu、Chen Shi、Xiaowei Sun、Xiaoming Wu、Hongbin Sun

  DOI：10.1016/j.bmc.2011.05.059

  日期：2011.7

  Eighteen octane-carboxamide based renin inhibitors with extended segments for mimicking P3' unit of angiotensinogen have been synthesized. The biological evaluation identified novel renin inhibitors with more potent activity than aliskiren. Molecular docking studies showed that the extended amide-tails matched the P3' position of angiotensinogen and exerted interactions with the S3' site of renin. An unexpected pi-pi stacking interaction was observed during docking study for compound 9r, which could be a reasonable explanation for the outstanding potency of this compound. Further study is in progress to reveal a feasibility for developing novel renin inhibitors based on the possible non-classical interactions between the ligands and the new subsite of renin. (C) 2011 Elsevier Ltd. All rights reserved.