5(S)-amino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-[2-(cis-2,6-dimethyl-morpholino)ethyl]amide | 956075-60-8

• 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: 5(S)-amino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-[2-(cis-2,6-dimethyl-morpholino)ethyl]amide
• 英文别名: (2R,4S,5S,7S)-5-amino-N-{2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]ethyl}-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-2,8-dimethylnonanamide；(2R,4S,5S,7S)-5-amino-N-[2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]ethyl]-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-2,8-dimethylnonanamide
• CAS: 956075-60-8
• 化学式: C₃₁H₅₅N₃O₆
• 分子量: 565.794
• InChiKey: FJPZRFMUNBBITF-VHSORMFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  40
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-[2-(cis-2,6-dimethyl-morpholino)-ethyl] amide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 5(S)-amino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-[2-(cis-2,6-dimethyl-morpholino)ethyl]amide
  参考文献：
  名称：

  Novel 2,7-Dialkyl-Substituted 5(S)-Amino-4(S)-hydroxy-8-phenyl-octanecarboxamide Transition State Peptidomimetics Are Potent and Orally Active Inhibitors of Human Renin

  摘要：

  The action of renin is the rate-limiting step of the renin-angiotensin system (RAS), a key regulator of blood pressure. Effective renin inhibitors directly block the RAS entirely at source and, thus, may provide a vital weapon for hypertension therapy. Our efforts toward identifying novel small-molecule peptidomimetic renin inhibitors have resulted in the design of transition-state isosteres such as I bearing an all-carbon 8-phenyl-octanecarboxamide framework. Optimization of the extended P3 portion of I and extensive P2' modifications provided analogues with improved in vitro potencies in the presence of plasma. X-ray resolution of rhrenin/38a in the course of SAR work surprisingly unveiled the exploitation of a previously unexplored pocket (S3(SP)) important for strong binding affinities. Several inhibitors demonstrated oral efficacy in sodium-depleted marmosets. The most potent, 38a, induced dose-dependently a pronounced reduction in mean arterial blood pressure, paralleled by complete blockade of active plasma renin, up to 8 h post-dose. Oral bioavailability of 38a was 16% in marmosets.

  DOI：

  10.1021/jm070314y

文献信息

• Methods of treating alzheimer's disease using aryl alkanoic acid amides
  申请人：John Varghese

  公开号：US20060154926A1

  公开（公告）日：2006-07-13

  Disclosed are methods for treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of compounds of formula (1) wherein the variables R 1 -R 8 and X are defined herein.

  本发明涉及使用式（1）中所述的化合物治疗阿尔茨海默病和其他疾病，抑制β-分泌酶酶活性和/或抑制Aβ肽在哺乳动物体内的沉积的方法，其中变量R1-R8和X在此定义。
• Delta-Amino-gamma-hydroxy-omega-aryl-alkansäureamide mit Enzym-, insbesondere Renin-hemmenden Eigenschaften
  申请人：Novartis AG

  公开号：EP0678503B1

  公开（公告）日：1999-09-01
• Novel 2,7-Dialkyl-Substituted 5(<i>S</i>)-Amino-4(<i>S</i>)-hydroxy-8-phenyl-octanecarboxamide Transition State Peptidomimetics Are Potent and Orally Active Inhibitors of Human Renin
  作者：Richard Göschke、Stefan Stutz、Vittorio Rasetti、Nissim-Claude Cohen、Joseph Rahuel、Pascal Rigollier、Hans-Peter Baum、Peter Forgiarini、Christian R. Schnell、Trixie Wagner、Markus G. Gruetter、Walter Fuhrer、Walter Schilling、Frédéric Cumin、Jeanette M. Wood、Jürgen Maibaum

  DOI：10.1021/jm070314y

  日期：2007.10.1

  The action of renin is the rate-limiting step of the renin-angiotensin system (RAS), a key regulator of blood pressure. Effective renin inhibitors directly block the RAS entirely at source and, thus, may provide a vital weapon for hypertension therapy. Our efforts toward identifying novel small-molecule peptidomimetic renin inhibitors have resulted in the design of transition-state isosteres such as I bearing an all-carbon 8-phenyl-octanecarboxamide framework. Optimization of the extended P3 portion of I and extensive P2' modifications provided analogues with improved in vitro potencies in the presence of plasma. X-ray resolution of rhrenin/38a in the course of SAR work surprisingly unveiled the exploitation of a previously unexplored pocket (S3(SP)) important for strong binding affinities. Several inhibitors demonstrated oral efficacy in sodium-depleted marmosets. The most potent, 38a, induced dose-dependently a pronounced reduction in mean arterial blood pressure, paralleled by complete blockade of active plasma renin, up to 8 h post-dose. Oral bioavailability of 38a was 16% in marmosets.