N-{3-[N-(2-methoxyethyl)aminoformyl]propyl}-5(S)-amino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropoxy)-phenyl]-octanamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-{3-[N-(2-methoxyethyl)aminoformyl]propyl}-5(S)-amino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropoxy)-phenyl]-octanamide
• 英文别名: (2R,4S,5S,7S)-5-amino-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-N-{3-[(2-methoxyethyl)carbamoyl]propyl}-2,8-dimethylnonanamide；(2R,4S,5S,7S)-5-amino-4-hydroxy-N-[4-(2-methoxyethylamino)-4-oxobutyl]-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-2,8-dimethylnonanamide
• 化学式: C₃₀H₅₃N₃O₇
• 分子量: 567.767
• InChiKey: BPHRVQBJSVSOCT-DNZIZEQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  40
• 可旋转键数：
  22
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  141
• 氢给体数：
  4
• 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-{3-[N-(2-methoxyethyl)carbamoyl]propyl} amide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 N-{3-[N-(2-methoxyethyl)aminoformyl]propyl}-5(S)-amino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropoxy)-phenyl]-octanamide
  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
• US5627182A
  申请人：——

  公开号：US5627182A

  公开（公告）日：1997-05-06