5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-2(S),7(S)-diisopropyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-(1,1-dimethyl-2-morpholino-ethyl) amide | 173337-95-6

• 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: 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-2(S),7(S)-diisopropyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-(1,1-dimethyl-2-morpholino-ethyl) amide
• 英文别名: tert-butyl N-[(3S,5S,6S,8S)-6-hydroxy-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-2,9-dimethyl-8-[(2-methyl-1-morpholin-4-ylpropan-2-yl)carbamoyl]decan-5-yl]carbamate
• CAS: 173337-95-6
• 化学式: C₃₈H₆₇N₃O₈
• 分子量: 693.965
• InChiKey: ZLLYVHKHWZCSLL-YDPTYEFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  49
• 可旋转键数：
  22
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-2(S),7(S)-diisopropyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-(1,1-dimethyl-2-morpholino-ethyl) amide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2S,4S,5S,7S)-5-amino-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-N-(2-methyl-1-morpholin-4-ylpropan-2-yl)-2-propan-2-ylnonanamide;hydrochloride
  参考文献：
  名称：

  Structural Modification of the P2‘ Position of 2,7-Dialkyl-Substituted 5(S)-Amino-4(S)-hydroxy-8-phenyl-octanecarboxamides:  The Discovery of Aliskiren, a Potent Nonpeptide Human Renin Inhibitor Active after Once Daily Dosing in Marmosets

  摘要：

  Due to its function in the rate limiting initial step of the renin-angiotensin system, renin is a particularly promising target for drugs designed to control hypertension, a growing risk to health worldwide. Despite vast efforts over more than two decades, no orally efficacious renin inhibitor had reached the market. As a result of a structure-based topological design approach, we have identified a novel class of small-molecule inhibitors with good oral blood-pressure lowering effects in primates. Further lead optimization aimed for improvement of in vivo potency and duration of action, mainly by P2' modifications at the hydroxyethylene transition-state isostere. These efforts resulted in the discovery of aliskiren (46, CGP060536B, SPP100), a highly potent, selective inhibitor of renin, demonstrating excellent efficacy in sodium-depleted marmosets after oral administration, with sustained duration of action in reducing dose-dependently mean arterial blood pressure. Aliskiren has recently received regulatory approval by the U.S. Food and Drug Administration for the treatment of hypertension.

  DOI：

  10.1021/jm070316i
• 作为产物：
  描述：

  tert-butyl (4S,5S)-4-[(2S)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutyl]-2,2-dimethyl-5-[(2S)-3-methyl-2-[(2-methyl-1-morpholin-4-ylpropan-2-yl)carbamoyl]butyl]-1,3-oxazolidine-3-carboxylate 在 对甲苯磺酸 甲醇 作用下， 以99 mg的产率得到5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-2(S),7(S)-diisopropyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-(1,1-dimethyl-2-morpholino-ethyl) amide
  参考文献：
  名称：

  Structural Modification of the P2‘ Position of 2,7-Dialkyl-Substituted 5(S)-Amino-4(S)-hydroxy-8-phenyl-octanecarboxamides:  The Discovery of Aliskiren, a Potent Nonpeptide Human Renin Inhibitor Active after Once Daily Dosing in Marmosets

  摘要：

  Due to its function in the rate limiting initial step of the renin-angiotensin system, renin is a particularly promising target for drugs designed to control hypertension, a growing risk to health worldwide. Despite vast efforts over more than two decades, no orally efficacious renin inhibitor had reached the market. As a result of a structure-based topological design approach, we have identified a novel class of small-molecule inhibitors with good oral blood-pressure lowering effects in primates. Further lead optimization aimed for improvement of in vivo potency and duration of action, mainly by P2' modifications at the hydroxyethylene transition-state isostere. These efforts resulted in the discovery of aliskiren (46, CGP060536B, SPP100), a highly potent, selective inhibitor of renin, demonstrating excellent efficacy in sodium-depleted marmosets after oral administration, with sustained duration of action in reducing dose-dependently mean arterial blood pressure. Aliskiren has recently received regulatory approval by the U.S. Food and Drug Administration for the treatment of hypertension.

  DOI：

  10.1021/jm070316i

文献信息

• .delta.-amino-.gamma.-hydroxy-.omega.-aryl-alkanoic acid amides
  申请人：Ciba-Geigy Corporation

  公开号：US05559111A1

  公开（公告）日：1996-09-24

  .delta.-Amino-.gamma.-hydroxy-.omega.-aryl-alkanoic acid amides of formula I ##STR1## and the salts thereof, have renin-inhibiting properties and can be used as antihypertensive medicinal active ingredients.

  公式I的.delta.-氨基-.gamma.-羟基-.ω-芳基-烷基酸酰胺及其盐具有抑制肾素的性质，可用作降压药物活性成分。
• 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。
• US5559111A
  申请人：——

  公开号：US5559111A

  公开（公告）日：1996-09-24
• US5627182A
  申请人：——

  公开号：US5627182A

  公开（公告）日：1997-05-06
• US5646143A
  申请人：——

  公开号：US5646143A

  公开（公告）日：1997-07-08