5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(4-hydroxybutyl)] amide | 173337-70-7

• 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-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(4-hydroxybutyl)] amide
• 英文别名: 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(4-hydroxybutyl)]amide；tert-butyl N-[(2R,4S,5S,7S)-4-hydroxy-1-(4-hydroxybutylamino)-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-2,8-dimethyl-1-oxononan-5-yl]carbamate
• CAS: 173337-70-7
• 化学式: C₃₂H₅₆N₂O₈
• 分子量: 596.805
• InChiKey: MZTCPKKCBVBIOG-BDGPUAICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  42
• 可旋转键数：
  22
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  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-(4-hydroxybutyl)] amide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2R,4S,5S,7S)-5-amino-4-hydroxy-N-(4-hydroxybutyl)-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-2,8-dimethylnonanamide
  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
• 作为产物：
  描述：

  (1S,3S,2'S,4'R)-[3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-1-(4'-methyl-5-oxo-tetrahydro-furan-2'-yl)-pentyl]-carbamic acid tert-butyl ester 、 4-氨基-1-丁醇 生成 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(4-hydroxybutyl)] 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

• [EN] METHODS OF TREATING ALZHEIMER'S DISEASE USING ARYL ALKANOIC ACID AMIDES<br/>[FR] METHODES DE TRAITEMENT DE LA MALADIE D'ALZHEIMER PAR DES AMIDES D'ACIDE ARYL ALCANOIQUE
  申请人：ELAN PHARM INC

  公开号：WO2003103653A1

  公开（公告）日：2003-12-18

  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 (1) wherein the variables R1-R8 and X are defined herein.

  揭示了一种治疗阿尔茨海默病和其他疾病，和/或抑制β-分泌酶，和/或通过使用式1（1）中定义的化合物在哺乳动物体内抑制Aβ肽的沉积的方法。其中变量R1-R8和X在此处定义。
• .delta.-amino-.gamma.-hydroxy-.omega.-aryl-alkanoic acid amides
  申请人：Ciba Geigy Corporation

  公开号：US05627182A1

  公开（公告）日：1997-05-06

  .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.

  式I中的.delta.-氨基-.gamma.-羟基-.ω.-芳基-脂肪酰胺及其盐具有抑制肾素的作用，可用作降压药物活性成分。
• .delta.-amino-.gamma.-hydroxy-.omega.-aryl-alkanoic acids
  申请人：Ciba-Geigy Corporation

  公开号：US05654445A1

  公开（公告）日：1997-08-05

  .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.

  I式化合物及其盐，其中，.delta.-氨基-.gamma.-羟基-.ω.-芳基-脂肪酸酰胺，具有抑制肾素的作用，可用作降血压药物的活性成分。
• Azido containing tetrahydro furan compounds
  申请人：Novartis Corporation

  公开号：US05705658A1

  公开（公告）日：1998-01-06

  .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.

  化学式为I的.delta.-氨基-.gamma.-羟基-.ω-芳基-烷基酰胺及其盐具有抑制肾素的作用，可用作降压药物的活性成分。
• US5705658A
  申请人：——

  公开号：US5705658A

  公开（公告）日：1998-01-06