(1S,2S,4R,2'S)-{4-butylcarbamoyl-2-hydroxy-1-[2'-(3-hydroxy-4-methoxy-benzyl)-3-methyl-butyl]-pentyl}-carbamic acid tert-butyl ester | 172900-97-9

• 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: (1S,2S,4R,2'S)-{4-butylcarbamoyl-2-hydroxy-1-[2'-(3-hydroxy-4-methoxy-benzyl)-3-methyl-butyl]-pentyl}-carbamic acid tert-butyl ester
• 英文别名: N-tert-butoxycarbonyl-2(R)-methyl-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-(3-hydroxy-4-methoxy-phenyl)-octanoic acid (N-butyl) amide；N-tert-butoxycarbonyl-2(R)-methyl-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-(3-hydroxy-4-methoxy-phenyl)-octanoic acid (N-butyl)amide；tert-butyl N-[(2R,4S,5S,7S)-1-(butylamino)-4-hydroxy-7-[(3-hydroxy-4-methoxyphenyl)methyl]-2,8-dimethyl-1-oxononan-5-yl]carbamate
• CAS: 172900-97-9
• 化学式: C₂₈H₄₈N₂O₆
• 分子量: 508.699
• InChiKey: LQPZSURPMBAWKR-SWUCNREESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,2S,4R,2'S)-{4-butylcarbamoyl-2-hydroxy-1-[2'-(3-hydroxy-4-methoxy-benzyl)-3-methyl-butyl]-pentyl}-carbamic acid tert-butyl ester 、 1-碘戊烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 以70%的产率得到N-tert-butoxycarbonyl-2(R)-methyl-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-(3-pentyloxy-4-methoxy-phenyl)-octanoic acid (N-butyl) 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
• 作为产物：
  描述：

  (1S,2S,4R,2'S)-{1-[2'-(3-benzyloxy-4-methoxy-benzyl)-3'-methyl-butyl]-4-butylcarbamoyl-2-hydroxy-pentyl}-carbamic acid tert-butyl ester 在 钯 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 (1S,2S,4R,2'S)-{4-butylcarbamoyl-2-hydroxy-1-[2'-(3-hydroxy-4-methoxy-benzyl)-3-methyl-butyl]-pentyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Azido containing tetrahydro furan compounds

  摘要：

  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。

  公开号：

  US05705658A1

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：US05646143A1

  公开（公告）日：1997-07-08

  .delta.-Amino-.gamma.-hydroxy-.omega.-aryl-alkanoic acid amides of formula I ##STR1##

  化学式为I的.delta.-氨基-.gamma.-羟基-.omega.-芳基-烷基酰胺
• .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。
• 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。
• 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。