(4S,5S,2'S,2''S)-5-(2'-hydroxymethyl-3-methylbutyl)-4-{2''-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester | 172900-90-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4S,5S,2'S,2''S)-5-(2'-hydroxymethyl-3-methylbutyl)-4-{2''-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: 3-tert-butoxycarbonyl-5(S)-[3-hydroxy-2(S)-isopropyl-propyl]-4(S)-{2(S)-isopropyl-3-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-propyl}-2, 2-dimethyl-1,3-oxazolidine；3-tert-butoxycarbonyl-5(S)-(3-hydroxy-2(S)-isopropyl-propyl)-4(S)-{2(S)-isopropyl-3-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-propyl}-2,2-dimethyl-1,3-oxazolidine；3-Oxazolidinecarboxylic acid, 5-[(2S)-2-(hydroxymethyl)-3-methylbutyl]-4-[(2S)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutyl]-2,2-dimethyl-, 1,1-dimethylethyl ester, (4S,5S)-；tert-butyl (4S,5S)-5-[(2S)-2-(hydroxymethyl)-3-methylbutyl]-4-[(2S)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 172900-90-2
• 化学式: C₃₃H₅₇NO₇
• 分子量: 579.818
• InChiKey: ZDXRFABUSUGHRE-UMNYJUJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  86.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4S,5S,2'S,2''S)-5-(2'-hydroxymethyl-3-methylbutyl)-4-{2''-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 在 potassium permanganate 、 四丁基溴化铵 、 sodium sulfite 作用下， 以 水 、 甲苯 为溶剂， 反应 48.5h， 生成 (αS,4S,5S)-3-[(叔丁氧基)羰基]-4-[(2S)-2-[[4-甲氧基-3-(3-甲氧基丙氧基)苯基]甲基]-3-甲基丁基]-2,2-二甲基-α-异丙基-5-噁唑烷丙酸
  参考文献：
  名称：

  [EN] METHODS OF TREATING ALZHEIMER'S DISEASE USING ARYL ALKANOIC ACID AMIDES
  [FR] METHODES DE TRAITEMENT DE LA MALADIE D'ALZHEIMER PAR DES AMIDES D'ACIDE ARYL ALCANOIQUE

  摘要：

  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。

  公开号：

  WO2003103653A1
• 作为产物：
  描述：

  (4S,5S,2'S,2''S)-5-(2'-benzyloxymethyl-3-methylbutyl)-4-{2''-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 在 钯 silica gel 、 ethyl acetate n-hexane 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 (4S,5S,2'S,2''S)-5-(2'-hydroxymethyl-3-methylbutyl)-4-{2''-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  .delta.-amino-.gamma.-hydroxy-.omega.-aryl-alkanoic acid amides

  摘要：

  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。

  公开号：

  US05627182A1

文献信息

• .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。
• METHODS FOR PREPARATION OF PHARMACEUTICAL INTERMEDIATES OF ALISKIREN
  申请人：Yin Xuezhi

  公开号：US20130231509A1

  公开（公告）日：2013-09-05

  Disclosed are methods for preparation of two pharmaceutical intermediates (I, II) of Aliskiren, said intermediates are obtained by reacting compound of formula I or II and tribromophosphorus oxide. The method replaces the method in the prior art which is using column chromatopraphy to produce the compounds I and II, and overcomes the defect that the method in the prior art hardly carry out in a large-scale industrial production. The product can be purified by recrystallization or vacuum distillation, and the chemical purity of the product is good.

  本发明公开了制备Aliskiren的两种药物中间体(I, II)的方法，所述中间体是通过将化合物I或II和三溴化磷氧反应获得的。该方法替代了先前技术中使用色谱柱制备化合物I和II的方法，并克服了先前技术中该方法难以进行大规模工业生产的缺陷。该产品可以通过重结晶或真空蒸馏进行纯化，产品的化学纯度良好。
• Structural Modification of the P2‘ Position of 2,7-Dialkyl-Substituted 5(<i>S</i>)-Amino-4(<i>S</i>)-hydroxy-8-phenyl-octanecarboxamides:  The Discovery of Aliskiren, a Potent Nonpeptide Human Renin Inhibitor Active after Once Daily Dosing in Marmosets
  作者：Jürgen Maibaum、Stefan Stutz、Richard Göschke、Pascal Rigollier、Yasuchika Yamaguchi、Frédéric Cumin、Joseph Rahuel、Hans-Peter Baum、Nissim-Claude Cohen、Christian R. Schnell、Walter Fuhrer、Markus G. Gruetter、Walter Schilling、Jeanette M. Wood

  DOI：10.1021/jm070316i

  日期：2007.10.1

  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.