(1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester

• 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,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester
• 英文别名: 5(S)-tert-butoxycarbonylamino-4(R,S)-hydroxy-2(S),7(S)-diisopropyl-8-[4-methoxy-3-(3-methoxy-propyloxy)-phenyl]-octyl-benzyl ether；3-(S)-Benzyloxymethyl-6(S)-(tert-butoxycarbonyl)amino-8(S)-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-2,9-dimethyl-decan-5(R,S)-ol；tert-butyl N-[(3S,5S,8S)-6-hydroxy-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-2,9-dimethyl-8-(phenylmethoxymethyl)decan-5-yl]carbamate
• 化学式: C₃₇H₅₉NO₇
• 分子量: 629.878
• InChiKey: FBKNBZNJUIGABN-JSEVFZLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  45
• 可旋转键数：
  22
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  95.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester 在 palladium dihydroxide 2-羟基吡啶 、 三甲基氯硅烷 、 四丙基高钌酸铵 、 氢气 、 N-甲基吗啉氧化物 、 三乙胺 、 苯酚 作用下， 以 二氯甲烷 为溶剂， 生成 阿利克仑
  参考文献：
  名称：

  Practical synthesis of an orally active renin inhibitor aliskiren

  摘要：

  A convergent synthesis of aliskiren was accomplished via the use of Segment AB as the key intermediate, which was prepared via the coupling of the Grignard reagent derived from Segment B with Segment A, followed by subsequent oxidative lactonization. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.07.028
• 作为产物：
  描述：

  (4R)-3-[(2S)-3-甲基-1-氧代-2-[(苄氧基)甲基]丁基]-4-苄基-2-恶唑啉酮 在 lithium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 双氧水 、 magnesium 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Practical synthesis of an orally active renin inhibitor aliskiren

  摘要：

  A convergent synthesis of aliskiren was accomplished via the use of Segment AB as the key intermediate, which was prepared via the coupling of the Grignard reagent derived from Segment B with Segment A, followed by subsequent oxidative lactonization. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.07.028

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。
• Alpha-aminoalkanoic acids and reduction products
  申请人：Novartis Corporation

  公开号：US05659065A1

  公开（公告）日：1997-08-19

  Compounds of formula I ##STR1## wherein R.sub.1 is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, aromatic or heteroaromatic radical, a hydroxy group that is aliphatically, araliphatically or heteroarylaliphatically etherified or protected by a hydroxy-protecting group, or an aliphatically etherified mercapto group, and R.sub.2 is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic or heteroarylaliphatic radical, or R.sub.1 and R.sub.2 together form a divalent aliphatic radical, R.sub.3 is free or aliphatically, araliphatically or aromatically esterified carboxy, formyl or hydroxymethyl, R.sub.4 is hydrogen, an aliphatic or araliphatic radical or an amino-protecting group, and R.sub.5 is hydrogen or an aliphatic radical, and the salts thereof can be used as intermediates in the preparation of medicinal active ingredients.

  化合物公式I的化合物 其中R.sub.1是脂肪族，环脂族，环脂族-脂肪族，芳香族或杂环芳香族基团，是脂肪基，芳基或杂环基团的羟基，被脂肪基，芳基或杂环基团的羟基保护，或是脂肪基醚化的巯基，而R.sub.2是脂肪族，环脂族，环脂族-脂肪族，芳基或杂环芳香族基团，或R.sub.1和R.sub.2一起形成二价的脂肪基团，R.sub.3是自由的或脂肪基，芳基或芳基酯化的羧基，甲酰基或羟甲基，R.sub.4是氢，脂肪基或芳基基团或氨基保护基团，而R.sub.5是氢或脂肪基，其盐可以用作药用活性成分的制备中间体。
• 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.
• Practical synthesis of an orally active renin inhibitor aliskiren
  作者：Hua Dong、Zhi-Liu Zhang、Jia-Hui Huang、Rujian Ma、Shu-Hui Chen、Ge Li

  DOI：10.1016/j.tetlet.2005.07.028

  日期：2005.9

  A convergent synthesis of aliskiren was accomplished via the use of Segment AB as the key intermediate, which was prepared via the coupling of the Grignard reagent derived from Segment B with Segment A, followed by subsequent oxidative lactonization. (c) 2005 Elsevier Ltd. All rights reserved.