阿利克仑-8 | 172900-83-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 阿利克仑-8
• 中文别名: [(1S,3S)-3-[3-(3-甲氧基丙氧基)-4-甲氧基苄基]-1-醛基-4-甲基戊基]氨基甲酸叔丁酯
• 英文名称: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester
• 英文别名: {(1S,3S)-1-formyl-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamic acid tert-butyl ester；2(S)-tert-butoxycarbonylamino-4(S)-isopropyl-5-[4-methoxy-3-(3-methoxopropyloxy)-phenyl]-pentanal；tert-butyl (1S,3S)-3-(3-(3-methoxypropoxy)-4-methoxybenzyl)-1-formyl-4-rnethylpentyl-carbamate；tert-butyl (1S,3S)-3-(3-(3-methoxypropoxy)-4-methoxybenzyl)-1-formyl-4-methylpentyl-carbamate；tert-butyl {1(S)-formyl-3(S)-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate；tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate；tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-5-methyl-1-oxohexan-2-yl]carbamate
• CAS: 172900-83-3
• 化学式: C₂₄H₃₉NO₆
• 分子量: 437.577
• InChiKey: KFDRZNSEFRKMIT-PMACEKPBSA-N

物化性质

• 沸点：
  554.4±50.0 °C(Predicted)
• 密度：
  1.045

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexan-1-ol	172900-82-2	C24H41NO6	439.593
  (AlphaS,γS)- Alpha-[[(叔丁氧基)羰基]氨基]-4-甲氧基-3-(3-甲氧基丙氧基)- γ-异丙基苯戊酸甲酯	methyl (2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate	656241-21-3	C25H41NO7	467.603
  ——	ethyl (2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate	172900-76-4	C26H43NO7	481.63
  ——	methyl (2S,4S)-2-amino-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate	656241-36-0	C20H33NO5	367.486
  2-(3-甲氧基丙氧基)-4-((R)-2-(溴甲基)-3-甲基丁基)-1-甲氧基苯	(2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl bromide	172900-69-5	C17H27BrO3	359.304
  (R)-[2-碘甲基-3-甲基丁基]-1-甲氧基-2-(3-甲氧基丙氧基)苯	(R)-­4-(2-(iodomethyl)­-3-­methylbutyl)-­1-­methoxy-2­-(3-­methoxypropoxy)benzene	900811-38-3	C17H27IO3	406.304
  (R)-2-[3-(3-甲氧基丙氧基)-4-甲氧基苄基]-3-甲基丁-1-醇	(R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutanol	172900-70-8	C17H28O4	296.407
  (ar)-4-甲氧基-3-(3-甲氧基丙氧基)-a-(1-甲基乙基)-苯丙酸	(R)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-(1-methylethyl)propanoic acid	172900-71-9	C17H26O5	310.39
  ——	(4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one	172900-72-0	C27H35NO6	469.578
  (2S,5R)-2,5-二氢-3,6-二甲氧基-2-[(2S)-2-[[4-甲氧基-3-(3-甲氧基丙氧基)苯基]甲基]-3-甲基丁基]-5-(1-甲基乙基)吡嗪	(2S,5R)-2,5-dihydro-3,6-dimethoxy-2-{(2S)-2-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-3-methylbutyl}-5-(1-methylethyl)pyrazine	656241-17-7	C26H42N2O5	462.63

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	tert-butyl (2S,3S,5S)-5-(3-(3-methoxypropoxy)-4-methoxybenzyl)-1-amino-2-hydroxy-6-methylheptan-3-ylcarbamate	861901-11-3	C25H44N2O6	468.634
  ——	tert-butyl (1S,3S)-3-(3-(3-methoxypropoxy)-4-methoxybenzyl)-4-methyl-1-((R)-oxiran-2-yl)pentylcarbamate	861901-07-7	C25H41NO6	451.604
  ——	((1S,2R,4S)-2-Hydroxy-4-hydroxymethyl-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl ester	866030-40-2	C30H53NO7	539.753
  ——	((1S,2S,4S)-2-hydroxy-4-hydroxymethyl-1-((S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl)-5-methyl-hexyl)-carbamic acid tert-butyl ester	866030-34-4	C30H53NO7	539.753
  ——	(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	——	C37H59NO7	629.878
  ——	(4S,5S,7S)-5-tert-Butoxycarbonylamino-4-hydroxy-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnon-2-ynoic acid ethyl ester	878276-68-7	C29H45NO8	535.678
  [1S-[1R*(R*),2R*,4R*]]-[4-[[(3-氨基-2,2-二甲基-3-氧代丙基)氨基]羰基]-2-羟基-1-[2-[[4-甲氧基-3-(3-甲氧基丙氧基)苯基]甲基]-3-甲基丁基]-5-甲基己基]-氨基甲酸叔丁酯	tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate	173338-07-3	C35H61N3O8	651.885
  [(1S,3S)-3-[[4-甲氧基-3-(3-甲氧基丙氧基)苯基]甲基]-4-甲基-1-[(2S,4S)-四氢-4-异丙基-5-氧代-2-呋喃基]戊基]-氨基甲酸叔丁酯	tert-butyl {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate	866030-35-5	C30H49NO7	535.722
  ——	tert-butyl (1S,3S)-1-((2R,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-4-methylpentylcarbamate	——	C30H49NO7	535.722
  阿利克仑	(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide	173334-57-1	C30H53N3O6	551.767

反应信息

• 作为反应物：
  描述：

  阿利克仑-8 在 palladium dihydroxide 2-羟基吡啶 、 三甲基氯硅烷 、 四丙基高钌酸铵 、 氢气 、 magnesium 、 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：

  methyl (2S,4S)-2-amino-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate 在 锂硼氢 、 三氧化硫吡啶 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 阿利克仑-8
  参考文献：
  名称：

  WO2007/123718

  摘要：

  公开号：

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。
• [EN] DIAMINO ALCOHOLS AND THEIR USE AS RENIN INHIBITORS<br/>[FR] DIAMINOALCOOLS ET UTILISATION DE CEUX-CI EN TANT QU'INHIBITEURS DE LA RENINE
  申请人：SPEEDEL EXPERIMENTA AG

  公开号：WO2005070877A1

  公开（公告）日：2005-08-04

  The application relates to novel amino alcohols of the general formula (I) where R, R1, R2, R3, R4, R5 and R6 each have the definitions illustrated in detail in the description, to a process for their preparation, and to the use of these compounds as medicines, in particular as renin inhibitors.

  该申请涉及一类新颖的氨基酸醇，其通用公式为(I)，其中R、R1、R2、R3、R4、R5和R6的定义在描述中详细说明，还涉及这些化合物的制备方法，以及将这些化合物用作药物，特别是作为肾素抑制剂的使用。
• [EN] ALTERNATIVE SYNTHESIS OF RENIN INHIBITORS AND INTERMEDIATES THEREOF<br/>[FR] SYNTHESE ALTERNATIVE D'INHIBITEURS DE RENINES ET D'INTERMEDIAIRES DE CELLES-CI
  申请人：NOVARTIS AG

  公开号：WO2006024501A1

  公开（公告）日：2006-03-09

  The present invention relates to synthetic routes to prepare a compound of the formula (A); wherein R< div="">

  这项发明涉及合成路线，用于制备化合物（A）的公式；其中 R
• Alternative synthesis of renin inhibitors and intermediates thereof
  申请人：NOVARTIS AG

  公开号：EP1978012A1

  公开（公告）日：2008-10-08

  The present invention relates to synthetic routes to prepare a compound of the formula wherein R1 is halogen, C1-6halogenalkyl, C1-6alkoxy-C1-6alkyloxy or C1-6alkoxy-C1-6alkyl; R2 is halogen, C1-4alkyl or C1-4alkoxy; R3 and R4 are independently branched C3-6alkyl; and R5 is cycloalkyl, C1-6alkyl, C1-6hydroxyalkyl, C1-6alkoxy-C1-6alkyl, C1-6alkanoyloxy-C1-6alkyl, C1-6aminoalkyl, C1-6alkylamino-C1-6alkyl, C1-6dialkylamino-C1-6alkyl, C1-6alkanoylamino-C1-6alkyl, HO(O)C-C1-6alkyl, C1-6alkyl-O-(O)C-C1-6alkyl, H2N-C(O)-C1-6alkyl, C1-6alkyl-HN-C(O)-C1-6alkyl or (C1-6alkyl)2N-C(O)-C1-6alkyl; or a pharmaceutically acceptable salt thereof as well as key intermediates obtained when following these routes as well as their preparation.

  本发明涉及合成路线以制备一个化合物，其化学式为：其中，R1为卤素，C1-6卤代烷基，C1-6烷氧基-C1-6烷氧基或C1-6烷氧基-C1-6烷基；R2为卤素，C1-4烷基或C1-4烷氧基；R3和R4分别是支链C3-6烷基；R5为环烷基，C1-6烷基，C1-6羟基烷基，C1-6烷氧基-C1-6烷基，C1-6酰氧基-C1-6烷基，C1-6氨基烷基，C1-6烷基氨基-C1-6烷基，C1-6二烷基氨基-C1-6烷基，C1-6酰胺基烷基，HO(O)C-C1-6烷基，C1-6烷基-O-(O)C-C1-6烷基，H2N-C(O)-C1-6烷基，C1-6烷基-HN-C(O)-C1-6烷基或(C1-6烷基)2N-C(O)-C1-6烷基；或其药学上可接受的盐，以及在遵循这些路线时获得的关键中间体及其制备方法。
• 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。