[(S*)-2-(3-benzyloxyphenyl)-1-((S*)-5-oxo-2,5-dihydrofuran-2-yl)ethyl]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: [(S*)-2-(3-benzyloxyphenyl)-1-((S*)-5-oxo-2,5-dihydrofuran-2-yl)ethyl]carbamic acid tert-butyl ester
• 英文别名: [(S*)-2-(3-Benzyloxy-phenyl)-1-((S*)-5-oxo-2,5-dihydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester；tert-butyl N-[(1S)-1-[(2S)-5-oxo-2H-furan-2-yl]-2-(3-phenylmethoxyphenyl)ethyl]carbamate
• 化学式: C₂₄H₂₇NO₅
• 分子量: 409.482
• InChiKey: AHQZRDQHUFLSRK-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(S*)-2-(3-benzyloxyphenyl)-1-((S*)-5-oxo-2,5-dihydrofuran-2-yl)ethyl]carbamic acid tert-butyl ester 在 5%-palladium/activated carbon 氢气 作用下， 以 四氢呋喃 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.0h， 以94%的产率得到[(S*)-2-(3-benzyloxy-phenyl)-1-((S*)-5-oxo-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Macrocyclic Compounds Useful as Bace Inhibitors

  摘要：

  本发明涉及具有公式(I)的新型大环化合物，其中所有变量如说明书中所定义，大环环中包含的环原子数为14、15、16或17，以自由碱形式或酸加成盐形式存在，以及它们的制备方法、作为药物的使用以及包含它们的药物。

  公开号：

  US20080132477A1
• 作为产物：
  描述：

  [1-benzenesulfonyl-2-(3-benzyloxy-phenyl)-ethyl]-carbamic acid tert-butyl ester 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 反应 1.08h， 生成 [(S*)-2-(3-benzyloxyphenyl)-1-((S*)-5-oxo-2,5-dihydrofuran-2-yl)ethyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] NOVEL DIBENZO[B,F]OXEPINE-10-CARBOXAMIDES AND PHARMACEUTICAL USES THEREOF
  [FR] NOUVEAUX DIBENZO[B,F]OXEPINE-10-CARBOXAMIDES ET UTILISATIONS PHARMACEUTIQUES DE CES COMPOSES

  摘要：

  公开号：

  WO2005014517A3

文献信息

• [EN] MACROCYCLIC COMPOUNDS HAVING ASPARTIC PROTEASE INHIBITING ACTIVITY AND PHARMACEUTICAL USES THEREOF<br/>[FR] COMPOSES MACROCYLIQUES PRESENTANT UNE ACTIVITE D'INHIBITION DE PROTEASE ASPARTIQUE ET UTILISATIONS PHARMACEUTIQUES DE CEUX-CI
  申请人：NOVARTIS AG

  公开号：WO2005003106A1

  公开（公告）日：2005-01-13

  The present invention relates to macrocyclic compounds of formula (I), wherein R1, is (C1-8)alkyl, (C1-4)alkoxy(C1-4)alkyl, hydroxy(C1-6)alkyl, (C1-4)alkylthio(C1-4)alkyl, (C1-6)alkenyl, (C3-­7)cycloalkyl, (C3-7)cycloalkyl(C1-4)alkyl, piperidinyl or pyrrolidinyl, R2 and R4, independently, are hydrogen or optionally substituted (C1-8)alkyl, (C3-7) cycloalkyl, (C3-7)cycloalkyl(C1-4)alkyl, aryl, aryl(C1-4)alkyl, heteroaryl or heteroaryl(C1-4) alkyl, or R2 and R4, together with the nitrogen to which they are attached, form an optionally substituted piperidino, pyrrolidinyl, morpholino or piperazinyl group, R3 is hydrogen or (C1-4)alkyl, X1 is CH2, X2 is CH2, O, S, CO, COO, OCO, NHCO, CONH, or NR, R being hydrogen or (C1-4)alkyl, Y is (C1-8)alkylen or (C1-­8)alkylenoxy(C1-6)alkylen, (C1-8)alkenylen or (C1-8)alkenylenoxy(C1-6)alkylen, Ar is a phenyl ring optionally mono- di­ or trisubstituted by, independently, hydroxy or halogen, whereby X1, and X2 are in meta or para position to each other, and either Z is CO, AA is a natural or unnatural alpha-amino-acid, and n is 0 or 1, or Z is S02, AA is an optionally substituted ethylencarbonyl group (derived from a natural or unnatural alpha-amino acid by replacement of the nitrogen by a methylen group), and n is 1; processes for the preparation of these compounds; pharmaceutical compositions and combinations comprising the same; and their use in the treatment of neurological and vascular disorders related to beta-amyloid generation and/or aggregation.

  本发明涉及式(I)的大环化合物，其中R1为(C1-8)烷基，(C1-4)烷氧基(C1-4)烷基，羟基(C1-6)烷基，(C1-4)烷基硫基(C1-4)烷基，(C1-6)烯基，(C3-7)环烷基，(C3-7)环烷基(C1-4)烷基，哌啶基或吡咯啉基，R2和R4，独立地，为氢或可选择取代的(C1-8)烷基，(C3-7)环烷基，(C3-7)环烷基(C1-4)烷基，芳基，芳基(C1-4)烷基，杂环芳基或杂环芳基(C1-4)烷基，或R2和R4与它们连接的氮一起形成可选择取代的哌啶基，吡咯啉基，吗啉基或哌嗪基，R3为氢或(C1-4)烷基，X1为CH2，X2为CH2，O，S，CO，COO，OCO，NHCO，CONH或NR，R为氢或(C1-4)烷基，Y为(C1-8)烷基或(C1-8)烷氧基(C1-6)烷基，(C1-8)烯基或(C1-8)烯氧基(C1-6)烷基，Ar为苯环，可选择单取代、双取代或三取代，取代基为羟基或卤素，其中X1和X2在彼此的间位或对位，且Z为CO时，AA为天然或非天然的α-氨基酸，n为0或1；或Z为SO2时，AA为可选择取代的乙烯羰基团（由天然或非天然的α-氨基酸通过用甲基烷基替换氮而得到），n为1；制备这些化合物的方法；包含这些化合物的药物组合物和药物组合物；以及它们在治疗与β-淀粉样蛋白生成和/或聚集相关的神经和血管疾病中的用途。
• Macrocyclic compounds having aspartic protease inhibiting activity and pharmaceutical uses thereof
  申请人：Betschart Claudia

  公开号：US20060223745A1

  公开（公告）日：2006-10-05

  The present invention relates to macrocyclic compounds of formula (I), wherein R 1 , is (C 1-8 )alkyl, (C 1-4 )alkoxy(C 1-4 )alkyl, hydroxy(C 1-6 )alkyl, (C 1-4 )alkylthio(C 1-4 )alkyl, (C 1-6 )alkenyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl(C 1-4 )alkyl, piperidinyl or pyrrolidinyl, R 2 and R 4 , independently, are hydrogen or optionally substituted (C 1-8 )alkyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl(C 1-4 )alkyl, aryl, aryl(C 1-4 )alkyl, heteroaryl or heteroaryl(C 1-4 )alkyl, or R 2 and R 4 , together with the nitrogen to which they are attached, form an optionally substituted piperidino, pyrrolidinyl, morpholino or piperazinyl group, R 3 is hydrogen or (C 1-4 )alkyl, X 1 is CH 2 , X 2 is CH 2 , O, S, CO, COO, OCO, NHCO, CONH, or NR, R being hydrogen or (C 1-4 )alkyl, Y is (C 1-8 )alkylen or (C 1-8 )alkylenoxy(C 1-6 )alkylen, (C 1-8 )alkenylen or (C 1-6 )alkenylenoxy(C 1-6 )alkylen, Ar is a phenyl ring optionally mono- di or trisubstituted by, independently, hydroxy or halogen, whereby X 1 , and X 2 are in meta or para position to each other, and either Z is CO, AA is a natural or unnatural alpha-amino-acid, and n is 0 or 1, or Z is SO 2 , AA is an optionally substituted ethylencarbonyl group (derived from a natural or unnatural alpha-amino acid by replacement of the nitrogen by a methylen group), and n is 1; processes for the preparation of these compounds; pharmaceutical compositions and combinations comprising the same; and their use in the treatment of neurological and vascular disorders related to beta-amyloid generation and/or aggregation.

  本发明涉及式（I）的大环化合物，其中R1为（C1-8）烷基，（C1-4）烷氧基（C1-4）烷基，羟基（C1-6）烷基，（C1-4）烷基硫基（C1-4）烷基，（C1-6）烯基，（C3-7）环烷基，（C3-7）环烷基（C1-4）烷基，哌啶基或吡咯烷基，R2和R4独立地为氢或可选取代的（C1-8）烷基，（C3-7）环烷基，（C3-7）环烷基（C1-4）烷基，芳基，芳基（C1-4）烷基，杂环芳基或杂环芳基（C1-4）烷基，或R2和R4与它们附着的氮一起形成可选取代的哌啶基，吡咯烷基，吗啉基或哌嗪基，R3为氢或（C1-4）烷基，X1为CH2，X2为CH2，O，S，CO，COO，OCO，NHCO，CONH或NR，其中R为氢或（C1-4）烷基，Y为（C1-8）烷基或（C1-8）烷氧基（C1-6）烷基，（C1-8）烯基或（C1-6）烯氧基（C1-6）烷基，Ar为苯环，可选取代，独立地为羟基或卤素，其中X1和X2在彼此的间位或对位，且Z为CO时，AA为天然或非天然α-氨基酸，n为0或1，或Z为SO2时，AA为可选取代的乙烯羰基（通过将氮替换为甲基烷基而来自天然或非天然α-氨基酸），n为1；制备这些化合物的方法；包含它们的制药组合物和组合物；以及它们在治疗与β-淀粉样蛋白生成和/或聚集有关的神经和血管疾病中的用途。
• MACROCYCLIC COMPOUNDS HAVING ASPARTIC PROTEASE INHIBITING ACTIVITY AND PHARMACEUTICAL USES THEREOF
  申请人：Betschart Claudia

  公开号：US20080070885A1

  公开（公告）日：2008-03-20

  The present invention relates to macro-cyclic compounds of formula (I), wherein R 1 , is (C 1-8 )alkyl, (C 1-4 )alkoxy(C 1-4 )alkyl, hydroxy(C 1-6 )alkyl, (C 1-4 )alkylthio(C 1-4 )alkyl, (C 1-6 )alkenyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl(C 1-4 )alkyl, piperidinyl or pyrrolidinyl, R 2 and R 4 , independently, are hydrogen or optionally substituted (C 1-8 )alkyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl(C 1-4 )alkyl, aryl, aryl(C 1-4 )alkyl, heteroaryl or heteroaryl(C 1-4 )alkyl, or R 2 and R 4 , together with the nitrogen to which they are attached, form an optionally substituted piperidino, pyrrolidinyl, morpholino or piperazinyl group, R 3 is hydrogen or (C 1-4 )alkyl, X 1 is CH 2 , X 2 is CH 2 , O, S, CO, COO, OCO, NHCO, CONH, or NR, R being hydrogen or (C 1-4 )alkyl, Y is (C 1-8 )alkylen or (C 1-8 )alkylenoxy(C 1-6 )alkylen, (C 1-8 )alkenylen or (C 1-8 )alkenylenoxy(C 1-6 )alkylen, Ar is a phenyl ring optionally mono- di or trisubstituted by, independently, hydroxy or halogen, whereby X 1 , and X 2 are in meta or para position to each other, and either Z is CO, AA is a natural or unnatural alpha-amino-acid, and n is 0 or 1, or Z is S0 2 , AA is an optionally substituted ethylencarbonyl group (derived from a natural or unnatural alpha-amino acid by replacement of the nitrogen by a methylen group), and n is 1; processes for the preparation of these compounds; pharmaceutical compositions and combinations comprising the same; and their use in the treatment of neurological and vascular disorders related to beta-amyloid generation and/or aggregation.

  本发明涉及公式（I）的大环化合物，其中R1是（C1-8）烷基，（C1-4）烷氧基（C1-4）烷基，羟基（C1-6）烷基，（C1-4）烷基硫基（C1-4）烷基，（C1-6）烯基，（C3-7）环烷基，（C3-7）环烷基（C1-4）烷基，哌啶基或吡咯烷基，R2和R4分别是氢或可选择取代的（C1-8）烷基，（C3-7）环烷基，（C3-7）环烷基（C1-4）烷基，芳基，芳基（C1-4）烷基，杂环芳基或杂环芳基（C1-4）烷基，或R2和R4与它们连接的氮一起形成可选择取代的哌啶基，吡咯烷基，吗啉基或哌嗪基，R3是氢或（C1-4）烷基，X1是CH2，X2是CH2，O，S，CO，COO，OCO，NHCO，CONH或NR，其中R是氢或（C1-4）烷基，Y是（C1-8）烷基或（C1-8）烷氧基（C1-6）烷基，（C1-8）烯基或（C1-8）烯氧基（C1-6）烷基，Ar是苯环，可选择单取代，二取代或三取代，独立的取代基为羟基或卤素，其中X1和X2相对于彼此处于间位或对位，且Z要么是CO，AA是天然或非天然α-氨基酸，n为0或1，要么Z是S02，AA是可选择取代的乙烯基羰基基团（通过将氮替换为甲基烷基团从天然或非天然α-氨基酸衍生而来），n为1；制备这些化合物的方法；包括这些化合物的药物组合物和制剂；以及它们在治疗与β-淀粉样蛋白生成和/或聚集有关的神经和血管疾病中的用途。
• Novel dibenzo [b, f] oxepine-10-carboxamides and pharmaceutical uses thereof
  申请人：Auberson Yves

  公开号：US20070111991A1

  公开（公告）日：2007-05-17

  The present invention pertains to novel dibenzo[b,f]oxepine-10-carboxamides compound to a process for the preparation of such compounds of formula I, their use as a pharmaceuticals, especially in the treatment of neurological and vascular disorders related to beta-amyloid generation and/or aggregation, and to pharmaceutical compositions and combinations comprising such compounds of formula I.

  本发明涉及一种新的二苯并[b,f]噁喹啉-10-羧酰胺化合物，以及制备该式I化合物的方法，其在药物学中的应用，尤其是在与β-淀粉样蛋白生成和/或聚集有关的神经和血管疾病的治疗中的应用，以及包含该式I化合物的药物组合物和制剂。
• Dibenzo[b,f]oxepine-10-carboxamides and pharmaceutical uses thereof
  申请人：Novartis AG

  公开号：US07612054B2

  公开（公告）日：2009-11-03

  The present invention pertains to novel dibenzo[b,f]oxepine-10-carboxamides compound to a process for the preparation of such compounds of formula I, their use as a pharmaceuticals, especially in the treatment of neurological and vascular disorders related to beta-amyloid generation and/or aggregation, and to pharmaceutical compositions and combinations comprising such compounds of formula I.

  本发明涉及新型二苯并[b,f]噁吩-10-羧酰胺化合物及其制备过程，其用作药物，尤其是用于治疗与β-淀粉样蛋白生成和/或聚集相关的神经和血管疾病，以及包含该化合物的药物组合物和制剂。