Epo A-lactam | 219989-85-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: Epo A-lactam
• 英文别名: [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-dihydroxy-8,8,10,12-tetramethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione；(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione
• CAS: 219989-85-2
• 化学式: C₂₆H₄₀N₂O₅S
• 分子量: 492.68
• InChiKey: LXPQEMJQPZOSQW-YUSADRHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Epo A-lactam 在 二氯二茂钛 、 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以47%的产率得到Z-Epo C-lactam
  参考文献：
  名称：

  Pd(0)-催化亲核取代反应在埃坡霉素天然产物内酰胺类似物的区域选择性和立体选择性合成中的新应用

  摘要：

  从未受保护的天然产物开始，使用简洁的半合成方法制备了埃坡霉素的几种内酰胺类似物。该策略中的重点是大环内酯的新型区域选择性和立体选择性 Pd(0) 催化叠氮化反应。所得叠氮酸中间体的随后还原和大环内酰胺化以令人满意的总产率提供了所需的大环内酰胺。整个三步序列被简化为埃坡霉素 B-内酰胺 BMS-247550 的“一锅”工艺，目前正在进行 I 期临床试验。完成了制备埃坡霉素 C 的内酰胺类似物的初始全合成路线，并与更直接的半合成方法进行了比较。所有内酰胺类似物都在体外进行了评估，并讨论了结果。

  DOI：

  10.1021/ja001899n
• 作为产物：
  描述：

  (3S,6R,7S,8S,12R,13S,15S)-15-amino-12,13-epoxy-4,4,6,8,16-pentamethyl-3,7-dihydroxy-17-(2-methyl-4-thiazolyl)-5-oxo-16(E)-heptadecenoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 Epo A-lactam
  参考文献：
  名称：

  Pd(0)-催化亲核取代反应在埃坡霉素天然产物内酰胺类似物的区域选择性和立体选择性合成中的新应用

  摘要：

  从未受保护的天然产物开始，使用简洁的半合成方法制备了埃坡霉素的几种内酰胺类似物。该策略中的重点是大环内酯的新型区域选择性和立体选择性 Pd(0) 催化叠氮化反应。所得叠氮酸中间体的随后还原和大环内酰胺化以令人满意的总产率提供了所需的大环内酰胺。整个三步序列被简化为埃坡霉素 B-内酰胺 BMS-247550 的“一锅”工艺，目前正在进行 I 期临床试验。完成了制备埃坡霉素 C 的内酰胺类似物的初始全合成路线，并与更直接的半合成方法进行了比较。所有内酰胺类似物都在体外进行了评估，并讨论了结果。

  DOI：

  10.1021/ja001899n

文献信息

• EPOTHILONE DERIVATIVES
  申请人：Vite D. Gregory

  公开号：US20070255055A1

  公开（公告）日：2007-11-01

  The present invention relates to compounds of the formula Q is selected from the group consisting of G is selected from the group consisting of alkyl, substituted alkyl, substituted or unsubstituted aryl, heterocyclo, W is O or NR 15 ; X is O or H,H; Y is selected from the group consisting of O; H,OR 16 ; OR 17 ,OR 17 ; NOR 18 ; H,NOR 19 ; H,NR 20 R 21 ; H,H; or CHR 22 ; OR 17 OR 17 can be a cyclic ketal; Z 1 and Z 2 are selected from the group consisting of CH 2 , O, NR 23 , S, or SO 2 , wherein only one of Z and Z 2 is a heteroatom; B 1 and B 2 are selected from the group consisting of OR 24 , or OCOR 25 , or O 2 CNR 26 R 27 ; when B 1 is H and Y is OH, H they can form a six-membered ring ketal or acetal; D is selected from the group consisting of NR 28 R 29 , NR 30 COR 31 or saturated heterocycle; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 13 , R 14 , R 18 , R 19 , R 20 , R 21 , R 22 , R 26 , and R 27 are selected from the group H, alkyl, substituted alkyl, or aryl and when R 1 and R 2 are alkyl can be joined to form a cycloalkyl; R 3 and R 4 are alkyl can be joined to form a cycloalkyl; R 9 , R 10 , R 16 , R 17 , R 24 , R 25 , and R 31 are selected from the group H, alkyl, or substituted alkyl; R 8 , R 11 , R 12 , R 28 , R 30 , R 32 , R 33 , and R 30 are selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, or heterocyclo; R 15 , R 23 and R 29 are selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, heterocyclo, R 32 C═O, R 33 SO 2 , hydroxy, O-alkyl or O-substituted alkyl, the pharmaceutically acceptable salts thereof and any hydrates, solvates or geometric, optical and stereoisomers thereof, with the proviso that compounds wherein W and X are both O; and R 1 , R 2 , R 7 , are H; and R 3 , R 4 , R 6 , are methyl; and R 8 , is H or methyl; and Z 1 , and Z 2 , are CH 2 ; and G is 1-methyl-2-(substituted-4-thiazolyl)ethenyl; and Q is as defined above are excluded.

  本发明涉及以下化合物的公式：其中Q选自G选自烷基，取代烷基，取代或未取代芳基，杂环烷基，W为O或NR15；X为O或H；Y选自O，H，OR16，OR17，NOR18，H，NOR19，H，NR20R21，H，H或CHR22；OR17OR17可以是环状缩酮；Z1和Z2选自CH2，O，NR23，S或SO2，其中仅Z和Z2中的一个为杂原子；B1和B2选自OR24，或OCOR25，或O2CNR26R27；当B1为H且Y为OH时，它们可以形成六元环缩酮或缩醛；D选自NR28R29，NR30COR31或饱和杂环；R1，R2，R3，R4，R5，R6，R7，R13，R14，R18，R19，R20，R21，R22，R26和R27选自H，烷基，取代烷基或芳基，当R1和R2为烷基时，可以连接成环烷基；R3和R4为烷基时，可以连接成环烷基；R9，R10，R16，R17，R24，R25和R31选自H，烷基或取代烷基；R8，R11，R12，R28，R30，R32，R33和R30选自H，烷基，取代烷基，芳基，取代芳基，环烷基或杂环烷基；R15，R23和R29选自H，烷基，取代烷基，芳基，取代芳基，环烷基，杂环烷基，R32C═O，R33SO2，羟基，O-烷基或O-取代烷基，其药学上可接受的盐和任何水合物，溶剂化合物或其几何，光学和立体异构体，但其中W和X都是O；并且R1，R2，R7为H；并且R3，R4，R6为甲基；并且R8为H或甲基；并且Z1和Z2为CH2；并且G为1-甲基-2-（取代-4-噻唑基）乙烯基；并且Q如上所定义被排除在外。
• Epothilone derivatives
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1526133A1

  公开（公告）日：2005-04-27

  The present invention relates to compounds of the formula Q is selected from the group consisting of G is selected from the group consisting of alkyl, substituted alkyl, substituted or unsubstituted aryl, heterocyclo, W is O or NR15; X is O or H,H; Y is selected from the group consisting of O; H,OR16; OR17,OR17; NOR18; H,NOR19; H,NR20R21; H,H; or CHR22; OR17 OR17 can be a cyclic ketal; Z1, and Z2 are selected from the group consisting of CH2, O, NR23, S, or SO2, wherein only one of Z and Z2 is a heteroatom; B1 and B2 are selected from the group consisting of OR24, or OCOR25, or O2CNR26R27; when B1 is H and Y is OH, H they can form a six-membered ring ketal or acetal; D is selected from the group consisting of NR28R29, NR30COR31 or saturated heterocycle R1, R2, R3, R4, R5, R6, R7, R13, R14, R18, R19, R20, R21, R22, R26, and R27 are selected from the group H, alkyl, substituted alkyl, or aryl and when R1 and R2 are alkyl can be joined to form a cycloalkyl; R3 and R4 are alkyl can be joined to form a cycloalkyl; R9, R10, R16, R17, R24, R25, and R31 are selected from the group H, alkyl, or substituted alkyl; R8, R11, R12, R28, R30, R32, R33, and R30 are selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, or heterocyclo; R15, R23 and R29 are selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, heterocyclo, R32C=O, R33SO2, hydroxy, O-alkyl or O-substituted alkyl, the pharmaceutically acceptable salts thereof and any hydrates, solvates or geometric, optical and stereoisomers thereof, with the proviso that compounds wherein W and X are both O; and R1, R2, R7, are H; and R3, R4, R6, are methyl; and R8, is H or methyl; and Z1, and Z2, are CH2; and G is 1-methyl-2-(substituted-4-thiazolyl)ethenyl; and Q is as defined above are excluded.

  本发明涉及公式化合物，其中Q选自以下组中的一种：G选自以下组中的一种：烷基，取代的烷基，取代或未取代的芳基，杂环基；W为O或NR15；X为O或H；Y选自以下组中的一种：O；H，OR16；OR17，OR17；NOR18；H，NOR19；H，NR20R21；H，H；或CHR22；OR17 OR17可以是环状的糖醇醚；Z1和Z2选自以下组中的一种：CH2，O，NR23，S或SO2，其中Z和Z2仅有一个是杂原子；B1和B2选自以下组中的一种：OR24，或OCOR25，或O2CNR26R27；当B1为H且Y为OH时，它们可以形成六元环糖醇醚或缩醛；D选自以下组中的一种：NR28R29，NR30COR31或饱和杂环基；R1、R2、R3、R4、R5、R6、R7、R13、R14、R18、R19、R20、R21、R22、R26和R27选自以下组中的一种：H，烷基，取代的烷基或芳基，当R1和R2为烷基时可以连接成环状烷基；当R3和R4为烷基时可以连接成环状烷基；R9、R10、R16、R17、R24、R25和R31选自以下组中的一种：H，烷基或取代的烷基；R8、R11、R12、R28、R30、R32、R33和R30选自以下组中的一种：H，烷基，取代的烷基，芳基，取代的芳基，环状烷基或杂环基；R15、R23和R29选自以下组中的一种：H，烷基，取代的烷基，芳基，取代的芳基，环状烷基，杂环基，R32C=O，R33SO2，羟基，O-烷基或O-取代的烷基，其药学上可接受的盐和任何水合物，溶剂化合物或几何、光学和立体异构体，但是排除了W和X都为O；R1、R2和R7都为H；R3、R4和R6都为甲基；R8为H或甲基；Z1和Z2为CH2；G为1-甲基-2-（取代-4-噻唑基）乙烯基；Q如上所述。
• Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases
  申请人：——

  公开号：US20030073677A1

  公开（公告）日：2003-04-17

  Compositions and methods are disclosed which are useful of the treatment and prevention of proliferative disorders.

  本发明揭示了用于治疗和预防增生性疾病的组合物和方法。
• Combination of epothilone analogs and chemotherapeutic agents for the treatment of prolferative diseases
  申请人：Lee Y.F. Francis

  公开号：US20050159461A1

  公开（公告）日：2005-07-21

  Compositions and methods are disclosed which are useful of the treatment and prevention of proliferative disorders.

  本研究公开了有助于治疗和预防增殖性疾病的组合物和方法。
• COMBINATION OF ANTI-CTLA4 ANTIBODY WITH TUBULIN MODULATING AGENTS FOR THE TREATMENT OF PROLIFERATIVE DISEASES
  申请人：Jure-Kunkel Maria

  公开号：US20100278828A1

  公开（公告）日：2010-11-04

  Compositions and methods are disclosed which are useful for the treatment and prevention of proliferative disorders, and which comprise an anti-CTLA4 antagonist with a tubulin modulating agent.