bis-TES-epothilone A | 247232-06-0

• 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: bis-TES-epothilone A
• 英文别名: [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-8,8,10,12-tetramethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-7,11-bis[(triethylsily)oxy]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione；[1S-[1R,3R(E),7R,10S,11R,12R,16S]]-8,8,10,12-tetramethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-7,11-bis[(triethylsilyl)oxy]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
• CAS: 247232-06-0
• 化学式: C₃₈H₆₇NO₆SSi₂
• 分子量: 722.19
• InChiKey: CUJMXWBANZPDJV-OTIUJXPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.15
• 重原子数：
  48.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  87.25
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  bis-TES-epothilone A 在 吡啶 、 pyridinium chlorochromate 、 magnesium bromide 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 [4S-[4R*,7S*,8R*,9R*,14S*,16R*(E)]]-14-bromo-4,8-bis(triethylsilyloxy)-5,5,7,9-tetramethyl-16-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-1-oxacyclohexadecane-2,6,13-trione
  参考文献：
  名称：

  SAR and pH Stability of Cyano-Substituted Epothilones

  摘要：

  graphic3-Cyano epothilones 15-18 are the only examples of non-hydroxy C-3-substituted analogues. Their tubulin binding affinity and cytotoxicity provide meaningful structure-activity relationship information on the dependence of C-1/C-3 conformation upon activity. 12-Cyano epothilone 24 has improved pH stability over epothilone B, and its activity further supports the hypothesis that C-12 stereochemistry is not critical for tubulin affinity.

  DOI：

  10.1021/ol026589j
• 作为产物：
  描述：

  埃博霉素C 在 Oxone 、 乙二胺四乙酸 、 1,1,1-三氟丙酮 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 bis-TES-epothilone A
  参考文献：
  名称：

  Synthesis and Biological Activity of Novel Epothilone Aziridines

  摘要：

  [GRAPHICS]A series of 12 alpha ,13 alpha -aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 positions. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. The results indicate that the aziridine moiety is a viable isosteric replacement for the epoxide in the case of epothilones.

  DOI：

  10.1021/ol016273w

文献信息

• AZIRIDINYL-EPOTHILONE COMPOUNDS
  申请人：Vite D. Gregory

  公开号：US20070276018A1

  公开（公告）日：2007-11-29

  The present invention is directed to aziridinyl epothilone compounds as further described herein, and/or pharmaceutically-acceptable salts and/or solvates thereof having the following Formula: wherein K is —O—, —S—, or —NR 7 —; A is —(CR 8 R 9 )—(CH 2 ) m -Z- wherein Z is —(CHR 10 )—, —C(═O)—, —C(═O)—C(═O)—, —OC(═O)—, —N(R 11 )C(═O)—, —SO 2 —, or —N(R 11 )SO 2 —; B 1 is hydroxyl or cyano and R 1 is hydrogen or B 1 and R 1 are taken together to form a double bond; R 2 , R 3 , and R 5 are, independently, hydrogen, alkyl, substituted alkyl, aryl or substituted aryl; or R 2 and R 3 may be taken together with the carbon to which they are attached to form an optionally substituted cycloalkyl; R 4 is hydrogen, alkyl, alkenyl, substituted alkyl, substituted alkenyl, aryl, or substituted aryl; R 6 is hydrogen, alkyl or substituted alkyl; R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, or substituted heteroaryl; and R 13 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.

  本发明涉及如下所述的吲哚环毒毒素化合物，以及/或其在下式中具有以下结构的药学上可接受的盐和/或溶剂：其中K为—O—、—S—或—NR7—；A为—(CR8R9)—(CH2)m-Z-，其中Z为—(CHR10)—、—C(═O)—、—C(═O)—C(═O)—、—OC(═O)—、—N(R11)C(═O)—、—SO2—或—N(R11)SO2—；B1为羟基或氰基，R1为氢或B1和R1一起形成双键；R2、R3和R5独立地为氢、烷基、取代烷基、芳基或取代芳基；或R2和R3可以与它们连接的碳一起形成可选择取代的环烷基；R4为氢、烷基、烯烃基、取代烷基、取代烯烃基、芳基或取代芳基；R6为氢、烷基或取代烷基；R7、R8、R9、R10、R11和R12独立地为氢、烷基、取代烷基、环烷基、取代环烷基、芳基、取代芳基、杂环烷基、取代杂环烷基、杂芳基或取代杂芳基；而R13为芳基、取代芳基、杂芳基或取代杂芳基。
• CONJUGATES OF AZIRIDINYL-EPOTHILONE ANALOGS AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME
  申请人：Vite D. Gregory

  公开号：US20070275904A1

  公开（公告）日：2007-11-29

  The present invention is directed to conjugated compounds comprising a folate, or an analog or derivative thereof, and an aziridinyl epothilone analog, as further described herein, and/or pharmaceutically-acceptable salts and/or solvates thereof, useful in the treatment of cancer or other folate-receptor associated conditions.

  本发明涉及包含叶酸、叶酸类似物或衍生物以及环氧紫杉烷类似物的共轭化合物，如下文进一步描述，并/或其药用可接受盐和/或溶剂，用于治疗癌症或其他叶酸受体相关疾病。
• Synthesis and Biological Activity of Novel Epothilone Aziridines
  作者：Alicia Regueiro-Ren、Robert M. Borzilleri、Xiaoping Zheng、Soong-Hoon Kim、James A. Johnson、Craig R. Fairchild、Francis Y. F. Lee、Byron H. Long、Gregory D. Vite

  DOI：10.1021/ol016273w

  日期：2001.8.1

  [GRAPHICS]A series of 12 alpha ,13 alpha -aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 positions. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. The results indicate that the aziridine moiety is a viable isosteric replacement for the epoxide in the case of epothilones.
• SAR and pH Stability of Cyano-Substituted Epothilones
  作者：Alicia Regueiro-Ren、Kenneth Leavitt、Soong-Hoon Kim、Gerhard Höfle、Michael Kiffe、Jack Z. Gougoutas、John D. DiMarco、Francis Y. F. Lee、Craig R. Fairchild、Byron H. Long、Gregory D. Vite

  DOI：10.1021/ol026589j

  日期：2002.10.1

  graphic3-Cyano epothilones 15-18 are the only examples of non-hydroxy C-3-substituted analogues. Their tubulin binding affinity and cytotoxicity provide meaningful structure-activity relationship information on the dependence of C-1/C-3 conformation upon activity. 12-Cyano epothilone 24 has improved pH stability over epothilone B, and its activity further supports the hypothesis that C-12 stereochemistry is not critical for tubulin affinity.