epofolate | 958646-17-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: epofolate
• 英文别名: BMS-753493；(S)-2-(4-((2-amino-4-oxo-3,4-dihydropteridin-6-yl)methylamino)benzamido)-5-((S)-3-carboxy-1-((S)-1-((S)-3-carboxy-1-((R)-1-carboxy-2-(2-(2-((2-((1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-5,9-dioxo-4-oxa-17-aza-bicyclo[14.1.0]heptadecan-17-yl)ethoxy)carbonyloxy)ethyl)disulfanyl)ethylamino)-1-oxopropan-2-ylamino)-5-guanidino-1-oxopentan-2-ylamino)-1-oxopropan-2-ylamino)-5-oxopentanoic acid；(2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(1R)-1-carboxy-2-[2-[2-[(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]-5,9-dioxo-4-oxa-17-azabicyclo[14.1.0]heptadecan-17-yl]ethoxycarbonyloxy]ethyldisulfanyl]ethyl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 958646-17-8
• 化学式: C₆₇H₉₂N₁₆O₂₂S₃
• 分子量: 1569.76
• InChiKey: TURJYGRXEJIBGT-OCOMGVANSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  108
• 可旋转键数：
  38
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  679
• 氢给体数：
  16
• 氢受体数：
  32

反应信息

• 作为反应物：
  描述：

  epofolate 在 3,3,3-膦三基三丙酸 作用下， 生成 (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-17-(2-hydroxyethyl)-8,8,10,12-tetramethyl-3-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4-oxa-17-azabicyclo[14.1.0]heptadecane-5,9-dione 、 (S)-2-(4-((2-amino-4-oxo-3,4-dihydropteridin-6-yl)methylamino)benzamido)-5-((S)-3-carboxy-1-((S)-1-((S)-3-carboxy-1-((S)-1-carboxy-2-mercaptoethylamino)-1-oxopropan-2-ylamino)-5-guanidino-1-oxopentan-2-ylamino)-1-oxopropan-2-ylamino)-5-oxopentanoic acid
  参考文献：
  名称：

  埃博霉素类似物和叶酸衍生的叶酸受体靶向药物的区域选择性合成

  摘要：

  描述了叶酸和衍生自天然埃博霉素的细胞毒性剂的缀合物的有效区域选择性合成。这些靶向叶酸受体（FR）的化合物是水溶性的，并在靶向FR的配体和母体药物之间结合了基于亲水肽的间隔单元和可还原的基于自消旋二硫键的接头系统。

  DOI：

  10.1016/j.bmcl.2010.06.016
• 作为产物：
  描述：

  2-((1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-5,9-dioxo-4-oxa-17-aza-bicyclo[14.1.0]heptadecan-17-yl)ethyl 2-(2-(pyridin-2-yl)disulfanyl)ethyl carbonate 在 碳酸氢钠 作用下， 以 水 、 四氢呋喃 为溶剂， 反应 0.75h， 生成 epofolate
  参考文献：
  名称：

  CONJUGATES OF AZIRIDINYL-EPOTHILONE ANALOGS AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME

  摘要：

  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。

  公开号：

  US20070275904A1

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.

  本发明涉及如下式的氮杂环丙烷基环庚二烯酮化合物，以及其药学上可接受的盐和/或溶剂化物：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共同形成双键；R2、R3和R5分别为氢、烷基、取代烷基、芳基或取代芳基；或R2和R3可以与它们所连接的碳共同形成可选择的取代环烷基；R4为氢、烷基、烯基、取代烷基、取代烯基、芳基或取代芳基；R6为氢、烷基或取代烷基；R7、R8、R9、R10、R11和R12分别为氢、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；R13为芳基、取代芳基、杂芳基或取代杂芳基。
• Aziridinyl-epothilone compounds
  申请人：Bristol-Mysers Squibb Company

  公开号：US07872145B2

  公开（公告）日：2011-01-18

  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 —NR7—; A is —(CR8R9)—(CH2)m—Z—wherein Z is —(CHR10)—, —C(═O)—, —C(═O)—C(═O)—, —OC(═O)—, —N(R11)C(═O)—, —SO2—, or —N(R11)SO2—; B1 is hydroxyl or cyano and R1 is hydrogen or B1 and R1 are taken together to form a double bond; R2, R3, and R5 are, independently, hydrogen, alkyl, substituted alkyl, aryl or substituted aryl; or R2 and R3 may be taken together with the carbon to which they are attached to form an optionally substituted cycloalkyl; R4 is hydrogen, alkyl, alkenyl, substituted alkyl, substituted alkenyl, aryl, or substituted aryl; R6 is hydrogen, alkyl or substituted alkyl; R7, R8, R9, R10, R11 and R12 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, or substituted heteroaryl; and R13 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.

  本发明涉及如下式所示的吡咯烷基环丙酮类化合物，以及其药学上可接受的盐和/或溶剂化物：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结合形成双键；R2、R3和R5分别为氢、烷基、取代烷基、芳基或取代芳基；或者R2和R3可以与它们所连接的碳原子结合形成可选择取代的环烷基；R4为氢、烷基、烯基、取代烷基、取代烯基、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、杂环芳基或取代杂环芳基；R13为芳基、取代芳基、杂环芳基或取代杂环芳基。
• Processes for making epothilone compounds and analogs
  申请人：Bristol-Myers Squibb Company

  公开号：US08143415B2

  公开（公告）日：2012-03-27

  A process for making epi-epothilone compounds according to formula A.1, by reacting a compound according formula C with at least one halogenating agent followed by treatment with base, where R1, R2, R3, R4, R5, R6, R12, R13, Z1 and Z2 in formulae (A.1) and (C) are as defined herein. The epi-epothilone compounds of formula (A.1) can be converted into aziridinyl epothilone compounds, which are useful for the treatment of cancer.

  根据公式A.1，通过将公式C的化合物与至少一个卤化剂反应，然后进行碱处理的方法制备环氧-依泼酮化合物，其中公式（A.1）和（C）中的R1，R2，R3，R4，R5，R6，R12，R13，Z1和Z2的定义如本文所述。公式（A.1）的环氧-依泼酮化合物可以转化为氮杂环氧-依泼酮化合物，用于治疗癌症。
• PROCESSES FOR MAKING EPOTHILONE COMPOUNDS AND ANALOGS
  申请人：Parlanti Luca

  公开号：US20100324302A1

  公开（公告）日：2010-12-23

  The present invention relates to processes for making epothilone compounds and analogs thereof, such as epi-epothilone A or epi-epothilone B, and aziridinyl-epothilone analogs.

  本发明涉及制备环丙沙星化合物及其类似物的过程，例如epi-epothilone A或epi-epothilone B，以及氮杂环丙烷基-环丙沙星类似物。
• WO2008/147941
  申请人：——

  公开号：——

  公开（公告）日：——