3,4-di-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranoyl bromide | 172939-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: 3,4-di-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranoyl bromide
• 英文别名: 3,4-di-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranosyl bromide；Xpaylvozewzdmp-uyxsqoijsa-；[(2R,3S,4S,6S)-3-acetyloxy-6-bromo-2-(trifluoromethyl)oxan-4-yl] acetate
• CAS: 172939-34-3
• 化学式: C₁₀H₁₂BrF₃O₅
• 分子量: 349.101
• InChiKey: XPAYLVOZEWZDMP-UYXSQOIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3,4-di-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranoyl bromide 生成 1,3,4-tri-O-acetyl-2,6-dideoxy-2-fluoro-5-C-(trifluoromethyl)-α-L-talopyranose
  参考文献：
  名称：

  Anthracycline derivative having a trifluoromethylated sugar

  摘要：

  现在已经生产出新型蒽环喜树碱衍生物，其抗肿瘤活性更高，毒性更低，比诸如多柔比星、阿霉素等已经临床使用的抗癌药物更优。换句话说，一种由通用式(I)代表的多柔比星醌或阿霉素醌衍生物已经被制造出来：##STR1## 其中R为氢原子或羟基。

  公开号：

  US05719130A1
• 作为产物：
  描述：

  1,3,4-tri-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-L-lyxo-hexopyranose 在 氢溴酸 、 溶剂黄146 作用下， 反应 5.0h， 以90%的产率得到3,4-di-O-acetyl-2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranoyl bromide
  参考文献：
  名称：

  5'-（三氟甲基）蒽环类苷：抗肿瘤活性7-O-（2,6-二脱氧-6,6,6-三氟-α-L-lyxo-己吡喃糖基）阿霉素的合成。

  摘要：

  已经通过以下方法制备了7-O-（2,6-二脱氧-6,6,6-三氟-α-L-lyxo-己吡喃糖基）阿德里亚姆（3），其在C-5'的取代基是亲脂性三氟甲基。 3,4-二-O-乙酰基-2,6-二脱氧-6,6,6-三氟-α-L-lyxo-己吡喃糖基溴化物（20）与14-O-（叔丁基二甲基甲硅烷基）去甲霉素的偶合Koenigs-Knorr条件。该合成过程中的关键步骤是10中衍生自D-lyxose的5-O-乙酰基-2,3-二-O-苄基-4-脱氧醛-L-赤型戊糖的C-三氟甲基化（10）步骤，在四丁基氟化铵存在下，用（三氟甲基）三甲基硅烷，得到1,1,1-三氟-L-阿拉伯糖基己糖醇（11）及其2-表异构体。与包括阿霉素的类似物相比，合成产物3在低剂量范围内显示出显着的体内抗肿瘤活性。

  DOI：

  10.1021/jm960177x

文献信息

• Fluorine-containing anthracycline derivatives having hydroxyl groups(s)
  申请人：Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

  公开号：US05789386A1

  公开（公告）日：1998-08-04

  To provide novel fluorine-containing anthracycline derivatives having high antitumor activities and a solubility in water, there have now been synthesized a 7-O-(2,6-dideoxy-2-fluoro-3-O- or -4-O- or -3,4-di-O-aminoalkanoyl-.alpha.-L-talopyranosyl)daunomycinone or -adriamycinone of general formula (I) shown below, as well as a 7-O-(3-O- or -4-O- or -3,4-di-O-aminoalkanoyl-2,6-dideoxy-2,6,6,6-tetrafluoro-.alpha.-L-talopyra nosyl- or -2,6-dideoxy-6,6,6-trifluoro-.alpha.-L-lyxo-hexopyranosyl)adriamycinone of general formula (II) shown below: General formula (I) ##STR1## General formula (II) ##STR2## wherein either one or both of A.sup.1 and A.sup.2 is or are an .alpha.-amino acid residue or an .omega.-amino acid residue and T denotes a fluorine or hydrogen atom. The novel fluorine-containing anthracycline derivatives of general formulae (I) and (II) are highly active against tumors and soluble in water, and they are useful as antitumor agents administrable in the form of injectable solution.

  为了提供具有高抗肿瘤活性和水溶性的新型含氟蒽环素衍生物，已合成了如下所示的通用式(I)的7-O-(2,6-二去氧-2-氟-3-O-或-4-O-或-3,4-二-O-氨基烷酰-α-L-戊糖苷)多柔比星醌或阿霉素醌，以及如下所示的通用式(II)的7-O-(3-O-或-4-O-或-3,4-二-O-氨基烷酰-2,6-二去氧-2,6,6,6-四氟-α-L-戊糖苷-或-2,6-二去氧-6,6,6-三氟-α-L-利克糖苷)阿霉素醌：通用式(I) ##STR1## 通用式(II) ##STR2## 其中A^1和A^2中的一个或两个是α-氨基酸残基或ω-氨基酸残基，T表示氟或氢原子。通用式(I)和(II)的新型含氟蒽环素衍生物对肿瘤具有很高的活性，并且在水中溶解，它们可作为抗肿瘤剂以注射溶液的形式使用。
• NOVEL ANTHRACYCLINE DERIVATIVES CONTAINING TRIFLUOROMETHYLATED SUGAR UNIT
  申请人：ZAIDAN HOJIN BISEIBUTSU KAGAKU KENKYU KAI

  公开号：EP0749976A1

  公开（公告）日：1996-12-27

  Novel anthracycline derivatives have now been produced, which exhibit higher antitumor activities and lower toxicities than those of daunomycin, adriamycin etc. that have been clinically used as anticancer agents. That is, a daunomycinone or adriamycinone derivative represented by the general formula (I): wherein R is a hydrogen atom or a hydroxyl group, and 7-O-(2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranosyl)adriamycinone derivative which is an adriamycinone derivative represented by formula (II): have now been newly synthesized. The novel anthracycline derivatives having the general formula (I) and formula (II), respectively, show excellent anticancer or antitumor activities and are of low toxicities. These novel compounds are very useful as anticancer or antitumor agents and are expected to be useful for the therapeutic treatments of a variety of cancers and tumors, similarly to daunomycin or adriamycin.

  目前已生产出新型蒽环类衍生物，与临床上用作抗癌剂的达霉素、阿霉素等相比，它们具有更高的抗肿瘤活性和更低的毒性。即由通式（I）代表的达霉素酮或阿霉素酮衍生物： 其中 R 是氢原子或羟基，7-O-(2,6-二脱氧-6,6,6-三氟-α-L-来苏己吡喃糖基)阿霉素酮衍生物是由式（II）表示的阿霉素酮衍生物： 的阿霉素衍生物。 分别具有通式(I)和式(II)的新型蒽环类衍生物显示出卓越的抗癌或抗肿瘤活性，而且毒性低。这些新型化合物作为抗癌剂或抗肿瘤剂非常有用，有望与达霉素或阿霉素类似，用于各种癌症和肿瘤的治疗。
• Fluorine-containing anthracycline derivatives having hydroxyl group(s) mono- or di-o-aminoalkanoylated in the sugar moiety thereof
  申请人：ZAIDAN HOJIN BISEIBUTSU KAGAKU KENKYU KAI

  公开号：EP0761678A1

  公开（公告）日：1997-03-12

  To provide novel fluorine-containing anthracycline derivatives having high antitumor activities and a solubility in water, there have now been synthesized a 7-O-(2,6-dideoxy-2-fluoro-3-O- or -4-O- or -3,4-di-O-aminoalkanoyl-α-L-talopyranosyl)daunomycinone or -adriamycinone of general formula (I) shown below, as well as a 7-O-(3-O- or -4-O-or -3,4-di-O-aminoalkanoyl-2,6-dideoxy-2,6,6,6-tetrafluoro-α-L-talopyranosyl- or -2,6-dideoxy-6,6,6-trifluoro-α-L-lyxo-hexopyranosyl)adriamycinone of general formula (II) shown below:- wherein either one or both of A1 and A2 is or are an α-amino acid residue or an ω-amino acid residue and T denotes a fluorine or hydrogen atom. The novel fluorine-containing anthracycline derivatives of general formulae (I) and (II) are highly active against tumors and soluble in water, and they are useful as antitumor agents administrable in the form of injectable solution.

  为了提供具有高抗肿瘤活性和水溶性的新型含氟蒽环类衍生物，现已合成了通式(I)如下的7-O-(2,6-二脱氧-2-氟-3-O-或-4-O-或-3,4-二-O-氨基烷酰基-α-L-吡喃甘露糖基)daunomycinone或-adriamycinone、以及下表所示通式(II)的 7-O-(3-O-或-4-O-或-3,4-二-O-氨基烷酰基-2,6-二脱氧-2,6,6,6-四氟-α-L-吡喃他酰胺基-或-2,6-二脱氧-6,6,6-三氟-α-L-来苏己吡喃糖基)阿霉素酮：- 其中 A1 和 A2 中的一个或两个是 α-氨基酸残基或 ω-氨基酸残基，T 表示氟原子或氢原子。通式(I)和(II)的新型含氟蒽环类衍生物具有很强的抗肿瘤活性，可溶于水，可作为抗肿瘤药物以注射液的形式给药。
• 5-GLYCOSYLOXY-6-HYDROXYNAPHTHO 2,3-f]QUINOLINE-7,12-DIONE HAVING ANTICANCER ACTIVITIES
  申请人：ZAIDAN HOJIN BISEIBUTSU KAGAKU KENKYU KAI

  公开号：EP1156056A1

  公开（公告）日：2001-11-21

  As novel compounds which exhibit reduced toxicities but enhanced anticancer activities in comparison with those of known carcinostatic anthracycline derivatives, there is provided a compound of general formula (I) wherein A is methyl group or CF3 group, and B is hydrogen atom, or an electron-withdrawing group chosen from halogeno group and others, provided that B stands for hydrogen atom when A is CF3 and that B stands for an electron-withdrawing group when A is methyl group, and R1 and R2 each are hydroxyl group, amino group or an acyloxy group or an aminoalkanoyloxy group, and others, or a pharmaceutically acceptable salt thereof. The compound of general formula (I) possesses activities inhibitory to proliferation of various human cancer cells and is of lower toxicity than that of adriamycin. Further, there is provided, as novel and water-soluble carcinostatic compounds, a compound of general formula (V) wherein A and B have the same meanings as defined above, and R5 is hydrogen atom or an ω-amino acid residue, and R6 and R7 have the same meanings as defined for R5, provided that R5, R6 and R7 do not represent hydrogen atom, simultaneously.

  作为新型化合物，与已知的致癌性蒽环类衍生物相比，其毒性降低，但抗癌活性增强，现提供通式（I）的化合物 其中 A 为甲基或 CF3 基团，B 为氢原子或从卤代基团及其他基团中选出的抽电子基团，但 A 为 时 B 代表氢原子，A 为甲基时 B 代表抽电子基团，R1 和 R2 分别为羟基、氨基或酰氧基或氨基烷酰氧基及其他基团，或其药学上可接受的盐。通式（I）化合物具有抑制各种人类癌细胞增殖的活性，其毒性低于阿霉素。 此外，还提供了通式（V）化合物，作为新型水溶性抗癌化合物 其中 A 和 B 的含义与上述定义相同，R5 为氢原子或ω-氨基酸残基，R6 和 R7 的含义与 R5 的定义相同，但 R5、R6 和 R7 同时不代表氢原子。
• ANTHRACYCLINE DERIVATIVES CONTAINING TRIFLUOROMETHYLATED SUGAR UNIT
  申请人：ZAIDAN HOJIN BISEIBUTSU KAGAKU KENKYU KAI

  公开号：EP0749976B1

  公开（公告）日：1999-04-28