(7S,9S)-7-<(2',3',4',6'-tetradeoxy-3'-(trifluoroacetamido)-α-L-threohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-9-<<(phenylcarbamoyl)oxy>methyl>-5,12-naphthacenedione | 91578-19-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: (7S,9S)-7-<(2',3',4',6'-tetradeoxy-3'-(trifluoroacetamido)-α-L-threohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-9-<<(phenylcarbamoyl)oxy>methyl>-5,12-naphthacenedione
• 英文别名: (1S)-cis-1-[(2,3,4,6-tetradeoxy-3-trifluoroacetamido-α-L-threohexopyranosyl)oxy]1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-3-(phenylcarbamoyloxy)methylnaphthacene；[(2S,4S)-2,5,12-trihydroxy-4-[(2S,4R,6S)-6-methyl-4-[(2,2,2-trifluoroacetyl)amino]oxan-2-yl]oxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]methyl N-phenylcarbamate
• CAS: 91578-19-7
• 化学式: C₃₄H₃₁F₃N₂O₁₀
• 分子量: 684.623
• InChiKey: HOADTRIMEMFKDD-ISJIDBBISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  49
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (7S,9S)-7-<(2',3',4',6'-tetradeoxy-3'-(trifluoroacetamido)-α-L-threohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-9-<<(phenylcarbamoyl)oxy>methyl>-5,12-naphthacenedione 生成 (7S,9S)-7-<(3'-amino-2',3',4',6'-tetradeoxy-α-L-threohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-9-<<(phenylcarbamoyl)oxy>methyl>-5,12-naphthacenedione hydrochloride
  参考文献：
  名称：

  ADAMS, NIGEL;BLAKE, COLIN;BROADHURST, MICHAEL J.;BUSHNELL, DAVID J.;HASSA+, J. MED. CHEM., 33,(1990) N, C. 2380-2384

  摘要：

  DOI：
• 作为产物：
  描述：

  (7S,9S)-9-(acetoxymethyl)-7-<(2',3',4',6'-tetradeoxy-3'-(trifluoroacetamido)-α-L-threohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trideoxy-5,12-naphthacenedione 在 吡啶 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 (7S,9S)-7-<(2',3',4',6'-tetradeoxy-3'-(trifluoroacetamido)-α-L-threohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-9-<<(phenylcarbamoyl)oxy>methyl>-5,12-naphthacenedione
  参考文献：
  名称：

  Synthesis and antitumor activity of 9-[(carbamoyloxy)alkyl]anthracyclines a novel class of anthracycline derivatives

  摘要：

  A number of 4-demethoxyanthracyclines having hydroxylalkyl functions at the 9-position have previously been synthesized and shown to have potent antitumor activity. A series of carbamate derivatives of these (hydroxyalkyl)anthracyclines have now been prepared, many of which possess considerably greater efficacy in an L-1210 leukemia test system than do the parent alcohols or the known anthracyclines daunorubicin (1), doxorubicin (2), and 4-demethoxydaunorubicin (3). Phenylcarbamate 8a was more active than methyl analogue 8b, while the 4'-deoxy and 4'-epi phenylcarbamates 17 and 18 showed particularly high efficacy at optimal dose levels similar to that of doxorubicin. Secondary carbamates were more potent, with the 13R isomer 23 having significantly higher efficacy than 13S analogue 24.

  DOI：

  10.1021/jm00171a011

文献信息

• Anthracycline glycosides
  申请人：Hoffmann-La Roche Inc.

  公开号：US04526960A1

  公开（公告）日：1985-07-02

  This invention relates to compounds of the formula ##STR1## wherein R is a hydrogen atom, a lower alkyl, aryl or aryl-(lower alkyl) group, a 5-membered or 6-membered heteroaromatic group in which the hetero atom is nitrogen, oxygen or sulphur or a group of the formula ##STR2## wherein R' is a hydroxy, lower alkoxy, amino, lower alkylamino, di-(lower alkyl)amino or arylamino group, n stands for an integer of 1 to 4, n' stands for an integer of 2 to 10, R.sup.1 and R.sup.2 each are a hydrogen atom or one of R.sup.1 and R.sup.2 is a hydrogen atom and the other is a hydroxy, lower alkoxy or benzyloxy group and X is a group of the formula ##STR3## and pharmaceutically acceptable acid addition salts thereof, a process for their manufacture and medicaments containing them. These compounds and salts possess antitumor activity.

  这项发明涉及以下公式的化合物：其中R是氢原子，较低烷基，芳基或芳基-(较低烷基)基，5-或6-成员杂芳基，其中杂原子是氮、氧或硫，或者是公式的基团：其中R'是羟基，较低烷氧基，氨基，较低烷基氨基，二-(较低烷基)氨基或芳基氨基，n代表1到4的整数，n'代表2到10的整数，R1和R2各自是氢原子，或者R1和R2中的一个是氢原子，另一个是羟基、较低烷氧基或苄氧基基团，X是以下公式的基团：及其药学上可接受的酸盐，以及包含它们的制备方法和含有它们的药物。这些化合物和盐具有抗肿瘤活性。
• ADAMS, NIGEL;BLAKE, COLIN;BROADHURST, MICHAEL J.;BUSHNELL, DAVID J.;HASSA+, J. MED. CHEM., 33,(1990) N, C. 2380-2384
  作者：ADAMS, NIGEL、BLAKE, COLIN、BROADHURST, MICHAEL J.、BUSHNELL, DAVID J.、HASSA+

  DOI：——

  日期：——
• Anthracyclinglykoside, deren Herstellung und Arzneimittel damit
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0104654B1

  公开（公告）日：1987-10-21
• US4526960A
  申请人：——

  公开号：US4526960A

  公开（公告）日：1985-07-02
• Synthesis and antitumor activity of 9-[(carbamoyloxy)alkyl]anthracyclines a novel class of anthracycline derivatives
  作者：Nigel Adams、Colin Blake、Michael J. Broadhurst、David J. Bushnell、Cedric H. Hassall、Hans R. Hartmann、Elizabeth Keech、Alan R. Stratton、Gareth J. Thomas

  DOI：10.1021/jm00171a011

  日期：1990.9

  A number of 4-demethoxyanthracyclines having hydroxylalkyl functions at the 9-position have previously been synthesized and shown to have potent antitumor activity. A series of carbamate derivatives of these (hydroxyalkyl)anthracyclines have now been prepared, many of which possess considerably greater efficacy in an L-1210 leukemia test system than do the parent alcohols or the known anthracyclines daunorubicin (1), doxorubicin (2), and 4-demethoxydaunorubicin (3). Phenylcarbamate 8a was more active than methyl analogue 8b, while the 4'-deoxy and 4'-epi phenylcarbamates 17 and 18 showed particularly high efficacy at optimal dose levels similar to that of doxorubicin. Secondary carbamates were more potent, with the 13R isomer 23 having significantly higher efficacy than 13S analogue 24.