(7S,9S)-7,8,9,10-tetrahydro-6,7,9,11-tetrahydroxy-9-<<(methylcarbamoyl)oxy>methyl>-5,12-naphthacenedione | 91578-09-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 英文名称: (7S,9S)-7,8,9,10-tetrahydro-6,7,9,11-tetrahydroxy-9-<<(methylcarbamoyl)oxy>methyl>-5,12-naphthacenedione
• 英文别名: (1S)-cis-1,2,3,4,6,11-hexahydro-1,3,5,12-tetrahydroxy-3-(methylcarbamoyloxy)methyl-6,11-dioxonaphthacene；(7S,9S)-7,8,9,10-tetrahydro-6,7,9,11-tetrahydroxy-9-{[(methylcarbamoyl)oxy]methyl}-5,12-naphthacenedione；[(2S,4S)-2,4,5,12-tetrahydroxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]methyl N-methylcarbamate
• CAS: 91578-09-5
• 化学式: C₂₁H₁₉NO₈
• 分子量: 413.384
• InChiKey: KMBAQLCIFXBCRF-QKVFXAPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  153
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (7S,9S)-7,8,9,10-tetrahydro-6,7,9,11-tetrahydroxy-9-<<(methylcarbamoyl)oxy>methyl>-5,12-naphthacenedione 在 sodium hydroxide 、 silver trifluoromethanesulfonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 [(2S,4S)-2,5,12-trihydroxy-4-[(2R,4S,5S,6S)-5-hydroxy-6-methyl-4-[(2,2,2-trifluoroacetyl)amino]oxan-2-yl]oxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]methyl N-methylcarbamate
  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
• 作为产物：
  描述：

  [(1S,17S)-3,14-dihydroxy-5,12-dioxo-19-phenyl-18,20-dioxa-19-borapentacyclo[15.3.1.02,15.04,13.06,11]henicosa-2(15),3,6,8,10,13-hexaen-17-yl]methyl acetate 、 异氰酸甲酯 生成 (7S,9S)-7,8,9,10-tetrahydro-6,7,9,11-tetrahydroxy-9-<<(methylcarbamoyl)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

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

  公开号：EP0104654A2

  公开（公告）日：1984-04-04

  Die Verbindungen der Formel worin R ein Wasserstoffatom, eine Niederalkyl-, Aryl- oder Aryl-(niederalkyl)-Gruppe, eine 5-gliedrige oder 6-gliedrige heteroaromatische Gruppe, worin das Heteroatom Stickstoff, Sauerstoff oder Schwefel ist, oder eine Gruppe der Formel oder bedeutet, R' eine Hydroxy-, Niederalkoxy-, Amino-Niederalkylamino-, Di-(niederalkyl)-amino- oder ArylaminoGruppe bedeutet, n für eine ganze Zahl von 1 bis 4 steht, n' für eine ganze Zahl von 2 bis 10 steht, R' und R2 jeweils ein Wasserstoffatom bedeuten oder eine der Gruppen R1 und R2 ein Wasserstoffatom bedeutet und die andere eine Hydroxy-, Nideralkoxy- oder Benzyloxygruppe bedeutet und X eine Gruppe der Formel bedeutet, und pharmazeutisch annehmbare Säureadditionssalze hiervon besitzen Antitumoraktivität.

  式中的化合物 其中 R 为氢原子、低级烷基、芳基或芳基（低级烷基）基团、5 元或 6 元杂芳族基团（其中杂原子为氮、氧或硫）或式中的基团 或 R' 代表羟基、低级烷氧基、氨基-低级烷基氨基、二（低级烷基）氨基或芳基氨基，n 代表 1 至 4 的整数，n' 代表 2 至 10 的整数，R' 和 R2 各代表一个氢原子，或 R1 和 R2 中的一个代表氢原子，另一个代表羟基、低级烷氧基或苄氧基，X 代表式中的一个基团。 及其药学上可接受的酸加成盐具有抗肿瘤活性。
• 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：——
• 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.