3'-deamino-3'-(4-morpholinyl)doxorubicin | 80790-68-7

• 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: 3'-deamino-3'-(4-morpholinyl)doxorubicin
• 英文别名: morpholinodoxorubicin；morpholino-doxorubicin；Morpholinyl doxorubicin；(7S,9S)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2R,4S,5S,6S)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• CAS: 80790-68-7
• 化学式: C₃₁H₃₅NO₁₂
• 分子量: 613.618
• InChiKey: SXCIMUIAZXOVIR-PUCKCBAPSA-N

物化性质

• 熔点：
  154-160 °C
• 沸点：
  659.48°C (rough estimate)
• 密度：
  1.3069 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  44
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  193
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  3'-deamino-3'-(4-morpholinyl)doxorubicin 、 4-甲氧基三苯基氯甲烷 生成 14-O-(p-anisyldiphenylmethyl)-3'-deamino-3'-(4-morpholinyl)doxorubicin
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  盐酸多柔比星 、 3,4-二羟基-四氢呋喃 生成 3'-deamino-3'-(4-morpholinyl)doxorubicin
  参考文献：
  名称：

  WALKER, MOSHER CAROL;LOW, TONG GEORGE;MC, INTOSH ACTON EDWARD

  摘要：

  DOI：

文献信息

• 3'-Deamino-3'-morpholino carminomycin
  申请人：Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

  公开号：US04374980A1

  公开（公告）日：1983-02-22

  Disclosed is 3'-deamino-3'-morpholino-carminomycin, a new anthracycline glycoside having both antimicrobial and antitumor activity. Also disclosed is a new N-alkylation procedure for preparing the above compound as well as the known anthracyclines, 3'-deamino-3'-morpholino-adriamycin and 3'-deamino-3'-morpholino-daunomycin, in high yield.

  本发明揭示了3'-去氨基-3'-吗啉基-卡米霉素，一种新的蒽环类糖苷，具有抗微生物和抗肿瘤活性。还揭示了一种新的N-烷基化方法，用于制备上述化合物以及已知的蒽环类抗生素3'-去氨基-3'-吗啉基阿霉素和3'-去氨基-3'-吗啉基多柔比星，产率高。
• Re-Exploring the Anthracycline Chemical Space for Better Anti-Cancer Compounds
  作者：Merle A. van Gelder、Sabina Y. van der Zanden、Merijn B. L. Vriends、Roos A. Wagensveld、Gijsbert A. van der Marel、Jeroen D. C. Codée、Herman S. Overkleeft、Dennis P. A. Wander、Jacques J. C. Neefjes

  DOI：10.1021/acs.jmedchem.3c00853

  日期：2023.8.24

  capacity to induce DNA- and chromatin damage. This coherent set of data allowed us to deduce a few guidelines on anthracycline design, as well as discover novel, highly potent anthracyclines that may be better tolerated by patients.

  蒽环类抗癌药物在临床上广泛用于治疗多种癌症。它们会产生 DNA 双链断裂，但最近引入染色质损伤的诱导作为抗癌活性的另一个主要决定因素。这两个事件的结合导致了所报告的副作用。虽然我们对蒽环类药物的结构-活性关系的了解有所提高，但许多结构变异仍然没有得到很好的探索。因此，我们在此报告了一组不同的蒽环类药物的制备方法，这些蒽环类药物在糖部分、胺烷基化模式、糖链和糖苷配基方面存在差异。我们评估了相关人类癌细胞系的体外细胞毒性，以及诱导 DNA 和染色质损伤的能力。这组连贯的数据使我们能够推断出一些关于蒽环类药物设计的指南，并发现患者可能更好耐受的新型高效蒽环类药物。
• Intensely potent morpholinyl anthracyclines
  作者：Edward M. Acton、George L. Tong、Carol W. Mosher、Richard L. Wolgemuth

  DOI：10.1021/jm00371a014

  日期：1984.5

  3'-Deamino-3'-(3-cyano-4-morpholinyl)doxorubicin is a new analogue that is 100 to 1000 times more potent than doxorubicin against tumors in cell culture or in mice, that is active by intraperitoneal, intravenous, or oral dosing, and that does not produce chronic myocardial lesions in mice. This analogue was encountered in studies on the reductive alkylation of doxorubicin and daunorubicin with 2,2' - oxybis [acetaldehyde], which constructs a morpholino ring incorporating the amino N. The morpholinyl nitrile byproducts are separated by virtue of their nonbasicity from the expected morpholino derivatives. The 13-dihydro and 5-imino derivatives are also described in this important new class of anthracyclines.
• BR96 conjugates of highly potent anthracyclines
  作者：H.Dalton King、Andrew J. Staab、Kahnie Pham-Kaplita、Derek Yurgaitis、Raymond A. Firestone、Shirley J. Lasch、Pamela A. Trail

  DOI：10.1016/s0960-894x(03)00375-5

  日期：2003.7

  The 6-maleimidocaproylhydrazone derivatives of highly potent antitumor agents 5-Diacetoxypentyidoxorubicin and Morpholinodoxorubicin were synthesized and conjugated to monoclonal antibody BR96 and control IgG. Immunoconjugate molar ratios were generally 7.5-8.5, and dimer aggregate levels were low. The linkers released parent drug at lysosomal pH 5, while they remained stable at neutral pH. BR96 conjugates were highly potent and antigen specific in vitro. The BR96-DAPDOX conjugate demonstrated an IC50 of 0.03 mum, and was at least 300-fold more potent than a non-binding IgG-DAPDOX control conjugate. (C) 2003 Elsevier Science Ltd. All rights reserved.
• UMEZAWA, HAMAO;TAKEUCHI, TOMIO;TATSUTA, KUNIAKI;TAKAHASHI, YOSHIKAZU
  作者：UMEZAWA, HAMAO、TAKEUCHI, TOMIO、TATSUTA, KUNIAKI、TAKAHASHI, YOSHIKAZU

  DOI：——

  日期：——