14-溴柔红霉素 | 65026-79-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 中文名称: 14-溴柔红霉素
• 英文名称: 14-bromodaunorubicin
• 英文别名: (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-9-(2-bromoacetyl)-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• CAS: 65026-79-1
• 化学式: C₂₇H₂₈BrNO₁₀
• 分子量: 606.424
• InChiKey: KQRWYZDETCDVGB-TZSSRYMLSA-N

物化性质

• 沸点：
  809.6±65.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  186
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  14-溴柔红霉素 在 potassium carbonate 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 0.67h， 生成 N-(trifluoroacetyl)-14-n-dodecyl-14-thiaadriamycin
  参考文献：
  名称：

  阿霉素类似物。一些新型14-硫代阿霉素的制备和生物学评价。

  摘要：

  在碳酸钾存在下，甲醇中的14-溴金红霉素与硫醇缩合，导致抗肿瘤抗生素阿霉素的14-硫杂类似物形成。然而，N-（三氟乙酰基）-14-碘柔红霉素与硫醇的类似缩合反应总是导致氧化还原反应，形成N-（三氟乙酰基）柔红霉素和二硫化物。因此，将N-（三氟乙酰基）-14-溴金红霉素用于与硫醇反应，以产生具有临床活性但不结合DNA的阿霉素类似物N-（三氟乙酰基）阿霉素14-戊酸酯（AD 32）的硫代类似物。14-溴阿霉素与α，ω-链烷二硫醇的反应产生了双（硫代阿霉素）类似物作为潜在的双功能嵌入剂。上述产品，以及两个相关的苯基硒醚衍生物，检查了体外生长抑制，体内抗肿瘤活性，以及​​在适当情况下的DNA结合。许多试剂，特别是14-（乙氧甲氧基甲基）-14-硫代阿霉素和N-（三氟乙酰基）-14-苯基-14-硒代阿霉素，在体内对鼠L1210白血病具有活性。几种氨基糖苷未取代的14-硫代阿霉素类似物表现出与阿霉素相同的DNA结合特性。

  DOI：

  10.1021/jm00355a003
• 作为产物：
  描述：

  柔红霉素 盐酸盐 在 氢溴酸 、 溴 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 丙酮 为溶剂， 反应 6.0h， 生成 14-溴柔红霉素
  参考文献：
  名称：

  一种戊柔比星合成方法

  摘要：

  本发明公开了一种戊柔比星合成方法，盐酸柔红霉素在原甲酸三乙酯对其羰基进行保护下，进行溴代反应，反应液经过浓缩处理，直接进入脱保护反应，脱保护反应结束后，即以盐析的方式将溴化物中间体结晶出来，结晶出来的溴化物中间体先与正戊酸钾反应，再与三氟醋酸酐反应成酰胺制得戊柔比星。本发明反应条件温和，反应时间较短，易于操作控制，适合大规模工业生产。

  公开号：

  CN108484689B

文献信息

• Synthesis and radioiodination of some daunorubicin and doxorubicin derivatives
  作者：Senait Ghirmai、Eskender Mume、Vladimir Tolmachev、Stefan Sjöberg

  DOI：10.1016/j.carres.2004.10.014

  日期：2005.1

  the corresponding benzoic acid, resulting in good yields. Nicotinic acids and benzoic acids, activated with a succinimidyl group, were coupled to the amino group of daunorubicin to give the corresponding amide derivatives. Amine derivatives were obtained by the reductive amination of aromatic aldehydes with daunorubicin hydrochloride. The stannylated ester and amide derivatives were used as precursors

  柔红霉素和阿霉素是有效的癌症治疗药物。然而，其无差别的毒性阻碍了它们的临床疗效。可通过将药物封装在脂质体中并使用肿瘤靶向剂选择性靶向肿瘤细胞来解决此问题。此外，可以通过将俄歇电子发射体（125）I连接到柔红霉素和阿霉素衍生物上来增强抗肿瘤作用。在这种情况下，合成了柔红霉素和阿霉素的许多酯，酰胺和胺衍生物。柔红霉素的苯甲酸酯衍生物是通过14-溴双柔红霉素与相应的苯甲酸钾盐的亲核酯化反应合成的，收率很高。被琥珀酰亚胺基活化的烟酸和苯甲酸，将其与柔红霉素的氨基偶联以得到相应的酰胺衍生物。通过用盐酸柔红霉素对芳族醛进行还原胺化反应，可得到胺衍生物。甲锡烷基化的酯和酰胺衍生物用作放射性碘化的前体。使用氯胺-T作为氧化剂进行（125）I的放射性标记。优化的标记导致放射性碘化柔红霉素和阿霉素衍生物的高放射标记产率（85-95％）。胺的放射性碘化在活化的苯环的邻位进行，从而提供中等的放射化学产率（55-7
• PRODRUGS ACTIVATED BY CASPASE
  申请人：Kim Sang-Yoon

  公开号：US20160144050A1

  公开（公告）日：2016-05-26

  Described are prodrug conjugates that release a chemotherapeutic agent upon activation by caspase, and methods using such prodrug conjugates to induce apoptosis, amplify apoptosis, and treat cancer.

  介绍了一种通过caspase激活释放化疗药物的前药偶联物，以及使用这种前药偶联物诱导细胞凋亡、增强细胞凋亡和治疗癌症的方法。
• NO release regulated by doxorubicin as the green light-harvesting antenna
  作者：Aurore Fraix、Cristina Parisi、Mariacristina Failla、Konstantin Chegaev、Francesca Spyrakis、Loretta Lazzarato、Roberta Fruttero、Alberto Gasco、Salvatore Sortino

  DOI：10.1039/d0cc02512g

  日期：——

  A novel NO photodonor operates through excitation with highly biocompatible green light of the widely used chemotherapeutic agent doxorubicin as the light-harvesting antenna without precluding its typical red emission and DNA binding properties.

  一种新型的NO光捐体通过使用高度生物相容的绿光激发广泛使用的化疗药物多柔比星作为光捕集天线来运作，而不妨碍其典型的红色发射和DNA结合特性。
• Adriamycin analogs. Preparation and biological evaluation of some thio ester analogues of adriamycin and N-(trifluoroacetyl)adriamycin 14-valerate
  作者：Ramakrishnan Seshadri、John M. Idriss、Mervyn Israel

  DOI：10.1021/jm00157a025

  日期：1986.7

  On the consideration that the highly active DNA-nonbinding adriamycin analogues N-(trifluoroacetyl)adriamycin 14-valerate and N-(trifluoroacetyl)adriamycin 14-O-hemiadipate undergo initial metabolic conversion to N-(trifluoroacetyl)adriamycin by the action of nonspecific serum and tissue esterases, a number of N-(trifluoroacetyl)adriamycin 14-thio esters have been prepared and studied for in vitro growth inhibition, vs. human-derived CCRF-CEM leukemic lymphocytes, and in vivo antitumor activity, vs. murine P388 leukemia, relative to the rate of thio ester deacylation induced by esterases present in mouse serum. Products were obtained by reaction of N-(trifluoroacetyl)-14-bromodaunorubicin with thioacetic, thiopropionic, thiobutyric, thiovaleric, and thiobenzoic acids in ethanol, in the presence of potassium carbonate. Because little is known about similar thio ester derivatives of adriamycin itself, the corresponding adriamycin 14-thio esters were also prepared and evaluated for antitumor activity; with these products, determination of their extent of interaction with calf thymus DNA was also performed. For the adriamycin thio ester products, significant in vivo anti-P388 activity was seen with the thioacetate, thiovalerate, and thiobenzoate derivatives, although no compound matched the curative effects of N-(trifluoroacetyl)adriamycin 14-valerate in this system. With respect to the N-(trifluoroacetyl)adriamycin 14-thio ester products, although the corresponding oxo ester analogues are all significantly biologically active, none of the thio ester derivatives showed activity in vitro or in vivo.
• Adriamycin analogs. Rationale, synthesis, and preliminary antitumor evaluation of highly active DNA-nonbinding N-(trifluoroacetyl)adriamycin 14-O-hemiester derivatives
  作者：Mervyn Israel、P. Gopalakrishnan Potti、Ramakrishnan Seshadri

  DOI：10.1021/jm00147a017

  日期：1985.9

  N-(Trifluoroacetyl)adriamycin 14-valerate (AD 32), a novel DNA nonbinding analogue of adriamycin with superior experimental antitumor activity, has undergone extensive clinical trial, with documentation of antitumor activity and low toxicity in human subjects. However, poor water solubility necessitates that the drug be administered to patients by continuous intravenous infusion at high dilution in a surfactant-containing formulation, with steroid prophylaxis to protect against a chest pain syndrome associated with the vehicle. On the basis of pharmacologic considerations, the title compounds have been prepared as second-generation analogues of N-(trifluoroacetyl)adriamycin 14-valerate with improved aqueous solubility; use is made of the available carboxylic acid function to solubilize the products in dilute aqueous alkaline medium. Target compounds were made by treating N-(trifluoroacetyl)-14-halodaunorubicin (bromo or iodo) with monosodium salts of dibasic acids (malonic, succinic, glutaric, adipic, pimelic, azelaic, sebacic) in aqueous acetone. All of the products showed significant in vivo antitumor activity against the murine P388 leukemia (ip tumor, ip treatment once daily on days 1, 2, 3, and 4); most compounds were superior to the +181% increase in life span afforded by adriamycin (optimal dose 3.0 mg/kg per day), one of two drugs used as positive controls for the assays. Several of the test compounds showed highly curative activity in this system, similar to N-(trifluoroacetyl)adriamycin 14-valerate, the other positive control agent. The hemiadipate product exhibited the most desirable properties of high antitumor efficacy (86% cure rate all P388 tumor-bearing animals through four levels of a 40-70 mg/kg dose-response range), aqueous solubility (60 mg/mL in pH 7.4 phosphate buffer), and solution stability (no decomposition at 4 degrees C, 0.5% hydrolysis at 27 degrees C, over 24 h at pH 7.4).