56420-45-2

• 常用中文名：表阿霉素
• 常用英文名：Epirubicin
• CAS号：56420-45-2
• 分子式：C₂₇H₂₉NO₁₁
• 分子量：543.519
• 相关类别： 原料药 抗肿瘤药 抗生素类抗肿瘤药
• 发布时间：2018-02-03 08:00:00
• 更新时间：2024-01-02 14:14:30
• Epirubicin是半合成的doxorubicin衍生物,能通过抑制拓扑异构酶起到抗肿瘤的作用。

名称

• 中文名: 表阿霉素
• 英文名: 4'-epidoxorubicin
• 中文别名: (8S,10S)-10-[(3'-氨基-2',3',6'-三脱氧-alpha-L-阿拉伯吡喃糖基)-O-]-6,8,11-三羟基-8-羟乙酰基-1-甲氧基-7,8,9,10-四氢并四苯-5,12-二酮; 10-[(3-氨基-2,3,6-三脱氧-Α-L-阿式-己吡喃糖基)氧]-7,8,9,10-四氢-6,8,11-三羟基-8-(羟乙酰基)-甲氧基-(8S-CIS)-并四苯-5,12-二酮; 表柔比星
• 英文别名: (1S,3S)-3,5,12-trihydroxy-3-(hydroxyacetyl)-10-(methyloxy)-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranoside; (1S,3S)-3,5,12-trihydroxy-3-(hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-a-L-arabino-hexopyranoside; (8S-cis)-10-[(3-Amino-2,3,6-trideoxy-a-L-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione; farmorubicin; (1S,3S)-3,5,12-trihydroxy-3-(hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranoside; 4'-EPIDOXORUBICIN; 5,12-naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, (8S,10S)-; 3-Glycoloyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl-3-amino-2,3,6-tridioxy-a-L-arabinohexopyranoside; epi-dx; Epirubicin; 4'-epi-DX; 5,12-naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-, (8S)-; WP 697; 5,12-Naphthacenedione, 10-((3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, (8S-cis)-; Pidorubicin; Epirubicin Ebewe; Epiadriamycin; (1S,3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranoside; 4'-Epidoxorubiein; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-, (8S,10S)-; Pharmorubicin; imi28; Adriblastin; 5,12-naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-a-L-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-, (8S,10S)-; (3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-tetracenyl 3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranoside; (1S,3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-tetracenyl 3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranoside; Farmarubicin; 4'-epiadriamycin

物化性质

• 密度: 1.6±0.1 g/cm3
• 沸点: 810.3±65.0 °C at 760 mmHg
• 分子式: C₂₇H₂₉NO₁₁
• 分子量: 543.519
• 闪点: 443.8±34.3 °C
• 精确质量: 543.174072
• PSA: 206.07000
• LogP: 2.82
• 蒸汽压: 0.0±3.0 mmHg at 25°C
• 折射率: 1.710
• 储存条件: 2-8℃
• 稳定性:

  盐酸表柔比星(Epirubicin Hydrochloride)：C27H29 NO11.HCI。[56390-09-1]。橘红色结晶，熔点185℃(分解)。 [α]_D²⁰+274°(C=0.01，甲醇)。溶液应避光保存。

• 分子结构:

  1、 摩尔折射率：131.52

  2、 摩尔体积（cm³/mol）：336.6

  3、 等张比容（90.2K）：1054.9

  4、 表面张力（dyne/cm）：96.4

  5、 极化率（10-24cm3）：52.13

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:6

  3.氢键受体数量:12

  4.可旋转化学键数量:5

  5.互变异构体数量:81

  6.拓扑分子极性表面积206

  7.重原子数量:39

  8.表面电荷:0

  9.复杂度:977

  10.同位素原子数量:0

  11.确定原子立构中心数量:6

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

生物活性

• 描述: Epirubicin是半合成的doxorubicin衍生物,能通过抑制拓扑异构酶起到抗肿瘤的作用。
• 相关类别:
  研究领域 >> 癌症
• 靶点:

  Topoisomerase

• 体外研究: 与阿霉素一样,表柔比星通过与DNA的复合物发挥其抗肿瘤作用,导致DNA损伤并干扰DNA,RNA和蛋白质的合成。表柔比星也可能影响细胞膜的完整性和活性。表柔比星引起的最大细胞杀伤发生在细胞周期的S期。随着浓度的增加,早期G2以及G1期和M期也会出现影响[1]。表柔比星显示出对抗大多数癌细胞的抗肿瘤活性。表柔比星对肝癌G2细胞具有细胞毒性,24小时IC50为1.6μg/ mL。 1.6μg/ mL表阿霉素诱导Hep G2细胞凋亡,过氧化氢酶活性增加50％,Se依赖型谷胱甘肽过氧化物酶活性增加110％,Cu,Zn超氧化物歧化酶增加172％,Mn-超氧化物歧化酶增加135％。 Epirbicin可增加NADPH-CYP 450还原酶的细胞表达,并降低GST-π的表达[2]。
• 体内研究: 表柔比星对多种肿瘤类型具有临床活性,包括乳腺癌,恶性淋巴瘤,软组织肉瘤,肺癌,胸膜间皮瘤,胃肠癌,头颈癌,卵巢癌,前列腺癌,膀胱移行癌等[ 3]。剂量为3.5mg/kg的表柔比星抑制人乳腺肿瘤异种移植物R-27的肿瘤质量达74.4％[4]。
• 细胞实验: 将Hep G2细胞（500个细胞/孔，单层）接种在96孔板中。第二天，在培养基中用表柔比星处理细胞。在孵育期结束时，加入15％体积的MTT染料溶液。在37℃温育1小时后，向每个孔中加入等体积的溶解/终止溶液（二甲基亚砜 - 氧化物），再孵育1小时。记录反应溶液在570nm处的吸光度。
• 参考文献:

  [1]. Cersosimo RJ, et al. Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. J Clin Oncol. 1986 Mar;4(3):425-39.

  [2]. Ozkan, A., et al. Epirubicin HCl toxicity in human-liver derived hepatoma G2 cells. Pol J Pharmacol, 2004. 56(4): p. 435-44.

  [3]. Bonadonna, G., et al. Drugs ten years later: epirubicin. Ann Oncol, 1993. 4(5): p. 359-69.

  [4]. Asanuma, F., et al. Antitumor activity of paclitaxel and epirubicin in human breast carcinoma, R-27. Folia Microbiol (Praha), 1998. 43(5): p. 473-4.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : QI9295840 CHEMICAL NAME : 5,12-Naphthacenedione, 10-((3-amino-2,3,6-trideoxy-beta-L-arabino-hexopyrano syl)oxy)- 7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacety l)-1-methoxy-, (8S-cis)- CAS REGISTRY NUMBER : 56420-45-2 LAST UPDATED : 199709 DATA ITEMS CITED : 16 MOLECULAR FORMULA : C27-H29-N-O11 MOLECULAR WEIGHT : 543.57 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 14270 ug/kg TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 16070 ug/kg TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 29300 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2 mg/kg TOXIC EFFECTS : Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - weight loss or decreased weight gain TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 28800 ug/kg/12W-I TOXIC EFFECTS : Cardiac - changes in coronary arteries Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 31200 ug/kg/13W-I TOXIC EFFECTS : Cardiac - changes in heart weight Blood - leukopenia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 7800 ug/kg/5D-I TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) Blood - changes in other cell count (unspecified) Blood - changes in leukocyte (WBC) count TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 15600 ug/kg/13W-I TOXIC EFFECTS : Blood - normocytic anemia Blood - leukopenia Biochemical - Metabolism (Intermediary) - other proteins TYPE OF TEST : Cytogenetic analysis TYPE OF TEST : Cytogenetic analysis MUTATION DATA TEST SYSTEM : Rodent - mouse DOSE/DURATION : 10 mg/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 160,39,1986

制备

化合物(I)经三氟乙酸酐N-酰化，以对氨基进行保护，得到化合物（Ⅱ)。再氧化为酮(Ⅲ)，然后还原为醇(Ⅳ)。在酸作用下去除醚键，再经三氟乙酸酐酯化为化合物(Ⅵ)，然后进行选择性氯代，得到所需的侧链(VII)。
化合物(Ⅷ)经二甲缩丙酮反应成缩酮(Ⅸ)，然后和上述制得的侧链(Ⅶ)反应，得到的化合物(X)水解，即得表柔比星。