阿扎胞苷杂质结构式
注射用阿扎胞苷Azacitidine-详细说明书与重点
注射用阿扎胞苷Azacitidine 【成份】阿扎胞苷。
化学名称：4-氨基-1-β-D-呋核亚硝脲-s-三嗪-2（1H）-，分子式：C8H12N4O5分子量：244，本品中所用辅料为甘露醇。
,化学结构式：【性状】本品为白色疏松块状物或粉末。
【适应症】本品适用于以下成年患者：·国际预后评分系统（IPSS）中的中危-2及高危骨髓增生异常综合征（MDS），·慢性粒-单核细胞白血病（CMML），·按照世界卫生组织（WHO)分类的急性髓系白血病(AML)、骨髓原始细胞为20-30%伴多系发育早常。
【规格】100mg【用法用量】1.首个治疗周期:对于所有患者，不考虑基线血液学实验室检查值如何，首个治疗周期的推荐起始剂量为75mg/m2，每天经皮下给药,共7天。
给予患者预防用药,以预防恶心和呕吐。
首次给药前应当收集患者全血细胞计数、肝脏生化指标和血清肌酐值。
2.后续治疗周期：每4周为一治疗周期。
建议患者至少接受6个周期的治疗。
但对于完全或部分缓解的患者可能需要增加治疗周期。
只要患者持续受益，即可持续治疗。
应当监测患者的血液学缓解情况和肾脏毒性（见【注意事项】)，可能有必要按照下文所述延迟给药或减小剂量。
3.基于血液学实验室检查值进行剂量调整：·对于基线(治疗开始)WBC≥3.0109/L、ANC≥1.5109/L，且血小板≥75.0X109/L的患者，基于任何治疗周期的最低值计数，剂量调整如下:·对于基线计数为WBC<3.0*109/L、ANC<1.5*109/L或血小板<75.0*109/L的患者，剂量调整应当基于最低值计数和最低值时骨髓活组织检查细胞构成。
如下文所述，除非下一个周期时细胞分化有明显改善(成熟粒细胞的百分比值高，ANC高于疗程起始时)，则应当继续使用当前治疗的剂量。
如果发生了二表中定义的最低值，如果随后WBC和血小板计数均比最低值增高>25%且正在升高，则下一个疗程应当在前一疗程开始后28天进行。
杂环化合物的结构
杂环化合物的结构杂环化合物是指分子中含有一个或多个非相邻原子构成的环结构，其中至少有一个原子不同于碳原子。
这类化合物在有机化学中具有重要的地位，广泛存在于自然界和许多药物分子中。
下面将通过讨论几个典型的杂环化合物，来介绍它们的结构。
1.噁唑类化合物：噁唑类化合物具有五元的氮杂环结构，化学式为C3H3N2、它是一类广泛存在于许多药物中的结构单元，也被广泛用于农药和染料的合成。
噁唑环由两个碳原子和三个非相邻的氮耦合而成，其中一个氮原子上还带有一个氢原子。
噁唑环可以在不同位置上被取代，形成各种不同的化合物，比如抗生素吡唑菌素。
2.噻吩类化合物：噻吩类化合物具有五元的硫杂环结构，化学式为C4H4S。
它是一种具有重要生物活性的结构单元，被广泛应用于制药和农药的合成。
噻吩环由一个碳原子、三个非相邻的碳原子和一个硫原子组成。
噻吩化合物可以在不同位置上被取代，形成具有不同生物活性的衍生物，比如抗癌药物紫杉醇。
3.品咔类化合物：品咔类化合物具有六元的氮杂环结构，化学式为C4H4N2、它是一类重要的有机光电功能材料，具有广泛的应用前景。
品咔环由一个碳原子、两个非相邻的碳原子和三个氮原子构成。
品咔类化合物可以通过在不同位置上取代，形成不同结构的衍生物，从而调控其光电性能。
4.哌啶类化合物：哌啶类化合物具有六元的氮杂环结构，化学式为C5H5N。
它是一类广泛存在于药物中的结构单元，被广泛应用于制药领域。
哌啶环由六个碳原子和一个氮原子构成。
哌啶类化合物可以在不同位置上被取代，形成各种不同的衍生物，比如抗忧郁药艾司唑仑。
除了上述几类典型的杂环化合物，还有许多其他形式的杂环，比如噻二唑类化合物、吡咯类化合物等。
这些杂环化合物的结构和性质差异巨大，但它们共同的特点是都含有非相邻原子构成的环结构，且至少有一个原子不同于碳原子。
杂环化合物的结构多样性使得它们具有广泛的应用前景，特别是在药物领域。
通过调控杂环化合物的结构，可以获得具有特定生物活性和光电性能的分子，为化学工业的发展和新药的研究提供了重要的基础。
阿扎胞苷的机遇和挑战
阿扎胞苷的机遇和挑战
阿扎胞苷是胞嘧啶核苷类似物，通过引起DNA 去甲基化和对骨髓中异常造血细胞的直接细胞毒作用而产生抗肿瘤作用。
阿扎胞苷在体外对DNA甲基化有最大抑制作用时的浓度对DNA的合成未见明显的抑制作用。
可用于治疗中危高危骨髓增生异常综合征、伴有20—30％骨髓原始细胞的急性髓系白血病（AML）和慢性粒单核细胞白血病（CMML）。
对乳腺癌、肠癌、黑色素瘤等也有一定疗效。
阿扎胞苷的原研企业是美国新基（CELGENE）公司，于20xx 年x月x日在美国首次上市，商品名为维达莎。
阿扎胞苷是美国FDA 批准的第一个MDS治疗药物，被美国国家综合癌症网络指南推荐为一线治疗用药。
该产品适用于对MDS所有亚型的治疗，并具有罕见病治疗药资格。
在我国抗肿瘤药物市场中，抗代谢药物是仅次于植物提取亚类居于第二位的品种。
在全部抗肿瘤用药的占有率从十年前的7.11%上升到了20.81%，有近27亿元人民币，前十个品种占据了抗肿瘤药物市场的20.39%。
而阿扎胞苷所属的抗代谢类药物总体市场已经超过百亿元的市场规模，进一步显示出抗代谢类药物在临床中的重要作用。
随着全球范围内肿瘤患者数目以较快速度不断增加，全球和国内的抗代谢药物市场均将继续增长。
而我们国家产业政策将治疗恶性肿瘤药物产业作为重点发展行业，对抗代谢药物行业的市场规模
增长具有极大的推动作用。
从长期角度来看，阿扎胞苷的市场容量较大，未来也有发展潜力。
阿扎胞苷作用机制-Medchemexpress-MCE中国
阿扎胞苷作用机制-Medchemexpress-MCE中国5-Azacytidine10% DMSO 40% PEG300 5% Tween-80 45% saline10% DMSO 90% (20% SBE-β-CD in saline)此?案可获得≥ 2.5 mg/mL (10.24 mM，饱和度未知) 的澄清溶液。
以 1 mL ?作液为例，取100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到900 μL 20% 的 SBE-β-CD ?理盐??溶液中，混合均匀。
请依序添加每种溶剂： 10% DMSO 90% corn oil3.Solubility: ≥ 2.5 mg/mL (10.24 mM); Clear solution此?案可获得≥ 2.5 mg/mL (10.24 mM，饱和度未知) 的澄清溶液，此?案不适?于实验周期在半个?以上的实验。
以 1 mL ?作液为例，取100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到900 μL ??油中，混合均匀。
BIOLOGICAL ACTIVITY物活性5-Azacytidine (Azacitidine; 5-AzaC; Ladakamycin) 是胞苷核苷类似物，特异型抑制 DNA 甲基化。
5-Azacytidine 与 DNA 结合共价捕获 DNA甲基转移酶 (DNA methyltransferases)，有益于逆转表观遗传变化。
5-Azacytidine 诱导细胞?噬 (autophagy)。
AutophagyIC?? & Target DNMT1NucleosideAntimetabolite/Analog体外研究Unmethylated CpG islands associated with a variety of genes become partially or fully methylated in tumors and can be reactivated by 5-Azacytidine[1]. 5-Azacytidine acts as weak inducers of erythroid differentiation of Frienderythroleukemia cells in the same concentration range where they affect DNA methyltransferase activity[2]. 5-Azacytidine inhibits L1210 cells with ID50 and ID90 values of 0.019 and circa 0.15 μg/mL, respectively[3].体内研究TdR-3H incorporation is significantly inhibited when the animals are exposed to 5-Azacitidine (100 mg/kg, i.p.) for 2 hr or longer[3].PROTOCOLKinase Assay [3] A crude cell-free extract is isolated from LI 210 cells in culture by suspension of the cells in a given volume of0.05mol/LTris-HCl buffer, pH 7.4, and sonic extraction with a Biosonik at 70% maximal output for 30 sec. Thesupernatant is collected after centrifugation at 105,000 × g for 60 min (4°C) in a Model L Spinco ultracentrifuge. The final protein concentration of the cell-free extracts is approximately 3 mg/mL. The extracts are used as the source of enzymes. Ribonucleotide reductase activity is measured. A unit of enzyme is defined as the amount that catalyzed dCMP synthesis at a rate of 1 mμmole/hr. The assay systems for the measurement of pyrimidine nucleoside (CR) and deoxynucleoside (TdR, CdR) kinases are essentially those described by Chu and Fischer. However, reactions are terminated by heating for 2 min in a boiling water bath, and the phosphorylated derivatives are isolated according to the method of Bach. Fifty-jul aliquots are applied to 1-inch discs of diethylaminoethyl paper, which are then placed in counting vials and eluted with 0.5 mL of 0.5 mol/LPCA. After 1 hr, 12 mL of Diotol are added, and the radioactivity isdetermined.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay [3]Twenty mL of cells (circa 1×104 cells/mL) are pipetted into sterilized culture tubes with screw caps and in cubated at 37°C overnight. The experiment is initiated by the addition of 1 mL of 5-Azacytidine (5-azaCR) or medium for a givenperiod (from 0 to 240 min) prior to the addition of 1 mL of metabolite (or medium). Cell growth is determined twice a day for 3 days by means of a Model A Coulter counter. To determine IDSO and ID90 values, 5 mL of L1210 cells (5×103 cells/mL) are incubated with the drug at 37°C for 3 days, and cell growth is determined.MCE has not independently confirmed the accuracy of these methods. They are for reference only.AnimalAdministration [3]For the in vivo experiments, leukemic mice (bearing circa 1×103 cells/animal) are given injections i.p. with 0.2 mL of 5-Azacytidine (5-azaCR) of a given concentration. Two hr later, the reaction is started by injecting 0.5 mL of labeled metabolite (TdR-3H or UR-3H, 10 /μCi/12.5 μg). After 1 hr, animals (3 mice/group) are killed by cervical fracture, and the ascites are treated with heparin, collected, pooled, and then centrifuged immediately in a Sorvall refrigerated centrifuge Model R2C-B at 800×g for 10 min (4°C).MCE has not independently confirmed the accuracy of these methods. They are for reference only.客户使?本产品发表的科研?献See more customer validations on/doc/508349884.html,REFERENCES[1]. Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene. 2002 Aug 12;21(35):5483-95.[2]. Creusot F, et al. Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidineand 5-aza-2'-deoxycytidine. J Biol Chem. 1982 Feb 25;257(4):2041-8.[3]. Li LH,et al. Cytotoxicity and mode of action of 5-azacytidine on L1210 leukemia. Cancer Res. 1970 Nov;30(11):2760-9.[4]. Marycz K, et al. 5-Azacytidine and Resveratrol Enhance Chondrogenic Differentiation of Metabolic Syndrome-Derived Mesenchymal Stem Cells by Modulating Autophagy.Oxid Med Cell Longev. 2019 May 12;2019:1523140.McePdfHeightCaution: Product has not been fully validated for medical applications. For research use only.Tel: 400-820-3792; 021-******** Fax: 021-******** E-mail: tech@/doc/508349884.html,Master of Small Molecules —您?边的抑制剂?师PLoS Pathog . 2020 Mar.Mol Oncol . 2018 Feb;12(2):180-195.? Cell Death Dis . 2018 Apr 27;9(5):497.? Cell Death Dis . 2018 Jan 26;9(2):129.? Cell Commun Signal . 2019 Aug 14;17(1):94.。
阿扎胞苷合成路线
N N H N NH 2O H N Si Si Mol. Wt.: 161.39Mol. Wt.: 112.09N N N HN OSi Si Mol. Wt.: 256.45N N N HNSi O OAc AcO O Mol. Wt.: 442.5NaOMe MeO OAc AcO OAc Mol. Wt.: 318.28N N NNH 2O OHHO O Mol. Wt.: 244.223步骤1操作程序：In a 22 L, 3-necked flask, a mixture of 5-azacytosine(1) (2.0 kg, 17.8 mol, 1.07 molar eq.), HMDS (9.162 kg) and ammonium sulfate (40.0 g) was heated at reflux for 2 hours. A fresh amount of ammonium sulfate (20.0 g) was added, and the reflux was continued for 6 hours longer. The initial slurry turned into a clear, pale-yellow, solution and no more gas evolved at the end of the reflux. The excess HMDS was evaporated off in vacuum to obtain an off-white residue, which is trimethylsilylated 5-azacytosine.步骤2操作程序：Trimethylsilylated 5-azacytosine (6) prepared according to the method of Example 1 was diluted with anhydrous dichloromethane (18.1 kg) in a 50 L, 3-necked, flask and solid, 1,2,3,5-Tetra-O-acetyl-β-D-ribofuranose (5.330 kg, 16.7 mol) (7) was charged to the mixture. An anhydrous dichloromethane rinse (0.533 kg) was used and the slurry was cooled to 0-5℃. TMS-triflate (4.75 kg, 1.2 molar eq.) was added to the mixture over 5-10 minutes. During the addition, the reaction temperatureincreased to 15-20℃. and the initial suspension turned into a clear, pale-yellow, solution. After 2 hours of stirring, the solution Was poured over a mixture of Na2C03 (2.00 kg), NaHC03(2.00 kg), water (29.9 kg) and ice (20.0 kg). The layers were separated. The water layer was extracted with dichloromethane (8.0 kg). The combined organics were washed with cold (0-5℃.) 10% NaHC03(2xl0 L). The combined washings were extracted with dichloromethane (8.0 kg). The combined organics were washed with cold water (2x5 kg), dried on MgS04 (2.0 kg), and filtered. The filtrate and dichloromethane washes on the pad (2x1.32 kg) were combined and reduced in volume using vacuum (-200 mmHg, 30℃). The distillation was continued until the majority of dichloromethane (app. 85-95% total) was removed. The residue was taken up in methanol (4.0 kg) and the remaining dichloromethane was removed to give a protected 5-azacytidine (8) as an off-white to yellow foam.步骤3操作程序：Protected 5-azacytidine (8) from Example 2 was diluted with methanol (35.5 kg), then 25% NaOMe in methanol (439 g, 0.11 mol. eq.) was charged. The initial clear solution became turbid and a solid started to precipitate. The slurry was left under nitrogen overnight. The solids were isolated and washed with methanol (7x2.4 kg). The solids were dried (-28 inHg and _85℃.) to a constant weight to give crude 5-azacytidine (1.835 kg; 44.9%) (5).AZBG精制工艺操作程序Crude 5-azacytidine was purified from DMSO/MeOH as follows: Crude 5-azacytidine (1.829 kg) was dissolved in preheated DMSO (5.016 kg; 87-90℃) under nitrogen. The solution was diluted with methanol in portions at approximate l0-minute intervals (9x1.4 kg then 1x0.58kg) while slowly cooling. After the addition, 45-55℃. was maintained for 1 hour and then the mixture was left to cool to ambient temperature overnight. The next day, the solids were isolated at ambient temperature, washed with MeOH (6xO.83 kg), and dried in vacuum (-30 inHg and _85℃.) to a constant weight to give 5-azacytidine (1.504 kg; 82.2% recovery)步骤2操作程序：。
瑞舒伐他汀Rosuvastatin全套杂质结构列表
瑞舒伐他汀钙相关杂质列表(现货)：深圳恒丰万达专业提供杂质对照品，标准品，快速优惠热线138****3301序列杂质简称相关杂质结构纯度1A 对接异构体-1RosuvastatinImpurity 23CAS No.N/A C29H40FN3O6S M.W.577.71R-097999.85%2Z-10对接异构体-2RosuvastatinImpurity 24CAS No.1378943-63-5C29H40FN3O6S M.W.577.71R-098099.74%3C 对接异构体-3RosuvastatinImpurity 25CAS No.N/A C29H40FN3O6S M.W.577.71R-098195.39%4E对接异构体（Z 式）-4(Z)-Rosuvastatin Impurity 15CAS No.1821422-50-7C29H40FN3O6S M.W.577.71R-097199.74%5Q对接光降解-1CAS No.N/A C29H40FN3O6S M.W.577.71R-099099.31%6P对接光降解-2CAS No.N/A C29H40FN3O6S M.W.577.71R-099299.69%7I丙酮加合物CAS No.N/A C32H46FN3O7S M.W.635.7998.23%8Z-12对接脱氟CAS No.N/AC29H41N3O6S M.W.559.72R-099399.46%9Z-16双键环氧脱丙酮叉CAS No.N/AC29H40FN3O7S M.W.593.7199.18%10B脱丙酮叉异构体-1ent-Rosuvastatin tert-Butyl Ester CAS No.615263-60-0C26H36FN3O6S M.W.537.65R-091899.90%11Z-11脱丙酮叉异构体-2(3S,5S)-Rosuvastatintert-Butyl Ester CAS No.2185805-16-5C26H36FN3O6S M.W.537.65R-097699.66%12D 脱丙酮叉异构体-3(3R,5R)-tert-ButylRosuvastatin (Rosuvastatin Impurity)CAS No.2162136-65-2C26H36FN3O6S M.W.537.65R-0911100%13F 脱丙酮叉异构体（Z 式）-4CAS No.1821422-51-8C26H36FN3O6S M.W.537.65R-099699.44%14S脱丙酮叉光降解-1CAS No.N/A C26H36FN3O6S M.W.537.65R-098999.61%15R脱丙酮叉光降解-2CAS No.N/A C26H36FN3O6S M.W.537.65R-099199.20%16J丙酮加合物脱丙酮叉Rosuvastatin EP Impurity A CAS No.1714147-49-5C29H42FN3O7S M.W.595.72R-099799.65%17Z-13无氟脱丙酮叉CAS No.N/AC26H37N3O6S M.W.519.65R-099599.17%18Z-255-甲氧基脱叉杂质RosuvastatinImpurity 42CAS No.N/A C27H38FN3O6S M.W.551.67R-0910098.80%19Z-263-甲氧基脱叉杂质RosuvastatinImpurity 47CAS No.N/A C27H38FN3O6S M.W.551.67R-0910598.65%203,5-二甲氧基脱叉杂质Rosuvastatin Impurity 44CAS No.N/A C28H40FN3O6S M.W.565.70R-0910698%21G钙盐异构体-1Rosuvastatin EP Impurity G Calcium Salt CAS No.1242184-42-4(free acid)C22H27FN3O6S.1/2Ca M.W.480.5420.0499.88%22Z-1钙盐异构体-2(3S,5S)Rosuvastatin Calcium Salt CAS No.1584149-34-7(free acid)C22H27FN3O6S.1/2Ca M.W.480.5420.04R-091598.15%23H钙盐异构体-3Rosuvastatin EP Impurity B Calcium Salt(3R,5R)-Rosuvastatin Calcium Salt CAS No.1422515-55-61094100-06-7(free acid)C22H27FN3O6S.1/2Ca M.W.480.5420.04R-091296.13%24V钙盐异构体（Z 式）-4Rosuvastatin Z-Isomer Calcium Salt CAS No.1444772-08-01445208-17-2(free acid)C22H27FN3O6S.1/2Ca M.W.480.5420.0499.51%25Z-245-甲氧基钠盐CAS No.N/AC23H29FN3NaO6S M.W.517.5599.50%26Z-273-甲氧基钠盐CAS No.N/AC23H29FN3NaO6S M.W.517.5596.83%27Z-293,5-二甲氧基钠盐CAS No.N/AC24H31FN3NaO6S M.W.531.5797.78%28U钙盐异构体光降解-5RosuvastatinImpurity 1Calcium Salt CAS No.854898-49-0854898-48-9(free acid)C22H27FN3O6S.1/2Ca M.W.480.5420.0499.75%29T 钙盐异构体光降解-6RosuvastatinImpurity 2Calcium Salt CAS No.854898-50-3854898-53-6(free base)C22H27FN3O6S.1/2Ca M.W.480.5420.0499.83%30Z-18钠盐异构体光降解-7(混合物)RosuvastatinImpurity 1Calcium SaltCAS No.N/A C22H27FN3O6S.1/2Ca M.W.480.5420.04R-093499.16%31Z-20钙盐异构体光降解-8Rosuvastatin Impurity CAS No.N/A C22H26FN3O6S M.W.479.5296.69%32Z-14钙盐无氟DesfluoroRosuvastatin Calcium Salt CAS No.N/A847849-66-5(acid)C22H28N3O6S.1/2Ca M.W.462.5420.04R-099499.78%33K 丙酮加合物钙盐Rosuvastatin EPImpurity A Calcium Salt CAS No.1714147-47-31715120-13-0(free acid)C25H33FN3O7S.1/2Ca M.W.538.6120.04R-092599.46%34M 内酯Rosuvastatin EPImpurity D CAS No.503610-43-3C22H26FN3O5S M.W.463.52R-09199.46%35N 内酯异构体CAS No.N/AC22H26FN3O5S M.W.463.5299.46%36内酯异构体CAS No.N/A C22H26FN3O5S M.W.463.5297%37Z-283-甲氧基内酯CAS No.N/AC23H28FN3O5S M.W.477.5598.97%38L5-氧代Rosuvastatin EP Impurity C freed acid CAS No.1620823-61-1(sodium salt)1422619-13-3(acid)C22H26FN3O6S M.W.479.5297.92%39Z-63-氧代3-Oxo Rosuvastatin Sodium Salt CAS No.1346606-28-71346747-49-6(acid)C22H25FN3O6S.Na M.W.478.5222.99R-091798.61%40O内酯脱水Rosuvastatin2,6-Diene Lactone Impurity CAS No.1246665-85-9C22H24FN3O4S M.W.445.5299.36%R-094141Z-44,6-二烯Rosuvastatin4,6-Diene Impurity CAS No.1422954-13-9C22H26FN3O5S M.W.463.53R-092795.44%42Z-152,6-二烯CAS NO.1422954-12-8(free acid)C22H26FN3O5S R-092695.70%43Z-8脱甲基二钠盐（体内代谢产物）N-Desmethyl Rosuvastatin Disodium Salt CAS No.371775-74-5(free base)C21H24FN3O6S.2Na M.W.465.50222.99R-09598.87%44W光降解内酯CAS No.854898-47-8C22H26FN3O5S M.W.463.5299.80%45X 光降解内酯CAS No.854898-46-7C22H26FN3O5S M.W.463.5297.84%46Z-2Z 式异构体内酯CAS No.N/A C22H26FN3O5S M.W.463.5296.52%47Z-9脱甲基内酯（体内代谢产物）N-Desmethyl Rosuvastatin Lactone CAS:1797419-58-9C21H24FN3O5S M.W.449.5097.42%48Z-7基因毒性杂质（体内代谢产物）Rosuvastatin Impurity 28CAS No.N/A C22H28FN3O7S M.W.497.54R-098498.94%49Z-5母核烯醛（工艺相关杂质）CAS No.890028-66-7C18H20FN3O3S M.W.377.4398.85%50Z-42母核无氟膦盐CAS No.N/A C34H35BrN3O2PS M.W.660.6099.14%51Y 本体脱丙酮叉CAS No.N/A C26H36FN3O6S M.W.537.6599.74%更多其他项目：雷西纳德，阿格列汀，依鲁替尼，唑吡坦，利奈唑胺，西他沙星，沙丁胺醇，罗替戈汀，丙戊酸钠，左乙拉西坦，西格列汀，特地唑胺，帕瑞昔布钠，帕布昔利布，赛乐西帕，伏硫西汀，曲格列汀，米拉贝隆，沙芬酰胺，达泊西汀，吡格列酮，达泊西汀，吉非替尼，去甲肾上素，阿昔洛韦，文拉法辛，普拉洛芬，普拉克索，曲唑酮，茚达特罗，阿扎胞苷，酮替芬，依折麦布，西那卡塞，氨曲南，替诺福韦，厄多司坦，孤法辛，雷贝拉唑，阿法替尼，依达拉奉，帕利哌酮，达比加群酯，鲁拉西酮，尼非卡兰，瑞巴派特，苯达莫司汀，利伐沙班，法舒地尔，普拉格雷，维格列汀，索非布韦，文拉法辛等。
HPLC法测定注射用阿扎胞苷的含量
HPLC法测定注射用阿扎胞苷的含量聂德平;郑玉丽;冯中【摘要】目的建立测定阿扎胞苷含量的高效液相色谱方法.方法采用WelchUltimateXB-C18（4.6mm×250mm,3μm）色谱柱,以0.02mol·L-1磷酸氢二钾溶液（以磷酸溶液调pH至6.5）-甲醇（90∶10）为流动相,检测波长为243nm,柱温为（15±2）℃.结果阿扎胞苷浓度在8.16～30.6μg·mL-1浓度范围内线性良好（r=0.9999）,平均回收率为98.97%,RSD为0.73%.结论本方法专属性强、准确度高,可用于阿扎胞苷的质量控制.【期刊名称】《药学研究》【年(卷),期】2015(034)006【总页数】2页(P330-331)【关键词】高效液相色谱法;注射用阿扎胞苷;含量【作者】聂德平;郑玉丽;冯中【作者单位】鲁南制药集团股份有限公司,山东临沂276000【正文语种】中文【中图分类】R927.2通讯作用：冯中，男，工程师，研究方向：新药开发和研究，Tel:0539-*******,E-mail:*******************Key words:HPLC;Azacitidine for Injection;Determination骨髓增生异常综合征(MDS)是一组以造血干细胞克隆性异常为特征的疾病，会导致造血功能衰竭，并有进展为急性髓细胞样白血病(AML)的高危险性。
阿扎胞苷是美国食品药品监督管理局(FDA)批准的第一个DNA脱甲基化的嘧啶类抗代谢药物，也是治疗骨髓增生异常综合征(MDS)的第一个有效药物，它通过恢复骨髓细胞的正常生长和分化而发挥作用[1～6]。
目前尚无文献报道阿扎胞苷含量测定的方法，按照《中国药典》2010年版[7]要求，首次建立了测定注射用阿扎胞苷含量的高效液相色谱(HPLC)法，结果表明，该方法准确可靠，灵敏度高，可用于测定注射用阿扎胞苷的含量。
新药阿扎胞苷(Azacitidine)合成检索总结报告
一、阿扎胞苷（Azacitidine）简介阿扎胞苷（Azacitidine）适应于急性髓性白血病的治疗。
2020年5月1日美国食品和药物管理局（FDA）已受理口服阿扎胞苷的新药申请，这是一种口服低甲基化剂，用于维持治疗强化诱导化疗后病情处于缓解期的急性髓性白血病（AML）成人患者。
具体为：用于在强化诱导化疗（有或无巩固化疗）后实现首次完全缓解（CR）或血细胞计数未完全恢复的完全缓解、不适合或选择不进行造血干细胞移植（HSCT）的AML成人患者的维持治疗。
阿扎胞苷（Azacitidine）分子结构式如下:CAS：320-67-2英文名称：Azacitidine中文名称：阿扎胞苷本文主要对阿扎胞苷（Azacitidine）的合成路线、关键中间体的合成方法及实验操作方法进行了文献检索并作出了总结。
二、阿扎胞苷（Azacitidine）合成路线一三、阿扎胞苷（Azacitidine）合成路线二(一)阿扎胞苷（Azacitidine ）中间体2的合成（线路一）合成方法实验步骤参考文献操作方法一To a solution of 1-O-methyl-β-D-ribofuranose 1(1.0Kg)in diisopropylether (400mL)was added and cooled to 4°C.Then acetic anhydride (80.0g)and acetic acid (48.0g)were added followed by pyridine (25.0g).The reaction mixture was cooled to 0°C and added concentrated sulphuric acid (88g).The reaction mixture was stirred for 24h at 0°C and added sodium acetate (216.5g).Ethyl acetate (1.2L)was added and stirred for 5min followed by the addition of saturated sodium bicarbonate to adjust the pH up to 7.3.Separated the layers and aqueous layers is extracted with ethyl aceate (1.0L)and combined organic layer dried with MgSO 4and concentrated to obtain crude 2,3,5-tri-O-acetyl -1-O-methyl-L-ribofuranose (1.5Kg).Crystallization done with ethanol by heating to 45°C and ramp cooling to room temperature to obtain 950g of 2,3,5-tri-O-acetyl-1-O -methyl-D-ribofuranose n Journal of Chemistry ;vol.30;nb.7;(2018);p.1521-1524.操作方法二A solution of D-ribose 1(5g,33.3mmol)in MeOH (100mL)was treated with H 2SO 4(0.5mL).After 6h of stirring at ambient temperature the reaction mixtrure was neutralized with Na 2CO 3(8g),filtered and evaporated to obtain a mixture of methyl α-and β-D-ribofuranosides as a yellow syrup (5.4g).Then to a solution of this mixture (5.4g,32.9mmol)in pyridine (10mL)was added Ac 2O (5mL).The reaction mixture was stirred at ambient temperature for 24h,then poured into a crushed icea nd the mixture was extracted with CH 2Cl 2(3×50mL).The combined organic fractions were washed with saturated aqueous NaHCO 3(3×100mL)and Na 2SO 4(3×100mL),dried with MgSO 4and evaporated to obtain a mixture of methyl 2,3,5-tri-O-acetyl-α-and β-D-ribofuranosides 2as a yellow syrup (5.9g).The anomers were separated by flash chromatography on a silica gel (eluent petroleum ether-ethyl actetate =3:1).Tetrahedron Letters ;vol.60;nb.47;(2019);Art.No:151276(二)阿扎胞苷（Azacitidine ）中间体3的合成方法一（线路一）合成方法实验步骤参考文献操作方法一A solution of thepure methyl 2,3,5-tri-O-acetyl-β-D-ribofuranoside 2(4g,13.8mmol)in glacial AcOH (10.5mL)and Ac 2O (14mL)was cooled (ice bath)and H2SO4(0.4mL)was added.The reaction was stirred at room temperature for 3h,and then was neutralized with solid sodium bicarbonate.The reaction mixture was evaporated and the brownish residue was dissolved in CHCl 3(50mL),washed with water (3×50mL),dried with MgSO 4,and the solvents were evaporated to dryness.The yellow oil was crystallized from EtOH to afford 3(3.3g,43%)as white crystals.Tetrahedron Letters ;vol.60;nb.47;(2019);Art.No:151276.(三)阿扎胞苷（Azacitidine ）中间体3的合成方法二（线路一）合成方法实验步骤参考文献操作方法一p-D-Ribose 4(9.4g,62.6mmol)and 25mL acetic anhydride (27.05g,265.0mmol)were mixed together and cooled to -60°C.Only 5µL 70%HClO 4was added to the suspension mixture and the reaction was then allowed to come to room temperature and stirred overnight.No solids appeared and NMR analysis gave an anomeric mixture of 3,4-diacetoxy -5-acetoxymethyltetrahydrofuran-2-yl acetate 3in quantitative yield.WO2005/70911;(2005);(A1)English (四)阿扎胞苷（Azacitidine ）中间体7的合成（线路一）合成方法实验步骤参考文献A mixture of 5-azacytosine 5(11.2g;0.1mol),hexamethyldisilazane 6(35mL)and ammonium sulphate (0.2g)was heated to reflux (oil bath 160°C)for 8h.TheWO2010/17374;。
阿糖腺苷杂质汇总分享
专业<杂质对照品>解决方案，代理中检所/EP/BP/USP/TRC/TLC/MC/STD等品牌。
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青霉素V、硫酸庆大霉素、紫苏霉素、强力霉素、阿霉素、卡那霉素碱、地红霉素、柔红霉素、非达霉素、达托霉素、
土霉素、表阿霉素、格尔德霉素、两性霉素B、硫酸新霉素、雷帕霉素、利福霉素、盐酸壮观霉素（盐酸壮大霉素）等；q：300-头孢系列：头孢丙烯，头孢西丁 ，头孢唑林，头孢呋辛，头孢克肟，氟氧头孢，头孢特仑新戊酯，头孢哌酮，头孢硫脒，-3438-头孢地尼，头孢克洛，头孢地嗪，头孢拉宗，头孢唑肟，头孢噻肟酸，头孢罗林酯，头孢吡肟，头孢拉定，头孢他美酯，
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5 氮杂胞嘧啶核苷
理化性质
密度：2.08g/cm3 熔点：226-232°C 沸 点 ： 5 3 4 . 5 ºC 闪 点 ： 2 7 7 ºC 折射率：1.823 外观：白色结晶性粉末 溶解性：溶于水和甲醇
分子结构数据
摩尔折射率：51.08 摩尔体积（cm3/mol）：117.0 等张比容（90.2K）：376.2 表面张力（dyne/cm）：106.7 极化率（10-24cm3）：20.25
R22：Harmful if swallowed. 吞食是有害的。 R45：May cause cancer. 可能致癌。 R46：May cause heritable genetic damage. 可能造成不可逆的遗传损害。
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5 氮杂胞嘧啶核苷
有机化合物
01 理化性质
03 用途
目录
02 分子结构数据 04 安全信息
5-氮杂胞嘧啶核苷，又名5-氮胞苷、阿扎胞苷，是一种有机化合物，化学式为C8H12N4O5，主要用作抗肿瘤 药，临床上用于治疗乳腺癌、肠癌、黑色素瘤、急性粒细胞性白血病等。
2017年10月27日，世界卫生组织国际癌症研究机构公布的致癌物清单初步整理参考，阿扎胞苷在2A类致癌物 清单中。
用途
主要用作抗肿瘤药，临床上用于治疗乳腺癌、肠癌、黑色素瘤、急性粒风险术语
S22：Do not breathe dust. 不要吸入粉尘。 S36/37/39：Wear suitable protective clothing, gloves and eye/face protection. 穿戴适当的防护服、手套和眼睛/面保护。 S45：In case of accident or if you feel unwell, seek medical advice immediately (show the lable where possible). 发生事故时或感觉不适时，立即求医（可能时出示标签）。 S53：Avoid exposure - obtain special instructions before use. 避免接触，使用前获得特别指示说明。
阿扎胞苷分子结构
阿扎胞苷分子结构
哇塞！一听到“阿扎胞苷分子结构”这么专业的词，我感觉脑袋都要大啦！这对于我这个小学生（初中生）来说，简直就像是外太空的神秘密码一样。
我就一直在想啊，这阿扎胞苷分子结构到底是个啥呢？它难道是像乐高积木一样，一块一块拼起来的？还是像我们搭的积木城堡，有各种奇奇怪怪的形状？
老师给我们讲的时候，我瞪大眼睛，努力想听明白。
可那些专业的名词，什么原子、化学键，就像一群调皮的小猴子在我脑子里上蹿下跳，把我弄得晕头转向。
我问同桌：“你能搞懂这阿扎胞苷分子结构吗？”同桌皱着眉头说：“我要是能懂，我不就成科学家啦！”
后来我又去问学习好的班长，班长倒是耐心地跟我解释：“你看啊，这就好比我们
搭房子，原子就是砖头，化学键就是把砖头连起来的水泥。
”我似懂非懂地点点头，心
里还是觉得这也太难理解啦！
回到家我跟爸爸妈妈说，他们也一脸迷茫。
爸爸说：“这东西对我来说，就像看天书！”妈妈笑着说：“孩子，你能接触到这么高深的知识已经很厉害啦，慢慢学。
”
我就一直在想，这阿扎胞苷分子结构到底有啥用呢？难道能像魔法一样治好很多病？还是能创造出超级厉害的东西？
我不停地在网上查资料，看那些复杂的图片和解释，感觉自己就像在一个巨大的迷宫里，怎么也找不到出口。
哎呀，我就不明白了，为什么这些科学的东西这么难呢？难道科学家们的脑袋里都装着超级计算机吗？
不过我可不会轻易放弃，我一定要搞明白这阿扎胞苷分子结构到底是怎么回事！我相信，只要我努力，总有一天我能弄清楚它的奥秘！
我的观点结论就是：虽然现在阿扎胞苷分子结构让我很头疼，但我不会被它打败，我会继续探索，直到把它搞明白！。