特立氟胺
| 中文名称 | 特立氟胺 |
|---|---|
| 中文同义词 | 特立氟胺;N -(4 - 三氟甲基)- 2 -氰基-3 - 羟基巴豆酰胺;来氟米特EP杂质B;来氟米特杂质1;来氟米特EP杂质B(特氟仑胺);来氟米特杂质1341;(Z)-2-氰基-3-羟基-N-(4-(三氟甲基)苯基)丁-2-烯酰胺;A 1726:特立氟胺(批次2) |
| 英文名称 | A77 1726 |
| 英文同义词 | A 1726;HMR 1726;(Z)-2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide;LeflunoMide EP IMpurity B;Leflunomide Impurity 2(Leflunomide EP Impurity B);A-771726;A 771726;A771726;A-771726;A 77-1726;A771726;HMR-1726;(2Z)-2-Cyano-3-hydroxy-N-[4-(triflu |
| CAS号 | 163451-81-8 |
| 分子式 | C12H9F3N2O2 |
| 分子量 | 270.21 |
| EINECS号 | 642-273-4 |
| 相关类别 | 医药原料药;医药中间体;原料药;医药原料;化学试剂-科研试剂;定制产品;药物杂质及中间体;中药对照品;Metabolites & Impurities;Tyrosine Kinase Inhibitors;医药原料;医用原料;化学试剂 |
| Mol文件 | 163451-81-8.mol |
| 结构式 |  |
特立氟胺 性质
| 熔点 | 229-232°C |
|---|---|
| 沸点 | 410.8±45.0 °C(Predicted) |
| 密度 | 1.424±0.06 g/cm3(Predicted) |
| 储存条件 | -20°C |
| 溶解度 | DMSO：可溶5mg/mL，澄清（加热） |
| 酸度系数(pKa) | 5.20±0.50(Predicted) |
| 形态 | 粉末 |
| 颜色 | 白色至米色 |
| 最大波长(λmax) | 203nm(MeOH)(lit.) |
| Merck | 14,9165 |
| 稳定性 | 吸湿性 |
| InChIKey | UTNUDOFZCWSZMS-YFHOEESVSA-N |
2018年7月23日之前，中国的复发缓解型多发性硬化患者只能皮下或者肌肉注射β-干扰素预防复发。2018年7月24日以后，中国患者可以免受皮肉之苦，通过口服特立氟胺来预防疾病复发。特立氟胺的商品名为奥巴捷。特立氟胺是一种具有抗炎作用的免疫调节剂，可抑制参与嘧啶从头合成的二氢乳清酸脱氢酶。吃了特立氟胺之后可能会出现头痛、脱发、腹泻、恶心、皮肤反应。服用特立氟胺前应监测血常规、肝功能、血压，并进行结核筛查；服用前6个月每月监测肝功能，之后每6个月监测一次。特立氟胺由赛诺菲成功开发，于2012年9月获得美国FDA批准上市。特立氟胺原研药（商品名：Aubagio）于2018年7月在中国获批上市，用于治疗复发型MS。
据赛诺菲2020年财报显示，Aubagio上市后销售额持续增长达20.45亿欧元，儿科适应症的获批有望成为Aubagio销售额新的增长动力。
值得关注的是，2020年8月，该药又在中国获批用于治疗临床孤立综合征（CIS）。目前特立氟胺已纳入国家医保乙类目录。
在国内，南京海纳制药和盛世泰科医药于2020年3月联合提交了特立氟胺片（新4类）的上市申请，并以“罕见病治疗药”为由纳入优先评审程序，历时近两年，首仿获批、首家视同过评。Teriflunomide (A77 1726) 是来氟米特的活性代谢产物，可用于类风湿性关节炎的研究。 它抑制嘧啶合成，因此有效降低T细胞和B细胞增殖。
Teriflunomide primarily acts as an inhibitor of dihydroorotate dehydrogenase (DHODH), a key mitochondrial enzyme involved in the de novo synthesis of pyrimidines in rapidly proliferating cells. By reducing the activity of high-avidity proliferating T lymphocytes and B lymphocytes, teriflunomide likely attenuates the inflammatory response to autoantigens in MS. Thus, teriflunomide can be considered a cytostatic rather than a cytotoxic drug to leukocytes.
Teriflunomide has demonstrated beneficial effects in two independent animal models of demyelinating disease. In the dark agouti rat model of experimental autoimmune encephalitis (EAE), teriflunomide administration results in clinical, histopathological, and electrophysiological evidence of efficacy both as a prophylactic and therapeutic agent. Similarly, in the female Lewis rat model of EAE, teriflunomide administration results in beneficial prophylactic and therapeutic clinical effects, with a delay in disease onset and symptom severity.
A77 1726 is the active metabolite of Leflunomide, a potent disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. LEF-M interferes with dendritic cell function. The second Phase III study evaluating the efficacy of Genzyme's teriflunomide therapy against relapsing forms of multiple sclerosis found the once-daily oral drug to be no less effective than injectable interferon beta 1a (Rebif).
Teriflunomide is the active metabolite of leflunomide. Teriflunomide is an immunomodulatory drug inhibiting pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase. It is uncertain whether this explains its effect on MS lesions. Teriflunomide inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. It has been found that teriflunomide blocks the transcription factor NF-κB.
| 更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
|---|---|---|---|---|---|
| 2024/01/16 | T3287 | 特立氟胺 Teriflunomide | 163451-81-8 | 100mg | 120元 |
| 2024/01/16 | S4169 | 特立氟胺 Teriflunomide | 163451-81-8 | 50mg | 798.01元 |