(R)-氟比洛芬

抗炎镇痛药毒性不良反应生物活性靶点体外研究体内研究 (R)-氟比洛芬试剂级价格

(R)-氟比洛芬

CAS号:51543-40-9
英文名:(R)-2-Flurbiprofen
中文名:(R)-氟比洛芬
CBNumber:CB8302496
分子式:C15H13FO2
分子量:244.26
MOL File:51543-40-9.mol

(R)-氟比洛芬化学性质

熔点 :110-113 °C(lit.)
沸点 :376.2±30.0 °C(Predicted)
密度 :1.199±0.06 g/cm3(Predicted)
储存条件 :Store at RT
溶解度 :DMF: 25 mg/ml; DMSO: 10 mg/ml; Ethanol: 25 mg/ml; PBS (pH 7.2): .9 mg/ml
酸度系数(pKa) :4.14±0.10(Predicted)
形态 :Crystalline Powder
颜色 :White to off-white

安全信息

危险品标志 :T
危险类别码 :25
安全说明 :26-36/37/39-45
危险品运输编号 :UN 2811 6.1/PG 2
WGK Germany :3
海关编码 :29163900

(R)-氟比洛芬性质、用途与生产工艺

抗炎镇痛药氟比洛芬又称苯氟布洛芬、氟联苯丙酸，是一种强效苯丙酸类解热抗炎镇痛药，能抑制前列腺素合成环氧合酶而起止痛、抗炎及解热作用。其消炎和镇痛作用分别为阿司匹林(亦称乙酰水杨酸)的250倍及50倍。口服吸收迅速，1.5小时后血药浓度达峰值，半衰期为3.5小时，组织分布广，PPB为99.4%，可与血浆蛋白结合率较高的药物发生竞争血浆蛋白的作用。在肝脏中代谢为羟基氟比洛芬及其醛酸结合物。T1/2为3.5 h。由尿和粪便排泄，分别约为60%和40%。年龄对药物代谢无明显影响。主要用于风湿性关节炎、类风湿性关节炎、强直性脊椎炎、变性关节炎。也可预防手术摘除晶状体后发生无晶状体囊样斑点状水肿，抑制手术中瞳孔收缩，白内障及小梁成形氩气激光手术后眼睛炎症的治疗。还适用于其他一些原因如外伤、扭伤、手术等引起的疼痛。
毒性非甾体类抗炎药(NSAID) 有抗炎、止痛和解热作用，毒性由小到大的排位是萘普酮、双水杨酯、舒林酸、双氯芬酸、布洛芬、酮基布洛芬、阿司匹林、萘普生、托美汀、氟比洛芬、炎痛喜康、苯氧布洛芬、吲哚美辛、氯甲灭酸。治疗的传统NSAID药物可首选阿司匹林，如患儿在治疗过程中不能耐受其不良反应时，可选用其他非甾体类抗炎药。目前已开发出选择性COX-2抑制剂，将全部替代传统的NSAID。已上市的选择性COX-2抑制剂有尼美舒利(尼蒙舒)、罗非昔布(万络)、塞来昔布 (西乐葆)、依托度酸(罗丁)、美洛昔康等。最近一项大规模、国际化、多中心、随机双盲化、前瞻性研究表明，选择性COX-2抑制剂的胃肠道、肾脏副作用极少，对血小板功能无明显影响，可作为JRA患儿早期联合治疗的首选药物而取代阿司匹林。
不良反应最常见的不良反应有消化不良，胃部不适等，偶有头痛、皮疹等。消化性溃疡、支气管哮喘病人及孕妇、哺乳期妇女不宜服用。
其他不良反应有恶心、腹泻、腹痛、视力模糊、尿路感染征候、皮炎等。少数有肝转氨酶增高，继续用药，可能发展，亦可保持不变或消失。滴入眼时有轻度的刺痛感和烧灼感及(或)视觉紊乱。因影响血小板聚集而延长出血时间，有眼科手术应用本药后增加眼内出血倾向的报道。动物实验中，氟比洛芬50～100 mg/kg，用药3月，可引起肾乳头坏死。对人类亦可有此作用。
生物活性 Tarenflurbil ((R)-Flurbiprofen) 是 Flurbiprofen 的 R 型对映体，Tarenflurbil ((R)-Flurbiprofen) 抑制 [3H]9-cis-RA 结合到 RXRα LBD，IC50 为 75 μM。
靶点

IC50: 75 μM (RXRα)
体外研究

Tarenflurbil ((R)-Flurbiprofen) can significantly reduce Aβ secretion, but at the same time, increases the level of intracellular Aβ. The binding between [ ³ H]9-cis-RA and RXRα is competitively inhibited by both unlabeled (R)-Flurbiprofen and 9-cis-RA. (R)-Flurbiprofen can interfere with the interaction between RXRα and 9-cis-retinoid acid (9-cis-RA), and that 9-cis-RA decreases Tarenflurbil ((R)-Flurbiprofen)’s reduction of Aβ secretion. Tarenflurbil ((R)-Flurbiprofen) treatment significantly increases the levels of intracellular Aβ species. The well characterized, nonsteroidal anti-inflammatory drug (nonsteroidal anti-inflammatory drug), Tarenflurbil ((R)-Flurbiprofen) affects only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.
体内研究

Effects of the early and late onset of treatment with Tarenflurbil ((R)-Flurbiprofen) are assessed in C57BL6/J mice that develop a non-remitting form of the disease, and in SJL mice that develop a relapsing-remitting (RR)-EAE. Tarenflurbil ((R)-Flurbiprofen) completely prevents the development of clinical EAE scores in C57BL6/J mice when the treatment is started within 3 days after immunization. This regimen is referred to as preventive treatment. The effect is dose-dependent, and the minimum daily dose for complete prevention is 5 mg/kg/day. Effects of Tarenflurbil ((R)-Flurbiprofen) are comparable to those of Fingolimod (FTY720, 0.5 mg/kg/day), which is used as the positive control. Tarenflurbil ((R)-Flurbiprofen) also significantly reduces clinical EAE scores in C57BL6/J mice when treatment is started shortly before onset of clinical manifestations, referred to as semi-therapeutic (10 mg/kg/day) and reduces clinical scores when the treatment is initiated after full development of the disease on day 13 (5 mg/g/day).
用途解热镇痛消炎药