中文名称帕利伐米中文同义词帕利伐米,>98%;N,N’-双(2-氯乙基)二氨基膦酸;帕利伐米英文名称Palifosfamide英文同义词Ifosforamidemustard;Ipam;N,N’-Di-(2-chloroethyl)phosphorodiamidicacid;N,N’-BIS(2-CHLOROETHYL)PHOSPHORODIAMIDATE;Isophosphamidemustard;palifosfamide;N,N’-Bis(2-chloroethyl)phosphorodiamidicacid;ZIO-201,>98%CAS号31645-39-3分子式C4H11Cl2N2O2P分子量221.02EINECS号相关类别有机原料;细胞周期;药物API与中间体Mol文件31645-39-3.mol结构式帕利伐米性质熔点106-107ºC沸点341.5±52.0°C(Predicted)密度1.411储存条件Storeat-20°C,protectfromlight,storedundernitrogen溶解度DMSO中≥22.1mg/mL;不溶于乙醇;温和加热和超声波下,水中≥19.4mg/mL形态粉末酸度系数(pKa)0.79±0.50(Predicted)颜色白色至米白色InChIInChI=1S/C4H11Cl2N2O2P/c5-1-3-7-11(9,10)8-4-2-6/h1-4H2,(H3,7,8,9,10)InChIKeyBKCJZNIZRWYHBN-UHFFFAOYSA-NSMILESP(NCCCl)(NCCCl)(O)=OCAS数据库31645-39-3帕利伐米用途与合成方法概述帕利伐米(IPM)是环磷酰胺(CPA)的常见代谢产物。帕利伐米被认为是CPA表现出的至少一部分抗肿瘤活性的原因。直接使用帕利伐米作为抗癌剂的努力未获成功,部分原因是该化合物的不稳定性。已经合成了帕利伐米并且已经对该化合物进行了初步的生物学评估,但遗憾的是帕利伐米太不稳定而不能被分离并用于人类治疗。生物活性PChemicalbookalifosfamide(ZIO-201,Isophosphamidemustard)是新型的DNA烷化剂,是异环磷酰胺(ifosfamide)的活性代谢产物,具有抗肿瘤活性。体外研究Palifosfamidelysine(ZIO-201)isastableformofpalifosfamide.Palifosfamidelysinehasbroadactivityinsarcomalinesinvitro.TheIC50rangesfrom2.25ro6.75μMformostcelllinesexceptOS222(IC50=31.5μM).体内研究TumorgrowthinhibitionisseeninbothOS31andOS33xenograftsandtheRMSxenograftresultinginasignificantdifferenceinevent-freesurvivalbetweenthecontrolandthetreatedgroups.DifferentialgeneexpressionofALDH3A1butnotALDH1A1isnotedintheOS31xenograft.StabilizedpalifosfamideadministeredtomicesuppressesMX-1tumorgrowthbygreaterthan80%with17%completeantitumorresponses.Oralbioavailabilityinratsis48-73%ofparenteraladministration,andantitumoractivityinmiceisequivalentbybothroutes.Treatmentwithpalifosfamide-triscombinedwithdocetaxelordoxorubicinatoptimalregimensresultsincompletetumorregressionin62-75%ofmice. |