Sulfasalazine_HNMR_14146_MedChemExpress
Gelucire-14-44-SDS-MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Nov.-23-2018Print Date:Nov.-23-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :Gelucire 14/44Catalog No. :HY-Y1892CAS No. :121548-04-71.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:NoneFormula:N/AMolecular Weight:N/ACAS No. :121548-04-74. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Pure form-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Oil)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2018 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
FDA批准的放射性药物都有哪些？
FDA批准的放射性药物都有哪些？展开全文中华医学会核医学分会放射性药物学组整理1、药物名称：Carbon-11 choline（11C-胆碱）生产商：Mayo Clinic 商品名：—用途：前列腺癌复发诊断2、药物名称：Carbon-14 urea（14C-尿素）生产商：Kimberly-Clark 商品名：PYtest用途：胃中幽门螺杆菌感染诊断3、药物名称：Fluorine-18 florbetaben（18F-AV1）生产商：Piramal Imaging 商品名：Neuraceq™用途：阿尔茨海默（AD）患者和痴呆患者评价4、药物名称：Fluorine-18florbetapir（18F-AV45）生产商：Eli Lilly 商品名：Amyvid™用途：阿尔茨海默症诊断与治疗5、药物名称：Fluorine-18sodium fluoride（18F-氟化钠）生产商：Various 商品名：—用途：成骨能力的骨显像剂6、药物名称：Fluorine-18fludeoxyglucose（18F-FDG）生产商：Various 商品名：—用途：肿瘤、癫痫病灶糖代谢异常检测7、药物名称：Fluorine-18flutemetamol（18F-PIB）生产商：GE Healthcare 商品名：Vizamyl用途：阿尔茨海默（AD）患者和痴呆患者评价8、药物名称：Gallium-67 citrate（67Ga-柠檬酸）生产商：Lantheus MedicalImaging、Mallinckrodt商品名：—用途：霍奇金病、淋巴瘤、支气管癌以及一些急性炎症病变诊断9、药物名称：Indium-111capromab pendetide（111In-卡罗单抗喷地肽）生产商：AytuPharmaceuticals 商品名：ProstaScint®用途：前列腺癌患者、前列腺癌术后高度怀疑转移患者的检测10、药物名称：Indium-111 chloride（111In-氯化铟）生产商：GE Healthcare、Mallinckrodt 商品名：Indiclor™用途：用于放射性标记11、药物名称：Indium-111 pentetate（111In-DTPA）生产商：GE Healthcare 商品名：—用途：放射性核素脑池造影12、药物名称：Indium-111oxyquinoline（111In-羟基喹啉）生产商：GE Healthcare 商品名：—用途：用于自体白细胞标记，炎症及感染的诊断13、药物名称：Indium-111pentetreotide（111In-奥曲肽）生产商：Mallinckrodt 商品名：Octreoscan™用途：原发性和转移性内神经分泌肿瘤生长抑素受体定位14、药物名称：Iodine I-123iobenguane（123I-MIBG）生产商：GE Healthcare 商品名：AdreView™用途：原发或转移性嗜铬细胞瘤或神经母细胞瘤的辅助诊断15、药物名称：Iodine I-123 ioflupane（123I-氟潘）生产商：GE Healthcare 商品名：DaTscan™用途：对疑似帕金森症患者的评估16、药物名称：Iodine I-123sodium iodide capsules（123I-碘化钠胶囊）生产商：Cardinal Health、Mallinckrodt 商品名：—用途：甲状腺功能及形态学评价17、药物名称：Iodine I-125 humanserum albumin（125I-人血清白蛋白）生产商：IsoTex Diagnostics 商品名：Jeanatope用途：全血及血浆容量测定18、药物名称：Iodine I-125iothalamate（125I-酞酸盐）生产商：IsoT ex Diagnostics商品名：Glofil-125用途：肾小球滤过率的评价19、药物名称：Iodine I-131 humanserum albumin（131I-人血清白蛋白）生产商：IsoTex Diagnostics 商品名：Megatope用途：全血及血浆量、心脏输出、心脏及肺血容量、蛋白质周转研究、脑肿瘤定位等20、药物名称：Iodine I-131sodium iodide（131I-碘化钠）生产商：DRAXIMAGE、Mallinckrodt 商品名：HICON™用途：甲状腺疾病的诊断与治疗21、药物名称：MolybdenumMo-99 generator（钼锝发生器）生产商：GE Healthcare、Lantheus MedicalImaging、Mallinckrodt商品名：DRYTEC™、T echnelite、UltraTechneKow®DTE用途：放射性药物的制备22、药物名称：Nitrogen-13 ammonia（13N-氨水）生产商：Various 商品名：—用途：心肌灌注评价冠状动脉疾病23、药物名称：Radium-223 dichloride（223Ra-二氯化镭）生产商：Bayer HealthCarePharmaceuticalsInc. 商品名：Xofigo®用途：去势性前列腺癌治疗24、药物名称：Rubidium-82 chloride（82Ru-氯化铷）生产商：Bracco Diagnostics 商品名：Cardiogen-82®用途：心肌灌注显像剂25、药物名称：Samarium-153lexidronam（153Sm-EDTMP）生产商：Lantheus MedicalImaging 商品名：Quadramet®用途：减轻骨转移患者的疼痛26、药物名称：Strontium-89 chloride（89Sr-氯化锶）生产商：GE Healthcare商品名：MetastronTM用途：减轻骨转移患者的疼痛27、药物名称：T echnetium-99mbicisate（99mT c-ECD）生产商：Lantheus MedicalImaging 商品名：Neurolite®用途：脑卒中患者卒中的诊断与治疗28、药物名称：Technetium-99mdisofenin（99mTc-地索芬宁）生产商：Pharmalucence 商品名：Hepatolite®用途：急性胆囊炎诊断29、药物名称：Technetium-99mexametazine（99mTc-HMPAO）生产商：GE Healthcare 商品名：C eretec™用途：脑卒中患者血脑灌注、白细胞标记显像用用于腹腔感染及肠道炎症定位30、药物名称：T echnetium-99mmacroaggregatedalbumin （99mT c-MAA）生产商：DRAXIMAGE 商品名：—用途：肺灌注评价、腹静脉分流畅通性评价31、药物名称：Technetium-99mmebrofenin（99mT c-甲溴苯宁）生产商：Bracco Diagnostics、Pharmalucence 商品名：Choletec®用途：肝胆显像剂32、药物名称：Technetium-99mmedronate（99mTc-MDP）生产商：DRAXIMAGE、GE Healthcare、Pharmalucence 商品名：MDP-25、MDP Multidose用途：骨显像剂33、药物名称：Technetium-99mmertiatide（99mTc-MAG3）生产商：Mallinckrodt 商品名：TechnescanMAG3TM用途：肾动态显像34、药物名称：Technetium-99moxidronate（99mT c-HDP）生产商：Mallinckrodt 商品名：Tec hnescan™HDP用途：骨显像剂35、药物名称：Technetium-99mpentetate（99mT c-DTPA）生产商：DRAXIMAGE 商品名：—用途：脑显像、肾显像36、药物名称：T echnetium-99mpyrophosphate（99mTc-PYP）生产商：Mallinckrodt、Pharmalucence 商品名：Technescan™、PYP™用途：骨显像、心脏显像剂、血池显像剂37、药物名称：Technetium-99m redblood cells（99mT c-红细胞）生产商：Mallinckrodt 商品名：UltraTag™用途：血池造影、消化道出血定位38、药物名称：T echnetium-99msestamibi（99mTc-MIBI）生产商：Cardinal Health、DRAXIMAGE、Lantheus MedicalImaging、Mallinckrodt、Pharmalucence商品名：Cardiolite®用途：心肌灌注，用于检测缺血、评价心机功能，乳腺成像39、药物名称：Technetium-99msodium pertechnetate （99mT c-高锝酸钠）生产商：GE Healthcare、Lantheus MedicalImaging、Mallinckrodt商品名：—用途：脑显像、甲状腺显像、胎盘定位、膀胱显像等40、药物名称：Technetium-99msuccimer（99mT c-DMSA）生产商：GE Healthcare 商品名：—用途：肾显像41、药物名称：Technetium-99msulfur colloid（99mT c-硫胶体）生产商：Pharmalucence 商品名：—用途：肝、脾、骨髓显像等42、药物名称：Technetium-99mtetrofosmin（99mTc-替曲膦）生产商：GE Healthcare 商品名：MyoviewTM用途：心肌灌注剂43、药物名称：Technetium-99mtilmanocept（99mTc-替马诺噻）生产商：NavideaBiopharmaceuticals,Inc. 商品名：Lymphoseek®用途：淋巴结定位44、药物名称：Thallium-201chloride（201Tl-氯化铊）生产商：GE Healthcare、Lantheus MedicalImaging、Mallinckrodt商品名：—用途：心肌灌注显像45、药物名称：Xenon-133 gas（133Xe气体）生产商：Lantheus MedicalImaging 商品名：—用途：肺功能评估与肺显像、脑血流评估46、药物名称：Yttrium-90chloride（90Y-氯化钇）生产商：MDS Nordion、Eckert＆ZieglerNuclitec商品名：—用途：放射性标记47、药物名称：Yttrium-90ibritumomab tiuxetan（90Y-替伊莫单抗）生产商：SpectrumPharmaceuticals商品名：Zevalin®用途：非霍奇金氏淋巴瘤治疗截止至2015年8月1日。
含萘三氮唑甲烷骨架的硫代乙酸类尿酸转运体1(URAT1)抑制剂的合成及其构效关系
含萘三氮唑甲烷骨架的硫代乙酸类尿酸转运体1(URAT1)抑制剂的合成及其构效关系辛晓;刘巍;谢亚非;刘长鹰;汤立达;徐为人;赵桂龙【摘要】分别以1-溴萘和酮或1-萘甲醛及有机金属试剂为原料,经12步反应合成了8个含萘三氮唑甲烷骨架的硫代乙酸类尿酸转运体1(URAT1)抑制剂(1h～1o),其结构经1H NMR,13C NMR和MS (ESI)表征.体外活性测试结果显示:对URAT1的抑制活性最强的是1k,是阳性对照药lesinurad的133倍[IC50=0.054 μmol·L-1(1k),7.18 μmol·L-1(lesinurad)].%Eight naphthyltriazolylmethane-based thioacetic acids(1h ～ 1o) were synthesized as uric acid transporter 1 (URAT1) inhibitors by 12 steps using 1-bromonaphthalene and ketones or 1-naphth-aldehyde and alkyl organometallic reagents as starting materials.The structures were characterized by 1H NMR,13C NMR and MS(ESI).In vitro URAT1 inhibitory assay showed that 1k was the most potent URAT1 inhibitor among target compounds,which was 133-fold more potent than positive contr ol lesinurad(IC5o =0.054 μmol · L-1 for 1k against human URAT1 vs 7.18 μmol · L-1 for lesinurad).【期刊名称】《合成化学》【年(卷),期】2017(025)006【总页数】14页(P461-474)【关键词】1-溴萘;1-萘甲醛;痛风;高尿酸血症;尿酸转运体1 (URAT1);合成;lesinurad;构效关系【作者】辛晓;刘巍;谢亚非;刘长鹰;汤立达;徐为人;赵桂龙【作者单位】天津中医药大学研究生院,天津300193;天津药物研究院天津市新药设计与发现重点实验室,天津300193;天津药物研究院天津市新药设计与发现重点实验室,天津300193;天津药物研究院天津市新药设计与发现重点实验室,天津300193;天津药物研究院天津市新药设计与发现重点实验室,天津300193;天津药物研究院天津市新药设计与发现重点实验室,天津300193;天津中医药大学研究生院,天津300193;天津药物研究院天津市新药设计与发现重点实验室,天津300193;天津药物研究院天津市新药设计与发现重点实验室,天津300193【正文语种】中文【中图分类】O623.626;O621.3痛风是困扰人类最古老的疾病之一[1]，是由于尿酸单钠盐(MSU)在关节和关节周围的组织等部位沉积引起的，是最常见的类风性关节炎。
【VIP专享】非索非那定片42
盐酸非索非那定片 ----毕馨
-------- 玉兴堂医药学术推广部
2020/5/19
盐酸ቤተ መጻሕፍቲ ባይዱ索非那定片
----毕馨
【分子式】 C32H39NO4·HCl 【分子量】 538.13 【性状】 本品为薄膜衣片，除去包衣后显白色或类白色。
2020/5/19
上市信息
赫斯特公司开发，1996年首次在欧洲上市 1996年FDA批准了SANOFI AVENTIS的新 药申请 2006年10月FDA批准口服混悬剂
1］和黏附到内皮细胞上的部分嗜酸性化 学介质的释放
2020/5/19
药理作用
非索非那定可以抑制人肥大细胞和嗜碱粒细胞释 放及贮存新合成的炎症介质，与嗜酸粒细胞共孵 育后，在较低浓度即能下调嗜酸粒细胞分泌嗜酸 粒细胞阳离子蛋白
2020/5/19
药理作用
临床研究表明非索非那定即使在较低的剂 量（20 mg，每日2次）下也能显著控制瘙 痒症状和减少风团数量，60 mg每日2次能 够显著改善慢性荨麻疹患者的生活质量， 安全性较好，副作用发生率与剂量无依赖 性
2020/5/19
药物代谢
药代特点 非索非那定达峰时间1.5小时，半衰期14～ 15小时，作用维持时间16小时。
2020/5/19
药物相互作用
与红霉素和酮康唑的药物间相互作用
盐酸非索非那定虽然表现出较小的肝脏代 谢率(5%)，但当与红霉素、酮康唑作用时 会导致盐酸非索非那定的血药浓度升高。 盐酸非索非那定对红霉素和酮康唑的药代 动力学没有影响。
非索非那定不被肝脏代谢，能安全用于肝 功能损害的患者
2020/5/19
药物相互作用
非索非那定不经过肝脏的生物转化，因此 它与那些依赖于肝代谢的药物之间不存在 相互作用。
亚硝脲类抗肿瘤药物的研究进展
亚硝脲类抗肿瘤药物的研究进展西l1辰抓lj韶,亚硝脲类抗肿瘤药物的研究进展山东省医学科学院药物研宄所!兰综述李风幂审较艮-7亚硝脉是一类重要的抗肿瘤药物,具有广谱的抗癌话性,临床研究已证实对多种恶性肿瘤有效.但是,由于其延迟性,蓄积性的血液毒性作用,使其临床应用受到了一定的限制.目前,人们已对亚硝腮类化合物的构效关系进行了广泛研究,合成了一系列恬性较高,毒性较低的新抗肿瘤药物.下面就亚硝脲类抗肿瘤药物的研究情况简介如下:一,历史回顾自1956年美国最先对亚硝臊化合物1一甲基～硝基一1一亚硝基胍研究以来,人们已开发了一系列活性显着的亚硝腮类抗肿瘤药物”,这包括六十年代中期进入l瞄床使用的卡奠司汀(Carmustir~e,BcNu)和链脲霉素, No■CNU七十年代上市的洛莫司汀(Lomustine,CCN 呷一一.0∞ccNUU)和司莫司汀(Semustine,MeCCNU)以及—C,∞Mo-~~NU1980年推向市场的尼莫司汀(Nimustine, -fcm一”,NOACNUACNU)等.近几年来,随着对亚硝脲类化合物的深入研究,人们又合成了一系列新的活性较高,毒性较低的亚硝脲类抗肿瘤药物. 一66—/,二,临床中研究的亚硝脲类抗肿瘤药物1.雷洛司汀(Ranomusfine,MCNU)MCNU是1987年在日本首次上市的新一t4o∞/0,———一VMCNU.”亚硝脲类抗肿瘤药物,为水溶性亚硝脲药的代表物,对多种实验肿瘤有效】.静注本品15mg/kg,对乳腺癌异种移植裸鼠肿瘤缓解率达73%显着优于CCNU和AcNU【. 药代动力学研究显示,人和动物(大鼠,狗)静注本品后,血药浓度呈双相性消失,连续使用可在脂肪,动脉,脑下垂体,甲状腺和肾上腺内蓄积,但无残留性.脑肿瘤患者静脉内给药后5o分钟脑瘤内浓度达峰值,以后和血浆内相似,呈双相性消失.本品的毒性较小,静注后的LD,o值,小鼠为41.2～45.Omg/kg,大鼠为31.8～32.2 rag/kg.大鼠使用本品1mg/kg以上剂量,可抑制体重增加,骨髓再生不良白细胞减少.狗使用本品0.5mg/kg以上剂量时,体重减轻,白细胞减少骨髓再生不良,精子细胞及胸腺萎缩.I,Ⅱ期的l瞄床研究显示”,静注本品的最佳适应症是红细胞增多,慢性骨髓样自血病,血小板增多等.在Ⅱ期临床研究中, Masaoka骞报道1.2a,静注本品50~160rag/ 111,间歇1～3个月可重复用药(据血小板和自细胞数情况)51例慢性骨髓样白血病(CML)的完全缓解率为8j为,16例血小板E螽二露疆瓦丽晤孺I};增多症的缓解率为鹊%,15例红细胞增多为98%.其中,5例严重的CML患者以前曾用过白消安治疗.另一组,在MCNU和白消安的对比研究中,共有77例可评价的CML患者,40例用MCNU治疗,37例用白消安治疗,两组的缓解率和生存率没有差异, 但是其完全缓解期则显着不同,用MCNU的患者缓解率高于后者.另外,Uzuka等报道,70例晚期骨髓瘤患者,用环磷酰胺和瓶的松龙(cP),BCNU,环磷酰胺,甲基苄肼和强的松龙(BCPP)及MCNU,环磷酰胺,氮芥和强的松龙(MCMP)~种不同方案作一线治疗,其总缓解率分别为76.2,86.I为和9l字矗,其中完全缓解率分别为’26.1,毛, 33.3笳和63.7.这个初步的实验结果表明,MCMP方案对多发性骨髓瘤患者具有很好的疗效.2.福莫司汀(Fotemustine)Fotemustlne(S10036’福莫司汀是1989年上市的脂溶性亚硝脲新药,对多种肿瘤有效u,尤其是对恶性黑色素瘤疗效显着,优于以往的亚硝脲类药物.临床上,153例可评价的播散性恶性黑色素瘤患者,客观缓解率达24.2两,其中, 脑转移为25.0,内脏为l9%,非内脏为31.8届,以前未治疗过的为30.7弗.此药用于中枢神经系统肿瘤,结,直肠癌,非小细胞肺癌,恶性淋巴瘤和肾癌等的临床研究正在进行中其疗效有待于临床评估.3.牛磺莫司~T(Tauromustine,TCNU)SO:H口●】)NOTCNUTCNU是临床上正在研究的一种新水溶性亚硝脲类抗肿瘤药物,对各种培养的人体肿瘤,具有与BCNU和CCNU相似的活性; l∞2年寡l8卷第2翔体内试验中对WaIkel”956肉瘤的治疗指数高于BCNU和CCNU2～4倍”:临床研究中”,,口服本品130m,间歇5周,可治疗多种恶性肿瘤,包括各种肺癌,肾癌,乳腺癌,卵巢癌,恶性黑色素瘤,恶性神经膝质瘤和淋巴瘤等,其疗效优于或等同于其它亚硝脲类药物.本品的毒性轻微,一般耐受性好.与BCNU比较,骨髓毒性较大(为剂量限制性毒性肝脏毒性较小总的来说,TCNU是一个很有前途的亚硝脲类抗肿瘤药物.4.TA一077ACNU,MCNU,GANU,CCNU, MeccNu等),且毒性较低.药代动力学研究表明n,本品的血药浓度呈相性消失,d相半减期为1.06分钟,口相半减胡为9.16 分钟.目前,本品已进入Ⅲ期临床研究,很有希望成为口服的药物大量上市.此外,临床上正在进行I或Ⅱ期研究的一6i一亚硝脲类新药还有PCNUt”,HeCNU’,SLGNU”,CGP-6809和CNUA’等,它们都显厅出较好的抗癌活性.oNNO.PCNLIIc脚kOH2】咖№HeCNU~GP~809另外,由于许多肿瘸占据筐体激素受俸,以及亚硝脲类药物内在的抗肿瘤活性特别强.因此,合成以甾体激素为骨架(或载体) 的亚硝脲类化合物,进行靶向化疗,将有可能显着提高抗癌效果根据这个构思,人们已经合成了一些甾体类亚硝脲化合物.其中,在二.一68一分结构制得1Ta—cNu∞’和CNC-ala-17E-2,在体外和动物试验时,都显示了抑制乳腺癌细胞的抗肿瘤活性.总之,由于亚硝脲类化台物具有广谱而显着的抗肿瘤作用因此,合成新的高效,低毒的或专一性强的亚硝脲类药物将是很有意义的.参考文献【i]DrugsFurl9a6.12:585[2]DrugsFut1986.11:762【3】ToanJCetai:JNeurooncol1990.8(1,:4I【1]Mi9ragamiMetak(ToKagakuRyoh~1990.17(2):2邓【5].~1ineuraKet81:Ac扭-NenrochlrWien1990, lO3(]r2,:62C6]MasaokoTetal:G&nToKagakuRyoho1990. 17(2):8Ol[]UzukaYetal;GanToKagakul~yoho1990,17(SPt1):1t81(8】Y amashlmaTetal:~eurosurgery1990.26(5) 794[9]KiyaKetal:GanToKagakuRyoho1990.17(2):991【10]Kitajim~KetaJ:OanToKagakuRyoho1989.is(11):3578[“]CourV etal:Onkologio1990.l3(1):f[12]J~cqui[1atcetakCancer1990.66(9):1878【I8】Le-Chev~[iorret”:EmJCancerC/in0n c0tL989.25(11):1651[1叼Gundersenseta】:EurJc0JQLC@fC/inoncof lg8.【4)655E15]SVhitt]e【ReaI:BrJ~ourosmgLgl(3).365[1叼GatzemeierUetai:OnkoLogie[990.I3(3】.【86 ElT]BachFetal:EurJCancerL990.26’4’545[18]DragsFur1985.10(2):189[19]KayashidaKetal;JPharma~obiodnl98’i10(10).528[203FeunIetal:Oncology1990.47(5):389口】]RubiesJM:InvestNeⅥ?Drugs1989.7(9—3) 239[22】~ieerLetal:BiochemPharm蛐I1989.39(6): 929[23]】.Lm14yetal:BiochemPhm&c.l1988.37【l3): 2625两二两再虿I前而≯”¨受饥MH洲～。
阿伐那非合成
田边三菱制药原研的世界专利第W020*******号，第WO200119802号和美国专利第US6656935号(下载此专利),报道了阿伐那非及其类似物的制备方法。
该方法是通过以甲硫基脲⑴和乙氧次甲基丙二酸二乙酯环合得到4-羟基-2-甲硫基嘧啶-5-羧酸乙酯;经三氯氧磷氯化得到4-氯-2-甲硫基嘧啶-5-羧酸乙酯; 取代反应后得到4-(3-氯-4-甲氧基苄胺基)-2_甲硫基嘧啶-5-羧酸乙酯;用过氧苯甲酸氧化得到4-(3-氯-4-甲氧基苄胺基)-2-甲磺酰基嘧啶-5-羧酸乙酯，亲核加成反应后生成4-[ (3-氯-4-甲氧基苄基)氨基]-2-[2-(羟甲基)-1-吡咯烷基]嘧啶-5-羧酸乙酯;水解后酰化反应制得阿伐那非（Avanafil)。
苏州明锐医药科技有限公司的专利第201310195854.5号（授权公告号：CN103265534A，(从下载次专利）报道了阿伐那非的制备方法。
以胞嘧啶为原料，和3-氯-4-甲氧基苄溴发生取代反应，生成N-(3-氯-4-甲氧基苄基)胞嘧啶;经过碘代反应并和侧链N-(2-甲基嘧啶)甲酰胺发生加成反应生成6-(3-氯-4-甲氧基苄胺基)-1，2- 二氢嘧啶-2-酮-5-(N-2-嘧啶基甲基)甲酰胺;与S-羟甲基吡咯烷发生缩合反应制得阿伐那非（Avanafil)。
制备阿伐那非(Stendra,Avanafil)的具体实施方式N-(3-氯-4-甲氧基苄基)胞嘧啶于三口瓶中加入胞嘧啶(2.22g，20mmol)、三乙胺(2.0g，20mmol)、碘化钾(0.2g,I % eq)和无水乙醇50mL,升温至50-55°C,搅拌至体系溶解均一。
缓慢滴加3_氯-4-甲氧基苄溴(III) (5.60g,24mol)至反应液中。
升温至80°C，继续反应3小时，TLC检测反应结束。
降至室温，过滤除去三乙胺氢溴酸盐。
滤液用盐酸调节PH至4-5。
减压回收乙醇，剩余物用乙酸乙酯重结晶，得到类白色固体N-(3-氯-4-甲氧基苄基)胞嘧啶4.78g，收率90.2%。