共查询到20条相似文献,搜索用时 140 毫秒
1.
2-丁基-5-硝基苯并呋喃和4-甲氧基苯甲酰氯经Friedel-Crafts反应、去甲基化、醚化、还原和甲磺酰化制得N-[2-丁基-3-[4-(3-氯丙氧基)苯甲酰基]-5-苯并呋喃基]甲磺酰胺,再经碘代后与正丁胺反应得到去丁基决奈达隆,结构经核磁共振氢谱、碳谱、红外光谱和质谱确证,该化合物可作为决奈达隆质控的对照物。 相似文献
2.
3.
抗心律失常新药决奈达隆的不良反应与相互作用 总被引:1,自引:0,他引:1
决奈达隆是一种化学结构与胺碘酮相似的新的抗心律失常药物。2011年美国版和2010年欧洲版心房颤动指南均推荐决奈达隆用于心房颤动的治疗。决奈达隆的疗效虽然不如胺碘酮,但不良反应及耐受性明显好于胺碘酮,无甲状腺毒性、肺毒性和眼毒性,致心律失常的可能性也很低。决奈达隆的不良反应主要是消化系统反应(腹泻、恶心和呕吐等)、循环系统反应(致尖端扭转型室速、心动过缓、心血管不良事件死亡率升高等)、升高血清肌酐水平及头晕、头痛等神经系统不良反应。决奈达隆与其他药物的不良相互作用主要涉及经CYP450 3A4和CYP450 2D9代谢(诱导剂和抑制剂)的药物。决奈达隆的不良反应及药物相互作用值得心血管内科临床医生重视。 相似文献
4.
目的 应用高效液相色谱技术建立盐酸决奈达隆片溶出度的测定方法. 方法 采用Agilent ZORBAX Eclipse Plus C18 色谱柱(100 mm×4.6 mm,3.5 μm)进行分离,以2 mmol.L-1磷酸二氢钠(氢氧化钠调至pH 7.0)-甲醇-乙腈(20:30:50)为流动相,流速1.5 mL.min-1,检测波长290 nm. 溶出度采用浆法,以水900 mL为溶出介质,转速125 r.min-1. 结果 辅料不干扰决奈达隆的测定;决奈达隆的线性相关系数(r)为1.000 0;检出限(以决奈达隆游离碱计)为0.19 mg.L-1;精密度和12 h稳定性RSD均<1%;回收率101.2%~102.1%. 3批样品溶出度的均一性良好(RSD<7%),平均溶出度均>75%. 结论 该方法准确、简单、快速,可作为盐酸决奈达隆片溶出度的测定方法. 相似文献
5.
6.
目的:筛选盐酸决奈达隆片的处方组成,并评价其溶出度。方法以盐酸决奈达隆的溶出度为指标,采用L9(34)正交试验优化盐酸决奈达隆片处方主要因素填充剂乳糖–淀粉比例、黏合剂聚维酮 K30的乙醇体积分数、增溶剂波洛沙姆用量、崩解剂交联聚维酮用量。以赛诺菲–安万特公司原研制剂迈达龙为参比制剂,采用 f2相似因子法进行盐酸决奈达隆溶出曲线的相似度评价。结果盐酸决奈达隆片的最佳处方为填充剂比例2∶1,选用5%PVP K3040%乙醇溶液为黏合剂,泊洛沙姆188用量为2%,交联聚维酮用量为3%。在不同pH值的溶出介质中,自制制剂和参比制剂的溶出曲线f2相似因子均大于50。结论自制制剂与参比制剂在不同pH值的溶出介质中得体外溶出行为相似。 相似文献
7.
8.
邓万俊 《中国新药与临床杂志》2010,(1)
决奈达隆为新型苯并呋喃衍生物,结构与胺碘酮相似。决奈达隆具有多通道阻滞的电生理特性。Ⅲ期临床试验证实,决奈达隆能有效减少心房颤动(Af)或心房扑动(AF)的复发,减慢Af/AF的心室率,减低心血管发病率及病死率。但在一项纳入重度心力衰竭(HF)及左室功能障碍患者的研究中,决奈达隆使病死率升高。决奈达隆耐受性好,不明显延长QTc间期,无显著肺、甲状腺、肝、眼和神经系统毒性,最常见的不良反应为腹泻、恶心及呕吐。决奈达隆可选择性用于Af/AF的治疗。但在预防Af复发时,决奈达隆疗效逊于胺碘酮,尚需更多有关决奈达隆与胺碘酮疗效的对比研究以确立决奈达隆在治疗中的地位。 相似文献
9.
10.
建立了LC-MS/MS法同时测定Beagle犬血浆中的决奈达隆及其N-去丁基代谢物SR35021,并考察了盐酸决奈达隆片在Beagle犬内的药动学。采用C_(18)色谱柱,以乙腈-甲醇-5 mmol/L乙酸铵溶液-甲酸(55:10:35:0.07)为流动相,大气压化学电离源,多反应监测(MRM)方式,正离子检测。用于定量分析的离子反应分别为m/z 557→100(决奈达隆)、m/z 501→114(代谢物SR35021)和m/z 449→252(内标,托伐普坦)。血浆中决奈达隆及其代谢物SR35021均在0.2~200 ng/ml浓度范围内线性关系良好。两者的日内和日间RSD均小于10%。主要药动学参数如下:c_(max)(495±208)和(61.6±15.9)ng/ml;t_(max)(1 67±0.61)和(1.75±0.42)h;t_(1/2)(5 92±0.59)和(3.01±0.60)h:AUC_(0-t)(2 785±1 409)和(325±137)ng·h·ml;AUC_(0-(?))(2 793±1 412)和(328±136)ng·h·m1。 相似文献
11.
Abd Elhafez OM El Khrisy Eel D Badria F Fathy Ael D 《Archives of pharmacal research》2003,26(9):686-696
Ethyl (coumarin-4-oxy)acetate 1 was prepared through the reaction of 4-hydroxycoumarin with ethyl bromoacetate. Compound 1 was allowed to react with hydrazine hydrate to produce coumarin-4-oxyacetic hydrazide 2. The synthesis of N-(arylidene and alkylidene)-coumarin-4-oxyacetic hydrazones 3-20 was performed. The preparation of 2-substituted-3-[(coumarin-4-oxy) acetamido]thiazolidinones 21-26 and 2-[(coumarin-4-oxy)methyl]-4-acetyl-5-substituted-delta2-1,3,4-oxadiazolines 27-33 was performed by the reaction of the hydrazones 3, 4, 7, 9, 12, 14 with mercaptoacetic acid and the hydrazones 3, 4, 5, 7, 12, 15, 16 with acetic anhydride, respectively. The antiviral activities, cytotoxicities and structure-activity relationship (SAR) towards different microorganisms of the prepared compounds were studied. 相似文献
12.
目的改进MGCD0103的合成工艺。方法以3-乙酰吡啶为原料,与N,N-二甲基甲酰胺二甲缩醛缩合后,与4-胍基甲基-苯甲酸环合,再与邻苯二胺缩合得到MGCD0103。结果与结论目标化合物经1H-NMR和MS鉴定,改进后的工艺合成路线缩短、反应条件温和,总收率为42%(以3-乙酰吡啶计,提高了16%),生产成本显著降低,更适合工业化生产。 相似文献
13.
14.
Condensation of aryl hydrazines with ethyl pyruvate gave the respective hydrazones 4-6; Fischer indolization led to substituted-1H-indole-2-carboxylic acid ethyl esters 7-9. The Mannich reaction of these compounds with formaldehyde and morpholine yielded ethyl 3-(morpholinomethyl)-substituted-1H-indole-2-carboxylates 10-12. The 5,7-dichloro-1H-indole-2-carbohydrazide 13 was cyclized with methyl orthoformate in DMF to give 6,8-dichloro[1,2,4]triazino[4,5-a]indol-1(2H)-one 14. Vilsmeier-Haack formylation of 7-9 gave ethyl 3-formyl-substituted-1H-indole-2-carboxylates 15-17 whose 2,2'-((5-chloro-2-(ethoxycarbonyl)-1H-indol-3-yl)methylene)bis-(sulfanediyl) diacetic acid 18 was prepared. The reaction of 15 and 16 with substituted anilines by conventional and microwave methods gave ethyl 3-(N-aryliminomethyl)-5-halo-1H-indole-2-carboxylates 19-29. In a cyclocondensation reaction of 19-25 with thiolactic acid or thioglycolic acid substituted indolylthiazolidinones 30-33 were prepared. Reaction of hydrazine hydrate with 15-17 did not give the respective hydrazones but directly led to the cyclized products substituted-3H-pyridazino[4,5-b]indol-4(5H)-ones 34-36, while a reaction with 2,4-dichlorophenylhydrazine yielded the uncyclized hydrazones. The chlorination of 35 and 36 with POCl3 gave pyridazino[4,5-b]indoles 39 and 40, respectively; reaction of the latter compounds with morpholine gave 4-(substituted-5H-pyridazino[4,5-b]indol-4-yl)morpholine 41 and 42. Mannich reaction of 34 with formaldehyde and N-ethylpiperazine gave 8-chloro-3-((4-ethylpiperazin-1-yl)methyl)-3H-pyridazino[4,5-b]indol-4(5H)-one 43. The microwave assistance of selected reactions has a profound effect on the reaction speed. The structures of the new compounds were confirmed by both analytical and spectral data. Some compounds were subjected to investigations concerning their antimicrobial, tranquilizing, and anticonvulsant activities. 相似文献
15.
M L van de Poll V Venizélos W M Niessen J H Meerman 《Chemical research in toxicology》1991,4(3):318-323
The sulfate ester of the liver carcinogen N-hydroxy-4'-fluoro-4-(acetylamino)biphenyl (FAABP-N-sulfate) is believed to be a reactive intermediate in the male rat liver in vivo. After reaction of FAABP-N-sulfate with double-stranded calf thymus DNA in vitro, 30% of the adducts was identified as N-(deoxyguanosin-8-yl)-4'-fluoro-4-(acetylamino)biphenyl(dG-C8- FAABP) and 16% was suggested to be 3-(deoxyguanosin-N2-yl)-4'-fluoro-4-(acetylamino)biphenyl. To investigate the identity of the remaining adducts, FAABP-N-sulfate was reacted with deoxyadenosine. Two adducts could be isolated, which were identified by 1H NMR and mass spectrometry as 3-(deoxyadenosin-N6-yl)-4'-fluoro-4-(acetylamino)biphenyl (3-dA-N6-FAABP) and -(deoxyadenosin-N6-yl)-4'-fluoro-4-(acetylimino)-3, 4-dihydrobiphenyl (3-dA-N6-FHAIBP). An additional center of chirality is introduced at C3 (biphenyl) in the latter adduct. Therefore, 3-dA-N6-FHAIPB exists as a pair of two diastereomers with H-3 (biphenyl) in the alpha or beta position. Hydrogen bonding between the proton on N6 (adenine) and the imine nitrogen or the acetylimino oxygen is suggested to stabilize 3-dA-N6-FHAIBP and to prevent its conversion to 3-dA-N6-FAABP by restoration of the aromatic system. The adduct 3-dA-N6-FHAIBP was also formed in the reaction of N-OSO3H-FAABP with DNA; it accounted for 3-6% of total covalent binding. 相似文献
16.
17.
4-溴-2-氟苯基氰经格氏反应得到4-溴-2-氟苯乙酮,先保护羰基,再经格氏反应和二羟硼基取代、溴代制得4-(2-溴乙酰基)-3-氟苯硼酸,总收率54%. 相似文献
18.
An anticoagulant, 4-hydroxy-3-[1,2,3,4-tetrahydro-3-(4-(4-trifluoromethylbenzyloxy)phenyl)-1-naphthyl]coumarin (Flocoumafen) was synthesized in 8 steps starting from phenylacetyl chloride and anisole. The key step in the synthesis involves the reaction of 3-(4-methoxyphenyl)-1-tetralol with 4-hydroxycoumarin to give 4-hydroxy-3-[1,2,3,4-tetrahydro-3-{4-methoxyphenyl}-1-naphthyl]coumarin. 相似文献
19.
20.
The reaction of anthranilic acid with excess of benzoylchloride in the presence of pyridine yielded 2-phenyl(3H) 4-oxo-3,1-benzoxazine(I). Interaction of (I) with 2-aminoethanol afforded 2-phenyl-3-hydroxy-ethyl(3H) 4-oxo-quinazoline (II). The condensation of (II) with beta-naphthol in the presence of conc. H2SO4 gave 1-(2'-phenyl-3'-ethyl-4'-oxo-quinazolyl) beta-naphthol (III). The reaction of (III) with primary aromatic amines in the presence of anhydrous zinc-chloride afforded 1-(2'-phenyl-3'-ethyl-4'-oxo-quinazolyl)-beta-naphthyl phenyl amine (IV). When (IV) was heated with sulphur and iodine, 1-(2'-phenyl 3'-ethyl -4'-oxo-quinazolyl)-benzophenothiazine (V) was obtained. All the five synthesised benzophenothiazines were screened for their antiviral activity and two compounds exhibited significant inhibition of virus multiplications. 相似文献