共查询到19条相似文献,搜索用时 71 毫秒
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《中国药物化学杂志》2015,(5):361-368
目的设计合成一系列4-(4-烷氧基苄基/苯乙基)-2H-1,2,4-三唑-3(4H)-酮类化合物,并评价其抗惊厥活性和神经毒性。方法以对羟基苄胺和对羟基苯乙胺为起始原料,通过氨基保护、羟基烷基化、氨基脱保护以及氨基成三唑酮环反应合成目标化合物。采用最大电惊厥实验(MES)评价化合物的抗惊厥活性,采用旋转棒法测定其神经毒性。结果与结论合成了26个未见文献报道的新化合物,其结构经IR、1H-NMR、13C-NMR和EI-MS谱确证。活性实验结果表明,所有化合物在不同剂量下都显示出抗惊厥活性。其中,4-[4-(3-氟苄氧基)苯乙基]-2H-1,2,4-三唑-3(4H)-酮(9f)的活性最强,其半数有效量ED50值为19.5 mg·kg-1,保护指数(PI)为5.1。该化合物的PI值高于阳性对照药丙戊酸钠,低于卡马西平。 相似文献
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目的设计合成一系列4-(4-烷氧基苯基)-3-乙基-1H-1,2,4-三唑-5(4H)-酮类化合物,并评价其抗惊厥活性和神经毒性。方法以对乙酰氨基酚为起始原料,经烷基化、水解、环合等反应合成1,2,4-三唑-5(4H)-酮类化合物。通过最大电惊厥实验(MES)和神经毒性实验(NT),分别测定目标化合物的抗惊厥活性和神经毒性。结果与结论合成了20个新化合物,其结构经IR、1H-NMR和ESI-MS确证。药理学实验结果表明,所有化合物在不同剂量下都显示出抗惊厥活性。其中,3-乙基-4-(4-戊氧基苯基)-1H-1,2,4-三唑-5(4H)-酮(4e)的活性最强,其半数有效量ED50值为26.9 mg·kg-1,保护指数(PI)为11.0,虽然该化合物的活性低于阳性对照药卡马西平,但其保护指数优于卡马西平(PI=6.4);3-乙基-4-(4-(3-氟苄氧基)苯基)-1H-1,2,4-三唑-5(4H)-酮(4n)的ED50值为61.1 mg·kg-1,但其PI大于17.0,明显优于卡马西平,具有进一步研究的价值。 相似文献
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异色满酮-4(1)与靛红类化合物缩合,可得高产率的辛可芬类似物7-羧基异色满并[4,3-b]喹啉衍生物(2a~e),此5个化合物尚未见文献报道。抗炎药理试验表明,2a~c 效果显著,2d、2e 稍差。2a 对角叉菜胶引起的水肿和白细胞游走均有抑制作用。 相似文献
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[1,2,4]三氮唑并[1,5-a]嘧啶类化合物的合成及其抗肿瘤活性 总被引:1,自引:0,他引:1
目的寻找具有抗肿瘤活性的新化合物,设计合成[1,2,4]三氮唑并[1,5-a]嘧啶衍生物,并评价其体外抗肿瘤活性。方法以γ-丁内酯为起始原料,经环合、氯代、取代、硫醚化和氨甲基化等反应合成7-苯基氨基-2-[3-(5-取代氨基甲基-呋喃-2-基-甲硫基)丙基]-5-甲基-[1,2,4]三氮唑并[1,5-a]嘧啶类化合物。采用MTT法,以顺铂为阳性对照药,以Bel-7402和HT-1080为测试细胞株对目标化合物的抗肿瘤活性进行了评价。结果与结论合成了12个未见文献报道的新化合物,结构经质谱、红外光谱和核磁共振氢谱确证。体外活性实验表明:化合物16显示出很好的抗肿瘤活性。 相似文献
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目的研究2-取代苯基-1,2,4-三氮唑[5,1-a]并吡啶类衍生物的合成及其抗早孕活性。方法 甲基取代吡啶胺化后,通过和取代苯甲腈缩合反应合成目标化合物,利用离体培养大鼠黄体细胞试验进行抗早孕活性筛选。结果 设计合成了14个未见文献报道的2-取代苯基-1,2,4-三氮唑[5,1-a]并唑啶类衍生物,均为新化合物。生物活性实验结果表明:除化合物7k以外,新合成的化合物都有一定溶黄体细胞的作用,其中化合物7b,71的作用更强,它们的ED50分别为0.5μg/mL和1.6μg/mL。结论 新合成的化合物具有一定的损伤黄体细胞的活性,值得进一步研究。 相似文献
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设计合成了21个1-[2-(取代苯基甲硫基)-2-(2,4-二氟苯基)乙基]-1H-1,2,4-三唑类化合物,其中19个为首次报道。体外抑菌试验表明:所有目标化合物对8种试验真菌均有不同程度的抗菌活性,其中化合物1,2,5对絮状表皮癣菌的活性为硫康唑的512倍以上;化合物5对白色念株菌的活性为硫康唑的32倍;化合物2对申克孢子丝菌的活性为硫康唑的32倍;化合物2,14对新型隐球菌的活性分别为硫康唑的64倍,32倍;化合物1,5对熏烟色曲菌的活性分别为硫康唑的16倍以上。 相似文献
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Savini L Chiasserini L Pellerano C Filippelli W Falcone G 《Il Farmaco; edizione pratica》2001,56(12):939-945
The synthesis of a series of 1,2,4-triazolo[4,3-a]quinoline derivatives is described; their structures were assigned by 1H NMR and analytical data. The new compounds were tested in vivo for their antiinflammatory and analgesic activities, as well as for their ulcerogenic action. Some of the tested triazoles showed an analgesic activity in the acetic acid writhing test and antiinflammatory properties on carrageenan paw edema assay. 相似文献
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Li‐Ping Guan Qing‐Hao Jin Shou‐Feng Wang Fu‐Nan Li Zhe‐Shan Quan 《Archiv der Pharmazie》2008,341(12):774-779
A series of novel 5‐phenyl‐[1,2,4]‐triazolo[4,3‐a]quinoline derivatives was synthesized by the cyclization of 2‐chloro‐4‐phenyl‐1,2‐dihydronaphthalene with formohydrazide. The starting material 2‐chloro‐4‐phenyl‐1,2‐dihydronaphthalene was synthesized from ethyl‐3‐oxo‐3‐phenylpropanoate and substituted aniline. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The maximal electroshock test showed that 7‐hexyloxy‐5‐phenyl‐[1,2,4]‐triazolo[4,3‐a]quinoline 4f was found to be the most potent compound with an ED50 value of 6.5 mg/kg and a protective index (PI = ED50 / TD50) value of 35.1, which was much higher than the PI of the reference drug phenytoin. 相似文献
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Starting from the 2-quinolylhydrazine 1 the title compounds were prepared according to Schemes 1 and 2. Some of them show activities described in the title of this paper. 相似文献
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A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ), and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox). The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4] triazole[4,3-a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having ED50 values of 17.17 mg/kg and 24.55 mg/kg and protective index (PI = TD50/ED50) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having ED50 values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital and valproate, which have PI values in the range of 1.6-8.1 in the MES test and < 0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also discussed. 相似文献
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Three main classes of quinoxaline derivatives have been synthesized. The first class comprises the synthesis of three novel series of 1,2,4-triazolo[4,3-a]quinoxalines; namely 1-substituted-1,2,4-triazolo[4,3-a]quinoxalines 3a-f, 1-substituted aminomethyl-1,2,4-triazolo[4,3-a]quinoxalines 14a-d and 1-cyano or ethoxycarbonylmethyl-1,2,4-triazolo[4,3-a]quinoxalines 6, 12. The second class involves the synthesis of 2-substituted-1 H-1,2,4-triazino[4,3-a]quinoxalines 4a-d. The third class deals with the synthesis of a variety of 2-pyrazolylquinoxalines, namely 2-(5-amino-3-arylpyrazol-1-yl)-3-phenylquinoxalines 5a-d, 2-[5-hydroxy-3-phenyl-4-(4-substituted sulfamoylphenyl)azopyrazol-1-yl]-3-phenylquinoxalines 15a, b, and 2-(5-hydroxy-4-nitroso-3-phenylpyrazol-1-yl)-3-phenylquinoxalin e (16). The prepared compounds were tested in vitro for their antimicrobial activity. Compounds 13 and 14b exhibited promising antifungal activity against C. albicans (MIC 25, 50 mu/ml respectively). Compound 13 was as active as the antibiotic nystatin. 相似文献
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In this study, a novel series of 7-alkoxy-1-amino-4,5-dihydro[1,2,4]triazole[4,3-a]quinolines were synthesized by using 6-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. These compounds were evaluated for anti-inflammatory activity through monitoring their ability to inhibit xylene-induced ear edema in mice. Some of the tested compounds exhibited significant activity, and the compounds 5f (7-(benzyloxy)-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolin-1-amine) and 5i (7-(p-chlorobenzyloxy)-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolin-1-amine) showed the highest anti-inflammatory activity (52% and 58% inhibition, respectively, at 2 h pre-administration) which were comparable to or even slightly more potent than the reference drug ibuprofen (55%). Furthermore, the structure-activity relationship of these 1,2,4-triazole quinolines was demonstrated. 相似文献