共查询到20条相似文献,搜索用时 100 毫秒
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非肽类纤维蛋白原受体拮抗剂阻止血小板聚集的最后一步,即活化的血小板与纤维蛋白原之间的结合[1,2],是一类有新作用机制的抗血栓剂,为80年代末,90年代初以来国际上抗血栓药物研究的热点。通过对纤维蛋白原及RGD肽的结构模拟,已获得一些高效化合物,且克服了肽类化合物的某些缺点,成为这类药物的研究方向[3]。前文[4,5]报道了O对甲脒苯胺基羰甲基及O对甲脒苯氧乙基N取代酪氨酸甲酯类化合物的合成及其抗血小板活性,已出现了一些有意义的苗头。为了进一步考察空间臂的极性和长度对化合物活性的影响,本文合成了一系列新的化合物IVa~i… 相似文献
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运用“违法传递”概念,根据白念珠菌对寡肽的传送特点,设计并合成了8个含L-4-氧代赖氨酸(以下称I-677)和N3-(4-甲氧基富马酰)-L-2,3-二氨基丙酸(以下称FMDP)的寡肽类似物,均系新化合物。体外抗白念珠菌试验表明:I-677-FMDP-肽(I-677-FMDP,I-677-AA-FMDP,其中AA=Nva,Val,Leu,Phe,Pro,D,L-p-Cl- Phe,D-Pgly)是I-677单体摩尔活性的40~770倍,是FMDP的60~1130倍,其摩尔最低抑菌浓度为6.56×10-9~3.5×10-10mol·disk-1。羧肽酶A存在时化合物I-677-FMDP体外抗菌试验表明,含FMDP的化合物I-677-FMDP能抵抗羧肽酶A的酶解。 相似文献
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4-S-(5-酰氨基-1,3,4-噻二唑-2-基)-4-脱氧-4′-去甲基表鬼臼毒素衍生物的合成与抗肿瘤活性 总被引:3,自引:0,他引:3
基于在4′-去甲基表鬼臼毒素母核C4位上联结含有杂原子的芳香环取代基,以此考察其结构与活性关系的设想,设计并合成了10个标题化合物。体外L1210白血病细胞与KB细胞生长抑制试验结果表明,这类化合物有较强的抗肿瘤活性。其中化合物SIPI-92-1772,1774,1775,1776,1777与1779的活性超过临床用药依托泊甙。其余化合物活性与依托泊甙相当或略低。 相似文献
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Synthesis of 35 new compounds of α-chloro-β-(5-nitro-2-furyl) acrylamides and 5-[α-chloro-β-(5-nitro-2-furyl ) vinyl]-oxadiazoles by known methods are reported. In preliminary test in mice 10 compounds were found to possess pronounced activity against Schistosomiasis japonica. Among these Ⅰ12, Ⅰ13, Ⅰ14, Ⅰ20, Ⅱ1 and Ⅱ8 were shown to be the most effective. 相似文献
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本文报道38个β-(5-硝基-2-呋喃)丙酰胺及其α,β-二溴取代衍生物的合成。这类化合物的制备是以相应的β-(5-硝基-2-呋喃)丙烯酰胺类化合物(Ⅰ)进行催化氢化或与溴加成而得。经动物筛选发现β-(5-硝基-2-呋喃)丙烯酰胺类的丙烯双键以氢饱和以后生成丙酰胺类化合物(Ⅱ),对感染日本血吸虫病的小白鼠完全失去治疗或预防作用。而以溴饱和双键的α,β-二溴化合物(Ⅲ)则仍然有较显著的杀虫作用。其中尤以β-(5-硝基-2-呋喃)-α,β-二溴丙酰异丙胺(Ⅲ11)和β-(5-硝基-2-呋喃)-α,β-二溴丙酰甘氨酸乙酯(Ⅲ24)最为显著,后者曾试用于临床,证明有一定疗效。 相似文献
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S-(2-18F-氟代乙基)-L-蛋氨酸的合成及其放射药理活性 总被引:1,自引:0,他引:1
目的研制肿瘤氨基酸代谢显像剂S-(2-18F-氟代乙基)-L-蛋氨酸(18FEMET),评价其区分炎症和肿瘤的价值。方法采用亲核取代反应,由两步法合成18FEMET。测定正常小鼠、肿瘤及炎症小鼠体内FEMET生物分布,对模型小鼠进行18FEMET PET显像,并与2-18F-2-脱氧-D-葡萄糖(FDG)和O-(2-18F-氟代乙基)-L-酪氨酸(FET)比较。结果18FEMET手工合成时间约为70 min,未校正总放化产率为15%~25%,放化纯度大于95%。正常小鼠中胰腺、肾脏、结肠、肝和心脏等脏器摄取18FEMET较高,且放射性滞留时间较长,血液和脑摄取18FEMET较低。肿瘤细胞可高度摄取18FEMET,FDG和FET,炎症组织也可高度摄取FDG,但几乎不摄取18FEMET和FET。结论18FEMET制备简便,能够区分肿瘤和炎症,可望成为一种有前景的特异性肿瘤氨基酸代谢PET显像剂。 相似文献
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Seventeen compounds having the structure of 2,3-diacetoxy-1,4-bis(3′,5′- dioxo-N4′-substituted piperazinyl methyl)benzene were designed and synthesized based on chelation hypothesis. Their antitumor activities on P388 cells,Hep cells and SGC 7901 cells in vitro were tested. Preliminary results showed that compound 4e has potent antitumor effect against P388 cells and.Hep cells in vitro. 相似文献
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Allan Fletcher Ian A. Cliffe Colin T. Dourish 《Trends in pharmacological sciences》1993,14(12):441-448
The 5-hydroxytryptamine 5-HT1A receptor has been the focus of considerable research effort for over a decade. However, the definitive classification of this receptor and the full characterization of its pharmacology have awaited the development of highly selective 5-HT1A receptor antagonists. The only compounds available until recently have been either nonselective or partial 5-HT1A receptor agonists (or a combination of both). Confusion has arisen owing to the use of different pharmacological models in examining the functional activity of 5-HT1A receptor ligands. Several partial agonists display only antagonist activity in models of postsynaptic 5-HT1A receptor function, whereas their agonist properties are revealed in models of presynaptic, somatodendritic 5-HT1A autoreceptor function. In view of these considerations, the term ‘silent antagonist’ has been introduced to distinguish true 5-HT1A receptor antagonists from partial agonists. Allan Fletcher and colleagues review the pharmacological properties of the first selective silent 5-HT1A receptor antagonists that have been recently discovered and discuss the potential therapeutic utility of these novel compounds. 相似文献
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采用两种新选择性保护方法由L-丝氨酸和α-酮戊二酸为原料经几步合成了8个目标化合物。体外抑菌该验表明除TMV外,对金葡球菌209P和大肠杆菌44822具有中等到强的活性。 相似文献
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1,4-二[3-(氨基硫代甲酰硫基)丙酰基]哌嗪类化合物的合成及其抗肿瘤活性 总被引:2,自引:1,他引:1
目的 寻找并合成低毒、有较强抗肿瘤活性的哌嗪类化合物。方法和结果 以1,4-二(3-溴丙酰基)哌嗪为先导物,合成了一系列1,4-二[3-(氨基硫代甲酰硫基)丙酰基]哌嗪类新化合物,并测试了这些化合物(4a-j)对8种瘤细胞株的体外抗肿瘤活性。结论 体外抗肿瘤活性试验结果表明,大多数化合物显示一定的抗肿瘤活性,尤其是化合物4c,4d和4e,浓度在10μmol.L-1时,对HL-60细胞抑制率分别为44%,90%和70%。 相似文献
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以L-丝氨酸和α-酮戊二酸为原料,采用三条合成路线,经6~8步反应,合成8个目标化合物。其部份中间体的结构经IR,PMR,MS及元素分析证实。产物的结构也经IR及PMR证实。体外抑菌试验表明,TM7和TM8显示较强的广谱抑菌活性,TM6则具有中等强度。TM2和TM3对金葡菌也有一定活性。 相似文献
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二氨基吡啶并嘧啶类化合物具有很强的抑制二氢叶酸还原酶的作用。这类化合物中BW301u已进行临床试验以治疗癌症。本文报道了17个2,4-二氨基-6-取代苄基-5-甲基-吡啶[2,3-d]并嘧啶类化合物的合成及对L_(1210)细胞的抑制作用。合成化合物的结构经由MS-EI,~1H-NMR及元素分析确证。以MTT法测定了它们对L_(1210)细胞的抑制作用。 相似文献
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本文报道了2,4-二氨基-6-N1,N2-二取代肼基-喹唑啉类衍生物的合成及其抗疟活性的研究。这类化合物的合成是以2,4-二氨基6-取代苄基氨基-喹唑啉为原料经亚硝化、还原成为2,4-二氨基6-(N1-取代苄基)—肼基喹唑啉,再与相应的醛缩合而成。此类化合物经伯氏鼠疟原虫抑制性治疗初筛表明有少数具有一定的效果。有11个化合物经约氏鼠疟原虫—斯氏按蚊系统病因性初筛有效。其中化合物Ⅱ1,7,8,11,15和Ⅲ1口服2.5mg/kg,连续3天,可使受试小鼠全部得到保护。 相似文献
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Roberto Invernizzi Mario Bramante Rosario Samanin 《European journal of pharmacology》1994,260(2-3):243-246
In animals given citalopram (10 mg/kg) twice daily for 14 days a further dose of 1 mg/kg, administered 24 h after the last dose, markedly increased cortical dialysate serotonin (5-hydroxytryptamine, 5-HT), but had no effect in control animals. The effect on dialysate 5-HT in the dorsal raphe was not increased by the chronic treatment. At 25 μg/kg, 8-hydroxy-2-(di-n-propylamino) tetralin, an agonist at 5-HT1A receptors, reduced cortical 5-HT output in controls but not in animals treated chronically with citalopram whereas 50 μg/kg reduced 5-HT output in both groups. These findings suggest that somatodendritic 5-HT1A receptors are desentisized after chronic treatment with citalopram and this results in facilitation of its effect on cortical dialysate 5-HT. These results also agree with the concept that the effect of 5-HT re-uptake inhibitors on increasing 5-HT output in the frontal cortex is attenuated by their simultaneous ability to activate somatodendritic 5-HT1A receptors via an increase of endogenous 5-HT in the raphe region. 相似文献
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Selected and localized lesions of serotonergic (5-HT) neurons were made by microinjection of 5,7-dihydroxytryptamine (5,7-DHT), after pretreatment with desipramine, into the cingulum bundle and fornix-fimbria; these are the major serotonergic hippocampal inputs from the median raphe nucleus. Two weeks after the lesion, the binding of [3H]5-HT (5-HT1 receptor) was determined in the hippocampus which receives the afferent terminals and, in addition, in the septum/hypothalamus and midbrain from where the fibers originate. Scatchard analysis showed there was no significant change in binding parameters in the hippocampus; however, a significant increase was observed in the Bmax in the midbrain (38%) with no change in the KD. The caudate which receives 5-HT inputs via other 5-HT tracts was not affected by the lesion. The changes in 5-HT1 receptor number or affinity were not observed 6 days or 5 weeks after the lesion. The binding of the ligands [3H]spiroperidol and [3H]ketanserin to the 5-HT2 receptor population was also determined in the same brain areas; no changes in receptor binding occurred two weeks after the lesion. These experiments demonstrate that a selective lesion of the serotonergic system can increase 5-HT1 receptors in the midbrain, which contains the serotonin cell bodies. In addition, as 5-HT2 binding is not altered, this further supports the hypothesis that 5-HT1 and 5-HT2 receptors are distinct populations of receptors. 相似文献