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以47个5-取代苄基-2,4-二氨基嘧啶类化合物(其中四个为新合成的化合物)对乳酪菌二氢叶酸还原酶及鸡肝二氢叶酸还原酶的表现抑制常数(Ki app)研究这类化合物的结构与选择性作用的关系。以取代基的van der Waals体积(Vw)代替MR得到和以前结果相似的定量构效相关式。在此基础上讨论了5-取代苄基-2,4-二氨基嘧啶类化合物的选择性作用。 相似文献
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以47个5-取代苄基-2,4-二氨基嘧啶类化合物(其中四个为新合成的化合物)对乳酪菌二氢叶酸还原酶及鸡肝二氢叶酸还原酶的表现抑制常数(Ki app)研究这类化合物的结构与选择性作用的关系。以取代基的van der Waals体积(Vw)代替MR得到和以前结果相似的定量构效相关式。在此基础上讨论了5-取代苄基-2,4-二氨基嘧啶类化合物的选择性作用。 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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《中国医药工业杂志》1972,(6)
根据近年来国外文献报道,甲氧苄氨嘧啶[2,4-二氨基-5-(3',4',5'-三甲氧基苄基)-嘧啶](Trimethoprim,简称TMP)为一种磺胺增强剂。磺胺药物的抗菌作用是由于抑制了二氢叶酸合成酶,使细菌不能利用对-氨基苯甲酸合成二氢叶酸,TMP则能抑制二氢叶酸还原酶,使二氢叶酸不能还原成四氢叶酸,TMP与磺胺药联合应用,双重阻断细菌的新陈代谢,使细菌不能合成生命必须的脱氧核糖核酸(DNA)和核糖核酸(RNA)而达到增强磺胺药抗菌作用的效果(见图)。 相似文献
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本文根据二氢叶酸还原酶(DHFR)抑制剂与酶的结合方式,以及可能产生双重抑制作用和长效作用的原理,设计合成了以下三类化合物:Ⅰ、双 -(2,4-二氨基喹唑啉-6-取代氨甲基)芳烃;Ⅱ、1,4-双〔ω-2,4-二氨基喹唑琳-6-取代氨基烷基〕哌嗪;Ⅲ、双-〔4-(2,4-二氨基喹唑啉-6)哌嗪-1〕烷烃或芳烷烃。所合成的29个目的物中,有28个未知化合物,经元素分析、光谱分析确证其结构。化合物I_(1~5)的合成,采用前此未见报道的2,4,6-三氨基喹唑琳与α,α′-二卤代甲基 相似文献
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本文报道2,4-二氨基-5-取代氨基嘧啶和2,4-二氨基-6-甲基-5-取代氨基嘧啶衍生物的合成及其抗疟活性的研究。这类化合物的合成是分别以2,4,5-三氨基嘧啶或2,4,5-三氨基-6-甲基嘧啶与相应的取代的苯甲醛缩合成席夫氏碱,然后经还原,亚硝化或甲酰化制得。经鼠疟原虫-斯氏按蚊系统的病因性预防初筛,发现有12个化合物有效,其中2,4-二氨基5-[(3′,4′-二氯代苯亚甲基)-氨基]嘧啶(化合物V3)和2,4-二氨基-5-[(4′-溴代苄基)-N-亚硝基-氨基]嘧啶(化合物Ⅶ4)效果最好,口服10 mg/kg共三天,可使小白鼠得到保护,血中未查见原虫。 相似文献
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Siddiqui AA Rajesh R;Mojahid-Ul-Islam Alagarsamy V De Clercq E 《Archiv der Pharmazie》2007,340(2):95-102
A variety of novel 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-substituted imino) pyrimidines were synthesized by reacting 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-amino pyrimidines with different substituted aromatic aldehydes, coumarin chloroisatin. The 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-amino pyrimidines were synthesized by reacting 3-(4'-substituted phenyl)-1-(4-nitrophenyl)-2-propen-1-ones with guanine hydrochloride. 3-(4-Substituted phenyl)-1-(4-nitrophenyl)-2-propen-1-ones were synthesized by reacting 4-nitroacetophenone with different para-substituted aromatic aldehydes. Spectral data (IR, NMR, and mass spectra) confirmed the structures of the synthesized compounds. The synthesized compounds were investigated for their antiviral, antituberculostic, and antibacterial activities. The results of antiviral, antituberculostic, and antibacterial activities indicated that the synthesized compounds exhibited mild to potent activities compared to the respective reference standards. 相似文献
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According to the principle of isosterism the-CH2-group of 5-(substituted benzyl)-2, 4-diaminopyrimidine was modified by—S—and—Se—and some 5-(substituted phenyl)thio-2, 4-diaminopyrimidines and 5-(substituted phenyl)seleno-2,4-diaminopyrimidines were synthesized. Their inhibitory activities on L. casei and chicken liver dihydrofolate reductase were determined. Preliminary data showed that the inhibitory activities of these compounds were less than those of the corresponding 5-(substituted benzyl)-2, 4-diaminopyrimidines. Their selectivities are also decreased. 相似文献
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Siddiqui AA Rajesh R Mojahid-Ul-Islam Alagarsamy V Meyyanathan SN Kumar BP Suresh B 《Acta poloniae pharmaceutica》2007,64(1):17-26
A variety of novel 4-[(4'-substituted phenyl)-6-(4"-hydroxyphenyl)-2-substituted imino] pyrimidines were synthesized by reacting 4-(4'-substituted phenyl)-6-(4"-hydroxyphenyl)-2-aminopyrimidines with different substituted aromatic aldehydes, with coumarin and with chloroisatin. The 4-(4'-chlorophenyl)-6-(4"-hydroxyphenyl)-2-aminopyrimidines were synthesized by reacting 3-(4'-substituted phenyl)-1-(4"-hydroxyphenyl)-2-propen-1-ones with guanine hydrochloride. The 3-(4'-substituted phenyl)-1-(4"-hydroxyphenyl)-2-propen-1-ones were synthesized by reacting 4-hydroxyacetophenone with different para substituted aromatic aldehydes. Spectral data (IR, NMR, and mass spectra) confirmed the structures of the synthesized compounds. The synthesized compounds were investigated for their antiviral, antituberculostic and antibacterial activities. The results indicated that the synthesized compounds have mild to potent activities with reference to their appropriate reference standards. However, mechanism related studies could be carried out to predict the structure activity relationship for all the compounds. 相似文献
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2,4-diamino-5-methyl-6-(substituted-phenyl)thiopyrrolo[2,3-d]pyrimidines 4-11 were synthesized as dihydrofolate reductase (DHFR) inhibitors against opportunistic pathogens that afflict patients with AIDS. Synthesis was achieved from 2,4-diamino-5-methypyrrolo[2,3-d]pyrimidine and substituted phenylthiols under modified conditions reported by Gangjee et al. Some of these compounds were potent and selective against DHFR from both Toxoplasma gondii and Mycobacterium avium compared to mammalian DHFR. Compound 11 with a 1-naphthyl substituent is 16-fold more potent and equally selective against Toxoplasma gondii DHFR as the clinically used trimethoprim. 相似文献
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A series of 18 2,4-diamino-5-[(1,2,3,4-tetrahydro-6-quinolyl)methyl]pyrimidines has been prepared by the condensation of 2,4-diamino-5-(hydroxymethyl)pyrimidine with 1,2,3,4-tetrahydroquinolines in acidic medium. Several derivatives were catalytically aromatized; others were synthesized from these by routine aromatic substitution or by condensations of (anilinomethyl)pyrimidines to give quinolinylmethyl analogues. Compounds with 4-methyl-8-methoxy substitution are closely related to trimethoprim (1a) in structure and are excellent inhibitors of bacterial dihydrofolate reductase, with activity at least equivalent to that of 1a. The highest degree of inhibition was achieved with the rigid aromatic series, but greater specificity was accomplished among the tetrahydroquinoline derivatives. This was directly related to N-1 substitution of 4-methyl-8-methoxy derivatives. The spatial relationships around N-1 and protonation at this site may both affect selectivity. Such compounds also had excellent broad-spectrum in vitro antibacterial activity. 相似文献
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Analgesics, VI: 2-(Diethylamino)pyrimidines Carrying Fluoroalkyl Groups By condensation of 1,1-diethylguanidine ( 1 ) with the appropriately substituted fluoro-β-diketones 2a - h , 2-(diethylamino)pyrimidines ( 3 ) are obtained which carry fluoroalkyl groups and possess simple alkyl groups, branched aliphatic substituents, or heterocyclic rings attached to the pyrimidine nucleus. 相似文献
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4-氯-3-三氟甲基苯胺(5)和氯甲酸苯酯反应得到[4-氯-3-(三氟甲基)苯基]氨基甲酸苯酯(6),再和对氨基苯酚缩合得到N-[4-氯-3-(三氟甲基)苯基]-N-(4-羟基苯基)脲(7)。另用2-吡啶甲酸(2)经氯化、酰胺化得中间体N-甲基-(4-氯-2-吡啶基)甲酰胺(4)。4和7经亲核取代及成盐反应制得对甲苯磺酸索拉非尼,总收率约62%(以5计)。 相似文献