N-酰基/磺酰基-吡唑衍生物的合成及其对COX-2抑制活性的预测
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摘要
吡唑作为一个基本结构广泛存在于许多具有生物活性的化合物中,吡唑类化合物可以用于一系列药物活性化合物的合成。本文主要进行了N-酰基/磺酰基吡唑衍生物的合成研究工作及其对环氧化酶2的抑制活性预测研究。
以水合肼为原料,合成了乙酰肼、对三氟苯甲酰肼、苯甲酰肼、对氟苯甲酰肼、对硝基苯甲酰肼、烟酰肼、肼基甲酸甲酯、苯磺酰肼、对甲苯磺酰肼、对氯苯磺酰肼、对硝基苯磺酰肼。以腈类和酯类为原料制备了相应β-腈酮类化合物。
在室温下,以β-腈酮化合物与酰肼、磺酰肼为原料合成了一系列新型氨基吡唑衍生物,通过对缩合反应条件进行研究,采用酸碱两步催化一锅反应的新方法有效提高了反应收率,并对机理进行了讨论。通过X-Ray单晶衍射对化合物12d进行了结构分析。
在Catalyst软件平台建立环氧化酶2药效团模型。本文得到的部分化合物与计算机模拟环氧化酶2受体特征药效团模型吻合较好,有用作下一步活性测试和筛选的价值,以及通过对其结构修饰进一步合成其他可能具有生物活性化合物的价值。
Pyrazoles have a widespread occurrence as substructures in a large variety ofcompounds with important biological activities and pharmacological properties. Theycan be used in the synthesis of a number of biologically active compounds. Here wewill report some research work about the synthesis of N-acyl/sulfuryl pyrazolederivatives and calculation of their activity of inhibition to COX-2.
Hydrazine hydrate was used to prepare acetylhydrazine, p-trifluorobenzoic acidhydrazide, benzoic acid hydrazide, p-fluorobenzoic acid hydrazide, p-nitro benzoicacid hydrazide, nicotinic acid hydrazide, hydrazine carboxylic acid methyl ester,benzenesulfonyl hydrazine, p-methylbenzenesulfonyl hydrazine and p-chlorobenzenesulfonyl hydrazine. p-nitrobenzenesulfonyl hydrazine. Nitriles and esters were used toprepareβ-Cyanoketones.
5-aminopyrazoles were obtained via the condensation ofβ-Cyanoketones andhydrazide/sulfonhydrazide with the subsequent cyclization. The overall high yieldwas obtained via an acid-catalyzed with a successive based-catalyzed one-pot reaction,which was first reported. The conditions of the reaction were investigated, thenmechanism of the reaction was also discussed. The configuration of the compound12dwasconfirmedbytheanalysisoftheX-raycrystal.
The pharmacophore model of COX-2 was constructed by Catalyst sofrware.Some of the target compounds accorded well with the model. Then these compoundscan be used for the test and screening of inhibition of COX-2. The modification ofthese compounds may lead to discovery of novel bioactive compounds.
以水合肼为原料,合成了乙酰肼、对三氟苯甲酰肼、苯甲酰肼、对氟苯甲酰肼、对硝基苯甲酰肼、烟酰肼、肼基甲酸甲酯、苯磺酰肼、对甲苯磺酰肼、对氯苯磺酰肼、对硝基苯磺酰肼。以腈类和酯类为原料制备了相应β-腈酮类化合物。
在室温下,以β-腈酮化合物与酰肼、磺酰肼为原料合成了一系列新型氨基吡唑衍生物,通过对缩合反应条件进行研究,采用酸碱两步催化一锅反应的新方法有效提高了反应收率,并对机理进行了讨论。通过X-Ray单晶衍射对化合物12d进行了结构分析。
在Catalyst软件平台建立环氧化酶2药效团模型。本文得到的部分化合物与计算机模拟环氧化酶2受体特征药效团模型吻合较好,有用作下一步活性测试和筛选的价值,以及通过对其结构修饰进一步合成其他可能具有生物活性化合物的价值。
Pyrazoles have a widespread occurrence as substructures in a large variety ofcompounds with important biological activities and pharmacological properties. Theycan be used in the synthesis of a number of biologically active compounds. Here wewill report some research work about the synthesis of N-acyl/sulfuryl pyrazolederivatives and calculation of their activity of inhibition to COX-2.
Hydrazine hydrate was used to prepare acetylhydrazine, p-trifluorobenzoic acidhydrazide, benzoic acid hydrazide, p-fluorobenzoic acid hydrazide, p-nitro benzoicacid hydrazide, nicotinic acid hydrazide, hydrazine carboxylic acid methyl ester,benzenesulfonyl hydrazine, p-methylbenzenesulfonyl hydrazine and p-chlorobenzenesulfonyl hydrazine. p-nitrobenzenesulfonyl hydrazine. Nitriles and esters were used toprepareβ-Cyanoketones.
5-aminopyrazoles were obtained via the condensation ofβ-Cyanoketones andhydrazide/sulfonhydrazide with the subsequent cyclization. The overall high yieldwas obtained via an acid-catalyzed with a successive based-catalyzed one-pot reaction,which was first reported. The conditions of the reaction were investigated, thenmechanism of the reaction was also discussed. The configuration of the compound12dwasconfirmedbytheanalysisoftheX-raycrystal.
The pharmacophore model of COX-2 was constructed by Catalyst sofrware.Some of the target compounds accorded well with the model. Then these compoundscan be used for the test and screening of inhibition of COX-2. The modification ofthese compounds may lead to discovery of novel bioactive compounds.
引文
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