新型1h-苯并[b][1,5]地氮平-2(3h)- 1衍生物的合成及生物学评价

Q4 Pharmacology, Toxicology and Pharmaceutics
D. Rishipathak, D. Patil, Hemant U Chikhale
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引用次数: 1

摘要

背景:尽管所有新颖和早期的治疗方法的可用性,癫痫发作的控制是出了名的复杂。为了发现最新和最终的治疗方法,药物化学家将继续寻找具有高特异性和低中枢神经系统毒性的新型抗癫痫化合物。对苯二氮卓类化合物的生物学效应进行了研究。苯和二氮平环融合在一起形成化学结构。附着在最内层结构1、2、5和7位的不同组合,其药理学性质、效力和药代动力学条件都受到不同侧基的影响。方法:合成了几种1h -苯并[b][1,5]二氮平-2(3H)- 1衍生物。N1上的取代基是苯甲酰,5-取代-1,3,4-噻二唑-2-基氨基乙酰基。正苯二胺与乙酰乙酸乙酯缩合得到7-取代-4-甲基- 1h -苯并[b][1,5]二氮平-2(3H)- 1,然后与苯甲酰氯和氯乙酰氯连接得到n1 -苯甲酰和n1 -氯乙酰基衍生物。利用微波辐照进一步将N1-氯乙酰基衍生物与5-取代-1,3,4-噻二唑胺连接。结果:用IR、1H-NMR和质谱对合成的化合物进行了鉴定。采用PTZ致惊厥法测定化合物的抗惊厥活性。与对照相比,化合物4a和4c在0.4 mg/kg时具有80%的保护作用,而化合物2a和2c在20和30 mg/kg时分别具有80%的保护作用。结论:与对照相比,1,3,4-噻二唑取代的1,5-苯二氮卓-2- 1片段的实验合成和药理学评估产生了一种潜在的活性抗惊厥药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and Biological Evaluation of Some Newer 1h-Benzo[b][1,5]diazepin-2(3h)-One Derivatives as Potential Anticonvulsant Agents
Background: Regardless of the availability of all novel and earlier treatments, seizure control is notoriously complicated. In the hopes of discovering the latest and ultimate therapy, medicinal chemists will keep on to hunt for new antiepileptic compounds with high specificity and low CNS toxicity. The biological effects of benzodiazepine compounds have been examined. Benzene and a diazepine ring are fused together to form the chemical structure. Diverse combinations of moieties attached to the innermost structure in positions 1, 2, 5, and 7 the pharmacological qualities, effect potency, and pharmacokinetic conditions are all influenced by the various side groups. Method: This paper describes the synthesis of several 1H-benzo[b][1,5]diazepin-2(3H)-one derivatives. The substituents at N1 are benzoyl, 5-substituted-1,3,4-thiadiazoles-2-yl-aminoacetyl. Condensation of orthophenylene diamine with ethyl acetoacetate gave 7-substituted-4-methyl-1H-benzo[b][1,5]diazepin-2(3H)-ones, which were then linked to benzoyl chloride and chloroacetyl chloride to yield N1-benzoyl and N1-chloroacetyl derivatives. N1- chloroacetyl derivatives were further linked with 5-substituted-1,3,4-thiadiazoles amines using microwave irradiation. Result: IR, 1H-NMR, and mass spectroscopy were used to authenticate the synthesized compounds. The PTZ produced convulsions method was used to test the compounds for anticonvulsant activity. Compounds 4a and 4c gave 80% protection at 0.4 mg/kg, whereas Compounds 2a and 2c offered 80% protection at 20 and 30 mg/kg, respectively, when compared to the Control. Conclusion: When compared to a control, the experimental synthesis and pharmacological assessment of the 1,5-benzodiazepin-2-one moiety replaced with 1,3,4-thiadiazole yields a potentially active anticonvulsant drug.
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来源期刊
CiteScore
0.10
自引率
0.00%
发文量
17
审稿时长
10 weeks
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