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一些新型取代吡啶和嘧啶衍生物作为镇痛、抗惊厥和抗帕金森病药物的合成与反应

Synthesis and reactions of some new substituted pyridine and pyrimidine derivatives as analgesic, anticonvulsant and antiparkinsonian agents.

作者信息

Amr Abd El-Galil E, Sayed Hayam H, Abdulla Mohamed M

机构信息

National Research Center, Cairo, Egypt.

出版信息

Arch Pharm (Weinheim). 2005 Sep;338(9):433-40. doi: 10.1002/ardp.200500982.

DOI:10.1002/ardp.200500982
PMID:16134091
Abstract

A series of substituted pyridine and pyrimidine derivatives were synthesized as analgesic, anti convulsant, and antiparkinsonian agents by using compounds 1, 2, and 9 as starting materials. Pyr idino-imide derivative 3 was prepared by condensation of 1 with tetrachlorophthalic anhydride and compounds 4 and 5 were also obtained by reaction of compound 1 with 1,2,4,5-benzene-tetra carboxylic dianhydride and 1,4,5,8-naphthalenetetracarboxylic dianhydride, respectively. Similarly, compound 2 was reacted with previous anhydrides to afford the corresponding imide 6 and bis-imide derivatives 7 and 8, respectively. Bis-arylmethylene derivatives 9 were treated with hydrogen peroxide to afford the corresponding bis-oxiranocycloalkanone derivatives 10, which condensed with thiourea to give the corresponding thioxopyrimidine derivatives 11. Treatment of compound 11 with chloroacetic acid in the presence of anhydrous sodium acetate afforded the corresponding thiazolopyrim idine derivative 12 which condensed with aromatic aldehydes in acetic acid/acetic anhydride to give arylmethylene derivative 13. Also, compounds 13 could be prepared by reaction of compounds 11 with chloroacetic acid, aromatic aldehydes, and sodium acetate in a mixture of acetic acid and acetic anhydride. The pharmacological screening showed that many of these obtained compounds have good analgesic, anticonvulsant, and antiparkinsonian activities comparable to Valdecoxib, Carbamazepine, and Benzatropine as reference drugs.

摘要

以化合物1、2和9为起始原料,合成了一系列取代吡啶和嘧啶衍生物,作为镇痛、抗惊厥和抗帕金森病药物。吡啶基酰亚胺衍生物3是由1与四氯邻苯二甲酸酐缩合制备而成,化合物4和5分别是由化合物1与1,2,4,5-苯四羧酸二酐和1,4,5,8-萘四羧酸二酐反应得到的。类似地,化合物2与上述酸酐反应,分别得到相应的酰亚胺6和双酰亚胺衍生物7和8。双芳基亚甲基衍生物9用过氧化氢处理,得到相应的双环氧环烷酮衍生物10,其与硫脲缩合,得到相应的硫代嘧啶衍生物11。在无水醋酸钠存在下,化合物11与氯乙酸反应,得到相应的噻唑并嘧啶衍生物12,其在乙酸/乙酸酐中与芳香醛缩合,得到芳基亚甲基衍生物13。此外,化合物13也可通过化合物11与氯乙酸、芳香醛和醋酸钠在乙酸和乙酸酐的混合物中反应制备。药理筛选表明,许多所得化合物具有良好的镇痛、抗惊厥和抗帕金森病活性,与作为参比药物的伐地昔布、卡马西平和苯海索相当。

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