Sci. Pharm. 2009; 77: 539–553
Antiarrhythmic Activities of Some Newly Synthesized Tricyclic and Tetracyclic Thienopyridine Derivatives
Naglaa A. ABDEL-HAFEZ * 1, Ashraf, M. MOHAMED 1, Abd El-Gelil E. AMR 1, Mohamed M. ABDALLA 1
1 Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo Egypt
2 Research Units, Hi-Care Pharmaceutical Co., Cairo, Egypt
* Corresponding author. E-mail: firstname.lastname@example.org (N. A. Abdel-Hafez).
3,5-Bis(4-chlorobenzylidene)-1-ethylpiperidin-4-one (1b) was condensed with malononitrile or cyanothioacetamide to yield pyranopyridine 2 and thiopyrido-pyridine 3b, respectively. Treatment of compound 3b with methyl iodide or ethyl chloroacetate in the presence of a base catalyst gave the corresponding compounds 4 and 5. Compound 3b was reacted with 2-chloro-N-arylacetamide derivatives to yield compounds 7a,b, which were reacted with benzoyl chloride or sodium nitrite to give the corresponding tetracyclic compounds 8a,b and 9a,b, respectively. Compound 2 was treated with acetic anhydride or formic acid to yield the corresponding N-acetylpyranopyridine 10 and pyranopyrimidine 11. Treatment of compound 2 with triethyl ortho-formate gave compound 12, which was cyclized with hydrazine hydrate to give N-aminopyrimidine 13. Some of the synthesized compounds showed high antiarrhythmic activities comparable with Procaine amide and Lidocaine as positive controls.
Pyridinethione Thienopyridine Thienopyrimidine Thienotriazine Pyranopyrimidine Antiarrhythmic agents
Received May 11th, 2009 | Accepted August 4th, 2009 | Published Online August 5th, 2009