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: rahma14_4@yahoo.com (N. A. Abdel-Hafez).
Abstract
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.
Keywords
Pyridinethione • Thienopyridine • Thienopyrimidine • Thienotriazine • Pyranopyrimidine • Antiarrhythmic agents
Received May 11th, 2009 | Accepted August 4th, 2009 | Published Online August 5th, 2009
