Synthesis and Neurotropic Activity of Piperazino-Derivatives of Pyrano[3,4-c]Pyridines

Synthesis of novel 1,2,3-triazole-based hybrids via click reactions

“…Finally, to add a piperazine group to the structure of the envisaged 1,2,3-triazoles we also synthesized some azide derivatives 8 according to Scheme 3. Thus, by the acylation of 3(6)-piperazine derivatives of fused pyridines 6 23,24 with chloroacetyl chloride, the relevant 1(8)-alkyl-3(6)-[4-(chloroacetyl)piperazin-1-yl]pyridine-4(5)-carbonitriles 7 were obtained. Reaction of these compounds with sodium azide led to the formation of 1(8)-alkyl-3(6)-[4-(azidoacetyl)piperazin-1-yl][c]pyridine-4(5)-carbonitriles 8 in high yields (Table 1).…”

“…Accordingly, our studies in this field have shown that piperazine derivatives of pyrano [3,4-c]pyridines display high antibacterial 23 and neurotropic activity. 24,25 In addition, bicyclic pyrano [3,4-c]pyridines synthesized by us were characterized by eliciting pronounced cardiotonic activities. 26 Thus, it was our intent to incorporate these moieties (types of structures) into the click-derived compounds, which also included examples containing dioxaspiro [4.4]nonane-1,6-dionesand carvone-derived terpenes.…”

Synthesis and antimicrobial activity of new 2‐piperazin‐1‐yl‐N‐1,3‐thiazol‐2‐ylacetamides of cyclopenta[c]pyridines and pyrano[3,4‐c]pyridines

“…The starting compounds for the syntheses were the new and previously synthesized 1‐alkyl(aryl)‐3‐chloro‐6,7‐dihydro‐5 H ‐cyclopenta[ c ]pyridine‐4‐carbonitriles 1a – f and 8‐alkyl(aryl)‐6‐chloro‐3,3‐dimethyl‐3,4‐dihydro‐1 H ‐pyrano[3,4‐ c ]pyridine‐5‐carbonitriles 1g – k , [ 12 ] containing a chlorine atom able to react with nucleophiles due to the presence of two activating (electron‐attracting) systems (the pyridinic nitrogen and the cyano group). The reaction of compounds 1a – k with piperazine easily gave the corresponding 1‐alkyl(aryl)‐3‐piperazin‐1‐yl‐6,7‐dihydro‐5 H ‐cyclopenta[ c ]pyridine‐4‐carbonitriles 2a – f and 8‐alkyl(aryl)‐6‐piperazin‐1‐yl‐3,3‐dimethyl‐3,4‐dihydro‐1 H ‐pyrano[3,4‐ c ]pyridin‐5‐carbonitriles 2g–k [ 6–8,13 ] (Scheme 1). It is noteworthy that the reaction occurred under mild conditions, that is, by simple refluxing in benzene, and gave high yields (76–89%) of the relevant substitution products.…”

“…Melting points were determined on a Boetius microheating stage. Compounds 1a – k [ 12 ] and 2c , g – k [ 6–8,13 ] have been already described.…”

“…[ 4,5 ] Our research showed that acylated piperazines exhibited weak β1‐ and β2‐adrenoblocking and antibacterial activities, [ 6 ] whereas oxalylated and N ‐alkylated derivatives evidenced a pronounced neurotropic activity and low toxicity. [ 7,8 ] Therefore, the synthesis of new derivatives of this class of compounds is timely and promising. The present work reports the synthesis of piperazine‐substituted pyrano[3,4‐ c ]pyridines/cyclopenta[ c ]pyridines and analyses of their antibacterial activity.…”