64500-73-8

Upstream product

• 41808-21-3 sodium salt of α-cyanoacetamide 
• 85302-08-5 2-((dimethylamino)methylene)-5-phenyl-cyclohexane-1,3-dione 
• 109-77-3 malononitrile 

Relevant academic research and scientific papers

Inotropic agents. Synthesis and structure-activity relationships of new milrinone related cAMP PDE III inhibitors

The synthesis of 6-substituted 5-acyl-1,2-dihydro-2-oxo-3-pyridinecarbonitriles 1b,c, 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarbonitriles 1d-g and esters of 5-cyano-1,6-dihydro-2-methyl-6-oxo-3-pyridinecarboxylic acid 2b-e is described. In the case of le and If, a careful elucidation of the reaction mechanism is discussed. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea pigs. The methyl and tile benzyl esters 2b and 2e showed an appreciable positive inotropic activity when compared to milrinone. A fitting study with the DISCO (Distance Comparison) model has been carried out on 2e. This modeling approach allowed for the improvement of the pharmacophoric requirements for a better interaction with the cAMP-specific PDE (PDE III), thought to be the final biological target of these cardiotonic agents.

Reaction of 2-Dimethylaminomethylene-1,3-diones with Dinucleophiles.V. Synthesis of 5-Acyl-1,2-dihydro-2-oxo-3-pyridinecarbonitriles and 1,2,5,6,7,8-Hexahydro-2,5-dioxo-3-quinolinecarboxamides

The reaction of open-chain sym-2-dimethylaminomethylene-1,3-diones Ia-d with sodium cyanoacetamide gave, generally in good yields, 6-substituted 5-acyl-1,2-dihydro-2-oxo-3-pyridinecarbonitriles IIa-d, whereas cyclohexane sym-2-dimethylaminomethylene-1,3-diones Ie-h afforded in general a mixture of 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarbonitriles and 5,6,7,8-tetrahydro-2,5-dioxo-2H-1-benzopyran-3-carboxamides, the latter being isolated in two cases.The reaction of Ie-h with cyanoacetamide in refluxing anhydrous ethanol gave 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarboxamides IIIe-h in excellent yields, whereas Ia-d did not react with the exception of Ia which afforded in good yield 3-pyridinecarboxamide IIIa.Other 3-pyridinecarboxamides were obtained by partial hydrolysis of nitriles IIb,d. 3-Pyridine and 3-quinoline carboxamides were hydrolyzed in satisfactory yields with hydrochloric acid to the corresponding carboxylic acids, which were decarboxylated in good yields to 5-acyl-2(1H)-pyridinones and 7,8-dihydro-2,5-(1H,6H)-quinolinediones, respectively, by reflux in quinoline containing a catalytic amount of copper powder.