Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity

The synthesis of the products of the 1,3-propanesultone ring opening during its interaction with amides of pyridinecarboxylic acids has been carried out. The dependence of the yield of the reaction products on the position (ortho-, meta-, para-) of the substituent in the heteroaromatic fragment and temperature condition was revealed. In contrast to the meta- and para-substituted substrates, the reaction involving ortho-derivatives at the boiling point of methanol unexpectedly led to the formation of a salt. On the basis of spectroscopic, X-Ray, and quantum-chemical calculation data, a model of the transition-state, as well as a mechanism for this alkylation reaction of pyridine carboxamides with sultone were proposed in order to explain the higher yields obtained with the nicotinamide and its N-methyl analog compared to ortho or meta parents. Based on the analysis of ESP maps, the positions of the binding sites of reagents with a potential complexing agent in space were determined. The in silico evaluation of possible biological activity showed that the synthetized compounds revealed some promising pharmacological effects and low acute toxicity.

Automated summary

The synthesis of products from the interaction of 1,3-propanesultone ring with amides of pyridinecarboxylic acids was investigated. The position of the substituent in the heteroaromatic fragment and temperature condition influenced the yield of the reaction products. A mechanism and transition-state model were proposed based on spectroscopic, X-Ray, and quantum-chemical calculation data. The synthesized compounds showed promising pharmacological effects and low acute toxicity.