4-Hydroxyquinolin-2-ones and their close structural analogues as a new source of highly effective pain-killers

Abstract

Reviewing the preliminary results of the complex research, which is far from its completion as yet, even now it is possible to state with certainty that 4-hydroxyquinolin-2-ones have actually appeared to be practically the inexhaustible source of highly effective pain-killers. One of these compounds – N-(3-pyridylmethyl)-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline- 3-carboxamide – possesses important analgesic properties on various experimental models; it is practically nontoxic, does not have the ulcerogenic action in therapeutic doses, greatly exceeds many currently known medicines by these parameters and thanks to these facts it is recommended to wide preclinical trials. Besides, according to the results of QSAR- 64 Pain and Treatment analysis not only relative contributions of some physical and chemical factors and the structural fragments to the analgesic activity of 1,2-dihydroquinolin-2-ones have been determined, but new potentially highly active virtual substances, which are suitable enough for synthesis and further testing, have been suggested. The primary pharmacological screening has also found some promising analgesics, but among 3-(3-R-carbamoyl-4-hydroxy-2-oxo-1,2-dihydroquinolin- 1-yl)propanenitriles already obtained and 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1- benzothiazine-3-carboxamides that are structurally related to them.