Pharmacologic studies on anti-inflammatory activity of di- and triketopiperidine derivatives

A number of derivatives of piperidine-2,4,6-trione and oxazine-2,4-dione with cyclohexyl and allyl substituents at their ring were evaluated pharmacologically. Piperidine-2,4,6-trione compounds, regardless of type of substituent, were readily absorbed from the site of their introduction and displayed similar biological activity. Introduction of the N-cyclohexylcarboxamide substituent diminished general toxicity of the derivative and increased anti-inflammatory activity in all tests. The oxazine-4,6-dione derivatives were poorly absorbed. The bis-(1-cyclohexyl-5,5-diallyl-piperidine-2,4,6-trione) derivative, product of condensation of two molecules of a simpler compound, was very well absorbed, strongly toxic, and showed distinct anti-inflammatory activity. Limited correlation between chemical structure and biological activity was noted, supporting the concept that introduction of cyclohexyl and allyl radicals imparts anti-inflammatory and immunosuppressive activity to derivatives of this type.