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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000921:Antibody-Producing Cells / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006940:Hyperemia / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D010881:Piperidones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D014374:Tuberculin Test
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D010880:Piperidines; D010881:Piperidones