Pyrophtalones VII. Synthese et activite anti-inflammatoire de (pyridinyl-4)-2 indanediones-1,3 substituees sur le noyau benzenique et/ou sur l'heterocycle

Article abstract of DOI:10.1016/0223-5234(87)90054-7

Pyrophthalones VII.Synthesis and anti-inflammatory activity of 2-(4-pyridinyl)indane-1,3-diones diversely substituted on the benzene ring.Access routes to 2-(1,4-dihydro 4-pyridinylidene) indane-1,3-diones diversely substituted on the benzene ring are studied.The regiospecific attack of these β diketoenamines by alkyl iodides leads to N-substituted compounds.These derivatives may be obtained by any of three possible methods: (1) condensation of 4-methyl pyridine with ethyl phthalates in the absence of catalyst; (2) oxidative condensation of N-alkyl-pyridinium bromides with indane-1,3-diones; (3) aminolysis of 2-(4-4H-pyranylidene) indane-1,3-diones.Pharmacomodulation by the introduction of oxygen or sulfur containing functions (ether, thioether, alcohol, ketone, acid, ester, amide) on the nitrogen of the basic molecule is not very fruitful; only the acetic derivative 19 manifests marked antiinflammatory activity unaccompanied by anti-coagulant action.The presence of chloro, nitro or methoxyl groups on 5 after N-substitution by ethyl or piperidinylethyl groups appears to be more favorable.The most active compound 57 decreases prostaglandin production and leukocyte migration without affecting either cyclooxygenase or 5-lipoxygenase.Its interference, direct or indirect, with phospholipasic A₂ activity may be envisaged in particular.Keywords - 2-(4-pyridinyl)indane-1,3-diones / heterocyclic β diketoenamines / partition coefficient / anti-inflammatory activity / mechanism of action