A large series (66 compounds) of indeno[1,2-c]pyridazin-5-ones (IPs) were synthesized and tested on their monoamine oxidase-A (MAO-A) and MAO-B inhibitory activity. All of the tested compounds acted preferentially on MAO-B displaying weak (nonmeasurable IC50 values) to high (submicromolar IC50 values) activities. The most active compound was p-CF3-3-phenyl-IP (IC50 = 90 nM). Multiple linear regression analysis of the substituted 3-phenyl-IPs yielded good statistical results (q2 = 0.74; r2 = 0.86) and showed the importance of lipophilic, electronic, and steric properties of the substituents in determining inhibitory potency. Various comparative molecular field analysis studies were performed with different alignments and including the molecular lipophilicity potential. This led to a model including the steric, electrostatic and lipophilicity fields and having a good predictive value (q2 = 0.75; r2 = 0.93).

The one-pot synthesis of nine SH-indeno[l,2-r]pyridazines is described. These compounds are shown to be potent, reversible inhibitors of monoamine oxidase B (MAO-B) with little or no effect on nionoamine oxidase A (MAO-A). Qualitative structure-activity relations indicate that the MAO-B inhibitory activity is strongly influenced by electronic and bulk properties of substituents.

Synthesis and Monoamine Oxidase Inhibitory Activity of 3-Substituted 5H-Indeno(1,2-c)pyridazines.-A facile one-pot procedure for the synthesis of the title indenopyridazines (III) and (V) (7 examples) starting from ninhydrin ( I) is presented. All these products and therefrom derived analogues are potent, selective and reversible inhibitors of monoamine oxidase B. Qualitative structure-activity relationships are discussed. -(KNEUBUEHLER, S.; CARTA, V.; ALTOMARE, C.; CAROTTI, A.; TESTA, B.; Helv. Chim. Acta 76 (1993) 5, 1956-1963 Inst. Chim. Ther., Ec. Pharm., Univ. Lausanne, CH-1015 Lausanne, Switz.; EN)

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.