The enaminonitrile 1 reacts with ethyl acetoacetate or ethyl beta-diet
hoxypropionate and titanium tetrachloride to yield the indeno[1,2-b]py
ridin-4-amines 3 and 4, respectively, while the enaminocarboxylic este
r 2 with ethyl acetoacetate under the same conditions forms the 4-pyri
done-3-carboxylic ester 5a. Compound 5a was oxidized by chromic acid r
o give the indenone 5b. The carboxylic acid 6, obtained by alkaline hy
drolysis of 5a, was decarboxylated by heating with quinoline and coppe
r. Under nitrogen 5c was formed, whereas in the presence of oxygen 5d
was received. The pyridones 5 are transformed into the 4-chloropyridin
es 7 using phosphorus oxychloride, which react with N-nucleophiles to
yield the secondary indeno[1,2-b]pyridin-4-yl-amines 8-11. Compound 8c
shows the best activity in vitro on the proliferation of Plasmodium f
alciparum strains. The EC50-value of 70 ng/ml is comparable with the a
ctivity of chloroquine against a multi-drug resistant strain (EC50 = 7
5 ng/ml). There is also observed a weak growth inhibition of Candida a
lbicans and Staphylococcus aureus by 8c.