Abstract
The versatile
hitherto unreported 3-[(
E)-3-(dimethylamino)acryloyl]-1,5-diphenyl-1
H-pyrazole-4-carbonitrile (
3) was prepared
via the reaction of 3-acetyl-1,5-diphenyl-1
H-pyrazole-4-carbonitrile (
1) with dimethylformamid-dimethylacetal (DMF-DMA). The latter product and 3-((
E)-3-morpholin-4-yl-acryloyl)-1,5-diphenyl–1
H-pyrazole-4-carbonitrile (
4) underwent regioselective 1,3-dipolar cycloaddition with nitrilimines to afford the corresponding pyrazole derivatives.
In vivo anti-estrogenic activity and acute toxicity after single oral dose of the newly synthesized compounds were evaluated.
In vitro disease-oriented primary antitumor screening utilizing 14 cell lines of breast and ovarian tumor subpanels has been also carried out. All tested compounds showed anti-estrogenic properties equipotent or superior to the reference drug, letrozole. 3-[3-(4-Cyano-1,5-diphenyl-1
H-pyrazole-3-yl)-1-(4-methylphenyl)-1
H-pyrazole-4-carbonyl]-1,5-diphenyl-1
H-pyrazole-4-carbonitrile (
27c) and 3-(3-acetyl-1-phenyl-1
H-pyrazole-4-carbonyl)-1,5-diphenyl-1
H-pyrazole-4-carbonitrile (
8a) showed a significant cytotoxic activity in a nanomolar range against certain types of breast and ovarian tumors with tolerable toxicity.
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