New prostaglandin synthetase inhibitors—Di- and triphenylacrylonitriles

Abstract

16 triphenylacrylonitriles (TPE) or diphenylacrylonitïiles (DPE) were synthesized by condensation of various. benzophenones or benzaldehydes with various phenylacetonitriles. The pharmacological potency of these compounds was studied by incubation of bovine seminal vesicle microsomes and PG-RIA. The results showed that the potency of inhibition of PG biosynthetase of DPE was stronger than that of TPE. Compounds with electron-releasing functional groups were proved to be more effective than those with electron-attracting groups. Compound DPE-9 was the most active one, the potency of which was 40 times stronger than that of naproxen. The structure of some compounds has been analysed by X-ray diffraction. The relationship between structure and activity was investigated by means of X-ray diffraction, UV and NMR.

Keywords

prostaglandin synthetase inhibitor / triphenylacrylonitrile / diphenyl-acrylonitrile

References

[1] Michel F, et al. The effect of various acry lonitriles and related compounds on prostaglandin biosynthesis.

[2] GilbertJ, et al.. Inhibition of prostaglandin synthetase by di- and triyphenylethylene derivates: a structure — activity study. J Med Chem, 1983, 26: 693-9

[3] PonsM, et al.. Influence of new hydroxylated triphenylethiene (TPE) derivatives on estradiol binding to uterine cystosol. J Steroid Biochem, 1984, 20: 137-47