Non-peptide GnRH antagonists.

摘要

Compounds according to general formula 1, wherein A¹-A³ are selected from A⁵ and A⁶ where A⁵ is either -CR¹³- or -N- and A⁶ is -NR¹⁴-, -O- or -S-; A⁴ is either a covalent bond or A⁵, provided that when A⁴ is a covalent bond one of A¹-A³ must be A⁶ and the other two must be A⁵ and when A⁴ is A⁵ then all of A¹-A³ must be A⁵; R¹ is selected from H, NHY' and COY², in which case R² is H, or R¹ and R² may both be methyl or together represent -O; R³, R⁴ and R⁵ are each independently selected from H and lower alkyl groups; R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ and R¹² are each independently selected from H, lower alkyl groups, NH₂, halogens (F, Cl and Br) O-alkyl, CH₂NM₂ and CF₃; R¹³ is selected from H, F, Cl, Br, NO₂, NH₂, OH, Me, Et, OMe, NMe₂ and CF₃; R¹⁴ is selected from H, methyl and ethyl; W is selected from -CH- and -N-; X is selected from CH₂, O, S, SO₂, NH and N-lower alkyl; Y¹ is selected from CO-lower alkyl, CO(CH₂)_bY³, CO(CH₂)_bCOY³ and CO(CH₂)_bNHCOY³, where b is 1-3; Y² is selected from OR¹⁵, NR¹⁶R¹⁷ and NH(CH₂)_cCOY3, where c is 1-3; Y³ is selected from OR¹⁵ and NR¹⁶R¹⁷; R¹⁵ is selected from H, lower alkyl and (CH₂)_aR¹⁶, where a is 0-4; R¹⁶ and R¹⁷ are each independently selected from H, lower alkyl and (CH₂)_aR¹⁶ or together are -(CH₂)₂-Z-(CH₂)₂-; R¹⁸ is OH, a phenyl group or an aromatic heterocycle selected from pyridyl, pyrimidinyl, pyrazinyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl and thiadiazolyl, each of which may optionally have a lower alkyl group substituent; and Z is selected from O, CH₂, S, SO₂, NH and N-lower alkyl, are new. They are useful in the treatment of breast and prostate cancer, endometriosis and benign prostate hyperplasia, in the regulation of fertility, and in in vitro fertilisation.