NON-PEPTIDE GnRH ANTAGONISTS

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 -NR 14-, -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, R11and R12 are each independently selected from H, lower alkyl groups, NH2, halogens (F, CI and Br) O-alkyl, CH2NM2 and CF3; R13 is selected from H, F, CI 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, NR 16R17 and NH(CH2)CCOY3, where c is 1-3; Y3 is selected from OR 15 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.