Non-peptide gnrh antagonists

Abstract

Compounds according to general formula 1, wherein A-Aare selected from Aand Awhere Ais either ═CR— or ═N— and Ais —NR—, —O— or —S—; Ais either a covalent bond or A, provided that when Ais a covalent bond one of A-Amust be Aand the other two must be Aand when Ais Athen all of A-Amust be A; Ris selected from H, NHY' and COY, in which case Ris H, or Rand R2 may both be methyl or together represent ═O; R, Rand Rare each independently selected from H and lower alkyl groups; R, R, R, R, R, Rand Rare each independently selected from H, lower alkyl groups, NH, halogens (F, Cl and Br) O-alkyl, CHNMand CF; Ris selected from H, F, Cl Br, NO, NH, OH, Me, Et, OMe, NMeand CF; Ris selected from H, methyl and ethyl; W is selected from ═CH— and ═N—; X is selected from CH, O, S, SO, NH and N lower alkyl; Yis selected from CO-lower alkyl, CO(CH)Y, CO(CH)COYand CO(CH)NHCOY, where b is 1-3; Y2 is selected from OR, NRRand NH(CH)COY, where c is 1-3; Yis selected from ORand NRR; Ris selected from H, lower alkyl and (CH)R, where a is 0-4; Rand Rare each independently selected from H, lower alkyl and (CH)Ror together are —(CH)-Z-(CH—; Ris 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, CH, S, SO, 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.