TRH-LIKE PEPTIDE DERIVATIVES AS INHIBITORS OF THE TRH-DEGRADING ECTOENZYME

摘要

Peptide derivatives useful as inhibitors of activity of thyrotropin-releasing hormone-degrading ectoenzyme (TRH-DE) are of formula Ia, wherein R1 is an optionally substituted 4-, 5- or 6-membered heterocyclic ring having one or more heteroatoms, in which at least one carbon of the ring is substituted with O or S; X1 is -CO- or -CS- or -CH¿2?CO- or CH(R?4¿) wherein R4 is H or optionally substituted alkyl or -COOH or -COOR11 wherein R11 is optionally substituted alkyl; X?2 and X3¿ (which may be the same or different) are -CO- or -CS-; Z is -CH¿2?- or -S- or -O- or -NH-; Q is O or S; R?2¿ is H or optionally substituted alkyl or an optionally substituted carbocyclic ring; R3 is H or optionally substituted alkyl or an optionally substituted mono- or polycyclic ring, optionally having one or more heteroatoms in the ring(s) and optionally being a fused ring; or R?2 and R3¿ together form an optionally substituted mono- or polycyclic ring optionally having one or more heteroatoms in the ring(s) and optionally being a fused ring; R?5 and R6¿ (which may be the same or different) are H, or lower alkyl; R?7 and R8¿ (which may be the same or different) are H, or optionally substituted lower alkyl; R?9 and R10¿ (which may be the same or different) are H, or optionally substituted alkyl or an optionally substituted carbocyclic ring; Y is -(CH¿2?)n- where n is 0, 1, 2 or 3 provided that when R?2 and R3¿ form part of the ring n is 0; and pharmaceutically acceptable salts thereof.