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 I, wherein R<1> 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; X<1> is -CO- or -CS- or -CH2CO- or CH(R<4>) wherein R<4> is H or optionally substituted alkyl or -COOH or -COOR<11> wherein R<11> is optionally substituted alkyl; X<2> and X<3> (which may be the same or different) are -CO- or -CS-; Z is -CH2- 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; R<3> 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 R<3> 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 R<6> (which may be the same or different) are H, or lower alkyl; R<7> and R<8> (which may be the same or different) are H, or optionally substituted lower alkyl; R<9> and R<10> (which may be the same or different) are H, or optionally substituted alkyl or an optionally substituted carbocyclic ring; Y is -(CH2)n- where n is 0, 1, 2 or 3 provided that when R<2> and R<3> form part of the ring n is 0; and pharmaceutically acceptable salts thereof.