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^a: wherein: R¹ is an optionally substituted 4-, 5- or 6-membered heterocyclic ring having one or more heteroatoms, in which at least one carbon atom of the ring is substituted with O or S; X¹ is —CO— or —CS— or —CH₂CO— or CH(R⁴) wherein R⁴ is H or optionally substituted alkyl or —COOH or —COOR¹¹ wherein R¹¹ is optionally substituted alkyl; X² and X³ (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; R² 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 R² 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; R⁵ and R⁶ (which may be the same or different) are H, or lower alkyl; R⁷ and R⁸ (which may be the same or different) are H, or optionally substituted lower alkyl; R⁹ and R¹⁰ (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 R² and R³ form part of the ring n is 0; and pharmaceutically acceptable salts thereof.