PEPTIDE-AGONISTS OF κ- OPIOID RECEPTORS Russian patent published in 2003 - IPC

FIELD: organic chemistry, peptides, medicine, pharmacy. SUBSTANCE: invention relates to synthetic amide of opioid peptide or its pharmaceutically acceptable salt eliciting affinity with respect to κ--opioid receptor that at least by 1 000 times exceeds its affinity with respect to μ--opioid receptor and elicits permanent effect in administration in vivo. This peptide has the following formula: H-Xaa₁-Xaa₂-X_aa3-X_aa4-Q wherein Xaa₁ represents (A)D-Phe, (C_αMe)D-Phe, D-Tyr, D-Tic or D-Ala (cyclopentyl or thienyl) being A represents H, NO₂, F, Cl or CH₃; Xaa₂ represents (A')D-Phe, D-1Nal, D-2Nal, D-Tyr or T-Trp wherein A' represents A or 3,4-Cl₂; Xaa₃ represents D-Nle, (B)D-Leu, D-Hle, D- Met, D-Val, D-Phe or D-Ala (cyclopentyl) being B represents H or C_αMe; Xaa₄ represents D-Arg, D-Har, D- nArg, D-Lys, D-Arg-(Et₂), D-Har-(Et₂), D-Amf, D-Gmf, D-Dbu, D-Om or D-Ior and Q represents NR₁R₂, morpholinyl, thiomorpholinyl, (C)piperidinyl, piperazinyl, 4-mono- or 4,4- disubstituted piperazinyl or ε- lysyl wherein R₁ is lower alkyl, substituted lower alkyl, benzyl, substituted benzyl, aminocyclohexyl, 2-thiazolyl, 2-picolyl, 3-picolyl, 4-picolyl, ω--(acylamino)-polymethylene or 4- polyoxyethylene group; R₂ is hydrogen atom or lower alkyl; C is hydrogen atom, 4-hydroxy- or 4-oxo-group. Proposed peptides enhance affinity with respect to κ- opioid receptors and permanent analgetic activity in vivo. EFFECT: valuable medicinal properties of peptides. 23 cl, 9 tbl, 9 ex