(ANF) ATRIAL NATRIURETIC FACTOR DERIVATIVES AND MEDICAMENTS

摘要

Disclosed herein are derivatives of atrial natriuretic peptides of formula 1, wherein the exocyclic N-terminal peptide segment is deleted and the two cysteinyl residues (at positions 105 and 121) of the natural sequence are replaced with a trivalent unit, -NHCH(CO-)-Q-X-Y-CH2CH2CO- wherein Q is methylene, ethylene or CR'R" wherein R' and R" each independently is lower alkyl, X is oxy or thio, an Y is methylene or des-Y. The derivatives may be optionally substituted at various positions including positions 106, 107, and 124. The derivatives possess ANF-like activity and are indicated for treating hypertension and for treating pathological conditions resulting from an imbalance of body fluids and electrolytes. Formula 1: CHEM wherein Q is is methylene, ethylene or CR'R" wherein R' and R" each independently lower alkyl; R1 and R4 each independently is Phe, 2FPhe, 3FPhe, 4FPhe, 2CF3Phe, 3CF3Phe or 4CF3Phe; R2 is Gly, Ala or D-Ala; R3 is Ile or Met; R5 is Tyr or des-R5; X is oxy or thio; Y is methylene or des-Y; and W is hydroxy, lower alkoxy, amino or lower alkylamino;