| 摘要 |
Disclosed herein are derivatives of atrial natriuretic peptides which are characterized by having (at positions 106 and/or 124) a phenylalanyl residue bearing a fluoro or trifluoromethyl substituent on the aromatic portion thereof. Optionally, the exocyclic N-terminal peptide segment and the first cystienyl residue (at position 105) are replaced by an optionally substituted thioalkanoyl residue. The derivatives possess useful diuretic, natriuretic and antihypertensive activities. The formula is as follows: <CHEM> wherein R<1> is Phe, 2FPhe, 3FPhe, 4FPhe, 2CF3Phe, 3CF3Phe or 4CF3Phe; R<2> is Gly, Ala or D-Ala; R<3> is Ile or Met; R<4> is Phe, 2FPhe, 3FPhe, 4FPhe, 2CF3Phe, 3CF3Phe or 4CF3Phe; R<5> is Tyr or des-R<5>; Y- is S-(lower alkylene)-CO or R<6>-Cys- wherein R<6> is H-Ser-Ser, H-Arg-Ser-Ser, H-Arg-Arg-Ser-Ser; H-Leu-Arg-Arg-Ser-Ser or H-Ser-Leu-Arg-Arg-Ser-Ser; and Z is hydroxy, amino or lower alkylamino; with the proviso that when R<1> is Phe, then R<4> is not Phe; |
