PEPTIDE DERIVATIVES HAVING AN ANTIHYPERTENSIVE EFFECT AND PROCESS FOR THEIR MANUFACTURE

摘要

1536677 Heptapeptides/octapeptides HOECHST AG 20 Nov 1975 [5 Dec 1974] 47769/75 Heading C3H A peptide of general formula wherein Y represents a sarcosyl, succinamoyl or succinoyl radical: which may be prepared by the reaction of an N-protected sarcosine, or succinic acid monoamide or anhydride, or an activated ester of sarcosine or succinic acid with a peptide of formula and elimination of protective groups with an acid. The peptides (I) may be complexed either with zinc ions, and optionally, phosphate ions, wherein the complex is precipitated by adjustment of pH to 7À2 to 9, or with gelatine crosslinked with hexamethyleneisocyanate and polyphloretin phosphate. In the examples, peptides prepared are: succinamoyl - Arg - Val - Tyr - Val - His - Pro- C - Ph.Gly - OH; H - Sar - Arg - Val - Tyr - Val- His - Pro - C - Ph.Gly - OH. Peptide intermediates isolated are: OCTAPEPTIDE: Boc - Sar - Arg - Val - Tyr(But)- Val-His-Pro-C-Ph.Gly-OBut. HEPTAPEPTIDES: Succinamoyl - Arg- Val - Tyr(But) - Val - His - Pro - C - Ph.Gly- OBut; Z - Arg(Z 2 ) - Val - Tyr(But) - Val - His- Pro - C - Ph.Gly - OBut; H - Arg - Val - Tyr (But) - Val-His-Pro-C-Ph.Gly-OBut. HEXAPEPTIDES: Z and H - Val- Tyr(But)-Val-His-Pro-C-Ph.Gly-OBut. PENTAPEPTIDES: Z and H - Tyr(But)- Val-His-Pro-C-Ph.Gly-OBut. TETRAPEPTIDES: Z and H - Val - His- Pro-C-Ph.Gly-OBut. Dipeptide derivatives isolated are: Z-Val- His-OCH 3 and OH. Pharmaceutical compositions, which are preferably solutions in unit dosage form or, which have been lyophilized, comprise peptides (I) (unit dose of preferably 1 or 2 ml. which contains 6 to 100 mg. of peptide), the zinc with, optionally, phosphate complex thereof (unit dose of 1 ml. which contains 50 to 500 mcg. of the peptide), or the gelatine cross-linked with hexamethylene isocyanate/polyphloretin phosphate complex thereof (unit dosage of 50 to 500 mcg. of peptide) in admixture or conjunction with a pharmaceutically-acceptable carrier.