Claims
- 1. A peptide having natriuretic, diuretic, and/or vasodilator activity in mammals which has the formula
- Y.sub.1 Y.sub.2 -R-I-D-R-I-Z.sub.2
- or
- Y.sub.1 -Y.sub.2 -R-M-D-R-I-Z.sub.2,
- wherein Y.sub.1 is a hydrophobic group selected from the group consisting of phenyalanine, acetyl phenlalanine, desaminophenylalanine, fluorenyl, methyloxycarbonyl, benzyloxycarbonyl, diphenylpropionyl, triphenylpropionyl, 3-indolepropionyl, 4-indolebutyryl, 1-adamantylacetyl, 1-naphthylacetyl, 2-naphthylacetyl, 1-naphthyloxyacetyl, 2-naphthyloxyacetyl, CBZ, FMOC, 4-biphenylacetyl, and cyclohexylacetyl,
- Y.sub.2 is a spacer group which is a peptide of 1-2 amino acid residues selected from the group consisting of G, S, A, Aib, and Sar, or a residue of the formula --NH(CH.sub.2).sub.n CO-- wherein n is 3-6; and
- Z.sub.2 is NH.sub.2 or NHR' wherein R' is a straight or branched chain alkyl of 1-6 carbons, or Z.sub.2 is a peptide of 1-3 amino acid residues, said residues selected from the group consisting of G, A, S, Sar, and Aib or the amide or alkylamide form thereof.
- 2. A peptide selected from the group consisting of:
- A-F-G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- F-G-G-R-I-D-R-I-G-A-A-NH.sub.2 ;
- A-F-G-G-R-I-D-R-I-G-NH.sub.2 ;
- A-F-G-G-R-I-D-R-I-NH.sub.2 ;
- des NH.sub.2 -F-G-G-R-I-D-R-I-NH.sub.2 ;
- Y-A-F-G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- F-G-G-R-I-G-R-I-G-A-NH.sub.2 ;
- F-G-G-R-I-D-R-I-NH.sub.2
- A-F-G-G-R-I-D-R-I-G-Y-NH.sub.2 ;
- A-F -G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- A-F-A -G-R-I-D-R-I-G-A-NH.sub.2 ;
- A-F-G-A -R-I-D-R-I-G-A-NH.sub.2 ;
- (desNH.sub.2 -F)-G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- (2-Naphthylacetyl)-G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- (2-Naphthoxyacetyl)-NH(CH.sub.2).sub.4 CO-R-I-D-R-I-NH.sub.2 ;
- (1-Adamantylacetyl)-G-G-R-I-D-R-I-NH.sub.2 ;
- (FMOC)-G-G-R-I-D-R-I-NH.sub.2 ;
- (FMOC)-G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- (Indolepropionyl)-G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- (2-Naphthylacetyl)-G-G-R-I-D-R-I-NH.sub.2 ;
- (1-Naphthoxyacetyl)-G-G-R-I-D-R-I-NH.sub.2 ;
- (4-Biphenylacetyl)-G-G-R-I-D-R-I-NH.sub.2 ;
- (2-Naphthoxyacetyl)-G-G-R-I-D-R-I-G-A-NH.sub.2 ;
- (2-Naphthoxyacetyl)-G-G-R-I-D-R-I-NH.sub.2 ;
- (2-Naphthylacetyl)-G-Sar-R-I-D-R-I-NH.sub.2
- (2-Naphthylacetyl)-G-Aib-R-I-D-R-I-NH.sub.2 ;
- (2-Naphthoxyacetyl)-A -G-R-I-D-R-I-NH.sub.2 ;
- (FMOC)-NH(CH.sub.2).sub.4 CO-R-I-D-R-I-NH.sub.2 ;
- (2-Naphthylacetyl)-NH(CH.sub.2).sub.4 CO-R-I-D-R-I-NH.sub.2 ;
- (2-Naphthoxyacetyl)-NH(CH.sub.2).sub.5 CO-R-I-D-R-I-NH.sub.2 ;
- (2-Naphthylacetyl)-NH(CH.sub.2).sub.3 CO-R-I-D-R-I-NH.sub.2
- (2-Naphthylacetyl)-G-G-R-I-D-R-I-NHCH.sub.2 CH.sub.3 ;
- (2-Naphthylacetyl)-NH(CH.sub.2).sub.5 CO-R-I-D-R-I-NH.sub.2 ;
- (2-Naphthylacetyl)-S -G-R-I-D-R-I-NH.sub.2 ;
- (Diphenylpropionyl)-G-G-R-I-D-R-I-G-A-NH.sub.2 ; and
- (Cyclohexylacetyl)-G-G-R-I-D-R-I-NH.sub.2
- wherein the indicates that the residue to which it is attached is in the D configuration.
- 3. A protein which comprises the peptide of claim 1.
- 4. A composition useful as a natriuretic, diuretic and/or vasodilator comprising a therapeutically effective amount of the compound of claim 1 together with a pharmaceutically acceptable carrier.
- 5. A method for inducing natriuresis, diuresis, or vasodilation in a mammalian host, which comprises administering to said host a pharmaceutically effective amount of the composition of claim 4.
Parent Case Info
This application is a continuation of application Ser. No. 921,360, filed Oct. 28, 1986, now abandoned.
US Referenced Citations (14)
Continuations (1)
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Number |
Date |
Country |
Parent |
921360 |
Oct 1986 |
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