Claims
- 1. A polypeptide compound useful as a natriuretic, diuretic, and/or vasodilator in mammals, said polypeptide compound having the formula: ##STR14## wherein x is hydrogen, acetyl, or an oligopeptide of up to 125 amino acid residues from the naturally occurring N-terminal Atrial Peptide Sequence, including the N-acetyl derivatives thereof;
- Y is hydroxyl, amido, Asn-OH, Asn-Ser-OH, Asn-Ser-Phe-OH, Asn-Ser-Phe-Arg-OH, Asn-Ser-Phe-Arg-Tyr-OH, or the C-terminal amide derivatives thereof; or an oligopeptide extension of up to 20 amino acid residues from the C-terminus of any of the foregoing, including the C-terminal amide derivatives thereof;
- each of AA.sub.6, AA.sub.7, AA.sub.13, and AA.sub.17 is independently selected from the group consisting of Gly and Ala; AA.sub.9 is selected from Ile, Met, and Val; and AA.sub.12 is selected from Ile and Val;
- wherein 0, 1 or 2 residues selected from residues 1-20 are substituted by the D-isomer thereof, and including such compound containing a disulfide bridge joining the cysteine residues and the pharmacologically acceptable salts thereof,
- and which compound contains at least one of the following substitutions for residues in formula (1):
- Pro in place of Gly or Ala at position 7;
- Lys in place of Arg at position 8;
- Glu in place of Asp at position 10;
- Lys in place of Arg at position 11; and
- Ala in place of Gly at position 19.
- 2. The compound of claim 1 wherein the residue at position 7 is Pro.
- 3. The compound of claim 1 wherein the residues at positions 5, 10, 12, 20 and 21 are in the L configuration.
- 4. The compound of claim 1 selected from the group consisting of: ##STR15##
- 5. A pharmaceutical composition comprising the compound of claim 1, 2, 3, or 4 in a therapeutically effective amount, together with a physiologically acceptable excipient.
- 6. A method to induce natriuresis, diuresis, or vasodilation, or inhibiting renin secretion, or modulating angiotensin-induced aldosterone release in a mammalian host, which comprises administering to said host a pharmaceutically effective amount of the compound of claim 1, 2, 3 or 4.
- 7. The compound of claim 1, 2, 3 or 4 wherein all residues are in the L configuration.
Parent Case Info
This is a continuation of application Ser. No. 870,795 filed, Jun. 5, 1986, now U.S. Pat. No. 5,212,286, which is a continuation of Ser. No. 766,030, filed May 8, 1985, now U.S. Pat. No. 4,764,504 which is a continuation of Ser. No. 602,117, filed Apr. 19, 1984, now U.S. Pat. No. 4,618,600.
Continuations (3)
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Number |
Date |
Country |
Parent |
870795 |
Jun 1986 |
|
Parent |
766030 |
May 1985 |
|
Parent |
602117 |
Apr 1984 |
|