Cyclooctapeptides

• US 4,358,439 A
• Filed: 12/15/1980
• Issued: 11/09/1982
• Est. Priority Date: 12/21/1979
• Status: Expired due to Fees

• Current Assignee: Ciba-Geigy Corporation (Novartis Ag)
• Original Assignee: Ciba-Geigy Corporation (Novartis Ag)
• Inventors: Sieber, Peter, Rink, Hans, Kamber, Bruno
• Primary Examiner(s): Phillips, Delbert R.
• Application Number:
  US06/216,353
• Time in Patent Office: 694 Days
• Field of Search: 260/112.5 S, 424/177
• US Class Current: 514/6.9
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: C07K 14/6555 at least 1 amino acid in D-form
• CPC Class Codes: Y10S 930/16 Somatostatin; related peptides

Abstract

Cyclic peptides of the formula ##STR1## in which trp represents L-Trp, D-Trp, or an analogous radical which carries a halogen atom in the indole nucleus, Ac_A represents hydrogen, or an acyl radical Ac of a carboxylic acid present at the ε-amino group, A represents L-Phe, D-Phe, L-Phg or D-Phg, or a corresponding radical having a substituted or saturated phenyl ring, and B represents the residue of a γ- or δ-amino-lower alkanecarboxylic acid which may carry an optionally substituted cyclic hydrocarbyl radical Ar, and also pharmacologically tolerable salts and therapeutically acceptable complexes thereof can be used as an antidiabetic in an analogous manner to somatostatin. They can be obtained by conventional processes of peptide chemistry, especially by cyclisation of corresponding linear peptides.

Claims

1. A cyclic octapeptide of the formula ##STR16## in which trp represent L-Trp, D-Trp or an analogous radical which carries a halogen atom in the indole nucleus, Ac_A represents hydrogen, A represents L-Phe, D-Phe, L-Phg or D-Phg, or the analogus residues having the cyclohexyl or p-hydroxyphenyl radical substituted for the phenyl radical, and B represents Gaba which is the residue of the unsubstituted α

-aminobutyric acid, or Gaba (Ar), which is an analogus residue carrying in the β

-position a mono- or bicyclic aryl radical Ar having not more than 12 carbon atoms, and also pharmacologically tolerable salts and activity-prolonging therapeutically acceptable complexes thereof.

2. A cyclic octapeptide according to claim 1, in which, formula I trp represents D-Trp or D-(5F)Trp, AC_A represents hydrogen, A represents L-Phe, D-Phe, L-Phg or D-Phg, or the analogus residues having the cyclohexyl or p-hydroxyphenyl radical substituted for the phenyl radical, and B represents Gaba which is the residue of the unsubstituted α

-aminobutyric acid, or Gaba (Ar), which is an analogus residue carrying in the β

-position a mono- or bicyclic aryl radical Ar having not more than 12 carbon atoms, and also pharmacologically tolerable salts and activity-prolonging therapeutically acceptable complexes thereof.

3. A cyclic peptide, according to claim 1, in which, in the formula I, trp represents D-Trp or D-(5F)Trp, Ac_A represents hydrogen, A represents L-Phe, D-Phe, L-Phg or D-Phg, or the analogus residues having the cyclohexyl or p-hydroxyphenyl radical substituted for the phenyl radical, and B represents the residue of the unsubstituted γ

-aminobutyric acid, and also pharmacologically tolerable salts and activity prolonging therapeutically acceptable complexes thereof.

6. A pharmaceutical preparation for the treatment of diabetes and/or gastrointestinal bleeding in humans and mammals, containing an effective amount of a compound according to any one of claims 1-5.

7. A therapeutic method for the treatment of diabetes and/or gastrointestinal bleeding in humans and mammals by administration of a therapeutically effective dose of a compound according to any one of claims 1-5 alone or in the form of a pharmaceutical preparation.

4. [D-Trp⁸,Phe¹²,Gaba¹³ ]-cyclosomatostatin(6-13)-octapeptide and pharmacologically activity prolonging therapeutically acceptable complexes thereof.

5. [D-Trp⁸,D-Phe¹²,Gaba¹³ ]-cyclosomatostatin(6-13)octapeptide and pharmacologically activity prolonging therapeutically acceptable complexes thereof.