Peptides and processes for the manufacture thereof

• US 4,316,890 A
• Filed: 03/10/1980
• Issued: 02/23/1982
• Est. Priority Date: 03/16/1979
• Status: Expired due to Term

• 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:
  US06/129,066
• Time in Patent Office: 715 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

The somatostatin-analogous peptides according to the invention of the general formula ##STR1## in which Bmp represents the desaminocysteine radical

X represents Asn or His,

trp represents D-Trp that may be substituted in the benzene ring by a halogen atom, and

Y represents the radical of a secondary α-amino acid having a maximum of 8 carbon atoms

and the corresponding peptide amides and also acid addition salts and complexes thereof are distinguished by strong insulin-antagonistic and glucagon-antagonistic effects and are therefore therapeutically acceptable, preferably in the form of pharmaceutical preparations, in similar indications to those of somatostatin, especially also as antidiabetics. The compounds are manufactured by conventional processes of peptide synthesis, especially by liberation from corresponding protected intermediates and by the formation of the cystine disulphide bridge by means of oxidation.

Claims

1. A somatostatin-analogous peptide of the general formula ##STR18## in which Bmp represents the desaminocysteine radical,

X represents Asn or His,

trp represents D-Trp that may be substituted in the benzene ring by a halogen atom, and

Y represents the radical of an alpha-(lower alkyl)amino-(lower alkyl)carboxylic acid having a minimum of 4 and a maximum of 8 carbon atoms or said radical in which the two lower alkyl radicals are connected to one another with a single C--C bond, an oxygen atom or a sulphur (II) atom, and a corresponding peptide amide, and also acid addition salts of said compounds.

2. A pharmaceutical preparation for treating acromegalia, diabetes or inhibiting blood loss in the gastro-intestinal tract, containing an effective amount of a compound of claim 1.

3. A method for treating acromegalia, diabetes or inhibiting blood loss in the gastro-intestinal tract in a warm-blooded animal including man, which comprises administering to said animal an effective amount of a compound of claim 1, together with at least one pharmaceutically acceptable auxiliary or carrier material.

4. A method of claim 3, wherein the compound is administered for the treatment of diabetes.

5. A compound of claim 1 in which

X represents Asn,

trp represents D-trp or 5-fluoro-D-Trp and

Y represents Pro, the radical of 4-thiaproline or N-methyl-Leu.

10. Pharmaceutically acceptable acid addition salts of compounds according to claim 1.

6. [Desamino-Cys³ -D-Trp⁸ -Pro¹³ ]-somatostatin(3-14).

7. [Desamino-Cys³ -(5-fluoro-D-Trp)⁸ -Pro¹³ ]-samatostatin(3-14).

8. [Desamino-Cys³ -D-Trp⁸ -Tpo¹³ ]-samatostatin(3-14).

9. [Desamino-Cys³ -D-Trp⁸ -MeLeu¹³ ]-samatostatin(3-14).