Therapeutic somatostatin analogs

• US 4,853,371 A
• Filed: 06/22/1988
• Issued: 08/01/1989
• Est. Priority Date: 06/17/1986
• Status: Expired due to Term

• Current Assignee: Administrators Of The Tulane Educational Fund (ADMINISTRATORS|DAVID H. COY)
• Original Assignee: Administrators Of The Tulane Educational Fund (ADMINISTRATORS|DAVID H. COY)
• Inventors: Coy, David H., Murphy, William A., Heiman, Mark L.
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US07/209,883
• Time in Patent Office: 405 Days
• Field of Search: 514/12, 514/806, 530/311
• US Class Current: 514/5.9
• 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: C07K 14/6555 at least 1 amino acid in D-form
• CPC Class Codes: Y10S 930/16 Somatostatin; related peptides

Abstract

An octapeptide of the formula: ##STR1## wherein each A₁ and A₂, independently, is H, C_1-12 alkyl, C_7-10 phenylalkyl, R₁ CO (where R₁ is C_1-20 alkyl, C_3-20 alkenyl, C_3-20 alkinyl, phenyl, naphthyl, or C_7-10 phenylalkyl, R₂ OCO (where R₂ is C_1-10 alkyl or C_7-10 phenylalkyl), provided that when one of A₁ or A₂ is R₁ CO or R₂ OCO, the other must be H; A₃ is CH₂ -A₆ (where A₆ is pentafluorophenyl, naphthyl, pyridyl, or phenyl); A₄ is o- m- or p-substituted X-Phe (where X is a halogen, H, NO₂, OH, NH₂, or C_1-3 alkyl), pentafluoro-Phe, or α-Nal; A₅ is Thr, Ser, Phe, Val, α-aminobutyric acid, or Ile, provided that when A₃ is phenyl, A₁ is H, and A₂ is H, A₅ cannot be Val; and A₇ is Thr, Trp, or β-Nal; or a pharmaceutically acceptable salt thereof.

Claims

1. An octapeptide of the formula D-β

-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH₂, or a pharmaceutically acceptable salt thereof.

2. The octapeptide of claim 1 of the formula D-Phe-Cys-β

-Nal-D-Trp-Lys-Val-Cys-Thr-NH₂.

3. A therapeutic composition capable of inhibiting the release of growth hormone, insulin, glucagon, or pancreatic exocrine secretion comprising a therapeutically effective amount of the compound of claim 1 together with a pharmaceutically acceptable carrier substance.

4. A method of treating a mammal in need of reduction of growth hormone, insulin, glycagon, or pancreatic exocrine secretion comprising administering to said mammal a therapeutically effective amount of the compound of claim 1.

5. The therapeutic composition of claim 3 wherein said composition is in the form of a pill, tablet, or capsule for oral administration to a human patient in need of said compound.

6. The therapeutic composition of claim 3 wherein said composition is in the form of a liquid for oral administration to a human patient in need of said compound.

7. The therapeutic composition of claim 5, said composition being coated with a substance capable of protecting said composition from the gastric acid in the stomach of said human patient for a period of time sufficient to allow said composition to pass undisintegrated into the small intestine of said human patient.

8. The therapeutic composition of claim 3, said composition being in the form of a cream, gel, spray, or ointment for application to the skin of a human patient in need of said compound.

9. The therapeutic composition of claim 3, said composition being in the form of a liquid capable of being administered nasally as drops or spray to a human patient in need of said compound.

10. The therapeutic composition of claim 3, said composition being in the form of a liquid for intravenous, subcutaneous, parenteral, or intraperitioneal administration to a human patient in need of said compound.

11. The therapeutic composition of claim 3, said composition being in the form of a biodegradable sustained release composititon for intramuscular administration to a human patient in need of said compound.