NOVEL OCTAPEPTIDE COMPOUNDS DERIVED FROM SOMATOSTATIN AND THERAPEUTIC USE THEREOF

摘要

Octapeptide compound (I) or its salt is new. Octapeptide compound of formula (H-2-Nal 1>-cyclo(Cys 2>-Tyr 3>-AA 4>-Lys 5>-Val 6>-Cys 7>)-Thr 8>-NH 2) (I) or its salt is new, where (I) excludes peptide compound of formulae (H-D-2-Nal 1>-cyclo(Cys 2>-Tyr 3>-beta (3-pyridyl)-D-Ala 4>-Lys 5>-Val 6>-Cys 7>)-Thr 8>-NH 2), (H-D-2-Nal 1>-cyclo(Cys 2>-Tyr 3>-D-Phe 4>-Lys 5>-Val 6>-Cys 7>)-Thr 8>-NH 2), and (H-D-2-Nal 1>-cyclo(Cys 2>-Tyr 3>-D-Try 4>-Lys 5>-Val 6>-Cys 7>) -Thr 8>-NH 2) and their salts. AA 4> : amino acid of formula (II); n4 : 0-3; R 4 : aryl radical, heteroaryl radical (both optionally substituted by one or more radical comprising halo, nitro, hydroxy, aryl or OR 41), H, or alkyl radical; R 41 : (-[(CH 2) n-O] m-R 42); R 42 : alkyl radical or H; n : 2-4; and m : 1-4, provided that all amino acids are in D or L configuration. [Image] ACTIVITY : Osteopathic; Cytostatic; Endocrine-Gen.; Antidiabetic; Ophthalmological; Nephrotropic; Antiinflammatory; Antidiarrheic; Hepatotropic; Hemostatic; Gastrointestinal-Gen.; Dermatological; Hypertensive; Antithyroid; Analgesic; Anorectic; Neuroprotective; Nootropic. MECHANISM OF ACTION : Somatostatin receptor binder. The ability of (I) to bind somatostatin receptor was tested in CHO-K1 transfected cells. The result showed that the binding affinity of H-D-2-Nal 1>-cyclo(Cys 2>-Tyr 3>-beta -(3-benzothienyl)-D-Ala 4>-Lys 5>-Val 6>-Cys 7>)-Thr 8>-NH 2 was >= 5 mu M.