Octapeptide compounds derived from somatostatin and the therapeutic use thereof
The present invention relates to novel octapeptide compounds of general formula (I): H-2-Nal 1 -cyclo(Cys 2 -Tyr 3 -AA 4 -Lys 5 -Val 6 -Cys 7 )-Thr 8 -NH 2 . Since these products have a good affinity for certain somatostatin receptor subtypes, they are particularly advantageous for treating pathological states or diseases in which one (or more) somatostatin receptor(s) is (are) involved. These compounds furthermore have physiochemical properties that make it possible to envisage them in diverse solutions for the formulation of medicaments, for example as a pharmaceutically acceptable carrier. The invention also relates to pharmaceutical compositions containing said products and to the use thereof for the preparation of a medicament.
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:
H-2-Nal l -cyclo(Cys 2 -Tyr 3 -AA 4 - Lys 5 -Val 6 -Cys 7 )-Thr 8 -NH 2 (I)(SEQ ID NO: 1)
wherein AA 4 is an amino acid radical bound to the amino acids Tyr 3 and Lys 5 according to the formula:
wherein n4 is 0 or 1 and
R4 is a hydrogen atom or an alkyl radical; and any of the amino acids can be in the D configuration.
2. The compound of claim 1 , wherein n4 is 0 and R4 is an alkyl radical.
3. The compound of claim 1 , wherein the alkyl radical is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl.
4. The compound of claim 1 , wherein AA 4 is the amino acid radical Ala.
5. The compound of claim 1 , wherein the compound is H-D-2-Nal 1 -cyclo (Cys 2 -Tyr 3 -D-Ala 4 -Lys 5 -Val 6 -Cys 7 )-Thr 8 -NH 2 ; or H-D-2-Nal 1 -cyclo (Cys 2 -Tyr 3 -D-Val 4 -Lys 5 -Val 6 -Cys 7 )-Thr 8 -NH 2 ; or a pharmaceutically acceptable salt thereof.
6. The compound of claim 5 , wherein the compound is H-D-2-Nal 1 -cyclo(Cys 2 -Tyr 3 -D-Val 4 -Lys 5 -Val 6 -Cys 7 )-Thr 8 -NH 2 or a pharmaceutically acceptable salt thereof.
7. The compound of claim 5 , wherein the compound is: H-D-2-Nal 1 -cyclo(Cys 2 -Tyr 3 -D-Ala 4 -Lys 5 -Val 6 -Cys 7 )-Thr 8 -NH 2 or a pharmaceutically acceptable salt thereof.