RU99115767A

RU99115767A - Derivatives of cyclopeptides

Info

Publication number: RU99115767A
Application number: RU99115767/04A
Authority: RU
Inventors: Гюнтер ХрЛЬЦЕМАНН; Клаус ФИТТШЕН; Симон ГУДМАН
Original assignee: Мерк Патент Гмбх
Priority date: 1996-12-19
Filing date: 1997-12-15
Publication date: 2001-05-20

Claims

1. The compounds of formula I
cyclo (Arg-X-Asp-R ¹ )
wherein X is Gly, Ala or NH-NH-CO, wherein said amino acids can also be derivatized, and amino acid residues are linked to each other via α-amino and α-carboxy groups by peptide bond type,
R ¹ is a residue of formula II

R ² , R ³ , R ⁴ each independently of one another denotes H, A, Ar, R ⁵ -Ar, Het or R ⁵ -Het,
A denotes alkyl with 1-6 C-atoms,
Ar means unsubstituted with either one, two or three times substituted phenyl residues R ⁷ , R ⁸ or R ⁹ or unsubstituted naphthyl,
R ⁵ denotes alkylene with 1 to 6 C-atoms,
R ⁶ , R ^{6 '} each independently of one another denotes H, A, benzyl or phenyl,
R ⁷ , R ⁸ , R ⁹ each independently of one another denotes R ⁶ , OR ⁶ , Hal, NO ₂ , NR ⁶ R ^{6 '} , NHCOR ⁶ , CN, NHSO ₂ R ⁶ , COOR ⁶ or COR ⁶ ,
Hal means F, Cl, Br or I and
Het is a single or dual-core heterocycle with 1-4 N-, O- and / or S-atoms, which may be unsubstituted or substituted one, two or three times Hal, A, NR ⁶ R ^{6 '} , CN or NO ₂ ,
moreover, if we are referring to residues of optically active amino acids and amino acid derivatives, these compounds include both D- and L-phlomas,
and their salts.

2. Enantiomer or diastereomer of the compound of formula I according to claim 1.

3. The compounds of formula I according to claim 1
a) cyclo (Arg-Gly-Asp-3-AMP-L-Phg);
b) cyclo (Arg-Gly-Asp-3-AMP-D-Phg);
c) cyclo (Arg-Gly-Asp-3-AMP-L-Val);
d) cyclo (Arg-Gly-Asp-3-AMP-D-Val);
d) cyclo (Arg-Gly-Asp-3-AMP-Phe); e) cyclo (Arg-Gly-Asp-3-AMP-D-Phe);
g) cyclo (Arg-Gly-Asp-3-AMP-Gly);
and their salts.

4. The method of obtaining compounds of the formula I according to claim 1 and their salts, characterized in that
a) compound of formula III
HZ-OH
in which Z stands for - Arg-X-Asp-R ¹ -, -X-Asp-R ¹ -Arg-, -Asp-R ¹ -Arg-X- or -R ¹ -Arg-X-Asp-, and X and R ¹ is as defined in claim 1, or the reactive derivative of the compound of formula II is treated with a cyclization agent or
b) a compound of formula I is released from one of its functional derivatives by treatment with a solvolysis agent or hydrogenolysis, and / or that the basic or acidic compound of formula I is converted by treatment with an acid or base to one of its salts.

5. A method for preparing pharmaceutical compositions, characterized in that an appropriate dosage form is prepared from a compound of formula I according to claim 1 and / or from one of its physiologically acceptable salts, together with at least one solid, liquid or semi-liquid carrier or auxiliary substance.

6. Pharmaceutical composition, characterized in that it contains at least one compound of formula I according to claim 1 and / or one of its physiologically acceptable salts.

7. The compounds of formula I according to claim 1 and their physiologically acceptable salts as integrin inhibitors to combat thrombosis, myocardial infarction, coronary heart disease, arteriosclerosis, tumors, osteoporosis, inflammation and infections.

8. The use of compounds of the formula I according to claim 1 and / or their physiologically acceptable salts in pathological processes associated with or due to angiogenesis.

9. The use of compounds of the formula I according to claim 1 and / or their physiologically acceptable salts for the manufacture of a medicine.

10. The use of compounds of the formula I according to claim 1 and / or their physiologically acceptable salts for the control of diseases.