Cyclopeptide derivatives with anti-integrin activity

Cyclic peptides having the following Formula I:

• c(R1-Arg-Gly-Asp-R2) (Formula I)
• where:
• c means cyclic;
• R1 an amino acid with general formula:
• —NX—CY(Z)—CO—;
• where
• X is selected from the group consisting of:
• H, linear or branched C1-C6 alkyl, C6-C10 aryl, benzyl, (CH2)n—COR, (CH2)n—NHR′, 4-COR-benzyl, 4-(CH2—NHR′)-benzyl;
• where n is an integer number from 1 to 5;
• Y is selected from the group consisting of:
• H, CHmFm′;
• where m+m′=3, in which m and m′ are integer numbers from 0 to 3;
• Z is selected from the group consisting of:
• H, linear or branched C1-C6 alkyl, C6-C10 aryl, (CH2)n1—COR, (CH2)n1—NHR′, 4-NHR′—(CH2)n1-benzyl, 4-COR-benzyl, where n1 is an integer number from 0 to 5;
• R is selected from the group consisting of:
• W, OW, N[CH2—CO—NH—CH2—O—(CH2CH2O)n2—CH2—COOW]2, NH—CH2—O—(CH2CH2O)n2—CH2—COOW, NW—(CH2—CH2NH)n2—CH2—CH2NHW;
• in which n2 is an integer number from 1 to 22;
• and
• W is selected from the group consisting of:
• H, C1-C3 alkyl;
• R′ is selected from the group consisting of:
• H, CO—(CH2)n2—COOW, CO—CH2—O—(CH2CH2O)n2—CH2—NHW, CO—CH2—O—(CH2CH2O)n2—CH2—COOW;
• where n2 has the meaning reported above;
• and
• R2 is selected from the group consisting of:
• D-Phe, D-Tyr, D-Trp, D-2-naphthyl-Ala, D-4-tert-butyl-Phe, D-4,41-biphenyl-Ala, D-4-CF3-Phe, D-4-acetylamine-Phe;
• their racemic mixtures, their single enantiomers, their single diastereoisomers, and their pharmaceutically acceptable salts.