PHARMACEUTICAL COMPOSITIONS COMPRISING NEUROPILIN INHIBITORS, AND THEIR USE FOR THE PREVENTION AND/OR TREATMENT OF ANGIOGENIC DISORDERS AND CANCERS

摘要

The present invention relates to a compound of general formula (I), wherein Z1 is S or O, preferably S; -Z2- is -NRa-, wherein Ra is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, preferably Ra is H; -N=; O; S; -CRb=, wherein Rb is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F, preferably H; -CHRC- wherein Rc is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F, or -CH2-; preferably -Z2- is -NH- or -N=; each of R1 and R2 independently is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F; preferably R1 and R2 together and with N and Z2 form an heterocycle eventually substituted, provided that said heterocycle is not an indole; R5 is H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, preferably R5 is NH2, NO2, C1, F, Br, I; more preferably R5 is H or CH3; even more preferably R5 is CH3; each of R8 and R9 independently is, H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F; preferably R8 and R9 together form a cycle comprising 5 or 6 atoms, preferably an heterocycle comprising 5 or 6 atoms, more preferably a 1,3- dioxacyclopentene or a 1,4-dioxane; and - each of R3, R4, R6, R7, R10 and R11 independently is, H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, NO2, F, C1, Br, I; preferably H, CH3, OCH3, OH, NH2, NO2, C1, F, Br, I; more preferably is H or CH3; even more preferably is H; and to a pharmaceutical composition comprising a compound of general formula (I) or esters or salts thereof, in association with at least one pharmaceutically acceptable vehicle; and to the use thereof for inhibiting the Neuropilin pathways in the treatment of cancer and of angiogenic diseases.