Scientific Patent
The present application relates to pyrazole derivatives as PD-1/PD-L1 interaction inhibitors. The applicants designed compounds of general formula (I), wherein R', R2, y3, R3, R4, R5, R6 and R7 are as defined herein, that are able to efficiently block PD-1/PD-L1 interactions in order to restore anti-tumor immune responses of subjects and eradicate dormant tumor cells and any tumors in which PD-L1 is involved in immunoevasion. The applicants confirmed that these compounds blocked the PD-1/PD-L1 interactions by carrying out physicochemical tests (MST, NanoDSF) and in vitro biological tests (FRET assay, Promega Blockade assay, T cell assay). These compounds had an affinity (Kd) of the order of pM that was higher than that of the antibody atezolizumab used in clinical use, and had a comparable or better IC50 than that observed with atezolizumab. Thus, the present invention also relates to a pharmaceutical composition comprising said compound(s) and their uses in the treatment of PD-1-PD-L1 interactions-related diseases (cancer, chronic inflammatory diseases, neurological diseases and chronic infections).
Inventors: THURU Xavier; BAILLY Christian; QUESNEL Bruno; KLUPSCH Frédérique; LE BIANNIC Raphaël; MILLET Régis
The present invention relates to novel pyrazolone derivatives of the following formula (I): (I) or a pharmaceutically acceptable salt and/or solvate thereof and to a pharmaceutical composition comprising thereof. The present invention also concerns the use of compound of formula (I) or the pharmaceutical composition comprising said compound as a drug, notably in the prevention and/or treatment of PD-L1-PD-1 interactions-related diseases, such as cancer, neurological diseases and chronic infections. The present invention also relates to a method for the preparation of a compound of formula (I).
Inventors: THURU Xavier; QUESNEL Bruno; MAGNEZ Romain; MILLET Régis; LELEU Natascha; KLUPSCH Frédérique
