Synthetic analogues of phosphatidyl-<i>myo</i>-inositol mannosides with an inhibitory activity of the inflammatory response

摘要

The present invention relates to novel synthetic analogs of phosphatidyl-myo-inositol mannosides (hereinafter referred to as PIMs) of general formula (I): or a pharmaceutically acceptable salt thereof, to the method for preparing same and to the use thereof in the prevention or treatment of a disease associated with the overexpression of cytokines or of chemokines, in particular of TNF and/or of IL-12. The invention also relates to a pharmaceutical composition comprising at least one synthetic derivative of PIM.;

主权项

1. A compound of general formula (I): in which:
R1 and R2 represent, independently of one another, a hydrogen atom, a C1-C20 alkyl radical or a C1-C20 acyl radical, it being understood that, when one of the substituents R1 or R2 is a hydrogen atom, the other substituent is other than hydrogen;Z1 and Z2 represent, independently of one another, a hydrogen atom, or at least one sugar chosen from the group comprising mannose, glucose and galactose, it being understood that, when one of the substituents Z1 or Z2 is a hydrogen atom, the other substituent is other than hydrogen;Q represents —OP(O)2O—, —OCO2—, —NHCO2— or —NHCONH—;Y represents a hydrogen atom, a hydroxyl radical, a C1-C6 alkoxy radical, or —(CH2)n—OH, with n being an integer equal to 1, 2 or 3, it being understood that, when Y is a hydroxyl radical, Z1 and Z2 do not both represent a hydrogen atom;A represents —CH2—;X represents a hydrogen atom;or A and X together form a bond so as to result in a 6-membered ring in which:
A represents a —CH—,X represents a —CH2—, —CH(OH)—, an oxygen atom, an —NR3— in which R3 is a hydrogen atom, a C1-C6 alkyl radical or a C1-C20 acyl radical, it being understood that, whenA and X form a bond so as to result in a 6-membered ring,X=—CH(OH)—,Y=—OH, andZ1 and Z2 represent, independently of one another, at least one sugar chosen from the group comprising mannose, glucose and galactose, the 6-membered ring is in the myo-inositol configuration with Z1 or Z2 in position 1 and representing at least one sugar;or a pharmaceutically acceptable salt thereof.