Highly efficient NRF2 activators-co-releasing molecule hybrids, their use in the treatment of inflammatory or cardiovascular diseases and their process of preparation
AssigneesCentre National De La Recherche Scientifique, Universite Paris Est Creteil Val De Marne, Institute National de la Sante et de la Recherche Medicale
InventorsRoberto Motterlini, Roberta Foresti, Anthony Ollivier, Michael Rivard, Thierry Martens
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Abstract
The present invention relates to highly efficient Nrf2 activators-CO-releasing molecules of formula (I) and (II) capable of increasing HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory or cardiovascular diseases, wherein CORM represents a carbonyl metal complex chosen from among: Mn(CO)5, formula (III), (IV), (V), (VI), (VII), (VIII) and (IX).
Claims13
A compound of the following formula (I):
- wherein:
- A represents:
- a single bond, or
- -Q-Z—, where:
- Q represents O, S or NR6, wherein R6 represents H, (C1-C6)alkyl, aryl, heteroaryl, (C1-C6)alkyl-aryl, (C1-C6)alkyl-heteroaryl, (C1-C6)alkyl-(C3-C8)heterocyclyl, —(C3-C14)cycloalkyl, or R6 and Z are connected to form a (C3-C8)heterocyclyl,
- Z represents —(C1-C6)alkyl-, —(C2-C6)alkenyl-, -aryl-, -heteroaryl-, —(C2-C6)alkynyl-, —(C3-C8)heterocyclyl-, —(C3-C14)cycloalkyl, —(C1-C6)alkyl-R7—(C1-C6)alkyl-, —(C2-C6)alkenyl-R7—(C1-C6)alkyl-, —(C1-C6)alkyl-R7—(C2-C6)alkenyl-, —(C2-C6)alkenyl-R7—(C2-C6)alkenyl-, —(C1-C6)alkyl-R7—(C2-C6)alkynyl-, —(C2-C6)alkenyl-R7—(C2-C6)alkynyl-, —(C2-C6)alkynyl-R7—(C2-C6)alkynyl-, —(C2-C6)alkynyl-R7—(C1-C6)alkyl-, —(C2-C6)alkynyl-R7—(C2-C6)alkenyl-, —(C1-C6)alkyl-OCO—, or —CH2—(CHOR7)CH2O—(C1-C6)alkyl, wherein R7 represents aryl, heteroaryl, (C3-C8)heterocyclyl, or (C3-C14)cycloalkyl, CORM represents a carbonyl metal complex selected from the group consisting of:
- wherein W represents O or NR8, wherein R8 represents (C1-C6)alkyl,
- L represents an ionic ligand, or a counter-ion,
- M represents Rh, Co, Ru, Mn, Mo, V or Fe, and
- n is an integer chosen so that the metal M has no free valency, and
- R1, R2, R3, R4 and R5 represent independently:
- H, —OH, —O(C1-C6)alkyl, SO3H, S(C1-C6)alkyl, or NRxRy wherein Rx and Ry represent independently H or (C1-C6)alkyl;
- or
- two consecutive radicals selected from R1, R2, R3, R4 and R5, taken together, form a bridging group selected from the group consisting of —(CH2)m—, or —O—(CH2)o—O—, m being 4 and o being 1 or 2.
Dependencies are inferred from the claim text.