Precursor compounds for providing retinoids of the vatamin a5 pathway and uses thereof
AssigneesUniversity of Debrecen, Universidade De Vigo, Universite De Strasbourg
InventorsWojciech KREZEL, Ralph RÜHL, Angel R. DE LERA
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Abstract
The invention relates to the field of retinoid X receptor (RXR) signaling and a novel vitamin A pathway called Vitamin A5 pathway. Compounds which are useful to provide (R)-9-cis-13,14-dihydroretinoic acid, an endogenous RXR ligand, are claimed as well as their uses and method for preparation thereof. The compounds of the invention are useful for pharmaceutical and nutritional uses.
Claims20
A composition for providing 9-cis-13,14-dihydroretinoic acid (9CDHRA) as an RXR ligand in a subject suffering from or endangered by impairment of RXR-mediated signaling or from mild to severe Vitamin A5 deficiency, said composition comprising
- an (R)-9-cis-13,14-dihydroretinoid compound of general formula (I), said compound being converted into (R)-9-cis-13,14-dihydroretinoic acid in mammalian tissue or organ or cells, and
- at least one pharmaceutically or nutraceutically acceptable excipient
- wherein in general formula (I)
- R is selected from a group consisting of A, —CH2OR2 and —COOR1 wherein
- R is A
- wherein Q1 is a substituted or unsubstituted C6-10 alkenyl or cycloalkenyl group, preferably a substituted or unsubstituted trimethylcycloalkenyl or more preferably a substituted or unsubstituted 2,6,6-trimethylcyclohexenyl, even more preferably unsubstituted 2,6,6-trimethylcyclohex-1-en-1-yl or 2,6,6-trimethylcyclohex-2-en-1-yl, or
- R is —CH2OR2
- wherein R2 is H or an acyl group —C(O)R3 wherein —C(O)R3 is a group which is removed by hydrolysis in mammalian tissue or organ or cells to result in (R)-9-cis-13,14-dihydroretinol (and a biologically acceptable tolerable compound), or
- R is —COOR1
- wherein R1 is a group which is removed by hydrolysis in a mammalian tissue or organ to result in (R)-9-cis-13,14-dihydroretinoic acid and a biologically acceptable tolerable compound.
A method
- for the treatment or reducing the risk of a retinoid X receptor (RXR)-mediated signaling related and/or dependent disease by providing 9-cis-13,14-dihydroretinoic acid (9CDHRA) as an RXR ligand in a subject or
- for providing 9-cis-13,14-dihydroretinoic acid (9CDHRA) as an RXR ligand for activation of RXR signaling in a subject suffering from or endangered by impairment of RXR-mediated signaling, or
- for the treatment or reducing the risk of (mild to severe) vitamin A5 deficiency,
- said method comprising the administration of a compound of general formula (I) to a mammalian subject suffering from or being endangered by a retinoid X receptor-mediated signaling related and/or dependent disease,
- wherein R is selected from a group of general formula (A), —CH2OR2 and —COOR1 wherein
- R is a group of general formula (A)
- wherein Q1 is a substituted or unsubstituted C6-10 alkenyl or cycloalkenyl group, preferably a substituted or unsubstituted trimethylcycloalkenyl or more preferably a substituted or unsubstituted 2,6,6-trimethylcyclohexenyl, even more preferably unsubstituted 2,6,6-trimethylcyclohex-1-en-1-yl or 2,6,6-trimethylcyclohex-2-en-1-yl, wherein if the trimethylcyclohexenyl, e.g. 2,6,6-trimethylcyclohexenyl group is substituted it is preferably hydroxyl-substituted or oxo-substituted, preferably oxo-substituted, and/or
- R is —CH2OR2, wherein R2 is H or an acyl group —C(O)R3 wherein —C(O)R3 is a group which is removed by hydrolysis in a mammalian tissue or organ to result in (R)-9-cis-13,14-dihydroretinol and a biologically acceptable tolerable compound and/or
- R is —COOR1, wherein R1 is a group which is removed by hydrolysis in a mammalian tissue or organ to result in (R)-9-cis-13,14-dihydroretinoic acid and a biologically acceptable tolerable compound,
- or a compound which is a 9-cis-β,β-carotene (9CBC) or a 9-cis-β,α-carotene,
- said compound being converted into (R)-9-cis-13,14-dihydroretinoic acid in a tissue or organ or cells of said mammalian subject.
Dependencies are inferred from the claim text.