US 12,029,715 B2
Precursor compounds for providing retinoids of the vitamin A5 pathway and uses thereof
Wojciech Krezel, Strasbourg (FR); Ralph Rühl, Debrecen (HU); and Angel R. De Lera, Vigo Pontevedra (ES)
Assigned to University of Debrecen, Debrecen (HU); Universidade de Vigo, Vigo Pontevedra (ES); and Université de Strasbourg, Strasbourg Cedex (FR)
Filed by UNIVERSITY OF DEBRECEN, Debrecen (HU); UNIVERSIDADE DE VIGO, Vigo Pontevedra (ES); and UNIVERSITÉ DE STRASBOURG, Strasbourg (FR)
Filed on Aug. 13, 2018, as Appl. No. 16/102,137.
Application 16/102,137 is a continuation in part of application No. 15/572,549, abandoned, previously published as PCT/IB2016/052639, filed on May 9, 2016.
Application 16/102,137 is a continuation in part of application No. PCT/HU2017/050047, filed on Nov. 17, 2017.
Claims priority of provisional application 62/158,634, filed on May 8, 2015.
Claims priority of application No. P1600629 (HU), filed on Nov. 17, 2016; and application No. P1700196 (HU), filed on May 5, 2017.
Prior Publication US 2019/0054056 A1, Feb. 21, 2019
Int. Cl. A61K 31/215 (2006.01); A61P 25/24 (2006.01)
CPC A61K 31/215 (2013.01) [A61P 25/24 (2018.01)] 17 Claims
 
1. A method for the treatment or reducing the risk of a retinoid X receptor (RXR)-mediated signaling dysfunction by providing (R)-9-cis-13,14-dihydroretinoic acid (9CDHRA) as an RXR ligand in a subject, said method selected from the group consisting of
ameliorating or reducing the development of, ameliorating at least one physical parameter of, or inhibiting cancer or depression,
ameliorating or reducing the risk of vitamin A5 deficiency, and
ameliorating or reducing memory impairment,
said method comprising administration of a compound of general formula (I) to a mammalian subject suffering from or being endangered by a retinoid X receptor-mediated signaling dysfunction in the nervous system,

OG Complex Work Unit Chemistry
wherein
R is a group of general formula (A)

OG Complex Work Unit Chemistry
wherein Q1 is an unsubstituted trimethylcyclohexenyl group so that the compound of general formula (I) is 9-cis-13,14-dihydro-β,β-carotene or a 9-cis-13,14-dihydro-β,α-carotene, 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, wherein R3 is a C1-25 alkyl or a C2-25 alkenyl, or
R is —COOH,
said compound of general formula (I) being converted into (R)-9-cis-13,14-dihydroretinoic acid in a tissue or organ or cells of the mammalian subject.