Resumen
In the present invention, there is disclosed the use of thiadiazolidine derivative of the general formula II, in which: Rea and Reb are selected independently on each another from the group consisting of hydrogen, alkyl, cycloalkyl, haloalkyl, aryl being optionally substituted with a group being selected from the group consisting of alkyl, halogen and alkoxy, (Z)in-aryl, wherein the aryl moiety can be optionally substituted; Z is independently selected from the group consisting of -C(Re3)(Re4)-, -C(O)-, -O-, -C(=NRe3)-, -S(O)it- and N(Re3)-; n is zero, one or two; t is zero, one or two; Re3 and Re4 are selected independently on each another from the group consisting of hydrogen, alkyl, aryl and a heterocyclic radical; X and Y are selected independently on each another from the group consisting of =O, =S, =N(Re3) and =C(Re1)(Re2); and Re1 and Re2 are selected independently on each another from the group consisting of hydrogen, alkyl, cycloalkyl, haloalkyl, aryl, -(Z)in-aryl, an aromatic heterocyclic radical, -ORe3, -C(O)Re3, -C(O)ORe3, -(Z)in- C(O)ORe3 and -S(O)it-; for the preparation of a pharmaceutical composition intended for the treatment of a disease in which the heterocyclic inhibitors of glycogen synthase kinase GSK-3 are involved, including Alzheimer's disease or non-insulin dependent diabetes mellitus or a hyperproliferative disease such as cancer, tissue dysplasia or metaplasia, psoriasis, arteriosclerosis or restenosis.
Reivindicaciones
1. The use of a compound having the general formula (II): <img class="EMIRef" id="459537437-ib0021" /> wherein: R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, haloalkyl, aryl, -(Z)<n> -aryl, heteroaryl, -OR<3> , -C(O)R<3> , -C(O)OR<3> , and -(Z)<n> -C(O)OR<3> ; Z is independently selected from -C(R<3> )(R<4> )-, -C(O)-, -O-, -C(=NR<3> )-, -S(O)<t> - and -N(R<3> )-; n is zero, one or two; t is zero, one or two; R<3> and R<4> are independently selected from hydrogen, alkyl, aryl and heterocyclic; X and Y are independently selected from =O, =S, =N(R<3> ) and =C(R<1> )(R<2> ); and R<1> and R<2> are independently selected from hydrogen, alkyl, cycloalkyl, haloalkyl, aryl,-(Z)<n> -aryl, heteroaryl, -OR<3> , -C(O)R<3> , -C(O)OR<3> , and -(Z)<n> -C(O)OR<3> ; in the preparation of a pharmaceutical composition for a method of the treatment of a disease in which GSK-3 is involved, the method comprising administering to a human in need of such a treatment an effective amount of a compound of formula (II). 2. A use according to claim 1, where the disease is selected from Alzheimer's disease and non-insulin dependent diabetes mellitus. 3. A use according to claim 1, where the disease is a hyperproliferative disease such as cancer, displasias or metaplasias of tissue, psoriasis, arteriosclerosis or restenosis. 4. A use according to any preceding claim, wherein in the compound of formula (II), R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -C(R<3> )(R<4> )-aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), -OR<3> , -C(O)OR<3> and -C(R<3> )(R<4> )-C(O)OR<3> , and R<3> and R<4> are independently selected from hydrogen, alkyl and heterocyclic. 5. A use according to claim 4, wherein in the compound of formula (II), R<a> and R<b> are independently selected from alkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -CH<2> -aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), and -CH<2> C(O)OR<3> , and R<3> is hydrogen or alkyl. 6. A use according to claim 5, wherein in the compound of formula (II), R<a> and R<b> are independently selected from methyl, ethyl, propyl, benzyl, phenyl (optionally substituted with a group selected from methyl, fluoro, chloro, bromo and methoxy) and -CH<2> C(O)O-ethyl. 7. A use according to claim 1, 2 or 3, wherein in the compound of formula (II), X and Y are independently selected from =O, =S and =NR<3> (wherein R<3> is heterocyclic). 8. A use according to claim 7, wherein in the compound of formula (II), X is =O. 9. A use according to claim 8, wherein in the compound of formula (II), X is =O and Y is =O. 10. A use according to any one of claims 1, 2 or 3, wherein: R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -C(R<3> )(R<4> )-aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), -OR<3> , -C(O)OR<3> and -C(R<3> )(R<4> )-C(O)OR<3> , R<3> and R<4> are independently selected from hydrogen, alkyl and heterocyclic, and X and Y are independently selected from =O, =S and =NR<3> . 11. A use according to claim 10, wherein: R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -C(R<3> )(R<4> )-aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), -OR<3> ,-C(O)OR<3> and -C(R<3> )(R<4> )-C(O)OR<3> , R<3> and R<4> are independently selected from hydrogen and alkyl; and X is = O. 12. A use according to claim 11, wherein: R<a> and R<b> are independently selected from methyl, ethyl, propyl, benzyl, phenyl (optionally substituted with a group selected from methyl, fluoro, chloro, bromo and methoxy) and-CH<2> -C(O)O-ethyl; X is =O; and Y is =O. 13. A use according to any of claims 1 to 3, wherein the compound of Formula (II) fits one of the following possibilities: CH<2>Ph Me O O Et Me O O Et nPr O O Et cyclohexyl O O Ph Me O O CH<2>CO<2>Et Me O O 4-OMePh Me O O CH<2>Ph Et O O Et iPr O O CH<2>Ph Et O S CH<2>Ph CH<2>Ph O S Ph Ph O S Et Et O S Cyclohexyl Me O O 4-MePh Me O O 4-BrPh Me O O 4-FPh Me O O 4-ClPh Me O O Et Me <img class="EMIRef" id="459537437-ib0022" /> O Et Et <img class="EMIRef" id="459537437-ib0023" /> O Et H <img class="EMIRef" id="459537437-ib0024" /> O Me Me <img class="EMIRef" id="459537437-ib0025" /> O Et Me <img class="EMIRef" id="459537437-ib0026" /> O Et Me <img class="EMIRef" id="459537437-ib0027" /> O Et Me <img class="EMIRef" id="459537437-ib0028" /> O Et Me <img class="EMIRef" id="459537437-ib0029" /> S 14. A use according to claim 13, wherein the compound of Formula (II) fits one of the following possibilities: CH<2>Ph Me O O Et Me O O Ph Me O O CH<2>CO<2>Et Me O O 4-OMePh Me O O 4-MePh Me O O 4-BrPh Me O O 4-FPh Me O O 4-CIPh Me O O CH<2>Ph CH<2>Ph O S Ph Ph O S 15. A pharmaceutical formulation containing as active ingredient a compound of formula (II) as defined in any of claims 1 to 14. 16. A compound having the general formula (II): <img class="EMIRef" id="459537437-ib0030" /> where the compound is one of the following: CH<2>Ph Me O O CH<2>CO<2>Et Me O O 4-OMePh Me O O 4-MePh Me O O 4BrPh Me O O
