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1. (WO2018226589) ACTIVATEURS DE PROTÉASOME À PETITES MOLÉCULES ET UTILISATIONS ASSOCIÉES
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

IM !!S

What is claimed is:

A compou nd of the formu


or a pharmaceutically acceptable salt, polymorph , prodrug, solvate or ciathrate thereof;

wherein :

X is halo ;

X! is O, S or NR3, wherei n R3 is alkyl or arylalkyl ;

R1 is H, substituted or unsubsti tuted alkyi , substituted or unsubstituted alkoxy, substituted or unsubstituted aryi , substituted or unsubstituted aryioxy or halo;

R2 is H, substituted or unsubstituted alkyi , substituted or unsubstituted alkoxy, substituted or unsubstituted ary! , substituted or unsubstituted aryioxy or halo;

A is aikyienyi , aryienyi, alkenvienyl or aikynyienyl , each of which can be substituted or unsubstituted ; and

X2 is H , sulfonic acid, sulfonate, carboxylic acid, ester, amide or a heterocycle.

2. The compound of claim 1 , wherein X is halo .

3. The compound of claim 2, wherein X is chioro .

4. The compound of claim 1 , wherein X1 Is S.

5. The compound of claim 1 , wherein R1 and R2 are each H.

6. The compound of claim 1 , wherein A is unsubstituted aikynyienyl .

7. The compound of claim 1 , wherein A is usubstituted aryienyi or

heterocyciyl and X2 is H.

8. The compound of claim 1 , wherein X2 Is sulfonic acid or a heterocycle.

9. The compound of claim 8, wherein the heterocyc!yl is 5- or 6-membered heterocycle.

10. The compound of claim 9, wherein the 6-membered heterocycle is a piperidinyl , plperazinyl or a morphoilnyi group.

1 1 . The compound of claim 1 , wherein X2 Is carboxyiic acid or an esier.

12. The compound of claim 1 , wherein :

X1 is O, S or NR3, wherein R3 Is aikyi or aryiaikyi ;

R1 is H, substituted or unsubstituted alkyl, substituted or unsubstituted a!koxy, substituted or unsubstituted aryi, substituted or unsubstituted aryioxy or halo;

R2 is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted ary!, substituted or unsubstituted aryioxy or halo;

A is aryieny! or aikynylenyi, each of which can be substituted or unsubstituted; and

X2 is carboxyiic acid or an ester.

13. A compound of claim 1 having the formula:


wherein G Is ~iCH2)3CH(CH3)2, -(CH2)4S03H, -(CI-fefeSOaH,


14. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

15. A method for method for reducing the accumulation of intrinsically disordered proteins (IDPs), in a subject, the method comprising

administering a therapeutically effective amount of one or more compounds of the formula (I) to a patient in need thereof.

18, The method of claim 15, wherein the !DP Is at least one of a-synucleln, tau, SOD1 , poiyQ, oxidatively damaged proteins, c-Fos, c- yc, and the BCL-2 family of disordered proteins.

17. A method for treating a neurodegenerative disease comprising

administering an effective amount of a compound of the formula (!) according to claim 1 to a subject in need thereof

18. The method of claim 17, wherein the neurogenerative disease is

Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) or amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease).

19. A method for treating cancer comprising administering an effective amount of a compound of the formula (I) according to claim 1 to a subject in need thereof.

20. The method of claim 19, wherein the cancer is myeloid leukemia, glioblastoma, melanoma, breast cancer, colon cancer, cervical cancer, small-cell lung carcinoma or osteosarcoma.