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1. WO2020118163 - INHIBITEURS DE DÉCARBOXYLASE POUR LE TRAITEMENT DE LA MALADIE DE PARKINSON

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

WO 2020/118163 AMENDED CLAIMS PCT/US2019/064896 received by the International Bureau on 21 APRIL 2020 (21 .04.2020)

WHAT IS CLAIMED IS:

1. A compound chosen from the following compounds



pharmaceutically acceptable salts thereof.

2. A compound chosen from the following compounds


3. A compound of formula (I):


or a pharmaceutically acceptable salt thereof,

wherein

n is 0 or 1 ;

R1 is H or -ORA, wherein RA is H, -C(0)Ci-6 alkyl, or an acylated sugar;

R2 is H, halogen, amino, Ci-6 alkyl, or -ORA, wherein RA is H or an acylated sugar;

R3 is H, a halogen, -OH, or Ci-6 alkyl optionally substituted with one or more halogens;

R4 is H, -NH2, -C(0)0CH3, or an acylated sugar;

R5 is H, -C(0)0H, -C(0)0Ci-6 alkyl, -C(0)Oglycoside, -C(0)NH0H, or -C(0)0(acylated sugar); and

R6 is H, halogen, or optionally substituted C1 -6 alkyl;

provided that at least one RA is present; or provided that R3 and/or R6 comprise a halogen, and

provided that the compound is not a compound of formula (I) wherein n is 0; R1 is H; R2 is -ORA, RA is H; R3 is H; R4 is H; R5 is -C(0)0H; R6 is H.

4. The compound of formula (I) according to claim 3, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (l-a):


(l-a).

5. The compound of formula (I) according to any one of claims 3 and 4, or a pharmaceutically acceptable salt thereof, wherein

n is 0 or 1 ;

R1 is H, -C(0)Ci-6 alkyl, or -ORA, wherein RA is H or an acylated sugar;

R2 is H, or -ORA, wherein RA is H or an acylated sugar;

R3 is H, or a halogen;

R4 is H, -NH2, or an acylated sugar;

R5 is -C(0)0H, -C(0)0Ci-6 alkyl, -C(0)Oglycoside, or -C(0)0(acylated sugar); and

R6 is H or optionally substituted C1-6 alkyl;

provided that at least one RA is present; or provided that R3 and/or R6 comprise a halogen.

6. The compound of formula (I) according to any one of claims 3 to 5, or a

pharmaceutically acceptable salt thereof, wherein R1 is -ORA.

7. The compound of formula (I) according to any one of claims 3 to 6, or a

pharmaceutically acceptable salt thereof, wherein R2 is H or -ORA.

8. The compound of formula (I) according to any one of claims 3 to 7, wherein each RA is H.

9. The compound of formula (I) according to any one of claims 3 and 4, or a pharmaceutically acceptable salt thereof, wherein R2 is a halogen.

10. The compound of formula (I) according to any one of claims 3 to 9, or a pharmaceutically acceptable salt thereof, wherein R3 is fluoro or chloro.

11. The compound of formula (I) according to any one of claims 3 to 9, or a pharmaceutically acceptable salt thereof, wherein R3 is H.

12. The compound of formula (I) according to any one of claims 3 to 11 , or a pharmaceutically acceptable salt thereof, wherein R4 is H.

13. The compound of formula (I) according to any one of claims 3 to 11 , or a pharmaceutically acceptable salt thereof, wherein R4 is -NH2.

14. The compound of formula (I) according to any one of claims 3 to 13, or a pharmaceutically acceptable salt thereof, wherein R5 is -C(0)0H.

15. The compound of formula (I) according to any one of claims 3 to 13, or a pharmaceutically acceptable salt thereof, wherein R5 is -C(0)Oacylated sugar.

16. The compound of formula (I) according to any one of claims 3, 4, and 6 to 13, or a pharmaceutically acceptable salt thereof, wherein R5 is H.

17. The compound of formula (I) according to any one of claims 3 to 16, or a pharmaceutically acceptable salt thereof, wherein R6 is H.

18. The compound of formula (I) according to any one of claims 3 to 16, or a pharmaceutically acceptable salt thereof, wherein R6 is a Ci-6 alkyl.

19. The compound of formula (I) according to any one of claims 3 to 16, or a pharmaceutically acceptable salt thereof, wherein R6 is a Ci-6 alkyl substituted with one, two, or three halogens.

20. The compound of formula (I) according to any one of claims 3 to 16, or a pharmaceutically acceptable salt thereof, wherein R6 is a Ci-6 alkyl substituted with one, two, or three fluorine atoms.

21. The compound of formula (I) according to any one of claims 3 to 20, or a pharmaceutically acceptable salt thereof, wherein n is 0.

22. The compound of formula (I) according to any one of claims 3 to 20, or a pharmaceutically acceptable salt thereof, wherein n is 1.

23. The compound of formula (I) according to any one of claims 3 and 4, or a pharmaceutically acceptable salt thereof, wherein

n is 0;

R1 is -OH;

R2 is halogen;

R3 is H, a halogen, or -OH, C1-6 alkyl optionally substituted with one or more halogens;

R4 is H, -NH2, or an acylated sugar;

R5 is H, -C(0)0H, -C(0)0Ci-6 alkyl, -C(0)Oglycoside, -C(0)NH0H, or -C(0)0(acylated sugar); and

R6 is H or optionally substituted C1-6 alkyl.

24. The compound of formula (I) according to anyone of claims 3, 4, and 23, or a pharmaceutically acceptable salt thereof, wherein

n is 0;

R1 is -OH;

R2 is halogen;

R3 is H;

R4 is H;

R5 is -C(0)0H; and

R6 is optionally substituted alkyl.

25. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and at least one entity chosen from the compounds according to any one of claims 1 to 24 and pharmaceutically acceptable salts thereof.

26. A method of treating Parkinson’s disease comprising administering to a subject in need thereof a therapeutically effective amount of at least one entity chosen from the compounds according to any one of claims 1 to 24 and pharmaceutically acceptable salts thereof or a pharmaceutical composition according to claim 25.

27. A method of inhibiting a decarboxylase-mediated conversion of L-DOPA to L-dopamine comprising contacting the decarboxylase with at least one entity chosen from the compounds according to any one of claims 1 to 24 and pharmaceutically acceptable salts thereof or a pharmaceutical composition according to claim 25.

28. The method of claim 27, wherein the decarboxylase is tyrosine decarboxylase.