Treatment of Fabry disease

Patent metadata

Field	Value
Publication number	US-10995067-B2
Application number	US-201716313057-A
Country	US
Kind code	B2
Filing date	Jun 14, 2017
Priority date	Jun 24, 2016
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

Disclosed herein are novel uses of a polyhydroxylated pyrrolidine for the manufacture of a medicament for treating Fabry disease (FD). Accordingly, the present disclosure provides a method of treating a subject having or suspected of having FD. The method includes the step of, administering to the subject a therapeutically effective amount of a compound of formula (I), a salt, an ester or a solvate thereof, wherein: R 1 is H, or C 1-3 amine optionally substituted with —COR 2 ; R 2 is alkyl or alkene optionally substituted with cycloalkyl or phenyl having at least one substituent selected from the group consisting of, halo, alkyl, haloalkyl, and alkoxyl; so as to ameliorate, alleviate mitigate and/or prevent symptoms associated with the FD. According to preferred embodiments of the present disclosure, the compound of formula (I) is a chaperon of a mutated human lysosomal α-galactosidase A (α-Gal A).

First claim

What is claimed is:

1. A method of treating a subject having or suspected of having Fabry disease comprising administering to the subject a therapeutically effective amount of a compound of formula (I), a salt, an ester or a solvate thereof,

wherein:
R 1 is C 1-3 amine optionally substituted with —COR 2 ;
R 2 is alkyl or alkene optionally substituted with cycloalkyl or phenyl having at least one substituent selected from the group consisting of, halo, alkyl, haloalkyl, and alkoxyl;
so as to ameliorate, alleviate, mitigate or prevent symptoms associated with the Fabry disease.

2. The method of claim 1 , wherein the compound of formula (I) is capable of suppressing α-GAL A activity.

3. The method of claim 2 , wherein the compound of formula (I) is a chaperon of a human lysosomal α-galactosidase A (α-Gal A) mutant.

4. The method of claim 3 , wherein the human α-Gal A mutant comprises a mutation selected from the group consisting of, R112H, P205T, Q279E, R301Q, R356W, and R363C.

5. The method of claim 4 , wherein the compound of formula (I) is selected from the group consisting of,

6. The method of claim 5 , further comprising administering to the subject a therapeutically effective amount of human α-Gal A, prior to, concurrently with, or after the administration of the compound of formula (I).

7. The method of claim 6 , wherein the compound of formula (I) is

8. The method of claim 6 , wherein the compound of formula (I) is

9. The method of claim 6 , wherein the compound of formula (I) is

10. The method of claim 5 , wherein the compound of formula (I) is administered to the subject in the amount of 0.001-500 g/day.

11. The method of claim 10 , wherein the compound of formula (I) is administered to the subject in the amount of 0.05-450 g/day.

Assignees

• Academia Sinica

Inventors

• Cheng Wei-Chieh

Classifications

• C07D207/12

  Oxygen or sulfur atoms · CPC title

• A61K31/40 Primary

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C12Y302/01022

  Alpha-galactosidase (3.2.1.22) · CPC title

• A61K38/47

  acting on glycosyl compounds (3.2), e.g. cellulases, lactases · CPC title