ADO-resistant cysteamine analogs and uses thereof
The present disclosure is directed to methods for treating diseases for which cysteamine is indicated and compounds useful in such methods.
1. A method of treating a patient suffering from Huntington's Disease, Parkinson's Disease, concussion, stroke, and traumatic brain injury (CTE) comprising administering to the patient an effective amount of a composition comprising a compound of formula I or a disulfide thereof, wherein the compound of formula I is selected from the group consisting of:
wherein:
R 1 and R 2 are independently selected from the group consisting of H and C 1-5 alkyl; or
R 1 and R 2 , taken together with the carbon atom to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered carbocyclic ring;
R 3 and R 4 are independently selected from the group consisting of H and C 1-5 alkyl; or
R 3 and R 4 , taken together with the carbon atom to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered carbocyclic ring;
G is selected from the group consisting of —NR 5 R 6 and —CR 7 R 8 NR 5 R 6 ;
R 5 and R 6 are independently selected from the group consisting of H and C 1-5 alkyl; or
R 5 and R 6 , taken together with the nitrogen atom to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered heterocyclic ring;
R 7 and R 8 are independently selected from the group consisting of H and C 1-5 alkyl; or
R 7 and R 8 , taken together with the carbon atom to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered carbocyclic ring;
R 2 and R 6 , taken together with the atoms to which they are attached, form a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocyclic ring;
R 4 and R 6 , taken together with the atoms to which they are attached, form a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocyclic ring;
R 2 and R 8 , taken together with the atoms to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered carbocyclic ring; or
R 2 and R 4 , taken together with the atoms to which they are attached, form a 3-, 4-, 5-, 6-, 7-, or 8-membered carbocyclic ring;
with the proviso that when G is —NH 2 , at least one of R 1 , R 2 , R 3 , and R 4 is other than H.
2. The method of claim 1 , wherein the compound of formula I or disulfide thereof is resistant to metabolism by cysteamine dioxygenase (ADO).
3. The method of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are independently selected from the group consisting of H and C 1-5 alkyl.
4. The method of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are independently selected from the group consisting of H and methyl.