Substituted N-aryl benzamides and related compounds for treatment of amyloid diseases and synucleinopathies
Substituted n-aryl benzamides, related compounds and their pharmaceutically acceptable derivatives, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided.
1. A compound selected from:
or a pharmaceutically-acceptable salt thereof, wherein M is S(O) 2 , R x is alkyl, and
R 1 , R 2 , R 3 and R 4 are each independently selected from OH, —NR 5 C(═O)R 6 and —NR 7 S(O 2 )R 8 , wherein R 5 and R 7 are each independently hydrogen or alkyl, and R 6 and R 8 are alkyl.
2. The compound of claim 1 , wherein, R 5 is isopropyl.
3. The compound of claim 1 , wherein R x is methyl.
4. The compound of claim 1 selected from
5. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable excipient.
6. The compound of claim 1 selected from:
7. The compound of claim 1 , wherein R 1 , R 2 , R 3 and R 4 are OH.
8. The compound of claim 1 , wherein R 5 is hydrogen.