Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid
View Patent ↗The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compounds that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to, the prevention and treatment of Alzheimer's disease.
1. A compound of Formula IV, or a pharmaceutically acceptable salt thereof:
wherein:
aa 1 is valine, lysine, serine, alanine, isoleucine, histidine, or O-benzylserine, and
aa 2 is valine, lysine, serine, alanine, isoleucine, histidine, O-benzylserine, or is absent.
2. The compound of claim 1 , which is of Formula V, or a pharmaceutically acceptable salt thereof:
wherein aa 1 is valine, lysine, serine, alanine, isoleucine, histidine, or O-benzylserine.
3. The compound of claim 1 , which is
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , which is
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , which is
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising a compound of claim 1 together with a pharmaceutically acceptable carrier.
7. A pharmaceutical composition comprising a compound of claim 1 together with a pharmaceutically acceptable carrier, which pharmaceutical composition is suitable for oral administration.
8. A pharmaceutical composition according to claim 7 , which is in the form of a hard shell gelatin capsule, soft shell gelatin capsule, cachet, pill, tablet, lozenge, powder, granule, pellet, dragee, which is optionally enteric coated, a solution, an aqueous liquid suspension, a non-aqueous liquid suspension, an oil-in-water liquid emulsion, a water-in-oil liquid emulsion, an elixir, a syrup, or a pastille.
9. A pharmaceutical composition comprising a compound having the structure
or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable carrier.
10. A process for converting a compound of claim 1 to 3-amino-1-propanesulfonic acid (3APS) comprising contacting said compound with plasma, blood and/or brain cells whereby said compound is converted to 3APS.
11. A method for treating Alzheimer's disease, mild cognitive impairment, Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, a degenerative dementia, a dementia of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, or diffuse Lewy body type of Alzheimer's disease, comprising administering a therapeutically effective amount of a compound of claim 1 to a human subject in need thereof.
12. The method according to claim 11 , which is for treating Alzheimer's disease, mild cognitive impairment, cerebral amyloid angiopathy, or degenerative dementia.
13. The method according to claim 11 , which is for treating Alzheimer's disease.
14. A method for treating Alzheimer's disease, mild cognitive impairment, Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, a degenerative dementia, a dementia of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, or diffuse Lewy body type of Alzheimer's disease, comprising administering a therapeutically effective amount of a compound having the structure
or a pharmaceutically acceptable salt thereof, to a human subject in need thereof.