Compounds for activating TGF-beta signaling
View Patent ↗Compositions and methods for treatment and prevention of disorders and conditions characterized by reduced TGF-β signaling are described.
1. A method for increasing TGF-β signaling activity in a mammalian subject comprising administering to the subject a compound corresponding to the formula:
wherein:
R 4 is selected from the group consisting of thiophene, furan and cyclic alkyl;
R 5 is either piperidine or N-substituted piperidine, wherein the piperidine or N-substituted piperidine is attached to a urea nitrogen atom via an intervening alkylene group; and
R 6 is phenyl or substituted phenyl.
2. The method of claim 1 , wherein:
R 4 is selected from the group consisting of
R 5 is selected from the group consisting of
3. The method of claim 2 , wherein the compound is selected from the group consisting of:
4. The method of claim 3 , where the compound is
5. The method of claim 1 , wherein the increasing TGF-β signaling activity is in the brain of the mammalian patient.
6. The method of claim 1 , wherein the mammalian patient has a disease or condition characterized by reduced TGF-β signaling activity.
7. The method of claim 6 , wherein the disease or condition is selected from the group consisting of stroke, heart disease, bone loss, cancer, multiple sclerosis, wound healing, inflammation, and a neurological disorder.
8. The method of claim 5 , wherein the increasing TGF-β signaling activity enhances neuroprotection in the brain.
9. The method of claim 5 , wherein the compound is effective to reduce the number of amyloid plaques in the brain.
10. The method of claim 5 , wherein the compound is effective to reduce the accumulation of Aβ in the brain.
11. The method of claim 5 , wherein the compound is effective to modulate the TGF-β pathway.
12. The method of claim 7 , wherein the disease or condition is Alzheimer's disease.
13. The method of claim 1 , wherein the compound is comprised in a composition further comprising a pharmaceutically-acceptable excipient.
14. The method of claim 13 , wherein the compound is administered by intraperitoneal, intravenous, or intramuscular administration.
15. The method of claim 13 , wherein the compound is administered orally.
16. The method of claim 5 , wherein the compound is effective to increase cognitive function.