Claims
- 1. A method of treating Alzheimer's disease, the method comprising administering to a patient having Alzheimer's disease a therapeutically effective amount of a compound of Formula I
- 2. A method according to claim 1, wherein R1 is hydrogen, halogen, alkoxy, or heteroaryl; and
R2 is hydrogen or alkoxy.
- 3. A method according to claim 1, wherein the compound is selected from:
4-Benzylidene-2-phenyl-4H-oxazol-5-one; 4-(4-Nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-Acetoxy-5-(5-oxo-2-phenyl-oxazol-4-ylidenemethyl)-benzoic acid; 4-1,3-Benzodioxol-5-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-(2-Methoxy-3,5-dinitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-Chloro-N,N-dimethyl-5-[1-(5-oxo-2-phenyl-oxazol-4-ylidene)-ethyl]-benzenesulfonamide; 4-Biphenyl-4-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-(3-Ethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,5-Dibromo-2-hydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Ethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2,6-Dichloro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2,2-Dimethyl-5-[4-(5-oxo-2-phenyl-oxazol-4-ylidenemethyl)-phenoxy]-pentanoic acid; 4-(2-Chloro-cyclohex-1-enylmethylene)-2-phenyl-4H-oxazol-5-one; 2-Phenyl-4-pyridin-3-ylmethylene-4H-oxazol-5-one; 4-(4-Hydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-Benzylidene-2-(4-nitro-phenyl)-4H-oxazol-5-one; N-[4-(4-Benzylidene-5-oxo-4,5-dihydro-oxazol-2-yl)-phenyl]-acetamide; 4-Benzylidene-2-(4-chloro-phenyl)-4H-oxazol-5-one; 4-Benzylidene-2-p-tolyl-4H-oxazol-5-one; 4-Benzylidene-2-(4-methoxy-phenyl)-4H-oxazol-5-one; 4-Benzo[1,3]dioxol-5-ylmethylene-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-3-nitro-phenyl)-4-(4-diethylamino-benzylidene)-4H-oxazol-5-one; 4-(4-Dimethylamino-naphthalen-1-ylmethylene)-2-phenyl-4H-oxazol-5-one; 4-(3,5-Dichloro-2-hydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2,3-Dihydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Phenoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Dimethylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Dimethylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-Naphthalen-1-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-Naphthalen-2-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-(4-Dipropylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-p-tolyl-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-(3,5-dinitro-phenyl)-4H-oxazol-5-one; 4-(2,4-Dichloro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-3-nitro-phenyl)-4-pyridin-4-ylmethylene-4H-oxazol-5-one; 2-(4-Chloro-phenyl)-4-pyridin-2-ylmethylene-4H-oxazol-5-one; 4-(2-Hydroxy-5-nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-3-nitro-phenyl)-4-(4-fluoro-benzylidene)-4H-oxazol-5-one; 4-(4-Dimethylamino-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Chloro-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Methoxy-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Methyl-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 2-(4-Bromo-phenyl)-4-(4-diethylamino-benzylidene)-4H-oxazol-5-one; 2-(2-Chloro-phenyl)-4-(4-diethylamino-benzylidene)-4H-oxazol-5-one; 2-(3-Nitro-phenyl)-4-pyridin-4-ylmethylene-4H-oxazol-5-one; 4-(2,3-Dimethoxy-benzylidene)-2-(2-iodo-phenyl)-4H-oxazol-5-one; 4-(2-Methoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Methoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Methoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2,3-Dimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-(2-hydroxy-phenyl)-4H-oxazol-5-one; 4-(2,3-Dimethoxy-benzylidene)-2-(4-nitro-phenyl)-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-(2-iodo-phenyl)-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-(4-nitro-phenyl)-4H-oxazol-5-one; 4-(2-Hydroxy-naphthalen-1-ylmethylene)-2-phenyl-4H-oxazol-5-one; 4-(4-Nitro-naphthalen-1-ylmethylene)-2-phenyl-4H-oxazol-5-one; 2-(4-Amino-phenyl)-4-(3,4-dimethoxy-benzylidene)-4H-oxazol-5-one; 2-Phenyl-4-(2,3,4-trihydroxy-benzylidene)-4H-oxazol-5-one; 4-(4-Dipentylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-[5-(4-Nitro-phenyl)-furan-2-ylmethylene]-2-p-tolyl-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Chloro-benzylidene)-2-(4-fluoro-phenyl)-4H-oxazol-5-one; 4-(3,4-Dichloro-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Fluoro-3-trifluoromethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dichloro-benzylidene)-2-(4-nitro-phenyl)-4H-oxazol-5-one; 2-Phenyl-4-(2-piperidin-1-yl-cyclohex-1-enylmethylene)-4H-oxazol-5-one; 4-(2,4-Dimethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2-Ethoxy-5-methoxymethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2-Nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Methyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-phenyl)-4-(1H-indol-3-ylmethylene)-4H-oxazol-5-one; 4-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 3-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-yildenemethyl]-benzoic acid; (4-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 2-[4-(3,4-Dichloro-benzylidene-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 2-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-yildenemethyl]-benzoic acid; (2-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxal-2-yl]-phenyl}-ammonium; 3-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; (3-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 4-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; and 4-(4-Chloro-3-trifluoromethyl-benzylidene)-2-phenyl-4H-oxazol-5-one. 4-(4-Bromo-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-[2-(2-Bromo-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid methyl ester; 4-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 3-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; (4-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 2-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 2-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; (2-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 3-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; (3-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 4-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; and 4-(4-Chloro-3-trifluoromethyl-benzylidene)-2-phenyl-4H-oxazol-5-one.
- 4. A method of inhibiting the aggregation of amyloid proteins to form amyloid deposits, the method comprising administering to a patient in need of inhibition of the aggregation of amyloid protein an amyloid protein aggregation inhibiting amount of a compound of claim 1.
- 5. A method of imaging amyloid deposits, the method comprising:
a. introducing into a patient a detectable quantity of a labeled compound according to claim 1;b. allowing sufficient time for the labeled compound to become associated with amyloid deposits; and c. detecting the labeled compound associated with the amyloid deposits.
- 6. The method of claim 5, wherein the patient has or is suspected to have Alzheimer's disease.
- 7. The method of claim 5, wherein the labeled compound is a radio labeled compound.
- 8. The method of claim 5, wherein the labeled compound is detected using MRI.
- 9. A compound of Formula I
- 10. A compound according to claim 1, wherein R1 is hydrogen, halogen, alkoxy, or heteroaryl; and
R2 is hydrogen or alkoxy.
- 11. A compound according to claim 1, wherein the compound is selected from:
4-Benzylidene-2-phenyl-4H-oxazol-5-one; 4-(4-Nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-Acetoxy-5-(5-oxo-2-phenyl-oxazol-4-ylidenemethyl)-benzoic acid; 4-1,3-Benzodioxol-5-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-(2-Methoxy-3,5-dinitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-Chloro-N,N-dimethyl-5-[1-(5-oxo-2-phenyl-oxazol-4-ylidene)-ethyl]-benzenesulfonamide; 4-Biphenyl-4-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-(3-Ethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,5-Dibromo-2-hydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Ethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2,6-Dichloro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2,2-Dimethyl-5-[4-(5-oxo-2-phenyl-oxazol-4-ylidenemethyl)-phenoxy]-pentanoic acid; 4-(2-Chloro-cyclohex-1-enylmethylene)-2-phenyl-4H-oxazol-5-one; 2-Phenyl-4-pyridin-3-ylmethylene-4H-oxazol-5-one; 4-(4-Hydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-Benzylidene-2-(4-nitro-phenyl)-4H-oxazol-5-one; N-[4-(4-Benzylidene-5-oxo-4,5-dihydro-oxazol-2-yl)-phenyl]-acetamide; 4-Benzylidene-2-(4-chloro-phenyl)-4H-oxazol-5-one; 4-Benzylidene-2-p-tolyl-4H-oxazol-5-one; 4-Benzylidene-2-(4-methoxy-phenyl)-4H-oxazol-5-one; 4-Benzo[1,3]dioxol-5-ylmethylene-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-3-nitro-phenyl)-4-(4-diethylamino-benzylidene)-4H-oxazol-5-one; 4-(4-Dimethylamino-naphthalen-1-ylmethylene)-2-phenyl-4H-oxazol-5-one; 4-(3,5-Dichloro-2-hydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2,3-Dihydroxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Phenoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Dimethylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Dimethylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-Naphthalen-1-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-Naphthalen-2-ylmethylene-2-phenyl-4H-oxazol-5-one; 4-(4-Dipropylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-p-tolyl-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-(3,5-dinitro-phenyl)-4H-oxazol-5-one; 4-(2,4-Dichloro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-3-nitro-phenyl)-4-pyridin-4-ylmethylene-4H-oxazol-5-one; 2-(4-Chloro-phenyl)-4-pyridin-2-ylmethylene-4H-oxazol-5-one; 4-(2-Hydroxy-5-nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-3-nitro-phenyl)-4-(4-fluoro-benzylidene)-4H-oxazol-5-one; 4-(4-Dimethylamino-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Chloro-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Methoxy-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 4-(4-Methyl-benzylidene)-2-(3-nitro-phenyl)-4H-oxazol-5-one; 2-(4-Bromo-phenyl)-4-(4-diethylamino-benzylidene)-4H-oxazol-5-one; 2-(2-Chloro-phenyl)-4-(4-diethylamino-benzylidene)-4H-oxazol-5-one; 2-(3-Nitro-phenyl)-4-pyridin-4-ylmethylene-4H-oxazol-5-one; 4-(2,3-Dimethoxy-benzylidene)-2-(2-iodo-phenyl)-4H-oxazol-5-one; 4-(2-Methoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Methoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Methoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2,3-Dimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-(2-hydroxy-phenyl)-4H-oxazol-5-one; 4-(2,3-Dimethoxy-benzylidene)-2-(4-nitro-phenyl)-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-(2-iodo-phenyl)-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-(4-nitro-phenyl)-4H-oxazol-5-one; 4-(2-Hydroxy-naphthalen-1-ylmethylene)-2-phenyl-4H-oxazol-5-one; 4-(4-Nitro-naphthalen-1-ylmethylene)-2-phenyl-4H-oxazol-5-one; 2-(4-Amino-phenyl)-4-(3,4-dimethoxy-benzylidene)-4H-oxazol-5-one; 2-Phenyl-4-(2,3,4-trihydroxy-benzylidene)-4H-oxazol-5-one; 4-(4-Dipentylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-[5-(4-Nitro-phenyl)-furan-2-ylmethylene]-2-p-tolyl-4H-oxazol-5-one; 4-(4-Diethylamino-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Chloro-benzylidene)-2-(4-fluoro-phenyl)-4H-oxazol-5-one; 4-(3,4-Dichloro-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(4-Fluoro-3-trifluoromethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dichloro-benzylidene)-2-(4-nitro-phenyl)-4H-oxazol-5-one; 2-Phenyl-4-(2-piperidin-1-yl-cyclohex-1-enylmethylene)-4H-oxazol-5-one; 4-(2,4-Dimethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2-Ethoxy-5-methoxymethyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(2-Nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Nitro-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3,4-Dimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one; 4-(3-Methyl-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-(4-Chloro-phenyl)-4-(1H-indol-3-ylmethylene)-4H-oxazol-5-one; 4-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 3-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-yildenemethyl]-benzoic acid; (4-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 2-[4-(3,4-Dichloro-benzylidene-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 2-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-yildenemethyl]-benzoic acid; (2-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxal-2-yl]-phenyl}-ammonium; 3-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; (3-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 4-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; and 4-(4-Chloro-3-trifluoromethyl-benzylidene)-2-phenyl-4H-oxazol-5-one. 4-(4-Bromo-benzylidene)-2-phenyl-4H-oxazol-5-one; 2-[2-(2-Bromo-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid methyl ester; 4-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 3-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; (4-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 2-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; 2-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; (2-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 3-[4-(3,4-Dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-benzoic acid; (3-Carboxy-phenyl)-{4-[4-(3,4-dichloro-benzylidene)-5-oxo-4,5-dihydro-oxazol-2-yl]-phenyl}-ammonium; 4-[2-(3,4-Dichloro-phenyl)-5-oxo-oxazol-4-ylidenemethyl]-benzoic acid; and 4-(4-Chloro-3-trifluoromethyl-benzylidene)-2-phenyl-4H-oxazol-5-one.
- 12. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
Parent Case Info
[0001] This Application claims the benefit of U.S. provisional application No. 60/397,901 filed on Jul. 23, 2002.
Provisional Applications (1)
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Number |
Date |
Country |
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60397901 |
Jul 2002 |
US |