Soluble honokiol derivatives
The invention provides a soluble honokiol derivative (such as a water soluble honokiol derivative) and its application in antagonizing glycoprotein VI receptor and providing antioxidant and neuroprotective effects.
1. A method of antagonizing glycoprotein VI receptor, comprising administration of a therapeutically effective amount of the following compound of Formula (I) to a subject:
wherein
X is (CH 2 ) 1-6 ;
R 1 is phosphate or carbonate;
R 2 and R 3 are each independently C 2-6 alkenyl, C 1-10 alkyl, —O—C 1-10 alkyl or —NH—C 1-10 alkyl, wherein the alkyl or alkenyl is unsubstituted or substituted; and
R 4 and R 5 are each independently one to three H, halogen, —OH, —NH 2 , NO 2 , C 1-10 alkyl, C 2-6 alkenyl, —O—C 1-10 alkyl or —NH—C 1-10 alkyl;
or a pharmaceutically acceptable salt thereof;
wherein the compound or a pharmaceutically acceptable salt thereof is administered by intravenous injection; and
wherein the compound or a pharmaceutically acceptable salt thereof is administered at a dose of about 0.01 to about 1.0 mg per kg body weight.
2. The method of claim 1 , wherein R 1 is phosphate; R 2 and R 3 are each independently C 2-6 alkenyl; and R 4 and R 5 are each independently H; or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein R 2 and R 3 are each independently ethenyl; or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt.
5. The method of claim 1 , wherein the compound is 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diyl bis(phosphate), or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the compound is sodium 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diylbis(phosphate).
7. The method of claim 1 , wherein platelet aggregation can be inhibited in the subject.
8. A method of providing antioxidant and neuroprotective effects in a subject, comprising administering a therapeutically effective amount of a compound of Formula (I) to a subject:
wherein
X is (CH 2 ) 1-6 ;
R 1 is phosphate or carbonate;
R 2 and R 3 are each independently C 2-6 alkenyl, C 1-10 alkyl, —O—C 1-10 alkyl or —NH—C 1-10 alkyl, wherein the alkyl or alkenyl is unsubstituted or substituted; and
R 4 and R 5 are each independently one to three H, halogen, —OH, —NH 2 , NO 2 , C 1-10 alkyl, C 2-6 alkenyl, —O—C 1-10 alkyl or —NH—C 1-10 alkyl;
or a pharmaceutically acceptable salt thereof;
wherein the compound or a pharmaceutically acceptable salt thereof is administered by intravenous injection; and
wherein the compound or a pharmaceutically acceptable salt thereof is administered at a dose of about 0.01 to about 1.0 mg per kg body weight.
9. The method of claim 8 , wherein R 1 is phosphate; R 2 and R 3 are each independently C 2-6 alkenyl; and R 4 and R 5 are each independently H; or a pharmaceutically acceptable salt thereof.
10. The method of claim 8 , wherein R 2 and R 3 are each independently ethenyl; or a pharmaceutically acceptable salt thereof.
11. The method of claim 8 , wherein the pharmaceutically acceptable salt is a sodium salt; and/or wherein the compound is 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diyl bis(phosphate), or a pharmaceutically acceptable salt thereof.
12. The method of claim 8 , which is sodium 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diyl bis(phosphate).
13. The method of claim 8 , wherein the method does not cause hemorrhage.
14. The method of claim 8 , wherein the method reduces edema.
15. The method of claim 8 , wherein the compound has a prolonged half-life compared to honokiol.
16. The method of claim 8 wherein the compound converts to honokiol in plasma.
17. The method of claim 8 , wherein the neuroprotective effect diminishes brain damage in the subject.
18. The method of claim 17 , wherein the brain damage is ischemic stroke.