SOLUBLE HONOKIOL DERIVATIVES
The invention provides a soluble honokiol detivative (such as a water soluble honokiol derivative) and its application in antagonizing glycoprotein VI receptor and providing antioxidant and neuroprotective effects.
1 . A compound having the following Formula (I),
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.
2 . The compound 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 compound of claim 1 , wherein R 2 and R 3 are each independently ethenyl; or a pharmaceutically acceptable salt thereof.
4 . The compound of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt.
5 . The compound of claim 1 , which is 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diyl bis(phosphate), or a pharmaceutically acceptable salt thereof.
6 . The compound of claim 1 , which is sodium 3′,5-diallyl-[1,1′-biphenyl]-2,4′-diyl bis(phosphate).
7 . A pharmaceutical composition, which comprises a therapeutically effective amount of a compound of claim 1 and optionally one or more pharmaceutically acceptable carriers and/or excipients.
8 . The pharmaceutical composition of claim 7 , which is in a dosage form.
9 . The pharmaceutical composition of claim 8 , wherein the dosage form is an injection dosage form.
10 . A method of antagonizing glycoprotein VI receptor, comprising administration of a therapeutically effective amount of a compound of claim 1 to a subject.
11 . The method of claim 10 , wherein the platelet aggregation can be inhibited.
12 . A method of providing antioxidant and neuroprotective effects in a subject, comprising administering a therapeutically effective amount of a compound of claim 1 to a subject.
14 . The method of claim 12 , wherein the method does not cause hemorrhage.
15 . The method of claim 12 , wherein the method reduces edema.
16 . The method of claim 12 , wherein the compound has a prolonged half-life compared to honokiol.
17 . The method of claim 12 , wherein the compound converts to honokiol in plasma.
18 . The method of claim 12 , wherein the neuroprotective effect diminishes brain damage in the subject.
19 . The method of claim 18 , wherein the brain damage is ischemic stroke.
20 . The method of claim 12 , wherein the administration is parenteral administration.
21 . The method of claim 20 , wherein the parenteral administration is intravenous, intramuscular or intracranial administration.