Chromones and chromone derivatives and uses thereof
AssigneeJenken Biosciences, Inc.
InventorsMao-Hsiung Yen, Edwin Wu
Life of this patent
Estimating the term…
Abstract
The present invention relates to chromones, novel chromone derivatives, and pharmaceutical formulations containing the same and methods of use thereof. Uses of the present invention include, but are not limited to, use for the prevention and treatment of septic shock, organ injury and other disorders. The compounds described herein can be salt forms and also water-soluble compounds.
Claims57
A compound according to formula I:
- wherein:
- R1, R2, and R3 are each independently H, alkyl, alkenyl, alkynyl, —SO3H, —PO3H2, or carbohydrate;
- or R1 and R2 are each independently (CH2)nY and [CH2CH(OH)CH2]Y, wherein Y is H, OR4, NR5R6, COOR4, or OONR5R6 wherein R4, R5, and R6 are each independently H, alkyl, alkenyl, alkynyl, or carbohydrate, and R5 and R6 together may form a 5 to 7-membered ring;
- or R1 and R2 together are heterocycles;
- or R2 and R3 together are heterocycles;
- and
- X1 and x2 are each independently of the formula:
- Ar—X3-T
- wherein Ar may or may not be present and when Ar is present, Ar is phenyl, furanyl, thienyl, pyridyl, cyclohexyl or benzyl;
- wherein X3 is H, C, N, NR′, NR′R″, NR′SO2 R″, O, or S, subject to the proviso that the compound according to formula I is not baicalein or 5,6,7-trihydroxyisoflavone, wherein R′ and R″ are each independently H, alkyl, alkenyl, alkynyl, or carbohydrate;
- wherein T is (CH2)nY or [CH2CH(OH)CH2]Y, wherein Y is H, OR4, NR5R6, COOR4, or OONR5R6 wherein R4, R5, and R6 are each independently H, alkyl, alkenyl, alkynyl, or carbohydrate, and R5 and R6 together may form a 5 to 7-membered ring;
- or pharmaceutically acceptable salts thereof.
A method of treating conditions selected from the group consisting of diseases associated with the overproduction of TNF-α, overproduction of superoxide anion radical, organ damage, arthritis, neurodegenerative diseases, cancer, and cardiac disorders, and combinations thereof, comprising administering to a subject in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the following:
A method of treating conditions selected from the group consisting of diseases associated with the overproduction of TNF-α, overproduction of superoxide anion radical, septic shock, organ damage, neurodegenerative diseases, cancer, and cardiac disorders, and combinations thereof, comprising administering to a subject in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula V:
- wherein:
- R7, R8, and R9 are each independently H, alkyl, —SO3H, —PO3H2, carbohydrate, or benzyl;
- or R7 and R8 together are heterocycles;
- or R8 and R9 together are heterocycles;
- X1 is H, C, NH2, NHCOCH3, NO2, or OR10, wherein R10 is H, alkyl, carbohydrate, or benzyl, or pharmaceutically acceptable salts thereof, with the proviso that when Ph-X1 is at the 2-position and R7, R8, and R9 are each independently H, alkyl or carbohydrate, the compound is not used to treat septic shock.
A method of treating conditions selected from the group consisting of diseases associated with the overproduction of TNF-α, overproduction of superoxide anion radical, septic shock, organ damage, neurodegenerative diseases, cancer, and cardiac disorders, and combinations thereof, comprising administering to a subject in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of baicalein-6-sulfate, baicalein-6,7-disulfate, bacalein-6-phosphate, bacalein-6,7-diphosphate, bacalein-5,6,7-triphosphate, sodium and potassium salt derivatives thereof, and pharmaceutically acceptable salts thereof.
A method of treating conditions selected from the group consisting of diseases associated with the overproduction of TNF-α, overproduction of superoxide anion radical, inflammation, septic shock, organ damage, neurodegenerative diseases, cancer, and cardiac disorders, and combinations thereof, comprising administering to a subject in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of 4′-(N,N-dimethylamino)-5,6,7-trimethoxyflavone, 4′-(methylamino)-5,6,7-trimethoxyflavone, 2,3-diphenyl-5,6,7-trimethoxychromone, 2,3-diphenyl-5,6,7-trihydroxychromone, 4′-(methylsulfonamido)-5,6,7-trimethoxyflavone or 4′-(Carbmethoxymethoxy)-5,6,7-trimethoxyflavone.
A method of synthesizing a compound of formula I, or pharmaceutically acceptable salts thereof, comprising reacting a compound of formula (VI):
- wherein R1, R2, and R3 are each independently H, alkyl, alkenyl, alkynyl, —SO3H, —PO3H2, or carbohydrate;
- or R1 and R2 are each independently (CH2)nY and [CH2CH(OH)CH2]Y, wherein Y is H, OR4, NR5R6, COOR4, or OONR5R6 wherein R4, R5, and R6 are each independently H, alkyl, alkenyl, alkynyl, or carbohydrate, and R5 and R6 together may form a 5 to 7-membered ring;
- or R1 and R2 together are heterocycles;
- or R2 and R3 together are heterocycles;
- with (ArCO)2O ArCO2Na and an acid sodium salt wherein Ar is as defined above.
A method of synthesizing a compound of formula I wherein X1 and X2 represent Ar—X3-T wherein X3 is H, R1, R2, and R3 are H or one of R1 and R2 is CH3, or pharmaceutically acceptable salts thereof, comprising reacting a compound of formula VII:
- wherein X1 and X2 represent Ar—X3-T wherein X3 is H, with aqueous hydrobromic acid (HBr) or boron tribromide (BBr3).
A method of synthesizing a compound of formula I, or pharmaceutically acceptable salts thereof, comprising reacting a compound of formula I wherein X1 and X2 represent Ar—X3-T wherein X3—T is OH or NH2 with an electrophile such as W(CH2)nY, W CH2CH(O)CH2, or HOCH2 CH(O) CH2 wherein W is a leaving group and Y is H, OR4, NR5R6, COOR4, or OONR5R6 wherein R4, R5, and R6 are each independently H, alkyl, alkenyl, alkynyl, or carbohydrate, and R5 and R6 together may form a 5 to 7-membered ring.
Dependencies are inferred from the claim text.