Patent EA-001172-B1 (EA)
Title: Polyhydroxyphenol derivatives containing medical compositions for using same for preventing and curing bone and cartilage diseases
Inventor: SAKAI KUNIKAZU
IPC: A61P43/00
Filed: 1997-05-14
Abstract: 1. A compound represented by the general formula (I)    or a salt thereof, wherein R1 represents a branched or straight-chain alkyl group of 1-15carbon atoms(providing that a methyl group is excluded), a substituted or unsubst1tuted benzyl group, or a substituted or unsubstituted aryl group; R2 represents a hydrogen atom. a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group, R3 represents a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, a substituted or unsubstituted benzyl group, a hydroxyl group, a branched or straight-chain alkoxy group of 1-15 carbon atoms, a branched or straight-chain alkenyloxy group of 2 -15 carbon atoms, or a substituted or unsubstltuted benzyloxy group, R4 represents a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, a substituted or unsubstituted benzyl group, or a hydroxyl group, and R5 and R6 independently represent a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group; providing that the compounds are excluded in which R2 and R3 are each a hydrogen atom, a 3-methyl-2-butenyl group, or a branched or straight-chain alkoxy group of 1-15 carbon atoms when R1 is a branched or straight-chain alkyl group of 1-15 carbon atoms, R4 is a hydroxyl group, and R5 and R6 are each a hydrogen atom or a branched or straight-chain alkyl group of 1-15 carbon atoms; where R2 is a hydrogen atom when R1 is a branched or straight-chain alkyl group of 1-15 carbon atoms or a substituted or unsubstituted aryl group, R4 and R5 are each a hydrogen atom, and R6 is a hydrogen atom or a branched or straight-chain alkyl group of 1-15 carbon atoms, where R2 and R3 are each a hydrogen atom, a 3-methyl-2-butenyl group, or a 3-methyl-n-butyl group when R1 is a 2-methylpropyl group. 2. The compound according to claim 1, wherein R1 denotes a 2-methylpropyl group, a 2,6-dimethylheptyl group, a benzyl group, or a phenyl group, or a salt thereof. 3. The compound according to claim 1 or claim 2, wherein R2 or R3 is a hydrogen atom, a 3-methyl-2-butenyl group, a 3,7-dimethyl-2,6-octadienyl group, or a benzyl group, or a salt thereof. 4. The compound according to claim 1, which is represented by the general formula (II)    wherein R1 represents a 2-methylpropyl group or a 2,6-dimethylheptyl group, and R2 and R3 independently represent a hydrogen atom, a 3-methyl-2-butenyl group, a 3,7-dimethyl-2,6-octadienyl group, or a substituted or unsubstituted benzyl group, providing that the case in which R1 is a 2-methylpropyl group and R2 and R3 independently are a hydrogen atom or a 3-methyl-2-butenyl group is excluded or a salt thereof. 5. The compound according to claim 1, which is represented by the general formula (III)    wherein R1 represents a branched or straight-chain alkyl group of 1-15 carbon atoms (providing that a methyl group is excluded), a substituted or unsubstituted benzyl group, or a substituted or unsubstituted aryl group, R2 and R4 lndependently represent a hydrogen atom, a branched or straight-chain alkyl group or alkenyl group of 1-15 carbon atoms, or a substituted or unsubstituted benzyl group, and R5, R6, and R7 independently represent a hydrogen atom, a branched or straight-chain alkyl group or alkenyl group of 1-15 carbon atoms, or a substituted or unsubstituted benzyl group or a salt thereof. 6. The compound according to clalm 1, 4, or 5, which is at least one member selected from the group consisting of: {3,5-bisbenzyl-2,4,6-trihydroxyphenyl} (2-methylpropyl) ketone,  {3,5-bis(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxy-phenyl} (2-methylpropyl) ketone,  {3-(3-methyl-2-butenyl)-2,4,5-trihydroxyphenyl} (2-methylpropyl) ketone,  {3,6-bis(3-methyl-2-butenyl)-2,4,5-trihydroxyphenyl} (2-methylpropyl) ketone,  {6-(3-methyl-2-butenyl)-2,4,5-trihydroxyphenyl} (2-methylpropyl) ketonemono(3-methyl-2-butenyl) ether,  (2,4,5-trihydroxyphenyl) (2-methylpropyl) ketonemono(3methyl-2-butenyl) ether,  {3,5-bis(3-methyl-2-butenyl)-2,4,6-trihydroxyphenyl} (phenylmethyl) ketone,  {3-(3-methyl-2-butenyl)-2,4,6-trihydroxyphenyl} (phenylmethyl) ketone,  {3,5-bis(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxy-phenyl} (phenylmethyl) ketone,  {3-(3,7-dimethyl-2,6-octadienyl)-2,4,6-trihydroxy-phenyl} (phenylmethyl) ketone,  {2-hydroxy-6-methyl-4-(3-methyl-2-butenyloxy)phenyl} (2-methylpropyl) ketone,  {2,4-dihydroxy-6-methyl-3-(3-methyl-2-butenyl)phenyl} (2-methylpropyl) ketone.  {4,6-dihydroxy-2-methyl-3-(3-methyl-2-butenyl)phenyl} (3-methylpropyl) ketone,  {3,5-bis(3-methyl-2-butenyl)-2-hydroxy-6-methyl-4-(3-methyl-2-butenyloxy)phenyl} (2-methylpropyl) ketone,  {2-hydroxy-4-(3-methyl-2-butenyloxy)phenyl}  (2-methylpropyl) ketone,  {2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl} (2-methyl-propyl) ketone, and  {2,4-dihydroxy-5-(3-methyl-2-butenyl)phenyl} (2-methyl-propyl) ketone or a salt thereof. 7. A compound represented by the general formula (IV)    or a salt thereof, wherein R1 represents a branched or straight-chain alkyl group of 1-15 carbon atoms, a substituted or unsubstituted benzyl group, or a substituted or unsubstituted aryl group, R2 represents a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group, R3 represents a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2 - 15 carbon atoms, or a substituted or unsubstituted benzyl group, and R8 represents a hydroxyl group, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group, providing that the case in which R2 and R3 are each a 3-methyl-2-butenyl group when R1 is a methyl group and R8 is a hydroxyl group and the case in which two or three members of the class consisting of R2, R3, and R8 are each a 3-methyl-2-butenyl group and the remaining member is a hydrogen atom or a hydroxyl group when R1 is a 2-propyl group, a 2-methylpropyl group or a 1-methylpropyl group are excluded or a salt thereof. 8. The compound according to claim 7, wherein R1 denotes a 2-methylpropyl group, a 2,6-dimethylheptyl group, or a phenyl group, or a salt thereof. 9. The compound according to claim 7 or 8, wherein R2 or R3 is a 3-methyl-2-butenyl group, a 3,7-dimethyl-2,6-octadienyl group, or a benzyl group, or a salt thereof. 10. The compound according to claim 7, represented by the general formula (V)    or a salt thereof, wherein R1 represents a 2-methylpropyl group or a 2,6-dimethylheptyl group, R2 represents a hydrogen atom, a 3-methyl-2-butenyl group, a 3,7-dimethyl-2,6-octadienyl group, or a substituted or unsubstituted benzyl group, and R3 represents a 3-methyl-2-butenyl group, a 3,7-dimethyl-2,6-octadienyl group, or a substituted or unsubstituted enzyl group, providing that the case in which R1 is a 2-methylpropyl group or a 2-propyl group, R2 is a hydrogen atom or a 3-methyl-2-butenyl group, and R3 is a 3-methyl-2-butenyl group is excluded or a salt thereof. 11. The compound according to claim 7, which is represented by the general formula (VI)    or a salt thereof, wherein R1 represents a 2-methylpropyl group or a substituted or unsubstituted aryl group and R2 and R3 each represent a 3-methyl-2-butenyl group or a substituted or unsubstituted benzyl group, providing that the case in which R1 is a 2-methylpropyl group and R2 and R3 are each a 3-methyl-2-butenyl group is excluded or a salt thereof. 12. The compound according to any one of claims 7, 10, and 11, which is at least one member selected from the group consisting of: 2,2-bis(3,7-dimethyl-2,6-octadienyl)-3,5-dihydroxy-6-(3-methyl-1-oxobutyl)cyclohexa-3,5-dienone,  3,5-dihydroxy-6-(3-methyl-1-oxobutyl)-2,2,4-tris(3,7-dimethyl-2,6-octadienyl)cyclohexa-3,5-dienone,  2,2-bisbenzyl-3,5-dihydroxy-6-(3-methyl-1-oxobutyl)-cyclohexa-3,5-dienone,  3,5-dihydroxy-6-(3-methyl-1-oxobutyl)-2,2,4-trisbenzyl-cyclohexa-3,5-dienone,  2,2-bis(3-methyl-2-butenyl)-3,5-dihydroxy-6-(3,7-dimethyl-1-oxooctyl)cyclohexa-3,5-dienone,  3,5-dihydroxy-6-(3,7-dimethyl-1-oxooctyl)-2,2,4-tris(3-methyl-2-butenyl)cyclohexa-3,5-dienone,  2,4-bis(3-methyl-2-butenyl)-6-(benzoyl)-2,3,5-tri-hydroxycyclohexa-3,5-dienone,  2,4-dimethyl-6-(3-methyl-1-oxobutyl)-2,3,5-trihydroxy-cyclohexa-3,5-dienone,  2,4-bisbenzyl-6-(3-methyl-1-oxobutyl)-2,3,5-trihydroxy-cyclohexa-3,5-dienone,  3,5-dihydroxy-6-(phenylacetyl)-2,2,4-tris(3-methyl-2-butenyl)cyclohexa-3,5-dienone,  3,5-dihydroxy-6-(phenylacetyl)-2,2-bis(3-methyl-2-butenyl)cyclohexa-3,5-dienone,  3,5-dihydroxy-6-(phenylacetyl)-2,2,4-tris(3,7-dimethyl-2,6-octadienyl)cyclohexa-3,5-dienone, and  3,5-dihydroxy-6-(phenylacetyl)-2,2-bis(3,7-dimethyl-2,6-octadienyl)cyclohexa-3,5-dienone or a salt thereof.  13. A medicinal composition, comprising one or more compounds set forth in claims 1-12 and a pharmaceutically acceptable carrier. 14. The medicinal composition according to claim 13, which is a preventive curative agent for diseases affecting bones and cartilages. 15. A method for preventing or curing diseases of bones cartilages, which comprises administering one or more compounds set forth in any of claims 1-12 in an amount effective in curing or preventing diseases of bones and cartilages. 16. A use of one or more compounds set forth in any of claims 1-12 for the production of a medicinal composition for preventing or curing diseases of bones cartilages. 17. A medicinal composition comprising a compound represented by the general formula (I)    wherein R1 represents a branched or str