Phenanthrenequinone-based compound and pharmaceutical composition containing the same for the treatment or prevention of disease involving metabolic syndrome

1. A pharmaceutical composition, comprising:

(a) a therapeutically effective amount of a compound represented by Formula 1:

wherein

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are each independently hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkene, C 1 -C 6 alkyloxy, C 3 -C 8 cycloalkyl, or heterocycloalkyl, C 4 -C 10 aryl or heteroaryl, or two substituents thereof may be taken together to form a cyclic structure or form a double bond;

R 9 and R 10 are each independently hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkene, C 1 -C 6 alkyloxy, C 3 -C 8 cycloalkyl, or heterocycloalkyl, C 4 -C 10 aryl or heteroaryl;

R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are each independently hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkene, C 1 -C 6 alkyloxy, C 3 -C 8 cycloalkyl, or heterocycloalkyl, C 4 -C 10 aryl or heteroaryl, or two substituents thereof may be taken together to form a cyclic structure or form a double bond;

m and n are each independently 0 or 1, when m or n is 0, carbon atoms adjacent to m or n may form a cyclic structure via a direct bond;

with the proviso that

(i) when m is 1, n is 0, carbon atoms adjacent to m or n form a cyclic structure via a direct bond, R 9 , R 10 and R 11 are hydrogen, R 12 and R 13 are hydrogen or are taken together to form a double bond, and R 1 to R 6 are hydrogen and R 7 and R 8 are methyl, R 14 is not methyl, and

(ii) when m is 1, n is 0, carbon atoms adjacent to m or n form a cyclic structure via a direct bond, R 9 , R 10 and R 11 are hydrogen, R 12 and R 13 are hydrogen or are taken together to form a double bond, R 1 , R 3 and R 5 are hydrogen, R 2 , R 4 , R 6 and R 8 are taken together to form a double bond, and R 7 is methyl, R 14 is not methyl; and

(b) a pharmaceutically acceptable carrier, a diluent, an excipient, or any combination thereof.

2. The pharmaceutical composition according to claim 1 , wherein the compound of Formula 1 is selected from compounds of Formulae 2 and 3:

wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are as defined in Formula 1.

3. The pharmaceutical composition according to claim 1 , wherein the compound of Formula 1 is selected from compounds of Formulae 4 and 5:

wherein, R 1 , R 3 , R 5 , R 7 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 R 15 , and R 16 are as defined in Formula 1.

4. The pharmaceutical composition according to claim 1 , wherein the compound of Formula 1 is a compound wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from the group consisting hydrogen, halogen, C 1 -C 6 alkyl and C 1 -C 6 alkyloxy, or two substituents thereof are taken together to form a double bond, and R 9 , R 10 R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are each independently hydrogen or C 1 -C 6 alkyl.

5. The pharmaceutical composition according to claim 1 , wherein the compound of Formula 1 is any one of compounds below:

2-Methyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

2,6,6-Trimethyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

2,6,6-Trimethyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

1, 1,2,6,6-Pentamethyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

1,2,2,6,6-Pentamethyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

3,3-Dimethyl-2,3,7,8,9,10-hexahydro-1H-4-oxa-chrysene-11,12-dione

2-Methyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

1,1,2-Trimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

2,5-Dimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

1,1,2,5-Tetramethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-tert-Butyl-2-methyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-tert-Butyl-1,1,2-trimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-Chloro-2-methyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

2,8-Dimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-Methoxy-2-methyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

3,3,6-Trimethyl-2,3-dihydro-1H-4-oxa-chrysene-11,12-dione.

6. A compound represented by the following Formula 1-1:

wherein

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are each independently hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkene, C 1 -C 6 alkyloxy, C 3 -C 8 cycloalkyl, or heterocycloalkyl, C 4 -C 10 aryl or heteroaryl, or two substituents thereof may be taken together to form a cyclic structure or form a double bond;

R 9 and R 10 are each independently hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkene, C 1 -C 6 alkyloxy, C 3 -C 8 cycloalkyl, or heterocycloalkyl, C 4 -C 10 aryl or heteroaryl;

R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are each independently hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkene, C 1 -C 6 alkyloxy, C 3 -C 8 cycloalkyl or heterocycloalkyl, C 4 -C 10 aryl or heteroaryl, or two substituents thereof may be taken together to form a cyclic structure or form a double bond;

m and n are each independently 0 or 1, when m or n is 0, carbon atoms adjacent to m or n may form a cyclic structure via a direct bond; and

with the proviso that

(i) when m is 1, n is 0, carbon atoms adjacent to m or n form a cyclic structure via a direct bond, R 9 and R 10 are hydrogen, R 1 to R 6 are hydrogen, and R 7 and R 8 are methyl, if R 12 and R 13 is hydrogen, then R 11 or R 14 is not methyl,

(ii) when m is 1, n is 0, carbon atoms adjacent to m or n form a cyclic structure via a direct bond, R 9 , and R 10 are hydrogen, R 1 to R 6 are hydrogen and R 7 and R 8 are methyl, if R 12 and R 13 form a double bond, then R 14 is not methyl,

iii) when m is 1, n is 0, carbon atoms adjacent to m or n form a cyclic structure via a direct bond, R 9 , and R 10 are hydrogen, R 1 , R 3 and R 5 are hydrogen, R 2 , R 4 , R 6 and R 8 are taken together to form a double bond, if R 7 is methyl and R 12 and R 13 are hydrogen, then R 14 is not methyl,

(iv) when m is 1, n is 0, carbon atoms adjacent to m or n form a cyclic structure via a direct bond, R 9 , and R 10 are hydrogen R 1 , R 3 and R 5 are hydrogen, R 2 , R 4 , R 6 and R 8 are taken together to form a double bond, if R 7 is hydrogen and R 12 and R 13 are hydrogen, then R 11 is not methyl,

(v) when m is 1, n is 0, carbon atoms adjacent to m or n form a cyclic structure via a direct bond, R 9 , and R 10 are hydrogen, R 1 , R 3 and R 5 are hydrogen, R 2 , R 4 , R 6 and R 8 are taken together to form a double bond, and if R 7 is methyl and R 12 and R 13 form a double bond, then R 14 is not methyl.

7. The compound or an isomer, prodrug, or solvate thereof according to claim 6 , wherein the compound of Formula 1-1 is a compound wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from the group consisting hydrogen, halogen, C 1 -C 6 alkyl and C 1 -C 6 alkyloxy, or two substituents thereof are taken together to form a double bond, and R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are each independently hydrogen or C 1 -C 6 alkyl.

8. The compound according to claim 6 , wherein the compound of Formula 1-1 is any one of compounds below:

2-Methyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

2,6,6-Trimethyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

1,1,2,6,6-Pentamethyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

1,2,2,6,6-Pentamethyl-1,2,6,7,8,9-hexahydro-phenanthro[1,2-b]furan-10,11-dione

3,3-Dimethyl-2,3,7,8,9,10-hexahydro-1H-4-oxa-chrysene-11,12-dione

1,1,2-Trimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

2,5-Dimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

1,1,2,5-Tetramethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-tert-Butyl-2-methyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-tert-Butyl-1,1,2-trimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-Chloro-2-methyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

2,8-Dimethyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

8-Methoxy-2-methyl-1,2-dihydro-phenanthro[1,2-b]furan-10,11-dione

3,3,6-Trimethyl-2,3-dihydro-1H-4-oxa-chrysene-11,12-dione.

9. A process for preparing the compound in accordance with claim 6 , wherein the compound, which is represented by Formula 1-1 and in which R 11 and R 12 is simultaneously not hydrogen, is synthesized via cyclization of 2-allyl-3-hydroxy-1,4-phenanthrenequinone derivatives in the condition of acid catalyst.

10. The process according to claim 9 , wherein the 2-allyl-3-hydroxy-1,4-phenanthrenequinone derivative is synthesized via rearrangement of 3-allyloxy-1,4-phenanthrenequinone derivatives.

11. The process according to claim 9 , wherein the 2-allyl-3-hydroxy-1,4-phenanthrenequinone derivative is synthesized via C-alkylation of 3-oxy-1,4-phenanthrenequinone and allyl halide.

12. The process according to claim 10 , wherein the 3-allyloxy-1,4-phenanthrenequinone derivative is synthesized via reaction with diene and 2-allyloxy-1,4-benzoquinone.

13. The process according to claim 12 , wherein the diene is 1-vinylcyclohenxene or styrene derivative.

14. A method of treating at least one disease selected from the group consisting of metabolic syndrome disease, obesity, an obesity complication, a liver disease, arteriosclerosis, cerebral apoplexy, myocardial infarction, a cardiovascular disease, an ischemic disease, diabetes, a diabetes-related complication or an inflammatory disease, comprising administering a therapeutically effective amount of the pharmaceutical compositions in accordance with claim 1 to a subject in need thereof.

15. The method according to claim 14 , wherein the diabetes-related complication is selected from the group consisting of hyperlipidemia, hypertension, retinopathy or renal failure.