PYRIMIDINE-CONTAINING 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 13 INHIBITORS

Claims

1. A compound represented by formula I, or a pharmaceutically acceptable salt or ester thereof: in which M represents S, SO, SO2, O, or NR7; R1 and R2 are each independently selected from the group consisting of: 1) Hydrogen; 2) Optionally substituted -C1-C8 alkyl; 3) Optionally substituted -C2-C8 alkenyl; 4) Optionally substituted - C2-C8alkynyl; 5) Optionally substituted -C3-C8cycloalkyl; 6) Optionally substituted aryl; 7) Optionally substituted arylalkyl; 8) Optionally substituted 3- to 8-membered heterocyclic alkyl; 9) Optionally substituted heteroaryl; and 10) Optionally substituted heteroarylalkyl; R3, R4, R5 and R6 are each independently selected from the group consisting of hydrogen, halogen, -CN, -OR9, -SR9, -C(O)R7, -C(O)OR7, -NR7R8, -C(O)NR7R8, optionally substituted -C1-C8alkyl, optionally substituted aryl and optionally substituted heteroaryl; alternatively, R5 and R6 are taken together with the carbon atoms to which they are attached to form an optionally substituted carbocyclic or heterocyclic ring; alternatively, R4 and R5 are taken together with the carbon atoms to which they are attached to form an optionally substituted carbocyclic or heterocyclic ring; alternatively, R3 and R4 are taken together with the carbon atoms to which they are attached to form an optionally substituted carbocyclic or heterocyclic ring; each R7 and R8 are independently selected from the group consisting of: 1) Hydrogen; 2) Optionally substituted -C1-C8 alkyl; 3) Optionally substituted - C2-C8 alkenyl; 4) Optionally substituted -C2-C8alkynyl; 5) Optionally substituted -C3-C8cycloalkyl; 6) Optionally substituted 3- to 8-membered heterocycloalkyl; 7) Optionally substituted aryl; 8) Optionally substituted arylalkyl; 9) Optionally substituted heteroaryl; and 10) Optionally substituted heteroarylalkyl; alternatively, R7 and R8 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclic ring; R9 is selected from the group consisting of: 1) Hydrogen; 2) Optionally substituted -C1-C8 alkyl; 3) Optionally substituted - C2-C8 alkenyl; 4) Optionally substituted -C2-C8alkynyl; 5) Optionally substituted -C3-C8cycloalkyl; 6) Optionally substituted 3- to 8-membered heterocycloalkyl; 7) Optionally substituted aryl; 8) Optionally substituted arylalkyl; 9) Optionally substituted heteroaryl; 10) Optionally substituted heteroarylalkyl; 11) -C(O)R 11 ; 12) -C(O)NR 11 R 12 ; 13) -C(O)OR 11 ; 14) -P(O)(OR 13 )2; and 15) -P(O)(OR 13 )(NR 11 R 12 ); each R 11 and R 12 independently selected from the group consisting of: 1) Hydrogen; 2) Optionally substituted -C1-C8 alkyl; 3) Optionally substituted - C2-C8 alkenyl; 4) Optionally substituted -C2-C8alkynyl; 5) Optionally substituted -C3-C8cycloalkyl; 6) Optionally substituted 3- to 8-membered heterocycloalkyl; 7) Optionally substituted aryl; 8) Optionally substituted arylalkyl; 9) Optionally substituted heteroaryl; and 10) Optionally substituted heteroarylalkyl; a R 13 represents hydrogen optionally substituted by -C1-C8 alkyl or Na + .

2. The compound of claim 1, wherein M is S or NR7, and R7 is as defined in claim 1.

3. The compound according to item 1, in which R1 is selected from the group consisting of the groups listed below, each group optionally substituted: And R2 is selected from the group indicated below, each group being optionally substituted:

4. The compound according to claim 1, represented by formula (IV) or formula (V), or a pharmaceutically acceptable salt thereof: in which R1, R2, R3, R4, R5, R9 and R7 are as defined in paragraph 1.

5. A compound according to claim 4, wherein R9 is selected from the group indicated below, each group being optionally substituted:

6. The compound according to claim 1, represented by formula (X) or formula (XI), or a pharmaceutically acceptable salt thereof: in which R1, R2, R7 and R9 are as defined in paragraph 1.

7. A compound according to claim 1, selected from the compounds represented by formula (X), or a pharmaceutically acceptable salt thereof, in which R9 represents hydrogen, and R1 and R2 are schematically represented for each compound in the table below:

8. The compound according to claim 1, selected from the compounds represented by formula (X), or a pharmaceutically acceptable salt thereof, in which R1, R2 and R9 are schematically represented for each connection in the table below:

9. A compound according to claim 1, selected from the compounds listed below, or a pharmaceutically acceptable salt thereof:

10. A pharmaceutical composition comprising a compound according to any one of claims 19 and a pharmaceutically acceptable carrier or excipient.

11. A method for preventing or treating a disease or condition mediated by 17β-HSD13 in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1-9.

12. The method of claim 11, wherein the disease or condition mediated by 17β-HSD13 is selected from the group consisting of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, liver fibrosis, and hepatocellular carcinoma (HCC).

13. Use of a compound according to any one of claims 1 to 9 in the manufacture of a medicament for the treatment or prevention of a disease or condition mediated by 17β-HSD13.

14. The use according to claim 13, wherein the disease or condition mediated by 17β-HSD13 is selected from the group consisting of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, liver fibrosis and hepatocellular carcinoma (HCC).