1-methyl-4-[(4-phenylphenyl)sulfonylmethyl]cyclohexyanol and 1-methyl-4-[[4-(2-pyridyl)phenyl]sulfonylmethyl]cyclohexanol compounds and their therapeutic use
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted 1-methyl-4-[(4-phenylphenyl)sulfonylmethyl]cyclohexanol and 1-methyl-4-[[4-(2-pyridyl)phenyl]sulfonylmethyl]cyclohexanol compounds (collectively referred to herein as CHMSA compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, e.g., multiple myeloma, diffuse large B-cell lymphoma, acute myeloid leukemia, eosinophilic leukemia, glioblastoma, melanoma, ovarian cancer, chemotherapy resistant cancer, radiation resistant cancer, inflammatory arthritis, rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus (SLE), lupus nephritis, asthma, chronic obstructive pulmonary disease (COPD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), autoimmune hepatitis, hidradenitis suppurativa, etc. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.
1. A compound of the following formula:
or a pharmaceutically acceptable salt thereof;
wherein:
═X— is independently —CH═ or —N═;
—R 1 is independently —H or —R 1X ;
—R 1X is independently —F, —Cl, —R 1C , —R 1F For —CN;
—R 1C is independently saturated linear or branched C 1-3 alkyl;
—R 1F is independently saturated linear or branched C 1-3 fluoroalkyl;
—R 2 is independently —H or —R 3X ;
—R 2X is independently —F, —Cl, —R 2C , —R 2F , or —CN;
—R 2C is independently saturated linear or branched C 1-3 alkyl;
—R 2F is independently saturated linear or branched C 1-3 fluoroalkyl;
—R 3 is independently —H or —R 3X ;
—R 3X is independently —F, —Cl, —R 3C , —R 3F , or —CN;
—R 3C is independently saturated linear or branched C 1-3 alkyl;
—R 3F is independently saturated linear or branched C 1-3 fluoroalkyl;
—R 4 is independently —H or —R 4X ;
—R 4X is independently —F, —Cl, —R 4C , —R 4F , or —CN;
—R 4C is independently saturated linear or branched C 1-3 alkyl;
—R 4F is independently saturated linear or branched C 1-3 fluoroalkyl;
—R 5 is independently —H or —R 5X ;
—R 5X is independently —F, —R 5C , or —R 5F ;
—R 5C is independently saturated linear or branched C 1-3 alkyl;
—R 5F is independently saturated linear or branched C 1-3 fluoroalkyl;
—R 6 is independently —H or —R 6X ;
—R 6X is independently —F, —R 6C , or —R 6F ;
—R 6C is independently saturated linear or branched C 1-3 alkyl; and
—R 6F is independently saturated linear or branched C 1-3 fluoroalkyl;
or —R 5 and —R 6 , taken together with the carbon atom to which they are attached, form saturated C 3-6 cycloalkyl.
2. A compound according to claim 1 , wherein —R 5 is —H and —R 6 is —H.
3. A compound according to claim 2 , wherein ═X— is —CH═.
4. A compound according to claim 2 , wherein ═X— is —N═.
5. A compound according to claim 3 , wherein:
—R 1 is independently —H, —F, —Cl, or —CN; and
—R 2 is independently —H, —F, —Cl, or —CN.
6. A compound according to claim 4 , wherein:
—R 1 is independently —H, —F, —Cl, or —CN; and
—R 2 is independently —H, —F, —Cl, or —CN.
7. A compound according to claim 3 , wherein:
—R 3 is independently —H, —F, —Cl, or —CN; and
—R 4 is independently —H or —CF 3 .
8. A compound according to claim 4 , wherein:
—R 3 is independently —H, —F, —Cl, or —CN; and
—R 4 is independently —H or —CF 3 .
9. A compound according to claim 5 , wherein:
—R 3 is independently —H, —F, —Cl, or —CN; and
—R 4 is independently —H or —CF 3 .
10. A compound according to claim 6 , wherein:
—R 3 is independently —H, —F, —Cl, or —CN; and
—R 4 is independently —H or —CF 3 .
11. A compound according to claim 3 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
12. A compound according to claim 5 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
13. A compound according to claim 7 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
14. A compound according to claim 9 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
15. A compound according to claim 3 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
16. A compound according to claim 5 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
17. A compound according to claim 7 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
18. A compound according to claim 9 , wherein the compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
19. A compound according to claim 1 , which is a compound of one of following formulae, or a pharmaceutically acceptable salt thereof:
20. A compound according to claim 1 , which is a compound of one of following formulae, or a pharmaceutically acceptable salt thereof:
21. A compound according to claim 1 , which is a compound of one of following formulae, or a pharmaceutically acceptable salt thereof:
22. A composition comprising a compound according to claim 1 , and a carrier, diluent, or excipient.