Glucocorticoid receptor modulators to treat pancreatic cancer

A method of treating a subject hosting a non-ACTH-secreting pancreatic tumor, the method comprising administering to the subject an effective amount of a chemotherapeutic agent, and administering to the subject a dose of a nonsteroidal selective glucocorticoid receptor modulator of between about 20 milligrams per day (mg/day) to about 1000 mg/day to reduce the tumor load of the pancreatic tumor, wherein the nonsteroidal selective glucocorticoid receptor modulator is a compound comprising a heteroaryl-ketone fused azadecalin structure having the formula:

• wherein
• R1 is a heteroaryl ring having from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S, optionally substituted with 1-4 groups each independently selected from R1a,
• each R1a is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, CN, N-oxide, C3-8 cycloalkyl, and C3-8 heterocycloalkyl;
• ring J is selected from the group consisting of a cycloalkyl ring, a heterocycloalkyl ring, an aryl ring and a heteroaryl ring, wherein the heterocycloalkyl and heteroaryl rings have from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S;
• each R2 is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkyl-C1-6 alkoxy, CN, OH, NR2aR2b, C(O)R2a, C(O)OR2a, C(O)NR2aR2b, SR2a, S(O)R2a, S(O)2R2a, C3-8 cycloalkyl, and C3-8 heterocycloalkyl, wherein the heterocycloalkyl groups are optionally substituted with 1-4 R2c groups;
• alternatively, two R2 groups linked to the same carbon are combined to form an oxo group (═O);
• alternatively, two R2 groups are combined to form a heterocycloalkyl ring having from 5 to 6 ring members and from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, wherein the heterocycloalkyl ring is optionally substituted with from 1 to 3 R2d groups;
• R2a and R2b are each independently selected from the group consisting of hydrogen and C1-6 alkyl;
• each R2c is independently selected from the group consisting of hydrogen, halogen, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, CN, and NR2aR2b,
• each R2d is independently selected from the group consisting of hydrogen and C1-6 alkyl, or two R2d groups attached to the same ring atom are combined to form (═O);
• R3 is selected from the group consisting of phenyl and pyridyl, each optionally substituted with 1-4 R3a groups;
• each R3a is independently selected from the group consisting of hydrogen, halogen, and C1-6 haloalkyl;
• and
• subscript n is an integer from 0 to 3;
• or salts and isomers thereof,
• whereby said subject hosting a non-ACTH-secreting pancreatic tumor is treated.

A method of treating a subject hosting a non-ACTH-secreting pancreatic tumor, the method comprising administering to the subject an effective amount of a chemotherapeutic agent and administering to the subject a dose of a nonsteroidal selective glucocorticoid receptor modulator of between about 20 milligrams per day (mg/day) to about 1000 mg/day to reduce the tumor load of the pancreatic tumor, wherein the nonsteroidal selective glucocorticoid receptor modulator is a compound comprising an octahydro fused azadecalin structure has the formula:

• wherein
• R1 is a heteroaryl ring having from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S, optionally substituted with 1-4 groups each independently selected from R1a,
• each R1a is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, N-oxide, and C3-8 cycloalkyl;
• ring J is selected from the group consisting of an aryl ring and a heteroaryl ring having from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S;
• each R2 is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkyl-C1-6 alkoxy, CN, OH, NR2aR2b, C(O)R2a, C(O)OR2a, C(O)NR2aR2b, SR2a, S(O)R2a, S(O)2R2a, C3-8 cycloalkyl, and C3-8 heterocycloalkyl having from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S;
• alternatively, two R2 groups on adjacent ring atoms are combined to form a heterocycloalkyl ring having from 5 to 6 ring members and from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, wherein the heterocycloalkyl ring is optionally substituted with from 1 to 3 R2c groups;
• R2a, R2b and R2c are each independently selected from the group consisting of hydrogen and C1-6 alkyl;
• each R3a is independently halogen;
• and
• subscript n is an integer from 0 to 3,
• or salts and isomers thereof,
• whereby said subject hosting a non-ACTH-secreting pancreatic tumor is treated.