| CPC A61K 31/513 (2013.01) [A61K 31/437 (2013.01); A61P 35/00 (2018.01)] | 14 Claims |
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1. A method of treating a neuroepithelial tumor that expresses the glucocorticoid receptor (GR+) in a subject, the method comprising administering to the subject a non-steroidal selective glucocorticoid receptor antagonist (SGRA) in an amount effective to reduce the tumor load of said GR+ neuroepithelial tumor in the patient with the proviso that the subject not be otherwise suffering from a disorder treatable with a SGRA, nor does the GR+ neuroepithelial tumor secrete adrenocorticotropic hormone (ACTH), wherein the GR+ neuroepithelial tumor is a schwannoma, an ependymoma, or a neurofibromatosis type 2 (NF 2) neuroepithelial tumor, and wherein said non-steroidal SGRA is selected from:
a) a cyclohexyl pyrimidine compound which has the formula:
 wherein
the dashed line is absent or a bond;
X is selected from the group consisting of O and S;
R1 is selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl and heteroaryl, optionally substituted with from 1 to 3 R1a groups;
each R1a is independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkyl OR1b, halogen, C1-6 haloalkyl, C1-6 haloaloxy, OR1b, NR1bR1c, C(O)R1b, C(O)OR1b, OC(O)R1b, C(O)NR1bR1C, NR1bC(O)R1c, SO2R1b, SO2NR1bR1c, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
R1b and R1c are each independently selected from the group consisting of H and C1-6 alkyl;
R2 is selected from the group consisting of H, C1-6 alkyl, C1-6 alkyl-OR1b, C1-6 alkyl NR1bR1c and C1-6 alkylene heterocycloalkyl;
R3 is selected from the group consisting of H and C1-6 alkyl;
Ar is aryl, optionally substituted with 1-4 R4 groups;
each R4 is independently selected from the group consisting of H, C1-6 alkyl, C1-6 alkoxy, halogen, C1-6 haloalkyl and C1-6 haloalkoxy;
L1 is a bond or C1-6 alkylene; and
subscript n is an integer from 0 to 3,
or salts and isomers thereof,
and
b) a fused azadecalin compound which has the formula:
 wherein
L1 and L2 are members independently selected from a bond and unsubstituted alkylene;
R1 is a member selected from unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted heterocycloalkyl, —OR1A NR1CR1D, —C(O)NR1CR1D, and —C(O)OR1A, wherein
R1A is a member selected from hydrogen, unsubstituted alkyl and unsubstituted heteroalkyl,
R1C and R1D are members independently selected from unsubstituted alkyl and unsubstituted heteroalkyl,
wherein R1C and R1D are optionally joined to form an unsubstituted ring with the nitrogen to which they are attached, wherein said ring optionally comprises an additional ring nitrogen;
R2 has the formula:
 wherein
R2G is a member selected from hydrogen, halogen, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, —CN, and —CF3;
J is phenyl;
t is an integer from 0 to 5;
X is —S(O2)—; and
R5 is phenyl optionally substituted with 1-5 R5A groups, wherein
R5A is a member selected from hydrogen, halogen, —OR5A1, S(O2)NR5A2R5A3, —CN, and unsubstituted alkyl, wherein
R5A1 is a member selected from hydrogen and unsubstituted alkyl, and
R5A2 and R5A3 are members independently selected from hydrogen and unsubstituted alkyl,
or salts and isomers thereof.
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