24-sulfur-substituted analogs of 1alpha, 25-dihydroxy vitamin D3
OwnerGary H. Posner, Kenneth R. Crawford +6inventors
InventorsGary H. Posner, Kenneth R. Crawford, Hong Woon Yang, Jay A. White, Glenville Jones, Byung-Chul Suh, HeungBae Jeon, Mark Hatcher
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Abstract
The present invention provides novel C24-aryl sulfone analogs of 1α,25-dihydroxy vitamin D3, compositions comprising these compounds and methods of using these compounds as selective inhibitors of CYP24. In particular, the compounds of the invention are useful for treating diseases which benefit from a modulation of the levels of 1α,25-dihydroxy vitamin D3, for example, cell-proliferative disorders.
Claims41
A compound of Formula I, and pharmaceutically acceptable salts, hydrates, solvates and prodrugs thereof:
- 59
- wherein
- R1 and R2 are independently selected from the group consisting of OH, OC1-4alkyl, and halo;
- R3 is C1-4alkyl;
- R4 is selected from the group consisting of C1-6alkyl, aryl and heteroaryl with both aryl and heteroaryl being unsubstituted or substituted with 1-5 groups independently selected from C1-4alkyl, hydroxy-substituted C1-6alkyl, OC1-4alkyl, OH, CF3, OCF3, halo, SH, SC1-4alkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)(C1-4alkyl), CN, C(O)OH, C(O)OC1-4alkyl, C(O)NHC1-4alkyl, CH═N—OC1-4alkyl, NHC(O)C1-4alkyl, OC(O)C1-4alkyl, SOC1-4alkyl, SO2C1-4alkyl, SO2NHC1-4alkyl and SO2NH2;
- R5 are either both H or together form ═CH2;
- R6 and R7 are independently H, C1-4alkyl or are taken together to form a C3-6cyloalkyl ring;
- x is 0-2;
- and
- represents a single or a double bond.
A compound of Formula I, and pharmaceutically acceptable salts, hydrates, solvates and prodrugs thereof:
- 60
- wherein
- R1 and R2 are independently selected from the group consisting of OH, OC1-4alkyl, and halo;
- R3 is C1-4alkyl;
- R4 is selected from the group consisting of aryl and heteroaryl with both aryl and heteroaryl being unsubstituted or substituted with 1-5 groups independently selected from C1-4alkyl, hydroxy-substituted C1-6alkyl, OC1-4alkyl;
- OH, CF3, OCF3, halo, SH, SC1-4alkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)(C1-4alkyl), CN, C(O)OH, C(O)OC1-4alkyl, C(O)NHC1-4alkyl, NHC(O)C1-4alkyl, OC(O)C1-4alkyl, SOC1-4alkyl, SO2C1-4alkyl, SO2NHC1-4alkyl and SO2NH2;
- R5 are either both H or together form ═CH2;
- R6 and R7 are independently H. C4alkyl or are taken together to form a C3-6cyloalkyl ring;
- x is 0-2;
- and
- represents a single or a double bond.
A compound of Formula I, and pharmaceutically acceptable salts, hydrates, solvates and prodrugs thereof:
- 61
- wherein
- R1 and R2 are independently selected from the group consisting of OH, OC1-4alkyl, and halo;
- R3 is C1-4alkyl;
- R4 is selected from the group consisting of C1-6alkyl, aryl and heteroaryl with both aryl and heteroaryl being unsubstituted or substituted with 1-5 groups independently selected from C1-4alkyl, hydroxy-substituted C1-6alkyl, OC1-4alkyl, OH, CF3, OCF3, halo, SH, SC1-4alkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)(C1-4alkyl), CN, C(O)OH, C(O)OC1-4alkyl, C(O)NHC1-4alkyl, CH═N—OC1-4alkyl, NHC(O)C1-4alkyl, OC(O)C1-4alkyl, SOC1-4alkyl, SO2C1-4alkyl, SO2NHC1-4alkyl and SO2NH2;
- R5 are either both H or together form ═CH2;
- x is 0-2;
- and
- represents a single or a double bond.
Dependencies are inferred from the claim text.