Low Calcemic, Highly Antiproliferative, Analogs of Calcitriol

A compound having formula I:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• is a single or double bond;
• X is independently O, NR2, S, S(O), or S(O)2;
• L1 is independently a direct bond, or substituted or unsubstituted alkyl, wherein alkyl is optionally independently substituted with 1 to 3 R9 groups;
• L2 is independently a direct bond, or substituted or unsubstituted alkyl, wherein alkyl is optionally independently substituted with 1 to 3 R9 groups;
• R1 is independently substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl, wherein R1 is optionally independently substituted with 1 to 5 R3 groups;
• R2 is H, alkyl, or perfluoroalkyl;
• R3 is independently H, F, Cl, Br, I, OH, CN, NO2, substituted or unsubstituted alkyl, perfluoroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —(CH2)jOR4, —(CH2)jC(O)R4, —(CH2)jC(NR7)R4, —(CH2)jC(NNR7)R4, —(CH2)jC(O)OR4, —(CH2)jNR5R6, —(CH2)jC(O)NR5R6, —(CH2)jOC(O)NR5R6, —(CH2)jNR7C(O)R4, —(CH2)jNR7C(O)OR4, —(CH2)jNR7C(O)NR5R6, —(CH2)jS(O)mR8, —(CH2)jNR7S(O)2R8, or —(CH2)jS(O)2NR5R6, wherein each j is independently an integer from 0 to 6, wherein m is independently an integer from 0 to 2, and wherein alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl are each optionally independently substituted with 1 to 3 R9 groups;
• R4 is independently H, substituted or unsubstituted alkyl, perfluoroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl, wherein R4 is optionally independently substituted with 1 to 3 R9 groups;
• R5, R6, R7 and R8 are each independently a direct bond, H, OH, —(CH2)jOR9, substituted or unsubstituted alkyl, perfluoroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl, wherein R5, R6, R7, and R8 are each optionally independently substituted with 1 to 3 R9 groups, or
• R7 and R8 are as described above, and R5 and R6, together with the N atom to which they are attached, form substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, wherein R5 and R6 are each optionally independently substituted with 1 to 3 R9 groups;
• and
• R9 is H, F, Cl, Br, I, OH, CN, NO2, alkyl, perfluoroalkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —(CH2)jOR10, —(CH2)jC(O)R10, —(CH2)jC(NR13)R4, —(CH2)jC(O)OR10, —(CH2)jNR11R12, —(CH2)jC(O)NR11R12, —(CH2)jOC(O)NR11R12, —(CH2)jNR13C(O)R14, —(CH2)jNR13C(O)OR10, —(CH2)jNR13C(O)NR11R12, —(CH2)jS(O)mR15, —(CH2)jNR13S(O)2R15, or —(CH2)jS(O)2NR11R12;
• wherein each j is independently an integer from 0 to 6, wherein m is independently an integer from 0 to 2;
• and
• R10, R11, R12, R13, R14, and R15 are each independently H, F, Cl, Br, I, OH, CN, NO2, alkyl, perfluoroalkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl.