Mineralocorticoid receptor modulator compounds and methods, and pharmaceutical compositions containing these compounds

A compound of Formula I:

• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof,
• wherein:
• R1 is selected from the group consisting of hydrogen, F, Cl, CN, OR16, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R2 is selected from the group consisting of hydrogen, F, Cl, CN, OR16 an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R10 is selected from the group consisting of hydrogen and OR16;
• X is selected from the group consisting of O, S, and NOR16;
• n is selected from 0, 1, and 2;
• and
• R3 is selected from the group consisting of (a), (b), (c), (d), (e), (f), (g), (h), (i), and (j):
• wherein,
• R11 is selected from the group consisting of hydrogen, F, Cl, CN, OR NR17R18, CH2R16, COR20, CO2R20, CONR20R20, SOR20, or SO2R20, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R12 is selected from the group consisting of hydrogen, F, Cl, CN, COR20, NO2, OR16, NR17R18, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R13 is selected form hydrogen, F, Cl, CN, and OR16, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R21 is selected from the group consisting of hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R22 is selected from the group consisting of F, Cl, OR16, NR17R18, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R23 is selected from the group consisting of hydrogen, F, Cl, OR16, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R24 is selected from the group consisting of hydrogen, F, Cl, and OR16;
• R25 is selected from the group consisting of hydrogen, F, Cl, OR16, CN, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R29 is selected from the group consisting of hydrogen, F, Cl, and OR16;
• R32 and R33 are each independently selected from the group consisting of hydrogen, F, Cl, OR16, CN, COR20, an optionally substituted C1-C8 alkyl an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• U is selected from the group consisting of O, and NR17;
• V is selected from the group consisting of O, S and NR17;
• W is selected from the group consisting of CR27 and N;
• Y is selected from the group consisting of NR26, S and O;
• Z and L are each selected from the group consisting of CH2, NR28, and O
• wherein
• either Z is CH2 and L is selected from the group consisting of NR28 and O,
• or L is CH2 and Z is selected from the group consisting of NR28 and O;
• M is selected from the group consisting of O and NOR30;
• each P is independently selected from the group consisting of N and CR31, provided that no more than two of the Ps are N;
• Q and T are each selected from the group consisting of S, O, NR17, and CR34 wherein
• either Q is CR34 and T is selected from the group consisting of S, O, NR17,
• or T is CR34 and Q is selected from the group consisting of S, O, NR17;
• K is selected from the group consisting of O and NR35;
• K is selected from the group consisting of O and S;
• and
• m is selected from 1 and 2;
• wherein,
• R16 is selected from the group consisting of hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R17 and R18 are independently selected from the group consisting of hydrogen, COR20, CO2R20, SO2R20, S(O)R20, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R20 is selected from the group consisting of hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R26 is selected from the group consisting of hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R27 is selected from the group consisting of hydrogen, F, Cl, Br, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R28 is selected from the group consisting of hydrogen, COR20, CO2R20, CONR20, SO2R20, an optionally substituted C1-C8 alkyl, an optionally substituted C2-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R30 is selected from the group consisting of hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• R31 is selected from the group consisting of hydrogen, F, Cl, and OR16;
• R34 is selected from the group consisting of hydrogen, F, Cl, NO2, OR16, NR17R18, CN, COR20, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl;
• and
• R35 is selected from the group consisting of hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C8 heterohaloalkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted C2-C8 heterocycle, an optionally substituted C5-C8 aryl, and an optionally substituted C3-C8 heteroaryl.