Selective spirocyclic glucocorticoid receptor modulators

A compound represented by Formula I or Formula II

• or a pharmaceutically acceptable salt or hydrate thereof, wherein:
• m is 0, 1, 2 or 3,
• n is 0, 1 or 2;
• -A-B—C-D is selected from the group consisting of:
• (1) —CH2—CH2—CH2—O—,
• (2) —CH2—CH2—C(O)—O—,
• (3) —CH═CH—C(O)—O—,
• (4) —O—CH2—CH2—CH2—,
• (5) —O—C(O)—CH2—CH2—,
• (6) —HC═CH—CH2—O—,
• (7) —CH2—HC═CH—O—,
• (8) —CH2—CH2—C(O)—NH—,
• (9) —CH2—NH—CH2—CH2—,
• (10) —CH2—NH—C(O)—O—,
• (11) —NH—C(O)—NH—C(O)—,
• (12) —C(O)—NH—C(O)—NH—,
• (13) —NH—C(O)—NH—CH2—,
• (14) —NH—C(O)—NH—C(═S)—,
• (15) —O—CH2—CH2—O—,
• (16) —S—CH2—CH2—S—;
• provided that when the atoms at positions B and C of -A-B—C-D- are both carbon atoms, said atoms may be joined together to form a ring selected from
• X and Y are each independently selected from CH2, S and O;
• R1 is selected from the group consisting of:
• (1) C1-6alkyl,
• (2) C2-6alkenyl,
• (3) C2-6akynyl,
• (4) C3-6cycloalkyl,
• (5) aryl,
• (6) —CH2-phenyl,
• (7) HET,
• wherein items (1) to (3) above are optionally substituted from one to three substituents independently selected from the group consisting of:
• halo, OR5, and NHR6, and items (4) to (7) are optionally substituted with from one to three substituents selected from the group consisting of:
• halo, OR5, NHR6, C1-3alkyl, C2-6alkenyl, C2-6akynyl;
• R2 and R3 are each independently selected from the group consisting of:
• (1) hydrogen,
• (2) halo,
• (3) C1-6alkyl,
• (4) C2-6alkenyl,
• (5) C2-6akynyl,
• (6) OR7,
• (7) NHR8,
• (8) aryl,
• (9) —CH2-phenyl;
• R5, R6, R7 and R8 are each independently selected from the group consisting of:
• (1) hydrogen,
• (2) methyl;
• each R4 is independently selected from the group consisting of
• (1) —OH,
• (2) —C1-6alkyl optionally substituted with 1, 2 or 3 substituents selected independently from hydroxy, oxo, —COOH, amino, methylamino, dimethylamino, ═S, and halo,
• (3) C2-6alkenyl optionally substituted with 1, 2 or 3 substituents selected independently from hydroxy, halo and —C(O)—O—C1-2alkyl,
• (4) C2-6alkynyl optionally substituted with 1, 2 or 3 substituents selected independently from hydroxy and halo,
• (5) phenyl optionally substituted with 1, 2 or 3 substituents selected independently from hydroxy, C1-2alkyl, —COOH, —C(O)—O—CH3 and halo,
• (6) —C1-2alkyl-phenyl optionally substituted with 1, 2 or 3 substituents independently selected from hydroxy, C1-2alkyl and halo,
• (7) —CO2H,
• (8) —CO2C1-3alkyl,
• (9) —OC1-3alkyl,
• (10) —SO2—C1-3alkyl,
• (11) —SO2-phenyl optionally substituted with 1, 2 or 3 substituents independently selected from hydroxy, C1-2alkyl and halo
• (12) —C1-2alkyl-O—C1-2alkyl,
• (13) —C1-2alkyl-O—C2-4alkenyl,
• (14) —C1-2alkyl-O-phenyl optionally substituted with with 1, 2 or 3 substituents independently selected from hydroxy, C1-2alkyl and halo,
• (15) —C1-2alkyl-C(O)O—C1-2alkyl,
• (16) 2-(1,3-dioxan)ethyl,
• (17) —C1-2alkyl-C(O)—NH-phenyl,
• (18) —C1-2alkyl-C(O)—NHN.