Modulators of the glucocorticoid receptor

A compound of the formula

• wherein A is of the formula
• X and Y are each independently hydrogen, fluoro, chloro, bromo, or (C1–C6)alkyl;
• R1 is (C2–C6)alkyl, (C3–C6)alkenyl, or optionally substituted benzyl;
• wherein said benzyl may be optionally substituted with one to three substituents independently selected from HO—, (C1–C6)alkyl-O—, halo and amino;
• R2 is (C1–C6)alkyl, (C2–C6)alkenyl, (C3–C6)alkynyl, (C3–C10)cycloalkyl, (C6–C10)aryl, (C1–C9)heterocyclyl, (C1–C9)heteroaryl, (C6–C10)aryl(C1–C4)alkyl, (C1–C9)heterocyclyl-(C1–C4)alkyl, (C1–C9)heteroaryl-(C1–C4)alkyl, or (C3–C10)cycloalkyl-(C1–C4)alkyl;
• wherein each of the aforesaid groups may optionally be substituted with one to three substituents independently selected from halo, (C1–C6)alkyl, (C1–C6)alkoxy, or —CF3;
• R3 is hydrogen, (C1–C6)alkyl, (C2–C6)alkenyl, (C2–C6)alkynyl, (C3–C10)cycloalkyl, (C1–C9)heterocyclyl, (C1–C9)heteroaryl, or (C6–C10)aryl;
• wherein each of the aforesaid groups may be optionally substituted with one to three substituents independently selected from HO—, (C1–C6)alkyl-O—, halo and amino;
• R4 is HO— or R14R15N—;
• R5 is a radical selected from the group consisting of hydrogen, halo, (C1–C6)alkyl, (C2–C6)alkenyl, (C3–C6)alkynyl, (C3–C10)cycloalkyl, (C6–C10)aryl—, (C1–C9)heteroaryl-, (C1–C9)heterocyclic-, —OH, (C1–C6)alkyl-O—, (C3–C10)cycloalkyl-O—, (C6–C10)aryl-O—, (C1–C9)heteroaryl-O—, (C1–C9)heterocyclic-O—, (C3–C10)cycloalkyl-(C1–C6)alkyl-O—, (C6–C10)aryl-(C1–C6)alkyl-O—, (C1–C9)heteroaryl-(C1–C6)alkyl-O—, (C1–C9)heterocyclic-(C1–C6)alkyl-O—, R16R17N—(C═O)—, R16—(C═O)—(R25—N)—, R16R17—N—SO2—, R18—SO2—, R18—SO2—(NR19)—, R18—SO3—, —C≡N, R18—(C═O)—O—, R18—(C═O)—, R16R17N—(C═O)—O—, R16R17N—(C═O)—(R25—N)—, R19—O—(C═O)—(R25—N)—and R19—O—(C═O)—;
• wherein each of said (C1–C6)alkyl, (C3–C10)cycloalkyl, (C6–C10)aryl, (C1–C9)heteroaryl, (C1–C9)heterocyclic moieties of said (C1–C6)alkyl, (C6–C10)aryl-, (C1–C9)heteroaryl-, (C1–C9)heterocyclic-, (C1–C6)alkyl-O—, (C3–C10)cycloalkyl-O—, (C6–C10)aryl-O—, (C1–C9)heteroaryl-O—, (C1–C9)heterocyclic-O—, (C3–C10)cycloalkyl-(C1–C6)alkyl-O—, (C6–C10)aryl-(C1–C6)alkyl-O—, (C1–C9)heteroaryl-(C1–C6)alkyl-O—and (C1–C9)heterocyclic-(C1–C6)alkyl-O— radicals, may optionally be substituted with one to three substituents independently selected from the group consisting of (C1–C6)alkyl, (C2–C6)alkenyl, (C2–C6)alkynyl, (C3–C10)cycloalkyl, (C6–C10)aryl, (C1–C9)heteroaryl(CH2)n—, (C1–C9)heterocyclic, halo, HO—, HO—(C═O)—, R20—O—(C═O)—, R21—(C═O)—, R22—CO2—, N≡C—, R23R24N—, R23R24N—(C1–C6)alkyl-, R23R24N—(C═O)—, R23R24—N—SO2—, R21—SO2—, R21—SO2—(NR21)—, R21—SO3—, R21(C═O)—NH—, R21(C═O)—[N—(C1–C6)alkyl]-;
• R21(C═O)—NH—(C1–C6)alkyl-;
• and R21(C═O)—[N—(C1–C6)alkyl]–(C1–C6)alkyl-;
• wherein said (C3–C10)cycloalkyl, (C6–C10)aryl, (C1–C9)heteroaryl(CH2)n—, (C1–C9)heterocyclic substituents may optionally be substituted on a ring carbon or nitrogen by one to three members per ring independently selected from halo, (C1–C6)alkyl, and (C1–C6)alkoxy;
• n is an integer from zero to four;
• each of R6, R7, R8 and R9 is independently selected from the group consisting of hydrogen, (C1–C6)alkyl, fluoro and —OH;
• each of R10 and R11 is independently selected from the group consisting of hydrogen and (C1–C6)alkyl;
• each of R12 and R13 is independently selected from the group consisting of hydrogen, fluoro and (C1–C6)alkyl;
• each of R14 and R15 is independently selected from hydrogen or (C1–C4)alkyl;
• each of R16 and R17 is independently selected from hydrogen, (C1–C6)alkyl, (C6–C10)aryl, (C1–C9)heteroaryl, (C1–C9)heterocyclic, (C1–C9)heteroaryl(C1–C6)alkyl, (C6–C10)aryl(C1–C6)alkyl, (C1–C9)heterocyclic(C1–C6)alkyl, HO—(C1–C6)alkyl, amino-(C1–C6)alkyl-, (C1–C6)alkylamino-(C1–C6)alkyl-, and [(C1–C6)alkyl]2amino-(C1–C6)alkyl-;
• wherein said each of said (C6–C10)aryl, (C1–C9)heteroaryl, and (C1–C9)heterocyclic moieties of said (C6–C10)aryl-, (C1–C9)heteroaryl-, (C1–C9)heterocyclic-, (C6–C10)aryl-(C1–C6)alkyl, (C1–C9)heteroaryl-(C1–C6)alkyl and (C1–C9)heterocyclic-(C1–C6)alkyl, may optionally be substituted with one to three substituents independently selected from the group consisting of halo, (C1–C6)alkyl or (C1–C6)alkoxy, or R16 and R17 are taken together to form an azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, (C1–C6)alkyl-piperazinyl, or morpholinyl ring;
• R18 is hydrogen, (C1–C6)alkyl, (C6–C10)aryl or (C1–C9)heteroaryl;
• wherein said (C1–C6)alkyl may optionally be substituted with a substituent selected from the group consisting of HO—, amino, (C1–C6)alkylamino, [(C1–C6)alkyl]2amino, (C6–C10)aryl, (C1–C9)heteroaryl, (C1–C9)heterocyclic, (C1–C6)alkoxy, HO—(C═O)—, (C1–C6)alkyl-O—(C═O)—, (C1–C6)alkyl-(C═O)—, N≡C—, [(C1–C6)alkyl]2N—(C═O)—and (C1–C6)alkyl(C═O)—NH—;
• R19 is hydrogen or (C1–C6)alkyl;
• R20 is hydrogen or (C1–C6)alkyl;
• R21 is hydrogen or (C1–C6)alkyl;
• R22 is hydrogen or (C1–C6)alkyl;
• each of R23 and R24 is independently selected from hydrogen, (C1–C6)alkyl, (C6–C10)aryl, (C1–C9)heteroaryl, (C1–C9)heterocyclic, (C1–C9)heteroaryl(C1–C6)alkyl, (C6–C10)aryl(C1–C6)alkyl, (C1–C9)heterocyclic(C1–C6)alkyl, HO—(C1–C6)alkyl, N≡C—(C1–C6)alkyl, amino-(C1–C6)alkyl-, (C1–C6)alkylamino-(C1–C6)alkyl-, and [(C1–C6)alkyl]2amino-(C1–C6)alkyl-;
• wherein said each of said (C6–C10)aryl, (C1–C9)heteroaryl, and (C1–C9)heterocyclic moieties of said (C6–C10)aryl-, (C1–C9)heteroaryl-, (C1–C9)heterocyclic-, (C6–C10)aryl-(C1–C6)alkyl, (C1–C9)heteroaryl-(C1–C6)alkyl and (C1–C9)heterocyclic-(C1–C6)alkyl, may optionally be substituted with one to three substituents independently selected from the group consisting of halo, (C1–C6)alkyl or (C1–C6)alkoxy, or R23 and R24 are taken together to form an azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, (C1–C6)alkyl-piperazinyl, or morpholinyl ring;
• R25 is hydrogen or (C1–C6)alkyl;
• or a pharmaceutically acceptable salt thereof.