Cyclic urea and carbamate inhibitors of 11β-hydroxysteroid dehydrogenase 1

A compound of the Formula (I)

• wherein:
• R1 is selected from the group consisting of
• (1) H;
• or
• (2) (C1-C8)alkyl, (C3-C7)cycloalkyl, heterocyclyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkylthio(C1-C4)alkyl, (C1-C4)alkylsulfinyl(C1-C4)alkyl, and (C1-C4)alkylsulfonyl(C1-C4)alkyl;
• or
• (3) phenyl, phenyl(C1-C4)alkyl, heteroaryl, and heteroaryl(C1-C4)alkyl;
• X is independently selected from the group consisting of OH, CH2OH, (C1-C3)alkyl, (C1-C3)haloalkyl, OR*, O((C1-C3)haloalkyl), CN, CH2CN, NO2, CH2NO2, SH, SR*, SO2H, CH2SO2H, SO2R*,CH2SO2R*, SO2NH2, SO2NHR*, SO2NR*2, CH2SO2NH2, CH2SO2NHR*, CH2SO2NR*2, SO2CF3, CH2SO2CF3, CONH2, CONHR*, CONR*2, CH2CONH2, CH2CONHR*, CH2CONR*2, CO2H, CH2CO2H, NH2, NHR*, NR*2, (C1-C3)alkyl(NH2), (C1-C3)alkyl(NHR*), (C1-C3)alkyl(NR*2), aryl, heteroaryl, SO3H, CH2SO3H and heterocyclyl optionally substituted with oxo, alkyl, haloalkyl or hydroxyl;
• and
• when R1 heterocyclyl or heteroaryl, X can also be oxo;
• m=0, 1,2 or3;
• R2 is selected from the group consisting of
• (1) H;
• or
• (2) (C1-C8)alkyl, (C3-C7)cycloalkyl, heterocyclyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkylthio(C1-C4)alkyl, (C1-C4)alkylsulfinyl(C1-4)alkyl, and (C1-C4)alkylsulfonyl(C1-C4)alkyl each optionally substituted with one to three substituents independently selected from the group consisting of OH, (═O), CONH2, CO2H, COCH3, C(O)2CH3, NH2, NHR*, NR*2, aryl, heteroaryl, cyano, OR*, SR*, S(═O)R*, S(═O)2R*, OP(═O)(OH)2, NHSO2R*, NR*SO2R*, NHC(═O)R*, NR*C(═O)R*, NHC(═O)OR*, NR*C(═O)OR*, NHC(═O)NH2, NHC(═O)NHR*, NHC(═O)N(R*)2, NR*C(═O)NH2, NR*C(═O)NHR*, NR*C(═O)N(R*)2, OC(═O)NH2, OC(═O)NHR*, OC(═O)N(R*)2, NHS(═O)2OR*, NR*S(═O)2OR*, NHS(═O)2NH2, NHS(═O)2NHR*, NHS(═O)2N(R*)2, NR*S(═O)2NH2, NR*S(═O)2NHR*, NR*S(═O)2N(R*)2, OS(═O)2NH2, OS(═O)2NHR*, OS(═O)2N(R*)2, and heterocyclyl;
• or
• (3) phenyl, phenyl(C1-C4)alkyl, heteroaryl and heteroaryl(C1-C4)alkyl each optionally substituted with one to three substituents independently selected from the group consisting of halogen, OH, CH2OH, (C1-C3)alkyl, (C1-C3)haloalkyl, OR, O((C1-C3)haloalkyl), CN, CH2CN, NO2, CH2NO2, SH, SR*, SO3H, CH2SO3H, SO2R*,CH2SO2R*, SO2NH2, SO2NHR*, SO2NR*2, CH2SO2NH2, CH2SO2NHR*, CH2SO2NR*2, SO2CF3, CH2SO2CF3, CONH2, CONHR*, CONR*2, CH2CONH2, CH2CONHR*, CH2CONR*2, CO2H, CH2CO2H, NH2, NHR*, NR*2, (C 1 -C3)alkyl(NH2), (C1-C3)alkyl(NHR*), (C1-C3)alkyl(NR*2) aryl, heteroaryl, SO2H, and CH2SO2H;
• each R* is independently C1-C3 alkyl;
• provided that
• 1) R1 and R2 are not both hydrogen when E is a bond;
• 2) R1 is not hydrogen when m is greater than 0;
• and
• 3) the compound of Formula (I) is not a hydrate or solvate;
• E is a bond, CH2, CHMe, CMe2, CH2CH2, OCH2, OCHMe, OCMe2, SCH2, SCHMe, or SCMe2, provided that O and S are attached to R1;
• G is a 1, 2, or 3 carbon alkylene chain;
• Y is independently selected from the group consisting of halogen, (C1-C3)alkyl, CF3, CONH2, CH2CONH2, CO2H, CH2CO2H, (C1-C3)alkylamino(C1-C3)alkyl and di(C 1-C3)alkyl amino (C 1-C3)alkyl ;
• n =0, 1,2 or 3;
• A =bond, CH2, CHMe, CMe2, or CH2CH2;
• Cy =(C7-C12)bicycloalkyl or (C9-C12)tricycloalkyl in which 1-2 carbon atoms are optionally replaced with heteroatoms independently selected from N and O and which is optionally substituted with 1 -3 groups independently selected from halogen, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, hydroxy, hydroxy(C1-C3)alkyl, amino, (C1-C4)acylamino, (C1-C3)alkylsulfonylamino, CH2CH2CO2H, (C1-C3)alkylcarbamoyl, di(C1-C3)alkylcarbamoyl, (C1-C3)alkylaminosulfonyl, di(C1-C3)alkylaminosulfonyl, aralkyl, aryl, heteroaryl, oxo-substituted heteroaryl, amino-substituted heteroaryl, heterocyclyl, oxo-substituted heterocyclyl, C(=NOH)NH2, CON(R4)2, CH2CON(R4)2, SO2N(R4)2, CO2R4, CH2CO2R4, SO2R4, NR4COR4, NR4CO2R4, NR4SO2R4 and OC(═O)N(R4)2,
• wherein each R4 is independently hydrogen, (C1-C10) alkyl, aryl or aralkyl;
• or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.