Compounds and compositions as inhibitors of cannabinoid receptor 1 activity

A compound of Formula I:

• in which:
• Y1 is selected from N and CR11;
• Y2 is selected from N and CR8;
• Z1 is selected from S, O, NH, CH—NO2, NS(O)2NH2, NC(O)NH2, NS(O)2CH3, N(OH) and N(CN);
• or C=Z1 of Formula I is replaced with CH2 or S(O)2;
• Z2 is selected from O, —CH2CHR1a—, —OCHR1a—, —CR1aR1b and —NR1a;
• R1a is selected from hydrogen, cyano, C1-6alkyl, cyano-substituted-C1-6alkyl, C2-6alkenyl, —X1R12, —X1NR13S(O)2R13, —X1OS(O)2R13, —X1NR13X1OR13, —X1OR13, —X1C(O)OR13, —X1S(O)2R12, —X1S(O)2NR13C(O)R13, —X1S(O)2R13, —X1C(O)R12, —X1NR13R13, —X1S(O)2NR13R13, —X1(O)C(O)NR13R13, —X1C(O)NR12R13, —X1NR13X1C(O)NR12, —X1NR13X1C(O)NR13R13, —X1C(O)NR13X1C(O)OR13, —X1C(O)NR13X1NR13R13, —X1C(O)NR13X1OR13 and —X1C(O)NR13R13;
• wherein R12 is selected from C6-10aryl, C5-10heteroaryl, C3-12cycloalkyl and C3-10heterocycloalkyl;
• wherein said aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R12 is optionally substituted by 1 to 3 radicals independently selected from hydroxy, bis-hydroxy-C1-6alkyl-amino, C1-6alkyl-amino, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-carbonyl, C1-6alkyl-sulphoxy, C1-6alkyl-carboxy, C1-6alkyl-sulfonyl, halo-substituted-C1-6alkyl, halo-substituted-C1-6alkoxy, C3-12cycloalkyl, C3-10heterocycloalkyl, C5-10heteroaryl and C6-10aryl optionally substituted with 1 to 3 halo radicals;
• wherein said cycloalkyl, heterocycloalkyl, heteroaryl and aryl substituents of R12 can be further optionally substituted with 1 to 3 C1-6alkyl radicals;
• wherein each R13 is independently selected from hydrogen, C1-6alkyl, hydroxy-C1-6alkyl, C6-10aryl, C3-10heterocycloalkyl;
• wherein said aryl or heterocycloalkyl of R13 is optionally substituted with a group selected from C1-6alkyl and C1-6alkoxy;
• wherein each X1 is independently selected from a bond and C1-4alkylene;
• R1b is selected from hydrogen, C1-6alkyl and C2-6alkenyl;
• R2a is selected from hydrogen, C1-6alkyl, halo-substituted-C1-6alkyl, C6-10aryl, —X2NR14X2NR14R14, —X2NR14C(O)X2NR14C(O)OR14, —X2NR14X2R15, —X2OC(O)NR14R14, —X2OC(O)NR14R15, —X2NR14R14, —X2NR14S(O)2R14, —X2NR14S(O)2R15, —X2S(O)0-2R15, —X2NR14C(O)R14, —X2NR14C(O)R15, —X2NR14C(O)X2NR14R14, —X2OSi(R14)3, —X2OC(O)NR14R15, —X2C(O)OR14, —X2OR14, —X2OX2R15, —X2R15 and —X2C(O)R15;
• wherein each R14 is independently selected from hydrogen and C1-6alkyl;
• R15 is selected from cyano, C6-10aryl, C5-10heteroaryl, C3-12cycloalkyl and C3-10heterocycloalkyl;
• wherein said aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R15 is optionally substituted by 1 to 3 radicals independently selected from hydroxy, C1-6alkyl, C1-6alkoxy, C1-6alkyl-sulphoxy, halo-substituted-C1-6alkyl, halo-substituted-C1-6alkoxy, —X3NR16R16, —X3ONR16R16, —X3OR16, —X3S(O)2R16, —X3NR16C(O)OR16, —X3NR16S(O)0-2R16, —X3R16, —X3C(O)OR16, —X3C(O)NR16R16, —X3OC(O)NR16R16, —X3S(O)0-2NR16R16, —X3C(O)R16, C6-10aryl and C5-10heteroaryl;
• wherein said aryl and heteroaryl substituents of R15 are optionally substituted with 1 to 3 halo radicals;
• each X2 and X3 are independently selected from a bond and C1-4alkylene;
• and each R16 is independently selected from hydrogen, C1-6alkyl, C6-10aryl, C5-10heteroaryl, C3-8cycloalkyl and C3-12heterocycloalkyl;
• wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R16 is optionally substituted by 1 to 3 radicals independently selected from halo, cyano, C1-6alkyl, C1-6alkyl-carbonyl-amino and C1-6alkoxy;
• R2b is selected from hydrogen and C1-6alkyl;
• or R2a and R2b together with the carbon atom to which R2a and R2b are attached form carbonyl;
• R3, R5, R6 and R7 are each independently selected from hydrogen, halo and amino;
• R4 is selected from hydrogen, halo, hydroxy, C1-6alkyl, C1-6alkoxy, halo-substituted-C1-6alkyl, halo-substituted-C1-6alkoxy, hydroxy-substituted-C1-6alkyl, hydroxy-substituted-C1-6alkoxy, cyano-substituted-C1-6alkyl, cyano-substituted-C1-6alkoxy, —OX5R4a and —OX5R4a;
• wherein X5 is selected from a bond and C1-4alkylene;
• R4a is selected from C1-6alkyl, C3-8cycloalkyl, C6-10aryl and C5-10heteroaryl;
• wherein any cycloalkyl, aryl or heteroaryl of R4a is optionally substituted with 1 to 3 radicals independently selected from halo, cyano, amino, C1-6alkyl, C1-6alkoxy, halo-substituted-C1-6alkyl, halo-substituted-C1-6alkoxy, hydroxy-substituted-C1-6alkyl, hydroxy-substituted-C1-6alkoxy, cyano-substituted-C1-6alkyl and cyano-substituted-C1-6alkoxy;
• R8, R9, R11 and R12a are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkoxy, halo-substituted-C1-6alkyl and halo-substituted-C1-6alkoxy;
• R10 is selected from halo, cyano, C1-6alkyl, C1-6alkoxy, halo-substituted-C1-6alkyl, halo-substituted-C1-6alkoxy, —X4OR17, —X4S(O)0-2R17 and —X4R17;
• wherein X4 is selected from a bond and C1-4alkylene;
• and R17 is selected from C6-10aryl and C5-10hetyeroaryl;
• wherein R17 is optionally substituted with 1 to 3 halo radicals;
• or a pharmaceutically acceptable salt thereof.