2-Azabicyclo[3.3.1]nonane derivatives

A compound of formula I:

• 23
• wherein Ra is H or a
• 24
• group;
• Wherein X is H, halogen, —CN, —C≡C—R3a or a —C1-C4 alkyl group optionally substituted with from one to three halogen atoms;
• Q is H, halogen, a C1-C6 alkyl, —CN, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)(C1-C4 alkyl), —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), —C(═O)N(C1-C4 alkyl)(C1-C4 alkyl), —NHC(═O)H, —NHC(═O)R8, or —NHS(═O)2R8;
• R1 and R2 are independently H, a C1-C6 alkyl, —(CH2)j-aryl, —(CH2)j-heteroaryl, wherein said alkyl, —(CH2)j-aryl or —(CH2)j-heteroaryl group is optionally substituted with one or more R10 groups, or with the carbon to which R1 and R2 are attached, R1 and R2 form a C3-C7 carbocyclic or 4- to 7-membered heterocyclic group, wherein said heterocyclic group comprises from one to three heteroatoms selected from the group consisting of O, S and N and said carbocyclic or heterocyclic group optionally contains a —C(═O) group or optionally contains one or more double bonds and is optionally fused to or substituted with a C6-C14 aryl or a 5-14 membered heteroaryl group;
• wherein said C3-C7 carbocyclic or 4- to 7-membered heterocyclic group formed by R1 and R2 may optionally be substituted with from one to three R10 groups, and said optionally fused or substituted aryl or heteroaryl group may each optionally independently be substituted with from one to six R10 groups;
• R10 groups are independently selected from R11, H, halogen, —OR11, —NO2, —CN, —C1-C6 alkyl, —C3-C6 cycloalkyl, —C(R3)R10aR10b, aryl optionally substituted with from 1 to 3 R3 groups, —(CH2)v—NR11R12, —NR11C(═O)R12, —C(═O)NR11R12, —OC(═O)R11, —C(═O)OR11, C(═O)R11, —NR11C(═O)OR12, —NR11C(═O)NR12R13, —NR12S(═O)2R11, —NR11S(═O)2NR12R13, and —S(═O)2R11;
• R3 is absent or is H, —C1-C4 alkyl, which optionally contains one or two unsaturated bonds, —OH, —O(C1-C4)alkyl, —(C1-C4)alkylOH, —(CH2)n—NR10aR10b, —(CH2)n—NHC(═O)(C1-C4 alkyl), —(CH2)n—NO2, —(CH2)n—C≡N, —(CH2)n—C(═O)NH2, —(CH2)n—C(═O)NH(C1-C4 alkyl) or —(CH2)n—C(═O)NR10aR10b;
• R3a is H or C1-C6 alkyl which may be optionally substituted with one or more halogen groups;
• each R4, R4a, R9 and R9a is independently H, —C1-C4 alkyl or —O—C1-C4 alkyl;
• each R8, R11, R12 and R13 is independently selected from H, —C1-C6 alkyl, C3-C6 cycloalkyl, aryl, —(C2-C4 alkyl)-O—(C1-C4alkyl), aryl, —(CH2)m—NR14R15, or a 4- to 7-membered heterocyclic group, or where any two groups selected from R11, R12 and R13 can form a heterocyclic ring with the atom to which they are attached, wherein said heterocyclic group or said heterocyclic ring is optionally substituted with at least one C1-C4 alkyl group;
• each R10a and R10b is independently selected from H, —C1-C4 alkyl;
• or, independently in each instance of —C(R3)R10aR10b, R10a and R10b connect to form a C3-C7 carbocyclic ring or a 4-7 membererd heterocyclic ring or in each instance of —(CH2)v—C(═O)NR10aR10b, R10a and R10b connect to form a 4-7 membererd heterocyclic ring;
• R14 and R15 are independently H, C1-C6 alkyl or together may form a 4- to 7-membered carbocyclic or heterocyclic ring;
• j is in each instance independently an integer from 0 to 5;
• m is 0 or an independently variable integer 2 or greater;
• n is in each instance independently an integer from 0 to 5;
• v is in each instance independently an integer from 0 to 5;
• and pharmaceutically acceptable salts thereof, with the provisos that
• a) when Ra is
• 25
• and n is 0, and when the carbon to which R1, R2 and R4 are bound is sp3 hybridized (i.e., “saturated”), then none of R1, R2 and R4 can be a heteroatom or contain a heteroatom which is directly linked to the carbon of said
• 26
• group;
• b) R8 cannot be H when part of a —NHS(═O)2R8 group, R11 cannot be H when part of a —NR12S(═O)2R11 and —S(═O)2R11;
• and
• c) v of —(CH2)v—cannot be 1 when said methylene unit is connected to N, O or S;