1-Amino 1H-imidazoquinolines

A compound of the Formula (II):

• 94
• wherein:
• each RA is independently selected from the group consisting of:
• halogen,
• hydroxy,
• alkyl,
• alkenyl,
• haloalkyl,
• alkoxy,
• alkylthio,
• —NH2,
• —NH(alkyl), and
• —N(alkyl)2;
• n is an integer from 0 to 4;
• R1′ is selected from the group consisting of hydrogen and alkyl;
• R1 is selected from the group consisting of:
• —R4,
• —Y—R4,
• —X—R5,
• —X—N(R6)—Y—R4,
• —X—C(R7)—N(R6)—R4, and
• —X—O—R4;
• or R1′ and R1 together with the nitrogen atom to which they are bonded can join to form a group selected from the group consisting of:
• 95
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4 is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from the group consisting of:
• 96
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• R7 is selected from the group consisting of ═O and ═S;
• R8 is C2-7 alkylene;
• A is selected from the group consisting of —CH(R6)—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• X is C2-20 alkylene;
• Y is selected from the group consisting of —C(R7)—, —C(R7)—O—, —S(O)2—, —S(O)2—N(R6)—, and —C(R7)—N(R9)—;
• wherein R9 is selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 97
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4;
• and
• R″ is hydrogen or a non-interfering substituent;
• or a pharmaceutically acceptable salt thereof.

A compound of the Formula (I-1):

• 98
• wherein:
• R1′ is selected from the group consisting of hydrogen and alkyl;
• R1 is selected from the group consisting of:
• —R4,
• —Y—R4,
• —X—R5,
• —X—N(R6)—Y—R4,
• —X—C(R7)—N(R6)—R4, and
• —X—O—R4;
• or R1′ and R1 together with the nitrogen atom to which they are bonded can join to form a group selected from the group consisting of:
• 99
• R2 is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R6)2,
• —N(R)—C(R7)—C1-10 alkyl,
• —N(R6)—S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• R3 is selected from the group consisting of:
• -Z′-R4′,
• -Z′-X′—R4′,
• -Z′-X′—Y′—R4′, and
• -Z′-X′—R5′;
• each R is independently selected from the group consisting of alkyl, alkenyl, alkoxy, halogen, fluoroalkyl, hydroxy, amino, alkylamino, and dialkylamino;
• n is an integer from 0 to 4;
• m is 0 or 1;
• with the proviso that when m is 1, then n is 0 or 1;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4 is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from the group consisting of:
• 100
• X is C2-20 alkylene;
• Y is selected from the group consisting of —C(R7)—, —C(R7)—O—, —S(O)2—, —S(O)2—N(R6)—, and —C(R7)—N(R9)—;
• wherein R9 is selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 101
• Z is selected from the group consisting of —O— and —S(O)0-2—;
• A is selected from the group consisting of —CH(R6)—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4;
• R4′ is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, arylalkylenyl, aryloxyalkylenyl, alkylarylenyl, heteroaryl, heteroarylalkylenyl, heteroaryloxyalkylenyl, alkylheteroarylenyl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, hydroxyalkyl, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, aryl, aryloxy, arylalkyleneoxy, heteroaryl, heteroaryloxy, heteroarylalkyleneoxy, heterocyclyl, amino, alkylamino, dialkylamino, (dialkylamino)alkyleneoxy, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo;
• R5′ is selected from the group consisting of:
• 102
• X′ is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, heteroarylene, and heterocyclylene wherein the alkylene, alkenylene, and alkynylene groups can be optionally interrupted or terminated by arylene, heteroarylene, or heterocyclylene and optionally interrupted by one or more —O— groups;
• Y′ is selected from the group consisting of:
• 103
• Z′ is a bond or —O—;
• A′ is selected from the group consisting of —CH2—, —O—, —C(O)—, —S(O)0-2—, and —N(R4′)—;
• Q is selected from the group consisting of a bond, —C(R7)—, —C(R7)—C(R7)—, —S(O)2—, —C(R7)—N(R11)—W—, —S(O)2—N(R11)—, —C(R7)—O—, and —C(R7)—N(OR12)—;
• V is selected from the group consisting of —C(R7)—, —O—C(R7)—, —N(R11)—C(R7)—, and —S(O)2—;
• W is selected from the group consisting of a bond, —C(O)—, and —S(O)2—;
• c and d are independently integers from 1 to 6 with the proviso that c+d is ≦7, and when A′ is —O— or —N(R4′)— then c and d are independently integers from 2 to 4;
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• each R7 is independently selected from the group consisting of ═O and ═S;
• each R8 is independently C2-7 alkylene;
• R10 is C3-8 alkylene;
• each R11 is independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C1-10 alkoxyC2-10 alkylenyl, and arylC1-10 alkylenyl;
• and
• R12 is selected from the group consisting of hydrogen and alkyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the Formula (I-2):

• 105
• wherein:
• RB is selected from the group consisting of alkyl, alkoxy, halogen, hydroxy, and trifluoromethyl;
• n is an integer from 0 to 4;
• R1′ is selected from the group consisting of hydrogen and alkyl;
• R1 is selected from the group consisting of:
• —R4,
• —Y—R4,
• —X—R5,
• —X—N(R6)—Y—R4,
• —X—C(R7)—N(R6)—R4, and
• —X—O—R4;
• or R1′ and R1 together with the nitrogen atom to which they are bonded can join to form a group selected from the group consisting of:
• 106
• R2 is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R)2,
• —N(R6)—C(R7)—C1-10 alkyl,
• —N(R6)—S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4 is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from the group consisting of:
• 107
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• each R7 is independently selected from the group consisting of ═O and ═S;
• R8 is C2-7 alkylene;
• A is selected from the group consisting of —CH(R6)—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• X is C2-20 alkylene;
• Y is selected from the group consisting of —C(R7)—, —C(R7)—O—, —S(O)2—, —S(O)2—N(R6)—, and —C(R7)—N(R9)—;
• wherein R9 is selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 108
• Z is selected from the group consisting of —O— and —S(O)0-2—;
• and
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4;
• or a pharmaceutically acceptable salt thereof.

A compound of the Formula (I-3):

• 110
• wherein:
• RB is selected from alkyl, alkoxy, halogen, hydroxy, and trifluoromethyl;
• n is an integer from 0 to 4;
• R1′ is selected from hydrogen and alkyl;
• R1 is selected from:
• —R4,
• —Y—R4,
• —X—R5,
• —X—N(R6)—Y—R4,
• —X—CR7—N(R6)—R4, and
• —X—O—R4;
• or R1′ and R1 together with the nitrogen atom to which they are bonded can join to form a group selected from:
• 111
• R2A is selected from:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from:
• —OH,
• -halogen,
• —N(R6)2,
• —CR7—N(R6)2,
• —SO2—N(R6)2,
• —N(R6)—CR7—C1-10 alkyl,
• —N(R6)—SO2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• R4 is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4 is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from:
• 112
• R6 is selected from hydrogen, alkyl, and arylalkylenyl;
• R7 is selected from ═O and ═S;
• R9 is C2-7 alkylene;
• R9 is selected from hydrogen, alkyl, and arylalkylenyl, or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 113
• A is selected from —CHR6—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• X is C2-20 alkylene;
• Y is selected from —CR7—, —SO2—, —SO2—N(R6)—, and —CR7—N(R9)—;
• Z is selected from —O— and —S(O)0-2—;
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4
• and pharmaceutically acceptable salts thereof.

A compound of the Formula (II-1):

• 114
• wherein:
• each RA is independently selected from the group consisting of:
• halogen,
• hydroxy,
• alkyl,
• alkenyl,
• haloalkyl,
• alkoxy,
• alkylthio,
• —NH2,
• —NH(alkyl), and
• —N(alkyl)2;
• n is an integer from 0 to 4;
• R1′ is selected from the group consisting of hydrogen and alkyl;
• R1 is selected from the group consisting of:
• —R4,
• —Y—R4,
• —X—R5,
• —X—N(R6)—Y—R4,
• —X—C(R7)—N(R6)—R4, and
• —X—O—R4;
• or R1′ and R1 together with the nitrogen atom to which they are bonded can join to form a group selected from the group consisting of:
• 115
• R2 is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R6)2,
• —N(R6)—C(R7)—C1-10 alkyl,
• —N(R6)—S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4 is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from the group consisting of:
• 116
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• each R7 is independently selected from the group consisting of ═O and ═S;
• R8 is C2-7 alkylene;
• A is selected from the group consisting of —CH(R6)—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• X is C2-20 alkylene;
• Y is selected from the group consisting of —C(R7)—, —C(R7)—O—, —S(O)2—, —S(O)2—N(R6)—, and —C(R7)—N(R9)—;
• wherein R9 is selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 117
• Z is selected from the group consisting of —O— and —S(O)0-2—;
• and
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4;
• or a pharmaceutically acceptable salt thereof.

A compound of the Formula (VII):

• 119
• wherein:
• each RB is independently selected from the group consisting of alkyl, alkoxy, halogen, hydroxy, and trifluoromethyl;
• n is an integer from 0 to 4;
• R2 is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R6)2,
• —N(R6)—C(R7)—C1-10 alkyl,
• —N(R6)— S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• R7 is selected from the group consisting of ═O and ═S;
• and
• Z is selected from the group consisting of —O—and —S(O)0-2—;
• or a pharmaceutically acceptable salt thereof

A compound of the Formula (IX):

• 120
• wherein:
• each RB is independently selected from the group consisting of alkyl, alkoxy, halogen, hydroxy, and trifluoromethyl;
• n is an integer from 0 to 4;
• R1′ is hydrogen or alkyl;
• R1 is selected from the group consisting of:
• —R4,
• —Y—R4,
• —X—R5,
• —X—N(R6)—Y—R4,
• —X—C(R7)—N(R6)—R4, and
• —X—O—R4;
• or R1′ and R1 together with the nitrogen atom to which they are bonded can join to form a group selected from the group consisting of:
• 121
• R2 is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R6)2,
• —N(R6)—C(R7)—C1-10 alkyl,
• —N(R6)—S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4 is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from the group consisting of
• 122
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• each R7 is independently selected from the group consisting of ═O and ═S;
• R8 is C2-7 alkylene;
• A is selected from the group consisting of —CH(R6)—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• X is C2-20 alkylene;
• Y is selected from the group consisting of —C(R7)—, —C(R7)—O—, —S(O)2—, —S(O)2—N(R6)—, and —C(R7)—N(R9)—;
• wherein R9 is selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 123
• Z is selected from the group consisting of —O— and —S(O)0-2—;
• and
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4;
• or a pharmaceutically acceptable salt thereof

A compound of the Formula (X):

• 124
• wherein:
• each RB is independently selected from the group consisting of alkyl, alkoxy, halogen, hydroxy, and trifluoromethyl;
• n is an integer from 0 to 4;
• R1′ is hydrogen or alkyl;
• R1a is selected from the group consisting of:
• —R4a,
• —Y—R4a,
• —X—R5,
• —X—N(R6)—Y—R4a,
• —X—C(R7)—N(R6)—R4a, and
• —X—O—R4a;
• or R1′ and R1a together with the nitrogen atom to which they are bonded can join to form a group selected from the group consisting of:
• 125
• R2a is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -alkylene-Z″-alkyl,
• -alkylene-Z″-aryl,
• -alkylene-Z″-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R6)2,
• —N(R6)—C(R7)—C1-10 alkyl,
• —N(R6)—S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heterocyclyl, and
• —C(O)-aryl;
• R4a is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4a is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from the group consisting of
• 126
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• each R7 is independently selected from the group consisting of ═O and ═S;
• R8 is C2-7 alkylene;
• A is selected from the group consisting of —CH(R6)—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• X is C2-20 alkylene;
• Y is selected from the group consisting of —C(R7)—, —C(R7)—O—, —S(O)2—, —S(O)2—N(R6)—, and —C(R7)—N(R9)—;
• wherein R9 is selected from the group consisting of hydrogen, alkyl and arylalkylenyl, or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 127
• Z″ is selected from the group consisting of —O— and —S(O)2—;
• and
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4;
• or a pharmaceutically acceptable salt thereof.

A compound of the Formula (XLII):

• 128
• wherein:
• R is selected from the group consisting of alkyl, alkenyl, alkoxy, halogen, fluoroalkyl, hydroxy, amino, alkylamino, and dialkylamino;
• l is 0 or 1;
• R2 is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R6)2,
• —N(R6)—C(R7)—C1-10 alkyl,
• —N(R6)—S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• R7 is selected from the group consisting of ═O and ═S;
• and
• Z is selected from the group consisting of —O— and —S(O)0-2—;
• or a pharmaceutically acceptable salt thereof.

A compound of the Formula (XLIII):

• 129
• wherein:
• R is selected from the group consisting of alkyl, alkenyl, alkoxy, halogen, fluoroalkyl, hydroxy, amino, alkylamino, and dialkylamino;
• l is 0 or 1;
• R1′ is hydrogen or alkyl;
• R1 is selected from the group consisting of:
• —R4,
• —Y—R4,
• —X—R5,
• —X—N(R6)—Y—R4,
• —X—C(R7)—N(R6)—R4, and
• —X—O—R4;
• or R1′ and R1 together with the nitrogen atom to which they are bonded can join to form a group selected from the group consisting of:
• 130
• R2 is selected from the group consisting of:
• -hydrogen,
• -alkyl,
• -alkenyl,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• -alkylene-Z-alkyl,
• -alkylene-Z-aryl,
• -alkylene-Z-alkenyl, and
• -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH,
• -halogen,
• —N(R6)2,
• —C(R7)—N(R6)2,
• —S(O)2—N(R6)2,
• —N(R6)—C(R7)—C1-10 alkyl,
• —N(R6)—S(O)2—C1-10 alkyl,
• —C(O)—C1-10 alkyl,
• —C(O)—O—C1-10 alkyl,
• —N3,
• -aryl,
• -heteroaryl,
• -heterocyclyl,
• —C(O)-aryl, and
• —C(O)-heteroaryl;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl groups can be unsubstituted or substituted by one or more substituents independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkylamino, (arylalkylenyl)amino, dialkylamino, and in the case of alkyl, alkenyl, alkynyl, and heterocyclyl, oxo, with the proviso that when R4 is a substituted alkyl group and the substituent contains a hetero atom which bonds directly to the alkyl group then the alkyl group contains at least two carbons between the substituent and the nitrogen atom to which R1 is bonded;
• R5 is selected from the group consisting of
• 131
• each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• each R7 is independently selected from the group consisting of ═O and ═S;
• R8 is C2-7 alkylene;
• A is selected from the group consisting of —CH(R6)—, —O—, —N(R6)—, —N(Y—R4)—, and —N(X—N(R6)—Y—R4)—;
• X is C2-20 alkylene;
• Y is selected from the group consisting of —C(R7)—, —C(R7)—O—, —S(O)2—, —S(O)2—N(R6)—, and —C(R7)—N(R9)—;
• wherein R9 is selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;
• or R9 and R4 together with the nitrogen atom to which R9 is bonded can join to form the group
• 132
• Z is selected from the group consisting of —O— and —S(O)0-2—;
• and
• a and b are independently integers from 1 to 4 with the proviso that when A is —O—, —N(R6)—, —N(Y—R4)—, or —N(X—N(R6)—Y—R4)— then a and b are independently integers from 2 to 4;
• or a pharmaceutically acceptable salt thereof.