1-Amino 1H-imidazoquinolines 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
US2005054640 A1 2005-03-10 [US20050054640]US7163947 B2 2007-01-16 [US7163947] / 2005-03-102007-01-16
申请号/申请日
2004US-10933658 / 2004-09-03
发明人
GRIESGRABER GEORGE W;MANSKE KARL J;
申请人
3M INNOVATIVE PROPERTIES;
主分类号
IPC分类号
A01N-043/42A61K-031/44C07D-471/02C07D-491/00C07D-498/00C07D-513/00
摘要
(US7163947) 1-Amino 1H-imidazoquinoline compounds, pharmaceutical compositions containing the compounds, intermediates, and methods of making and methods of use of these compounds as immunomodulators, for modulating cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases are disclosed.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2003US-60453128 2003-03-07 2003US-60532191 2003-12-23 2004US-10794099 2004-03-05 2004US-10933658 2004-09-03
主权利要求
(US7163947) What is claimed is: 1.  A compound of the Formula (I-1): wherein: R1' is selected from the group consisting of hydrogen, alkyl, alkoxyalkylenyl, and hydroxyalkylenyl wherein the alkylenyl group contains at least two carbon atoms between the hydroxy or alkoxy substituent and the nitrogen atom to which R1' is bonded;  R1 is selected from the group consisting of:  -- R4, -- Y -- R4, -- X -- R5, -- X -- N(R6) -- Y -- R4, -- X -- C(R7) -- N(R6) -- R4, -- X -- S(O)2 -- N(R6) -- R4, and -- X -- O -- R4;R2 is selected from the group consisting of: hydrogen,alkyl,alkenyl,aryl,heteroaryl,heterocyclyl,-alkylene-Z-alkyl,-alkylene-Z-aryl,-alkylene-Z-alkenyl, andalkyl 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) -- C(R7)-aryl, -- N(R6) -- S(O)2 -- C1-10 alkyl, -- N(R6) -- S(O)2-aryl, -- C(O) -- C1-10 alkyl, -- O -- C(R7) -- C1-10 alkyl, -- O -- C(R7)-aryl, -- O -- C(R7) -- N(R6) -- C1-10 alkyl, -- O -- C(R7) -- N(R6)-aryl;  -- 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, 1, or 2;R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl wherein the alkyl, alkenyl, alkynyl, aryl, heteroaxyl, 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, heterocyclyalkylenyl, 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: 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 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, heteroaryalkylenyl, 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: 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 azylene, heteroarylene, or heterocyclylene and optionally interrupted by one or more  -- O --  groups;Y' is selected from the group consisting of: 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 .dbd.O and .dbd.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 alkoxy C2-10 alkylenyl, and arylC1-10 alkylenyl;  and    R12 is selected from the group consisting of hydrogen and alkyl; or a pharmaceutically acceptable salt thereof. 2. The compound or salt of claim 1 wherein 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;  R1' is selected from the group consisting of hydrogen and alkyl;  and 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. 3. The compound or salt of claim 1 wherein R1 is selected from the group consisting of  -- R4,  -- Y -- R4, and  -- X -- N(R6) -- Y -- R4 wherein Y is  -- C(R7) -- ,  -- S(O)2 -- , or  -- C(R7) -- N(R9) -- . 4. The compound or salt of claim 3 wherein R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkylenyl, arylalkenylenyl, heteroarylalkylenyl, heteroarylalkenylenyl, aminoalkylenyl, alkoxyalkylenyl, acyl, alkylsulfonylaminoalkylenyl, arylsulfonylaminoalkylenyl, alkylcarbonylaminoalkylenyl, alkylaminocarbonyl, alkylaminocarbonylaminoalkylenyl, arylaminocarbonyl, (arylalkylenyl)aminoalkylenyl, heterocyclylcarbonylaminoalkylenyl, arylaminocarbonylaminoalkylenyl, heteroarylcarbonylaminoalkylenyl, and heteroarylaminocarbonylaminoalkylenyl. 5. The compound or salt of claim 4 wherein R1 is selected from the group consisting of hydrogen, methyl, isopropyl, butyl, 2-methylpropyl, 1-ethylpropyl, 3-methylbutyl, cyclohexyl, benzyl, 3-phenylpropyl, cinnamyl, furan-2-ylmethyl, and  -- CH2CH2CH2 -- NHR13, wherein R13 is selected from the group consisting of methylcarbonyl, isopropylcarbonyl, cyclopentylcarbonyl, tetrahydropyran-4-ylcarbonyl, methanesulfonyl, phenylsulfonyl, benzyl, ethylaminocarbonyl, isopropylaminocarbonyl, morpholine-4-carbonyl, phenylaminocarbonyl, pyridin-3-ylcarbonyl, and pyridin-3-ylaminocarbonyl. 6. The compound or salt of claim 1 wherein R1' is hydrogen. 7. The compound or salt of claim 1 wherein R1 and R1' are each independently alkyl. 8. The compound or salt of claim 1 wherein R2 is selected from the group consisting of hydrogen, alkyl, alkoxyalkylenyl, and hydroxyalkylenyl. 9. The compound or salt of claim 8 wherein R2 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, n-butyl, methoxymethyl, 2-methoxyethyl, ethoxymethyl, hydroxymethyl, 2-hydroxyethyl, and 3-hydroxypropyl. 10. The compound or salt of claim 1 wherein n is 0. 11. The compound or salt of claim 1 wherein n is 0, and R3 is selected from the group consisting of -Z'-R4', -Z'-X -- R4', and -Z'-X -- Y' -- R4'. 12. The compound or salt of claim 11 wherein R3 is selected from the group consisting of 2-(pyridin-3-yl)ethyl, pyridinyl, (hydroxymethyl)pyridinyl, phenyl, (hydroxymethyl)phenyl, ethoxyphenyl, (morpholine-4-carbonyl)phenyl, 3-(methanesulfonylamino)phenyl, 2-(methanesulfonylamino)ethoxy, 3-(methanesulfonylamino)propoxy, and benzyloxy. 13. The compound or salt of claim 1 wherein m is 0 and n is 1. 14. The compound or salt of claim 13 wherein R is halogen or hydroxy. 15. The compound or salt of claim 1 wherein m and n are each 0. 16. A compound of the Formula (I-2): 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: 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: each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;each R7 is independently selected from the group consisting of .dbd.O and .dbd.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 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. 17. The compound or salt according to claim 16 wherein R1 is selected from the group consisting of  -- R4,  -- Y -- R4, and  -- X -- N(R6) -- Y -- R4 wherein Y is  -- C(R7) -- ,  -- S(O)2 -- , or  -- C(R7) -- N(R9) -- . 18. The compound or salt according to claim 17 wherein R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkylenyl, arylalkenylenyl, heteroarylalkylenyl, heteroarylalkenylenyl, aminoalkylenyl, alkoxyalkylenyl, acyl, alkylsulfonylaminoalkylenyl, arylsulfonylaminoalkylenyl, alkylaminocarbonyl, arylaminocarbonyl, (arylalkylenyl)aminoalkylenyl, and arylaminocarbonylaminoalkylenyl. 19. The compound or salt according to claim 18 wherein R1 is selected from the group consisting of hydrogen, methyl, isopropyl, butyl, 2-methylpropyl, 1-ethylpropyl, 3-methylbutyl, cyclohexyl, benzyl, cinnamyl, furan-2-ylmethyl, and  -- CH2CH2CH2 -- NHR13, wherein R13 is selected from the group consisting of methanesulfonyl, phenylsulfonyl, benzyl, and phenylaminocarbonyl. 20. The compound or salt according to claim 16 wherein R1' is hydrogen. 21. The compound or salt of claim 16 wherein R1 and R1' are each independently alkyl. 22. The compound or salt of claim 16 wherein R1 and R1' join to form the group: 23.  The compound or salt according to claim 16 wherein R2 is selected from the group consisting of hydrogen, alkyl, and alkoxyalkylenyl. 24. The compound or salt according to claim 23 wherein R2 is selected from the group consisting of hydrogen, butyl, 2-methoxyethyl, and ethoxymethyl. 25. The compound or salt according to claim 16 wherein n is 0. 26. The compound or salt according to claim 16 wherein n is 1, and RB is halogen or hydroxy. 27. A compound of the Formula (I-3): 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: 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(R2)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: R6 is selected from hydrogen, alkyl, and arylalkylenyl;R7 is selected from .dbd.O and .dbd.S;R8 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 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. 28. The compound or salt according to claim 27 wherein R1 is selected from  -- R4,  -- Y -- R4, and  -- X -- N(R6) -- Y -- R4 wherein Y is  -- CR7 -- ,  -- SO2 -- , or  -- CR7 -- N(R9) -- . 29. The compound or salt according to claim 28 wherein R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkylenyl, arylalkenylenyl, heteroarylalkylenyl, heteroarylalkenylenyl, aminoalkylenyl, alkoxyalkylenyl, acyl, alkylsulfonylaminoalkylenyl, arylsulfonylaminoalkylenyl, alkylaminocarbonyl, arylaminocarbonyl, (arylalkylenyl)aminoalkylenyl, and arylaminocarbonylaminoalkylenyl. 30. The compound or salt according to claim 29 wherein R1 is selected from hydrogen, isopropyl, butyl, cyclohexyl, benzyl, cinnamyl, and  -- CH2CH2CH2 -- NHR13, wherein R13 is selected from methanesulfonyl, phenylsulfonyl, benzyl, and phenylaminocarbonyl. 31. The compound or salt according to claim 27 wherein R1' is hydrogen. 32. The compound or salt according to claim 27 wherein R2A is selected from hydrogen, alkyl, and alkoxyalkylenyl. 33. The compound or salt according to claim 32 wherein R2A is selected from hydrogen, butyl, methoxyethyl, and ethoxymethyl. 34. The compound or salt according to claim 27 wherein n is 0. 35. A compound of the Formula (II-1): 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, alkyl, alkoxyalkylenyl, and hydroxyalkylenyl wherein the alkylenyl group contains at least two carbon atoms between the hydroxy or alkoxy substituent and the nitrogen atom to which R1' is bonded;R1 is selected from the group consisting of:  -- R4, -- Y -- R4, -- X -- R5, -- X -- N(R6) -- Y -- R4, -- X -- C(R7) -- N(R6) -- R4, -- X -- S(O)2 -- N(R6) -- R4, and -- X -- O -- R4;R2 is selected from the group consisting of: hydrogen,alkyl,alkenyl,aryl,heteroaryl,heterocyclyl,-alkylene-Z-alkyl,-alkylene-Z-aryl,-alkylene-Z-alkenyl, andalkyl 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) -- C(R7)-aryl, -- N(R6) -- S(O)2 -- C1-10 alkyl, -- N(R6) -- S(O)2-aryl, -- C(O) -- C1-10 alkyl, -- O -- C(R7) -- C1-10 alkyl, -- O -- C(R7)-aryl, -- O -- C(R7) -- N(R6) -- C1-10 alkyl, -- O -- C(R7) -- N(R6)-aryl;  -- 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, heteroaxyl, heteroaryloxy, heteroarylalkoxy, heterocyclyl, heterocyclylalkylenyl, amino, alkykmino, (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: each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;each R7 is independently selected from the group consisting of .dbd.O and .dbd.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 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. 36. The compound or salt of claim 35 wherein 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;  R1' is selected from the group consisting of hydrogen and alkyl;  and 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. 37. The compound or salt according to claim 36 wherein R1 is selected from the group consisting of  -- R4,  -- Y -- R4, and  -- X -- N(R6) -- Y -- R4 wherein Y is  -- C(R7) -- ,  -- S(O)2 -- , or  -- C(R7) -- N(R9) -- . 38. The compound or salt according to claim 37 wherein R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkylenyl, arylalkenylenyl, heteroarylalkylenyl, heteroarylalkenylenyl, aminoalkylenyl, alkoxyalkylenyl, acyl, alkylsulfonylaminoalkylenyl, arylsulfonylaminoalkylenyl, alkylaminocarbonyl, arylaminocarbonyl, (arylalkylenyl)aminoalkylenyl, and arylaminocarbonylaminoalkylenyl. 39. The compound or salt according to claim 38 wherein R1 is selected from the group consisting of hydrogen, methyl, isopropyl, butyl, 2-methylpropyl, 1-ethylpropyl, 3-methylbutyl, cyclohexyl, benzyl, cinnamyl, furan-2-ylmethyl, and  -- CH2CH2CH2 -- NHR13, wherein R13 is selected from the group consisting of methanesulfonyl, phenylsulfonyl, benzyl, and phenylaminocarbonyl. 40. The compound or salt according to claim 37 wherein R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkylenyl, arylalkenylenyl, heteroarylalkylenyl, heteroarylalkenylenyl, aminoalkylenyl, alkoxyalkylenyl, acyl, alkylsulfonylaminoalkylenyl, arylsulfonylaminoalkylenyl, alkylaminocarbonyl, alkylaminocarbonylaminoalkylenyl, arylaminocarbonyl, (arylalkylenyl)aminoalkylenyl, heterocyclylcarbonylaminoalkylenyl, and arylaminocarbonylaminoalkylenyl. 41. The compound or salt according to claim 40 wherein R1 is selected from the group consisting of hydrogen, methyl, isopropyl, butyl, 2-methylpropyl, 1-ethylpropyl, 3-methylbutyl, cyclohexyl, benzyl, 3-phenylpropyl, cinnamyl, furan-2-ylmethyl, and  -- CH2CH2CH2 -- NHR13, wherein R13 is selected from the group consisting of methanesulfonyl, phenylsulfonyl, benzyl, isopropylaminocarbonyl, morpholine-4-carbonyl, and phenylaminocarbonyl. 42. The compound or salt of claim 37 wherein R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkylenyl, arylalkenylenyl, heteroarylalkylenyl, heteroarylalkenylenyl, aminoalkylenyl, alkoxyalkylenyl, acyl, alkylsulfonylaminoalkylenyl, arylsulfonylaminoalkylenyl, alkylcarbonylaminoalkylenyl, alkylaminocarbonyl, alkylaminocarbonylaminoalkylenyl, arylaminocarbonyl, (arylalkylenyl)aminoalkylenyl, heterocyclylcarbonylaminoalkylenyl, arylaminocarbonylaminoalkylenyl, heteroarylcarbonylaminoalkylenyl, and heteroarylaminocarbonylaminoalkylenyl. 43. The compound or salt of claim 42 wherein R1 is selected from the group consisting of hydrogen, methyl, isopropyl, butyl, 2-methylpropyl, 1-ethylpropyl, 3-methylbutyl, cyclohexyl, benzyl, 3-phenylpropyl, cinnamyl, furan-2-ylmethyl, and  -- CH2CH2CH2 -- NHR13, wherein R13 is selected from the group consisting of methylcarbonyl, isopropylcarbonyl, cyclopentylcarbonyl, tetrahydropyran-4-ylcarbonyl, methanesulfonyl, phenylsulfonyl, benzyl, ethylaminocarbonyl, isopropylaminocarbonyl, morpholine-4-carbonyl, phenylaminocarbonyl, pyridin-3-ylcarbonyl, and pyridin-3-ylaminocarbonyl. 44. The compound or salt according to claim 36 wherein R1' is hydrogen. 45. The compound or salt of claim 36 wherein R1 and R1' are each independently alkyl. 46. The compound or salt according to claim 36 wherein R2 is selected from the group consisting of hydrogen, alkyl, and alkoxyalkylenyl. 47. The compound or salt according to claim 46 wherein R2 is selected from the group consisting of hydrogen, butyl, 2-methoxyethyl, and ethoxymethyl. 48. The compound or salt according to claim 46 wherein R2 is selected from the group consisting of hydrogen, methyl, propyl, butyl, 2-methoxyethyl, and ethoxymethyl. 49. The compound or salt of claim 35 wherein R2 is selected from the group consisting of hydrogen, alkyl, alkoxyalkylenyl, and hydroxyalkylenyl. 50. The compound or salt of claim 49 wherein R2 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, n-butyl, methoxymethyl, 2-methoxyethyl, ethoxymethyl, hydroxymethyl, 2-hydroxyethyl, and 3-hydroxypropyl. 51. The compound or salt according to claim 36 wherein n is 0. 52. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 1 and a pharmaceutically acceptable carrier. 53. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 16 and a pharmaceutically acceptable carrier. 54. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 27 and a pharmaceutically acceptable carrier. 55. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of claim 35 and a pharmaceutically acceptable carrier. 56. A compound of the Formula (X): 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: 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 each R6 is independently selected from the group consisting of hydrogen, alkyl, and arylalkylenyl;each R7 is independently selected from the group consisting of .dbd.O and .dbd.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 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. 57. A compound of the Formula XLII: wherein: R is selected from the group consisting of alkyl, alkenyl, alkoxy, halogen, fluoroalkyl, hydroxy, amino, alkylamino, and dialkylamino;1 is 0, 1, or 2;R2 is selected from the group consisting of: hydrogen,alkyl,alkenyl,aryl,heteroaryl,heterocyclyl,-alkylene-Z-alkyl,-alkylene-Z-aryl,-alkylene-Z-alkenyl, andalkyl 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) -- C(R7)-aryl, -- N(R6) -- S(O)2 -- C1-10 alkyl, -- N(R6) -- S((...)
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