Substituted pyrimidine compounds and methods of use

A compound of formula

• or a pharmaceutically acceptable salt thereof, wherein
• wherein R1 is -Z-Y, provided that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3;
• and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R1 is 0-4;
• wherein each Z is a bond;
• each Y is independently a
• (1) hydrogen radical;
• (2) halo or nitro radical;
• (3) —C(O)—R20 or —C(NR5)—NR5R21 radical;
• (4) —OR21, —O—C(O)—R21, —O—C(O)—NR5R21 or —O—C(O)—NR22—S(O)2—R20 radical;
• (5) —SR21, —S(O)—R20, —S(O)2—R20, —S(O)2—NR5R21, —S(O)2—NR22—C(O)—R21, —S(O)2—NR22—C(O)—OR22 or —S(O)2—NR22—C(O)—NR5R21 radical;
• or
• (6) —NR5R21, —NR22—C(O)—R21, —NR22—C(O)—OR20, —NR22—C(O)—NR5R21, —NR22—C(NR5)—NR5R21, —NR22—S(O)2—R20 or —NR22—S(O)2—NR5R21 radical;
• wherein each R5 is independently
• (1) hydrogen radicals;
• (2) alkyl, alkenyl or alkynyl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, hydroxy, alkoxy, alkylthio, —SO3H or halo;
• or
• (3) aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl or cycloalkylalkyl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, hydroxy, alkoxy, alkylthio, alkyl or haloalkyl;
• and
• wherein each R20 is independently
• (1) alkyl, alkenyl or alkynyl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, N-(alkoxycarbonyl)-N-(alkyl)amino, aminocarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halo or aralkoxy, aralkylthio, aralkylsulfonyl, cycloalkyl, heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkanoyl, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halo, alkyl or haloalkyl;
• (2) heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkyl or haloalkyl;
• or
• (3) aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxy, alkoxy, alkylthio, cyano, halo, azido, alkyl or haloalkyl;
• each R21 is independently hydrogen radical or R20;
• each R22 is independently
• (1) hydrogen radical;
• (2) alkyl radical optionally substituted by a radical of heterocyclyl, aryl or heteroaryl optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl;
• or
• (3) heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl;
• provided when Y is —NR22—C(O)—NH2, then R22 is other then an optionally substituted aryl radical;
• and
• R11 is an aryl radical, wherein the aryl radical is substituted by 1-2 radicals of
• (1) R30;
• (2) halo or cyano radicals;
• (3) —C(O)—R30, —C(O)—OR29, —C(O)—NR31R32 or —C(NR31)—NR31R32 radicals;
• or
• (4) —OR29, —SR29, —S(O)—R30, —S(O)2—R30, —S(O)2—NR31R32, —NR31R32 or —NR33—C(O)—R29 radicals;
• R12 is a heteroaryl radical, wherein the heteroaryl radical is optionally substituted by 1-2 radicals of
• (1) R30;
• (2) halo or cyano radicals;
• (3) —C(O)—R30, —C(O)—OR29, —C(O)—NR31R32 or —C(NR31)—NR31R32 radicals;
• or
• (4) —OR29, —SR29, —S(O)—R30, —S(O)2—R30, —S(O)2—NR31R32, —NR31R32 or —NR33—C(O)—R29 radicals;
• provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals substituted on each of R11 and R12 is 0-1;
• wherein each R30 is independently
• (1) alkyl, alkenyl or alkynyl radicals optionally substituted by 1-3 radicals of —NR31R31, —CO2R23, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo or aralkoxy, aralkylthio, aralkylsulfonyl, heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl;
• (2) heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl;
• or
• (3) aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl;
• each R29 is independently hydrogen radical or R30;
• each R31 and R32 are each independently
• (1) hydrogen radicals;
• (2) alkyl radical optionally substituted by an cycloalkyl, aryl, heterocyclyl or heteroaryl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl;
• or
• (3) aryl, heteroaryl, heterocyclyl or cycloalkyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl;
• and
• wherein each R33 is independently
• (1) hydrogen radical;
• or
• (2) alkyl radical optionally substituted by a radical of heterocyclyl, aryl or heteroaryl optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl;
• and
• provided that (1) when R11 is phenyl and R12 is 4-pyridyl, then R1 is other than H, methyl, or amino;
• and (2) when R11 is 2-methylphenyl and R12 is 2-pyridyl, then R1 is other than n-propyl.