2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use

A compound of formula I

• wherein A is O or S;
• wherein D is selected from CR1, CR2, CR3, CR4 and N;
• wherein E is selected from CR1, CR2, CR3, CR4 and N;
• wherein F is selected from CR1, CR2, CR3, CR4 and N;
• wherein G is selected from CR1, CR2, CR3, CR4 and N;
• wherein J is selected from NR6, S, O, CR1, CR2, CR3 and CR4;
• wherein K is selected from NR6, S, O, CR1, CR2, CR3 and CR4;
• wherein L is selected from NR6, S, O, CR1, CR2, CR3 and CR4;
• wherein Q is selected from H, hydroxy, —N(R5)2, —NR5C(O)R5, —(C1–C8)alkyl-OR5, —(C1–C8)alkyl-S(O)nR5,
• substituted aryl, an unsubstituted or substituted monocyclic or bicyclic, non-aromatic carbocyclic ring, an unsubstituted or substituted monocyclic or bicyclic, heteroaryl and an unsubstituted or substituted monocyclic or bicyclic, non-aromatic heterocyclic ring, wherein the ring is unsubstituted or substituted with one or more groups selected from H, halo, aryl, alkynyl, alkenyl, —OR5, —N(R5)2, —(C1–C8)alkyl-N(R5)2, —(C1–C8)alkyl-S(O)nR5, —N(R5)2(C1–C8)alkyl-N(R5)2, lower alkoxyalkyl, —S(O)nR5, —NR5S(O)nR5, cyano, (C1–C8)alkyl, lower cyanoalkyl, lower alkylaminoalkoxy, lower aminoalkoxyalkyl (C3–C10cycloalkyl, nitro, optionally substituted 4–7 membered heterocyclyl, optionally substituted phenoxyalkyl, optionally substituted heterocyclyloxyalkyl, —SO2NR5R5, —NR5SO2R5, —C(O)N(R5)2, —CO2R5, —CO2NR5R5, —SO2NHC(O)R5, optionally substituted phenylalkyl, optionally substituted heterocyclylalkyl, —NR5C(O)N(R5)2, —NR5C(O)R5, —NR5CO2R5 and —C(O)R5;
• wherein W is selected from thienyl, thiazolyl, oxazolyl, imidazolyl, pyrrolyl, furyl, pyrazolyl, isoxazolyl, thiadiazolyl, triazolyl and isothiazolyl that is unsubstituted or substituted with one or more groups selected from halo, aryl, cycloalkyl, —OR5, (C2–C8)alkenyl, (C2–C8)alkynyl, —N(R5)2, —(C1–C8)alkyl-N(R5)2, —SO2NR5R5, —(C1–C8)alkyl-SO2R5, —(C1–C8)alkyl-SO2—(C1–C8)alkyl-R5, —C1–C8)alkyl-SO2—(C1–C8)aryl, —(C1–C8)alkyl-SO2—(C1–C8)heteroaryl, (C1–C8)alkyl, (C3–C10)cycloalkyl, nitro, cyano, optionally substituted 5–6 membered heterocyclyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, —NR5S(O)nR5, —C(O)N(R5)2, —CO2R5, optionally substituted phenylalkyl, optionally substituted heterocyclylalkyl, —NR5C(O)N(R5)2, —NR5C(O)R5 and —NR5CO2R5;
• wherein Y is selected from H, —N(R5a)2, —SR5a, —OR5a, and —C(R5a)3;
• wherein Z is selected from H, —N(R5a)2, —SR5a, —OR5a, and —C(R5a)3;
• wherein n is 0, 1 or 2;
• wherein R1, R2, R3, and R4 are independently selected from H, —OR5, alkylenedioxy, halo, optionally substituted aryl, alkenyl, alkynyl, —NR52, —(C1–C8)alkyl-N(R5)2, —S(O)n—NR5R5, —S(O)nR5, (C1–C8)alkyl, (C1–C8)haloalkyl, hydroxy-(C1–C8)alkyl, optionally substituted (C3–C10)cycloalkyl, nitro, cyano, optionally substituted 4–10 membered heterocyclyl, —C(O)R5, —NR5SO2R5, —C(O)N(R5)2, —CO2R5, optionally substituted arylalkyl, optionally substituted 4–10 membered heterocyclylalkyl, —NR5C(O)N(R5)2, —NR5C(O)R5 and —NR5CO2R5;
• wherein R1 and R2 may be joined to form a 5–10 membered saturated or unsaturated carbocyclic or heterocyclic ring;
• wherein R2 and R3 may be joined to form a 5–10 membered saturated or unsaturated carbocyclic or heterocyclic ring;
• or wherein R3 and R4 may be joined to form a 5–10 membered saturated or unsaturated carbocyclic or heterocyclic ring;
• wherein R5 is independently selected from H, lower alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted C3–C6 cycloalkyl, optionally substituted C3–C6 cycloalkyl-alkyl, lower alkyl-NR5-lower alkyl, and lower haloalkyl;
• wherein R5a is independently selected from H, and (C1–C6)alkyl;
• wherein R6 is selected from H, (C1–C2)alkyl, and a lone pair of electrons;
• wherein each alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkynyl, alkynyl, and alkoxy moiety of any R1, R2, R3, R4, or can optionally join with another adjacent or vicinal R1, R2, R3, R4, or R5 form a 3–7 membered ring;
• and
• wherein each aryl, heteroaryl, cycloalkyl, and heterocyclyl moiety of any R1, R2, R3, R4, R5, Y, Z, Q, and W is optionally substituted with one or more groups selected from halo, —NH2, —OH, —CO2H, (C1–C6)alkylamino, (C1–C6)alkoxy, (C1–C6)alkoxyalkyl, (C1–C6)alkyl, di(C1–C6)alkylamino, phenyl, and heterocyclyl;
• provided Q is not pyridinium;
• further provided the compound is not 3-(2-pyridin-3-yl-thiazol-4-yl)-3,4-dihydro-1H-quinazolin-2-one or 6-methyl-3-(2-pyridin-2-yl-thiazol-4-yl)-3,4-dihydro-1H-quinazolin-2-one,
• and pharmaceutically acceptable salt thereof.