2-(Pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-ones

A compound of the formula I:

• 16
• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein:
• the dashed line represents an optional bond,
• X1, X2, and X3 are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C8 alkoxy, C1-C8 alkoxyalkyl, CN, NO2, OR5, NR5R6, CO2R5, COR5, S(O)nR5, CONR5R6, NR5COR6, NR5SO2R6, SO2NR5R6, and P(O)(OR5)(OR6);
• with the proviso that at least one of X1, X2, and X3 must be hydrogen;
• n=0-2;
• R1 is, in each instance, independently, hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydoxyalkyl, or C3-C7 cycloalkyl;
• R2 and R4 are independently selected from hydrogen, halogen, C1-C8 alkyl, C3-C7 cycloalkyl, C1-C8 alkoxy, C1-C8 alkoxyalkyl, C1-C8 haloalkyl, C1-C8 hydroxyalkyl, C2-C8 alkenyl, C2-C8 alkynyl, nitrile, nitro, OR5, SR5, NR5R6, N(O)R5R6, P(O)(OR5)(OR6), (CR5R6)mNR7R8, COR5, (CR4R5)mC(O)R7, CO2R5, CONR5R6, C(O)NR5SO2R6, NR5SO2R6, C(O)NR5OR6, S(O)nR5, SO2NR5R6, P(O)(OR5)(OR6), (CR5R6)mP(O)(OR7)(OR8), (CR5R6)m-aryl, (CR5R6)m-heteroaryl, T(CH2)mQR5, —C(O)T(CH2)mQR5, NR5C(O)T(CH2)mQR5, and —CR5═CR6C(O)R7;
• or
• R1 and R2 may form a carbocyclic group containing 3-7 ring members, preferably 5-6 ring members, up to four of which can optionally be replaced with a heteroatom independently selected from oxygen, sulfur, and nitrogen, and wherein the carbocyclic group is unsubstituted or substituted with one, two, or three groups independently selected from halogen, hydroxy, hydroxyalkyl, nitrile, lower C1-C8 alkyl, lower C1-C8 alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino, and mono or dialkylamino, (CH2)mC(O)NR5R6, and O(CH2)mC(O)OR5, provided, however, that there is at least one carbon atom in the carbocyclic ring and that if there are two or more ring oxygen atoms, the ring oxygen atoms are not adjacent to one another;
• T is O, S, NR7, N(O)R7, NR7R8W, or CR7R8;
• Q is O, S, NR7, N(O)R7, NR7R8W, CO2, O(CH2)m-heteroaryl, O(CH2)mS(O)nR8, (CH2)-heteroaryl, or a carbocyclic group containing from 3-7 ring members, up to four of which ring members are optionally heteroatoms independently selected from oxygen, sulfur, and nitrogen, provided, however, that there is at least one carbon atom in the carbocyclic ring and that if there are two or more ring oxygen atoms, the ring oxygen atoms are not adjacent to one another, wherein the carbocyclic group is unsubstituted or substituted with one, two, or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, trifluoromethyl, N-hydroxyacetamide, trifluoromethylalkyl, amino, and mono or dialkylamino;
• W is an anion selected from the group consisting of chloride, bromide, trifluoroacetate, and triethylammonium;
• m=0-6;
• R4 and one of X1, X2 and X3 may form an aromatic ring containing up to three heteroatoms independently selected from oxygen, sulfur, and nitrogen, and optionally substituted by up to 4 groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluoromethylalkylaminoalkyl, amino, mono- or dialkylamino, N-hydroxyacetamido, aryl, heteroaryl, carboxyalkyl, nitrile, NR7SO2R8, C(O)NR7R8, NR7C(O)R8, C(O)OR7, C(O)NR7SO2R8, (CH2)mS(O)nR7, (CH2)m-heteroaryl, O(CH2)m-heteroaryl, (CH2),C(O)NR7R8, O(CH2)mC(O)OR7, (CH2)mSO2NR7R8, and C(O)R7;
• R3 is hydrogen, aryl, C1-C8 alkyl, C1-C8 alkoxy, C3-C7 cycloalkyl, or C3-C7-heterocyclyl;
• R5 and R6 independently are hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, arylalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or heterarylalkyl;
• or
• R5 and R6, when attached to the same nitrogen atom, taken together with the nitrogen to which they are attached, form a heterocyclic ring containing from 3-8 ring members, up to four of which members can optionally be replaced with heteroatoms independently selected from oxygen, sulfur, S(O), S(O)2, and nitrogen, provided, however, that there is at least one carbon atom in the heterocyclic ring and that if there are two or more ring oxygen atoms, the ring oxygen atoms are not adjacent to one another, wherein the heterocyclic group is unsubstituted or substituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluoromethylalkylaminoalkyl, amino, nitrile, mono- or dialkylamino, N-hydroxyacetamido, aryl, heteroaryl, carboxyalkyl, NR7SO2R8, C(O)NR7R8, NR7C(O)R8, C(O)OR7, C(O)NR7SO2R8, (CH2)mS(O)nR7, (CH2)m-heteroaryl, O(CH2)m-heteroaryl, (CH2)mC(O)NR7R8, O(CH2)mC(O)OR7, and (CH2)SO2NR7R8;
• R7 and R8 are, independently, hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, arylalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or heterarylalkyl;
• or
• R7 and R8, when attached to the same nitrogen atom, taken together with the nitrogen to which they are attached, may form a heterocyclic ring containing from 3-8 ring members, up to four of which members are optionally heteroatoms independently selected from oxygen, sulfur, S(O), S(O)2, and nitrogen, provided, however, that there is at least one carbon atom in the heterocyclic ring and that if there are two or more ring oxygen atoms, the ring oxygen atoms are not adjacent to one another, wherein the heterocyclic group is unsubstituted or substituted with one, two or three groups independently selected from halogen, hydroxy, hydroxyalkyl, lower alkyl, lower alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, aminoalkyl, aminoalkylcarbonyl, trifluoromethyl, trifluoromethylalkyl, trifluoromethylalkylaminoalkyl, amino, nitrile, mono- or dialkylamino, N-hydroxyacetamido, aryl, heteroaryl, carboxyalkyl;
• and
• the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.