Pyrimidine derivatives for the treatment of abnormal cell growth

A compound of the formula 1

• or a pharmaceutically acceptable salt thereof,
• wherein n is 1;
• R1 is a substituent independently selected from the group consisting of hydrogen, hydroxy, and —(C1-C6)alkyl optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —CN, —(C1-C6)alkyl, —NR5R6, —OR5, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, —CONR5R6 and —CONR5R8;
• R2 is a substituent independently selected from the group consisting of hydrogen and —(C1-C6)alkyl, optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —NO2, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —C═N—OH, —C═N—O((C1-C6)alkyl), —NR5R6, —OR5, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, —CONR5R6, —CONR5R8, —SR7, —SOR7, —SO2R7, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7, wherein said —(C2-C6)alkenyl and —(C2-C6)alkynyl R2 moieties may be optionally substituted by one to three R5 groups;
• R3 is —(C1-C9)heteroaryl, optionally substituted by one to three moieties independently selected from the group consisting of halogen, hydroxy, —(C1-C6)alkyl, (C3-C10)cycloalkyl, —NHSO2(C1-C6)alkyl, —NHSO2(C3-C6)cycloalkyl, N((C1-C6)alkyl)(SO2(C1-C6)alkyl), —N((C1-C6)alkyl)(SO2(C3-C6)cycloalkyl), —O(C1-C6)alkyl, —O—SO2(C1-C6)alkyl, SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, SO2NH2, SO2NH(C1-C6)alkyl, —SO2NH(C3-C6)cycloalkyl, —SO2N((C1-C6)alkyl)2, —SO2N((C3-C6)cycloalkyl)2, and —SO2NR5R6;
• R4 is a substituent selected from the group consisting of hydrogen, (C1-C6)alkyl, —(C3-C7)cycloalkyl, and —(C2-C9)heterocyclyl;
• wherein said (C1-C6)alkyl, —(C3-C7)cycloalkyl, and —(C2-C9)heterocyclyl R4 substituents are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, —(C1-C6)alkyl, —CN, —NR52, —OR5, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, and —CONR5R8;
• with the proviso that a heteroatom of the foregoing R4 substituents may not be bound to an sp3 carbon atom bound to another heteroatom;
• and wherein R5 and R8 of said —CONR5R8 group may be taken together with the atoms to which they are attached to form a —(C3-C10)cycloalkyl or —(C2-C9)heterocyclyl;
• R5 and R6 are each substituents independently selected from the group consisting of hydrogen, —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl;
• wherein said —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl R5 or R6 substituents are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, —CF3, —CN, —(C1-C6)alkyl, —NH(C1-C6)alkyl, —NH(C3-C7)cycloalkyl, —NH(C2-C9)heterocyclyl, —NH(C6-C10)aryl, —NH(C1-C9)heteroaryl, —N((C1-C6)alkyl)2, —N((C3-C7)cycloalkyl)2, —N((C2-C9)heterocyclyl)2, —N((C6-C10)aryl)2, —N((C1-C9)heteroaryl)2, —O(C1-C6)alkyl, —O(C3-C7)cycloalkyl, —O(C2-C9)heterocyclyl, —O(C6-C10)aryl, —O(C1-C9)heteroaryl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R7, —CONH2, —CONHR7, and —CONR7R8;
• with the proviso that a heteroatom of the foregoing R5 or R6 substituents or moieties may not be bound to an sp3 carbon atom bound to another heteroatom;
• and wherein R7 and R8 of said —CONR7R8 group may be taken together with the atoms to which they are attached to form a —(C1-C9) heteroaryl;
• R7 is a substituent selected from the group consisting of —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, and —(C1-C9) heteroaryl;
• wherein said —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, and —(C1-C9) heteroaryl R7 substituents are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —CN, —(C1-C6)alkyl, and —O(C1-C6)alkyl, with the proviso that a heteroatom of the foregoing R7 substituents or moieties may not be bound to an sp3 carbon atom bound to another heteroatom;
• R8 is a substituent selected from the group consisting of hydrogen, —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, and —(C1-C9) heteroaryl;
• wherein said —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, and —(C1-C9) heteroaryl R8 radicals are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —CN, —(C1-C6)alkyl, —NH2, —NHR9, —NR92, OR9, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R10, —CONH2, —CONHR10, and —CONR10R11;with the proviso that a heteroatom of the foregoing R8 substituents or moieties may not be bound to an sp3 carbon atom bound to another heteroatom;
• and wherein R10 and R11 of —CONR10R11 may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
• R9 and R10 are each —(C1-C6)alkyl and may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
• and
• R11 is hydrogen or —(C1-C6)alkyl.