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US 7,351,712 B2Granted
Pyrimidine derivatives for the treatment of abnormal cell growth
AssigneePfizer Inc.
InventorsJohn Charles Kath, Michael Joseph Luzzio
Life of this patent
Estimating the term…
Abstract
The present invention relates to a compound of the formula 1 wherein R1-R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.
Claims6
A method for the treatment of cancer solid tumor in a mammal comprising administering to said mammal an amount of a compound of the formula 1
- or a pharmaceutically acceptable salt thereof,
- wherein n is an integer from 1 to 3;
- each R1 is a substituent independently selected from the group consisting of hydrogen, hydroxy, —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —O(C1-C6)alkyl, —O(C3-C7)cycloalkyl, —O(C2-C9)heterocyclyl, —NR5R6, —SR7, —SOR7, —SO2R7, —CO2R5, —CONR5R6, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7;
- with the proviso that a heteroatom of the foregoing R1 substituents may not be bound to an sp3 carbon atom bound to another heteroatom;
- and said R1 substituents, —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —O(C3-C7)alkyl, —O(C1-C6)cycloalkyl, —O(C2-C9)heterocyclyl, —NR5R6, —SR7, —SOR7, —SO2R7, —CO2R5, —CONR5R6, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7 groups are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —CN, —(C1-C6)alkyl, —NR5R5, —OR5, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, —CONR5R6 and —CONR5R8;
- with the proviso that a heteroatom of the foregoing optional R1 moieties may not be bound to an sp3 carbon atom bound to another heteroatom;
- each R2 is a substituent independently selected from the group consisting of hydrogen, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C7)cycloalkyl, —(C2-C9)heteroclyl, —CO2R5, and —CONR5R6;
- with the proviso that a heteroatom of any of the foregoing R2 substituents may not be bound to an sp3 carbon atom that is bound to another heteroatom;
- and said R2 substituents, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, -CO2R5, and —CONR5R8, are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —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;
- and with the proviso that a heteroatom of the foregoing optional R2 moieties may not be bound to an sp3 carbon atom bound to another heteroatom;
- R1 and R2 may be taken together with the atom(s) to which they are attached to form a cyclic group, —(C3-C10)cycloalkyl or —(C2-C9)heterocyclyl, wherein said cyclic group is optionally substituted by one to three moieties selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —NO2, —CN, —(C1-C6)alkyl, —(C2-C9)alkenyl, —(C2-C6)alkynyl, —C═N—OH, —C═N—O((C1-C6)alkyl), —NR5R6, —OR6, —(C3-C7)cycloalkyl, —(C2-C9)heterocycyl, —CO2R5, —CONR5R6, —CONR5R8, —SR7, —SOR7, —SO2R7, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7, wherein said —(C2-C6)alkenyl and —(C2-C6)alkynyl moieties of said cyclic group may be optionally substituted by one to three R5 groups, and said cyclic group is optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— and —NR5, with the proviso that any of the foregoing cyclic group moieties or elements may not be bound to an sp3 carbon atom that is bound to another heteroatom;
- R3 is a suitable substituent, including, but not limited to a substituent selected from the group consisting of:
- (a) hydrogen:
- (b) (C6-C10)aryl or —(C1-C9)heteroaryl, optionally substituted by one to three moieties independently selected from the group consisting of halogen, hydroxy, —(C1-C6)alkyl, —(C1-C6)alkyl-P(O)(O(C1-C6)alkyl)2, —(C3-C10)cycloalkyl, (C6-C10)aryl, (C2-C9)heterocyclyl, —(C1-C9)heteroaryl, —NR5R8, —NHSO2(C1-C6)alkyl, —NHSO2(C3-C6)cycloalkyl , —N((C1-C6)alkyl)(SO2C1-C6)alkyl), —N((C1-C6)alkyly)(SO2(C3-C6)cycloalkyl), —O(C1-C8)alkyl, —O—SO2(C1-C6)alkyl, —(CO)(C1-C6)alkyl, —(CO)CF3, —(CO)(C3-C10)cycloalkyl, —(CO)(C6-C10)aryl, —(CO)(C2-C9)heterocyclyl, —(CO)(C1-C9)heteroaryl, —(CO)O(C1-C6)alkyl, —(CO)O((C3-C10)cycloalkyl, —(CO)O(C2-C10)aryl, —(CO)O(C2-C9)heterocyclyl, —(CO)O(C1-C9)heteroaryl, —(CO)(C1-C6)alkyl-O(C1-C6)alkyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, SO2CF3, SO2NH2, SO2NH(C1-C6)alkyl, —SO2NH(C3-C6)cycloalkyl, —SO2N((C1-C6)alkyl)2, —SO2N((C3-C6)cycloalkyl)2, —SO2NR5R6, and —SO2N (C1-C6)alkyl-(C6-C10)aryl;
- wherein said —(C6-C10) aryl or —(C1-C9) heteroaryl are optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— and —NR5;
- and R5 and R6 of said NR5R6 R3(b) group may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl:
- (c) —(C3-C10)cycloalkyl, —(C2-C9)heterocyclyl, and —(C1-C6)alkyl-(C2-C9) heterocyclyl, optionally substituted by one to three moieties independently selected from the group consisting of halogen, hydroxy, —(C1-C6)alkyl, —(C1-C6)alkyl-P(O)(O(C1-C6)alkyl)2, —(C3-C10)cycloalkyl, (C6-C10)aryl, (C2-C9)heterocyclyl, —(C1-C9)heteroaryl, —NR5R6, —NSO2(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, —O—SO2(C1-C6)alkyl, —(CO)(C1-C6)alkyl, —(CO)CF3, —(CO)(C6-C10)cycloalkyl, —(CO)(C6-C10)aryl, —(CO)(C2-C9)heterocyclyl, —(CO)(C1-C9)heteroaryl, —(CO)O(C1-C6)alkyl, —(CO)O(C3-C10)cycloalkyl, —(CO)O(C6-C10)aryl, —(CO)O(C2-C9)heterocyclyl, —(CO)O(C1-C9)heteroaryl, —(CO)(C1-C6)alkyl—O(C1-C6)alkyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, SO2CF3, SO2NH2, SO2NH(C1-C6)alkyl, —SO2NH(C3-C6)cycloalkyl, —SO2N((C1-C6)alkyl)2, —SO2N2((C3-C6)cycloalkyl)2, —SO2NR5R6, and —SO2N(C1-C6)alkyl-(C6-C10)aryl;
- wherein said —(C3-C10)cycloalkyl, —(C2-C9)heterocyclyl, and —(C1-C6)alkyl-(C2-C9) heterocyclyl are optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— and —NR5;
- and R5 of said NR5R6 R3(b) group may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
- (d) —(C1-C6)alkyl optionally substituted by one to three moieties selected from the group consisting of halogen, hydroxy, —(C1-C6)alkyl —(C1-C6)alkyl-P(O)(O(C1-C6)alkyl)2, —(C3-C10)cycloalkyl, (C6-C10)aryl, (C2-C9)heterocyclyl, —(C1-C9)heteroaryl, —NR5R5, —NSO2(C1-C6)alkyl, —NHSO2(C3-C6)cycloalkyl, —N((C1-C6)alkyl)(SO2C1-C6)alkyl), —N((C1-C6)alkyl)(SO2(C3-C6)cycloalkyl, —O(C1-C6)alkyl, —O—SO2(C1-C6)alkyl, —(CO)(C1-C6)alkyl, —(CO)CF3, —(CO)(C3-C10)cycloalkyl, —(CO)(C6-C10)aryl, —(CO)(C2-C9)heterocyclyl, —(CO)(C1-C9)heteroaryl, —(CO)O(C1-C6)alkyl, —(CO)O(C3-C10)cycloalkyl, —(CO)O(C6-C10)aryl, —(CO)O(C2-C9)heterocyclyl, —(CO)O(C1-C9)heteroaryl, —(CO)(C1-C6)alkyl-O(C1-C6)alkyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, SO2CF3, SO2NH2, SO2NH(C1-C6)alkyl, —SO2NH(C3-C6)cycloalkyl, —SO2N((C1-C6)alkyl)2, —SO2N((C3-C6)cycloalkyl)2, —SO2NR5R6, and —SO2N(C1-C6)alkyl-(C6-C10)aryl;
- wherein said —(C1-C6)alkyl is optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2—, —S—, —O—, —N—, —NH— and —NR5;
- and R5 and R6 of said NR5R5 R3(b) group may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
- and wherein each R3 (b)-(d) substituent, moiety, or element is optionally substituted by one to three radicals independently selected from the group consisting of hydrogen, halogen, hydroxy, —CF—, —NO2, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, —(C1-C9)heteroaryl, —O(C1-C6)alkyl, —O(C3-C7)cycloalkyl, —O(C2-C9)heterocyclyl, —C═N—OH, —C═N—O(C1-C5 alkyl), —NR5R6, —SR7, —SOR7, —SO2R7, —CO2R5, —CONR5R6, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7;
- with the proviso that a heteroatom of the foregoing R3 (b)-(d) substituents, moieties, elements or radicals may not be bound to an sp3 carbon atom bound to another heteroatom;
- and wherein R5 and R6 of said —NR5R6, —CONR5R6, —SO2NR5R6, and —NR5CONR5R6 groups may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
- 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, —NR25, —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, —(C5-C10)aryl, and —(C1-C9)heteroaryl;
- wherein siad —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, and —(C1-C9)heteroaryl R5 or R6 substituents 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 heteroatoms;
- 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;
- R5 and R6 may be taken together with the atom(s) to which they are attached to form a cyclic group, —(C3-C10)cycloalkyl or —(C2-C9)heterocyclyl, wherein said cyclic group is optionally substituted by one to three moieties selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —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, —CONR5R5, —CONR5R6, —SR7, —SOR7, —SO2R7, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7, wherein said —(C2-C6)alkenyl and —(C2-C6)alkynyl moieties of said cyclic group may be optionally substituted by one to three R7 groups, and said cyclic group is optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— and —NR5, with the proviso that any of the foregoing cyclic group moieties or elements may not be bound to an sp3 carbon atom that is bound to another heteroatom;
- 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;
- herein 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, —NR52, 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, —NR29, 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 that is effective in treating said cancer solid tumor, wherein said cancer solid tumor is breast cancer.
40 more elements
A composition comprising a compound of the formula 1
- or a pharmaceutically acceptable salt thereof,
- wherein n is an integer from 1 to 3:
- each R1 is a substituent independently selected from the group consisting of hydrogen, hydroxy, —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —O(C1-C9)alkyl, —O(C3-C7)cycloalkyl, —O(C2-C9)heterocyclyl, —NR5R6, SR7, —SOR7, —SO2R7, —CO2R5, —CONR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7;
- with the proviso that a heteroatom of the foregoing R1 substituents may not be bound to an sp3 carbon atom bound to another heteroatom;
- and said R1 substituents, —(C1-C6)alkyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —O(C1-C6)alkyl, —O(C3-C7)cycloalkyl , —O(C2-C9)heterocyclyl, —NR5R6, —SR7, —SOR7, —SO2R7, —CO2R5, —CONR5R6, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7 groups are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —CN, —(C1-C6)alkyl, —NR5R6, —OR5, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, —CONR5R6 and —CONR5R8;
- with the proviso that a heteroatom of the foregoing optional R1 moieties may not be bound to an sp3 carbon atom bound to another heteroatom;
- each R2 is a substituent independently selected from the group consisting of hydrogen, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, and —CONR5R6;
- with the proviso that a heteroatom of any of the foregoing R2 substituents may not be bound to an sp3 carbon atom that is bound to another heteroatom;
- and said R2 substituents, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, and —CONR5R6, are optionally substituted by one to three moieties independently selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —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, —NHCOR6, —NR5CONR5R6, and —NR6SO2R7, wherein said —(C2-C6)alkenyl and —(C2-C6)alkynyl R2 moieties may be optionally substituted by one to three R5 groups;
- and with the proviso that a heteroatom of the foregoing optional R2 moieties may not be bound to an sp3 carbon atom bound to another heteroatom;
- R1 and R2 may be taken together with the atom(s) to which they are attached to form a cyclic group, —(C3-C10)cycloalkyl or —(C2-C9)heterocyclyl, wherein said cyclic group is optionally substituted by one to three moieties selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —NO2, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —C═N—OH, —C═N—O((C1-C6)alkyl), —NR5R6, —OR6, —(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 moieties of said cyclic group may be optionally substituted by one to three R6 groups, and said cyclic group is optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— and —NR5, with the proviso that any of the foregoing cyclic group moieties or elements may not be bound to an sp3 carbon atom that is bound to another heteroatom;
- R3 is a suitable substituent, including, but not limited to a substituent selected from, the group consisting of:
- (a) hydrogen;
- (c) —(C6-C10)aryl or —(C1-C9)heteroaryl, optionally substituted by one to three moieties independently selected from the group consisting of halogen, hydroxy, —(C1-C6)alkyl-P(O)CO(C1-C6)alkyl)2, —(C3-C10)cycloalkyl, (C6-C10)aryl, (C2-C9)heterocyclyl, —(C1-C9)heteroaryl, —NR5R6, —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, —(CO)(C1-C6)alkyl, —(CO)CF3, —(CO)(C3-C10)cycloalkyl, —(CO)(C6-C10)heteroaryl, —(CO)(C2-C9)heterocyclyl, —(CO)(C1-C9)heteroaryl, —(CO)O(C1-C6)alkyl, —(CO)O(C3-C10)cycloalkyl, —(CO)O(C6-C10)aryl, —(CO)O(C2-C9)heterocyclyl, —(CO)O(C1-C9)heteroaryl, —(CO)(C1-C6)alkyl-O(C1-C6)alkyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, SO2CF3, SO2NH2, SO2NH(C1-C6)alkyl, —SO2NH(C3-C6)cycloalkyl, —SO2N((C1-C6)alkyl)2, —SO2N((C3-C6)cycloalkyl)2, —SO2NR5R6, and —SO2N(C1-C6)alkyl-(C6-C10)aryl;
- wherein said —(C6-C10) aryl or —(C1-C9) heteroaryl are optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— AND —NR5;
- and R5 and R6 of said NR5R6R3(b) group may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
- (c) —(C3-C10)cycloalkyl, —(C2-C9)heterocyclyl, and —(C1-C6)alkyl-(C2-C9) heterocyclyl, optionally substituted by one to three moieties independently selected from the group consisting of halogen, hydroxy, —(C1-C6)alkyl, —(C1-C6)alkyl-P(O)(O(C1-C6)alkyl)2, —(C3-C10)cycloalkyl, (C6-C10)aryl, (C2-C9)heterocyclyl, —(C1-C9)heteroaryl, —NR5R6, —NSO2(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, —O—SO2(C1-C6)alkyl, —(CO)(C1-C6)alkyl, —(CO)CF3, —(CO)(C3-C10)cycloalkyl, —(CO)(C6-C10)aryl, —(CO)(C2-C9)heterocyclyl, —(CO)(C1-C9)heteroaryl, —(CO)O(C1-C6)alkyl, —(CO)O(C3-C10)cycloalkyl, —(CO)O(C6-C10)aryl, —(CO)O(C2-C9)heterocyclyl, —(CO)O(C1-C9)heteroaryl, —(CO)(C1-C6)alkyl-O(C1-C6)alkyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, SO2CF3, SO2HN2, SO2NH(C1-C6)alkyl, —SO2NH(C3-C6)cycloalkyl, —SO2N((C1-C6)alkyl)2, —SO2N((C3-C6)cycloalkyl)2, —SO2NR5R6, and —SO2N(C1-C6)alkyl-(C6-C10)aryl;
- wherein said —(C3-C10)cycloalkyl, —(C2-C9)heterocyclyl, and —(C1-C6)alkyl-(C2-C9) heterocyclyl are optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— and —NR5;
- and R5 and R6 of said NR5R6 R3(b) group may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
- (d) —(C1-C6)alkyl optionally substituted by one to three moieties selected from the group consisting of halogen, hydroxy, —(C1-C6)alkyl, —(C1-C6)alkyl-P(O)(O(C1-C6)alkyl)2, —(C3-C10)cycloalkyl, (C6-C10)aryl, (C2-C9)heterocyclyl, —(C1-C9)heteroaryl, —NR5R6, —NSO2(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, —(CO)(C1-C6)alkyl, —(CO)CF3, —(CO)(C3-C10)(C3-C10)(C3-C10)cycloalkyl, —(CO)(C6-C10)aryl, —(CO)(C2-C9)heterocyclyl, —(CO)(C1-C9)heteroaryl, —(CO)O(C1-C6)alkyl, —(CO)O(C3-C10)cycloalkyl, —(CO)O(C6-C10)aryl, —(CO)O(C2-C9)heterocyclyl, —(CO)O(C1-C9)heteroaryl, —(CO)(C1-C6)alkyl-O(C1-C6)alkyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, SO2CF3, SO2NH2, SO2NH(C3-C6)alkyl, —SO2NH(C3-C6)cycloalkyl, —SO2N((C1-C6)alkyl)2, —SO2N((C3-C6)cycloalkyl2, —SO2NR5R6, and —SO2N(C1-C6)alkyl-(C6-C10)aryl;
- wherein said —(C1-C6)alkyl is optionally interrupted by one to three elements selected from the group consisting of —(C═O), —SO2, —S—, —O—, —N—, —NH— and —NR5;
- and R5 and R6 of said NR5R6 R3(b) group may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
- and wherein each R3 (b)-(d) substituent, moiety, or element is optionally substituted by one to three radicals indeoendently selected from the orouo consisting of hydrogen, halogen, hydroxy, —CF3, —NO2, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —(C6-C10)aryl, —(C1-C9)heteroaryl, —O(C1-C6)alkyl, —(C3-C7)cycloalkyl, —O(C2-C9)heterocyclyl, —C═N—OH, —C═N—O(C1-C6 alkyl), —NR5R6, —SR7—SOR7, SO2R7, —CO2R6, —CONR5R6, —NHCOR5, —NR5CONR5R6, and —NR5SO2R7;
- with the proviso that a heteroatom of the foregoing R3 (b)-(d) substituents, moieties, elements or radicals may not be bound to an sp3 carbon atom bound to another heteroatom;
- end wherein R5 and R6 of said —NR6R8, —CONR5R6, —SO2NR5R6, and —NR5CONR5R6 groups may be taken together with the atoms to which they are attached to form a —(C2-C9)heterocyclyl;
- R4 is a substituent selected from the rou 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 indeuendently 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 tthe 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 R8 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 heteroatoms;
- 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;
- R5 and R8 may be taken together with the atom (s) to which they are attached to form a cyclic group, —(C3-C10)cycloalkyl or —(C2-C9)heterocyclyl, wherein said cyclic group is optionally substittned by one to three moieties selected from the group consisting of hydrogen, halogen, hydroxy, —CF3, —NO2, —CN, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —C═N—OH, —C═N—((C1-C6)alkyl), —NR5R6, —OR5, —(C3-C7)cycloalkyl, —(C2-C9)heterocyclyl, —CO2R5, —CONR5R6, —CONR5R8, —SR7, —SOR7, —SO2R7, —SO2NR5R6, —NHCOR5, —NR5CONR5R6, and —NR8SO2R7, wherein said —(C2-C6)alkenyl and —(C2-C8)alkynylmoities of said cyclic group may be optionally substituted by one to three R7 groups, and said cyclic group is optionally interrupted by one to three elements selected from the group consisting of —(C═O), —S—, —O—, —N—, —NH— and —NR6, with the proviso that any of the foregoing cyclic group moieties or elements may not be bound to an sp3 carbon atom that is bound to another hetematom;
- 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, —NR52, 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);
- 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, and a pharmaceutically acceptable carrier.
40 more elements
Dependencies are inferred from the claim text.