1460903047-3f5c4586-83a0-479b-a01d-1dfdccffa74a

1. A display device comprising:
display emissive elements arranged in a matrix within a display region for emitting light in accordance with a drive current;
a measurement emissive element which is formed in a position different from the display region and formed by the same process as the organic EL elements formed in the display region;
a drive voltage supply circuit for supplying drive voltage to the measurement emissive element;
a drive state detection circuit for detecting a drive state of the measurement emissive element in the case where the drive voltage is supplied by the drive voltage supply circuit; and
a correction circuit for correcting voltage to be applied to each display emissive element in the display region based on the drive state detected by the drive state detection circuit;
wherein the drive voltage to be supplied to the display emissive elements in the display region is a specified voltage and the drive of the display emissive elements in the display region is a digital drive where the drive voltage to be supplied to the measurement emissive element is a predetermined voltage and the supply time of the drive voltage is controllable; and
the correction circuit changes positive or negative power supply voltage of the display emissive elements in the display region.
2. The display device according to claim 1 wherein:
the drive state detection circuit detects the drive current flowing in the measurement emissive element.
3. The display device according to claim 1 wherein:
the drive state detection circuit detects the emission amount of the measurement emissive element.
4. The display device according to claim 1 wherein:
the drive voltage supply circuit supplies drive voltage, which represents the drive voltage supplied to the display emissive elements in the display region, to the measurement emissive element for measurement purposes.
5. The display device according to claim 4 wherein:
the drive voltage supply circuit supplies typical pulsed voltage, which digitally drives the display emissive elements in the display region, to the measurement emissive element.
6. The display device according to claim 1 wherein:
the drive voltage supply circuit detects the degradation over time of the display emissive elements in the display region based on a detection value of the drive state detect circuit by continuously supplying drive voltage, which is same as the voltage to the display emissive elements in the display region, to the measurement emissive element.
7. The display device according to claim 1 wherein:
the display emissive elements in the display region and the measurement emissive elements have the three colors of red (R), green (G) and blue (B), and
the display device comprises a display data set circuit that calculates the maximum luminance of each color of RGB from the drive state of the measurement emissive element of each color of RGB, which is detected by the drive state detect circuit, in the drive state detection circuit and sets display data within a range where the white color is executable.
8. The display device according to claim 1 wherein:
the display emissive elements in the display region and the measurement emissive element are organic EL elements.
9. A method of displaying pixels with a predetermined white balance in a display region emitting light in accordance with a drive current, the display method comprising the steps of:
setting an initialization value of a power source line when a display is turned on;
measuring a current of a plurality of measurement pixels;
calculating a maximum luminance based on the measured current of the measurement pixels;
determining whether calculated value of the maximum luminance is within a targeted range of a set luminance;
resetting the value of the power source line positively if the maximum luminance is greater than the targeted range, and negatively if the maximum luminance is less than the targeted range, and repeating the first four steps above;
setting a maximum gradation of display pixels achieving the predetermined white balance for the display if the calculated value of the maximum luminance is within the targeted range; and
setting a display data of display pixels for the display.
10. The method according to claim 9, wherein the targeted range is \xb110% of the set luminance.
11. A method of displaying pixels with a predetermined white balance in a display region emitting light in accordance with a luminance emission, the display method comprising the steps of:
setting an initialization value of a power source line when a display is turned on;
measuring the luminance emission of a plurality of measurement pixels;
calculating a maximum luminance based on the measured luminance emission of the measurement pixels;
determining whether calculated value of the maximum luminance is within a targeted range of a set luminance;
resetting the value of the power source line positively if the maximum luminance is greater than the targeted range, and negatively if the maximum luminance is less than the targeted range, and repeating the first four steps above;
setting a maximum gradation of display pixels achieving the predetermined white balance for the display if the calculated value of the maximum luminance is within the targeted range; and
setting a display data of display pixels for the display.
12. The method according to claim 11, wherein the targeted range is \xb110% of the set luminance.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A method of inhibiting activity of one or more kinases in a patient, wherein the kinases are selected from the group consisting of Checkpoint kinases, Pim kinases, and Aurora kinases, the method comprising administering a therapeutically effective amount of at least one compound, or a pharmaceutically acceptable salt, solvate, ester or prodrug of the compound, the compound being selected from the group consisting of the compounds represented by any of the structural formulas I through VI below:
wherein:
R is H, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkylalkyl, alkenylalkyl, alkynylalkyl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl (including N-oxide of said heteroaryl), \u2014(CHR5)n-aryl, \u2014(CHR5)n-heteroaryl,
\u2003wherein each of said alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R2 is selected from the group consisting of H, R9, alkyl, alkenyl, alkynyl, CF3, heterocyclyl, heterocyclylalkyl, halogen, haloalkyl, aryl, arylalkyl, heteroarylalkyl, alkynylalkyl, cycloalkyl, heteroaryl, alkyl substituted with 1-6 R9 groups which can be the same or different and are independently selected from the list of R9 shown below, aryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, aryl fused with an aryl or heteroaryl group, heteroaryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, heteroaryl fused with an aryl or heteroaryl group,
\u2003wherein one or more of the aryl andor one or more of the heteroaryl in the above-noted definitions for R2 can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, \u2014CN, \u2014OR5, \u2014SR5, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014NR5R6, \u2014C(O)NR5R6, CF3, alkyl, aryl and OCF3;
R3 is selected from the group consisting of H, halogen, \u2014NR5R6, \u2014OR6, \u2014SR6, \u2014C(O)N(R5R6), alkyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl,
\u2003wherein each of said alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl for R3 and the heterocyclyl moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, CN, \u2014OCF3, \u2014(CR4R5)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR4R5)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7, \u2014N(R5)C(R4R5)nN(R5R6) and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R4 is H, halo or alkyl;
R5 is H, alkyl, aryl, heteroaryl, arylalkyl or cycloalkyl;
R6 is selected from the group consisting of H, Boc, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR4R5, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)NR4R5, \u2014C(O)R5, \u2014SO3H, \u2014SR5, \u2014S(O2)R7, \u2014S(O2)NR4R5, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR4R5;
or optionally (i) R5 and R10 in the moiety \u2014NR5R10, or (ii) R5 and R6 in the moiety \u2014NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of said cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups;

R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein each of said alkyl, cycloalkyl, heteroarylalkyl, aryl, heteroaryl and arylalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7 and \u2014S(O2)R7;
R9 is selected from the group consisting of halogen, CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
m is 0 to 4, and
n is 1 to 4; and
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof,
wherein:
R2 is selected from the group consisting of halo; \u2014CF3; \u2014CN; \u2014SR6; \u2014NO2; \u2014NR5R6a; \u2014C(O)R6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)NR5R10; alkyl; alkenyl; alkynyl; heterocyclyl; heterocyclylalkyl; halo; haloalkyl; cycloalkyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; heteroarylalkyl; alkynylalkyl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group;
\u2003wherein each of the alkyl, alkenyl, alkynyl, heterocyclyl, heterocyclylalkyl, haloalkyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, and alkynylalkyl groups and the heterocyclic moieties shown immediately above for R2 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014C(\u2550N\u2014OH), \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R3 is selected from the group consisting of H; \u2014NR5R6a; \u2014OR6b; \u2014SR6; CF3; \u2014C(O)N(R5R6); alkyl; alkenyl, alkynyl; cycloalkyl; aryl; arylalkyl; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl;
\u2003wherein each of the alkyl, alkynyl; cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, and the heterocyclic moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014C(\u2550N\u2014OH), \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R4 is selected from the group consisting of \u2014CF3; \u2014CN; \u2014NR5R6a; \u2014(CR5R11)pC(O2)R6; \u2014(CR5R11)pC(O)NR5R10; \u2014C(O)\u2014N(R5R10); \u2014OR6b; \u2014SR6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014C(O)R6; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)R7; \u2014N(R5)C(O)NR5R10; alkenyl; alkenyl (substituted with alkoxy); hydroxyalkyl; alkynyl; heterocyclyl; heterocyclylalkyl; aryl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group; substituted alkyl; cycloalkyl;
\u2003wherein each of the alkyl, cycloalkyl; heterocyclyl, heterocyclylalkyl, aryl, fused aryl, heteroaryl and fused heteroaryl groups of R4 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(R5)(\u2550N\u2014OR5), \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety, and wherein the substituted alkyl group of R4 is independently substituted with one or more of the above moieties;
R5 is H, alkyl, aryl or cycloalkyl;
R6 is selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6a is selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6b is selected from the group consisting of alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, \u2014CF3, \u2014OCF3, \u2014CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7, \u2014C(\u2550N\u2014OH), and \u2014N(R5)C(O)NR5R10;
R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl, wherein each of the alkyl, cycloalkyl, heteroarylalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014OR6, \u2014NR5R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7, \u2014C(\u2550N\u2014CN)\u2014NH2, \u2014C(\u2550NH)\u2014NHR5, heterocyclyl, \u2014S(O2)R7, and
R9 is selected from the group consisting of halo, \u2014CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10; and
R10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014SO3H, \u2014SR5, \u2014S(O2)R7, \u2014S(O2)NR5R11, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R 5)C(O)NR5R11;
or optionally (i) R5 and R10 in the moiety \u2014NR5R10, or (ii) R5 and R6 in the moiety \u2014NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of the cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups;

R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein each of said alkyl, cycloalkyl, heteroarylalkyl, aryl, heteroaryl and arylalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7 and \u2014S(O2)R7;
R9 is selected from the group consisting of halogen, CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
m is 0 to 4, and
n is 1 to 4; and
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof,
wherein:
R2 is selected from the group consisting of halo; \u2014CF3; \u2014CN; \u2014SR6; \u2014NO2; \u2014NR5R6a; \u2014C(O)R6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)NR5R10; alkyl; alkenyl; alkynyl; heterocyclyl; heterocyclylalkyl; halo; haloalkyl; cycloalkyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; heteroarylalkyl; alkynylalkyl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group;
\u2003wherein each of the alkyl, alkenyl, alkynyl, heterocyclyl, heterocyclylalkyl, haloalkyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, and alkynylalkyl groups and the heterocyclic moieties shown immediately above for R2 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014C(\u2550N\u2014OH), \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R3 is selected from the group consisting of H; \u2014NR5R6a; \u2014OR6b; \u2014SR6; CF3; \u2014C(O)N(R5R6); alkyl; alkenyl, alkynyl; cycloalkyl; aryl; arylalkyl; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl;
\u2003wherein each of the alkyl, alkynyl; cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, and the heterocyclic moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014C(\u2550N\u2014OH), \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R4 is selected from the group consisting of \u2014CF3; \u2014CN; \u2014NR5R6a; \u2014(CR5R11)pC(O2)R6; \u2014(CR5R11)pC(O)NR5R10; \u2014C(O)\u2014N(R5R10); \u2014OR6b; \u2014SR6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014C(O)R6; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)R7; \u2014N(R5)C(O)NR5R10; alkenyl; alkenyl (substituted with alkoxy); hydroxyalkyl; alkynyl; heterocyclyl; heterocyclylalkyl; aryl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group; substituted alkyl; cycloalkyl;
\u2003wherein each of the alkyl, cycloalkyl; heterocyclyl, heterocyclylalkyl, aryl, fused aryl, heteroaryl and fused heteroaryl groups of R4 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(R5)(\u2550N\u2014OR5), \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety, and wherein the substituted alkyl group of R4 is independently substituted with one or more of the above moieties;
R5 is H, alkyl, aryl or cycloalkyl;
R6 is selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6a is selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6b is selected from the group consisting of alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, \u2014CF3, \u2014OCF3, \u2014CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7, \u2014C(\u2550N\u2014OH), and \u2014N(R5)C(O)NR5R10;
R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl, wherein each of the alkyl, cycloalkyl, heteroarylalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014OR6, \u2014NR5R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7, \u2014C(\u2550N\u2014CN)\u2014NH2, \u2014C(\u2550NH)\u2014NHR5, heterocyclyl, \u2014S(O2)R7, and
R9 is selected from the group consisting of halo, \u2014CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10; and
R10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R11, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)NR5R11, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014SO3H, \u2014SR5, \u2014S(O2)R7, \u2014S(O2)NR5R11, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R 5)C(O)NR5R11;
or optionally (i) R5 and R10 in the moiety \u2014NR5R10, or (ii) R5 and R6 in the moiety \u2014NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of the cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups;

R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein each of said alkyl, cycloalkyl, heteroarylalkyl, aryl, heteroaryl and arylalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7 and \u2014S(O2)R7;
R9 is selected from the group consisting of halogen, CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
m is 0 to 4, and
n is 1 to 4; and
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof,
wherein:
R2 is selected from the group consisting of halo; \u2014CF3; \u2014CN; \u2014SR6; \u2014NO2; \u2014NR5R6a; \u2014C(O)R6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)NR5R10; alkyl; alkenyl; alkynyl; heterocyclyl; heterocyclylalkyl; halo; haloalkyl; cycloalkyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; heteroarylalkyl; alkynylalkyl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group;
\u2003wherein each of the alkyl, alkenyl, alkynyl, heterocyclyl, heterocyclylalkyl, haloalkyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, and alkynylalkyl groups and the heterocyclic moieties shown immediately above for R2 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014C(\u2550N\u2014OH), \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R3 is selected from the group consisting of H; \u2014NR5R6a; \u2014OR6b; \u2014SR6; CF3; \u2014C(O)N(R5R6); alkyl; alkenyl, alkynyl; cycloalkyl; aryl; arylalkyl; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl;
\u2003wherein each of the alkyl, alkynyl; cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, and the heterocyclic moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014C(\u2550N\u2014OH), \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R4 is selected from the group consisting of \u2014CF3; \u2014CN; \u2014NR5R6a; \u2014(CR5R11)pC(O2)R6; \u2014(CR5R11)pC(O)NR5R10; \u2014C(O)\u2014N(R5R10); \u2014OR6b; \u2014SR6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014C(O)R6; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)R7; \u2014N(R5)C(O)NR5R10; alkenyl; alkenyl (substituted with alkoxy); hydroxyalkyl; alkynyl; heterocyclyl; heterocyclylalkyl; aryl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group; substituted alkyl; cycloalkyl;
\u2003wherein each of the alkyl, cycloalkyl; heterocyclyl, heterocyclylalkyl, aryl, fused aryl, heteroaryl and fused heteroaryl groups of R4 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(R5)(\u2550N\u2014OR5), \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety, and wherein the substituted alkyl group of R4 is independently substituted with one or more of the above moieties;
R5 is H, alkyl, aryl or cycloalkyl;
R6 is selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6a is selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6b is selected from the group consisting of alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, \u2014CF3, \u2014OCF3, \u2014CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7, \u2014C(\u2550N\u2014OH), and \u2014N(R5)C(O)NR5R10;
R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl, wherein each of the alkyl, cycloalkyl, heteroarylalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014OR6, \u2014NR5R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7, \u2014C(\u2550N\u2014CN)\u2014NH2, \u2014C(\u2550NH)\u2014NHR5, heterocyclyl, \u2014S(O2)R7, and
R9 is selected from the group consisting of halo, \u2014CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10; and
R10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R11, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)NR5R11, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014SO3H, \u2014SR5, \u2014S(O2)R7, \u2014S(O2)NR5R11, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R11;
or optionally (i) R5 and R10 in the moiety \u2014NR5R10, or (ii) R5 and R6 in the moiety \u2014NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of the cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups;

R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl, wherein each of said alkyl, cycloalkyl, heteroarylalkyl, aryl, heteroaryl and arylalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7 and \u2014S(O2)R7;
R9 is selected from the group consisting of halogen, CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
m is 0 to 4, and
n is 1 to 4; and
or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof,
wherein:
R2 is selected from the group consisting of halo; \u2014CF3; \u2014CN; \u2014SR6; \u2014NO2; \u2014NR5R6a; \u2014C(O)R6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)NR5R10; alkyl; alkenyl; alkynyl; heterocyclyl; heterocyclylalkyl; halo; haloalkyl; cycloalkyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; heteroarylalkyl;
alkynylalkyl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group;
\u2003wherein each of the alkyl, alkenyl, alkynyl, heterocyclyl, heterocyclylalkyl, haloalkyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, and alkynylalkyl groups and the heterocyclic moieties shown immediately above for R2 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014C(\u2550N\u2014OH), \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R3 is selected from the group consisting of H; \u2014NR5R6a; \u2014OR6b; \u2014SR6; CF3; \u2014C(O)N(R5R6); alkyl; alkenyl, alkynyl; cycloalkyl; aryl; arylalkyl; heterocyclyl;
heterocyclylalkyl; heteroaryl; heteroarylalkyl;
\u2003wherein each of the alkyl, alkynyl; cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, and the heterocyclic moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014C(\u2550N\u2014OH), \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R4 is selected from the group consisting of \u2014CF3; \u2014CN; \u2014NR5R6a; \u2014(CR5R11)pC(O2)R6; \u2014(CR5R11)pC(O)NR5R10; \u2014C(O)\u2014N(R5R10); \u2014OR6b; \u2014SR6; \u2014S(O2)R7; \u2014S(O2)NR5R10; \u2014C(O)R6; \u2014N(R5)S(O2)R7; \u2014N(R5)C(O)R7; \u2014N(R5)C(O)NR5R10; alkenyl; alkenyl (substituted with alkoxy); hydroxyalkyl; alkynyl; heterocyclyl; heterocyclylalkyl; aryl; aryl fused with an aryl or heteroaryl group; heteroaryl; heteroaryl fused with an aryl or heteroaryl group; substituted alkyl; cycloalkyl;
\u2003wherein each of the alkyl, cycloalkyl; heterocyclyl, heterocyclylalkyl, aryl, fused aryl, heteroaryl and fused heteroaryl groups of R4 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(R5)(\u2550N\u2014OR5), \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety, and wherein the substituted alkyl group of R4 is independently substituted with one or more of the above moieties;
R5 is H, alkyl, aryl or cycloalkyl;
R6 is selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6a is selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R6b is selected from the group consisting of alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkenyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, \u2014CF3, \u2014OCF3, \u2014CN, \u2014OR5, \u2014NR5R10, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7, \u2014C(\u2550N\u2014OH), and \u2014N(R5)C(O)NR5R10;
R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl, wherein each of the alkyl, cycloalkyl, heteroarylalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014OR6, \u2014NR5R6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7, \u2014C(\u2550N\u2014CN)\u2014NH2, \u2014C(\u2550NH)\u2014NHR5, heterocyclyl, \u2014S(O2)R7, and
R9 is selected from the group consisting of halo, \u2014CN, \u2014NR5R10, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014C(\u2550N\u2014OH), \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10; and
R10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of the alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl groups can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R11, \u2014C(R5R11)p\u2014R9, \u2014N(R5)Boc, \u2014(CR5R11)pOR5, \u2014C(O2)R5, \u2014C(O)NR5R11, \u2014C(O)R5, \u2014C(\u2550N\u2014OH), \u2014SO3H, \u2014SR5, \u2014S(O2)R7, \u2014S(O2)NR5R11, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R 5)C(O)NR5R11;
or optionally (i) R5 and R10 in the moiety \u2014NR5R10, or (ii) R5 and R6 in the moiety \u2014NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of the cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups;

R11 is H, halo or alkyl;
m is 0 to 4;
n is 1 to 4; and
p is 1 to 4;
with the provisos that
(1) when R2 is alkyl, carboxyl, phenyl or cycloalkyl, then R3 is selected from the group consisting of \u2014NR5R6a; \u2014C(O)N(R5R6); alkynyl; arylalkyl; heterocyclyl; heterocyclylalkyl; heteroaryl; heteroarylalkyl;
\u2003wherein each of the alkynyl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, and the heterocyclic moieties whose structures are shown immediately above for R3 is unsubstituted or independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of \u2014CN, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O)NR5R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6;
(2) when R2 is halo, then R3 is selected from the group consisting of \u2014OR6b; \u2014SR6; \u2014C(O)N(R5R6); cycloalkyl; heterocyclyl; heterocyclylalkyl;
\u2003wherein each of the cycloalkyl, heterocyclyl, heterocyclylalkyl, and the heterocyclic moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halo, alkyl, aryl, cycloalkyl, \u2014CF3, \u2014CN, \u2014OCF3, \u2014(CR11R11)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR5R11)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety; and
(3) when R2 is NH2, R3 is not methyl.
5. The method according to any of claims 1 to 4, wherein the compound of Formula I is selected from the group consisting of:
6. The method according to any of claims 1 to 4, wherein the compound of Formula I is selected from the group consisting of:
7. The method according to any of claims 1 to 4, wherein the compound of Formula I is selected from the group consisting of:
8. The method according to any of claims 1 to 4, wherein the compound of Formula VI is selected from the group consisting of:
9. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
10. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
11. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
12. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
13. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
14. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
15. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
16. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
17. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
18. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
19. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
20. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
21. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
22. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
23. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
24. The method according to any of claims 1 to 4, wherein the compound of Formula I is:
25. The method according to any of claims 1 to 4, wherein the compound of Formula VI is:
26. The method according to any of claims 1 to 4, wherein the compound of Formula VI is:
27. The method according to any of claims 1 to 4, wherein the compound of Formula II is:
28. The method according to any of claims 1 to 4, wherein the compound of Formula II is:
29. The method according to any of claims 1 to 4, wherein the compound of Formula II is:
30. The method according to any of claims 1 to 4, wherein the compound of Formula II is:
31. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
32. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
33. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
34. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
35. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
36. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
37. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
38. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
39. The method according to any of claims 1 to 4, wherein the compound of Formula III is:
40. The method according to claim 3, wherein the one or more anti-cancer agent is selected from the group consisting of a cytostatic agent, cisplatin, doxorubicin, taxotere, taxol, etoposide, irinotecan, camptostar, topotecan, paclitaxel, docetaxel, epothilones, tamoxifen, 5-fluorouracil, methoxtrexate, temozolomide, cyclophosphamide, SCH 66336, R115777, L778,123, BMS 214662, Iressa, Tarceva, antibodies to EGFR, Gleevec, intron, ara-C, adriamycin, cytoxan, gemcitabine, Uracil mustard, Chlormethine, Ifosfamide, Melphalan, Chlorambucil, Pipobroman, Triethylenemelamine, Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine, Streptozocin, Dacarbazine, Floxuridine, Cytarabine, 6-Mercaptopurine, 6-Thioguanine, Fludarabine phosphate, oxaliplatin, leucovirin, ELOXATIN\u2122, Pentostatine, Vinblastine, Vincristine, Vindesine, Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Teniposide 17\u03b1-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone, Fluoxymesterone, Dromostanolone propionate, Testolactone, Megestrolacetate, Methylprednisolone, Methyltestosterone, Prednisolone, Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide, Estramustine, Medroxyprogesteroneacetate, Leuprolide, Flutamide, Toremifene, goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine, Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene, Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine, Hexamethylmelamine, Avastin, herceptin, Bexxar, Velcade, Zevalin, Trisenox, Xeloda, Vinorelbine, Porfimer, Erbitux, Liposomal, Thiotepa, Altretamine, Melphalan, Trastuzumab, Lerozole, Fulvestrant, Exemestane, Fulvestrant, Ifosfomide, Rituximab, C225, Campath, Clofarabine, cladribine, aphidicolon, rituxan, sunitinib, dasatinib, tezacitabine, Sml1, fludarabine, pentostatin, triapine, didox, trimidox, amidox, 3-AP, and MDL-101,731.
41. The method according to any of claims 1 to 4, wherein the Checkpoint kinase is CHK1.
42. The method according to any of claims 1 to 4, wherein the Checkpoint kinase is CHK2.
43. A method of inhibiting activity of a Checkpoint kinase, the method comprising administering a therapeutically effective amount of at least one compound, or a pharmaceutically acceptable salt, solvate, ester or prodrug of the compound to a patient in need thereof, the compound being represented by the structural formula I:
wherein:
R is H, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkylalkyl, alkenylalkyl, alkynylalkyl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl (including N-oxide of said heteroaryl), \u2014(CHR5)n-aryl, \u2014(CHR5)n-heteroaryl,
\u2003wherein each of said alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R2 is selected from the group consisting of H, R9, alkyl, alkenyl, alkynyl, CF3, heterocyclyl, heterocyclylalkyl, halogen, haloalkyl, aryl, arylalkyl, heteroarylalkyl, alkynylalkyl, cycloalkyl, heteroaryl, alkyl substituted with 1-6 R9 groups which can be the same or different and are independently selected from the list of R9 shown below, aryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, aryl fused with an aryl or heteroaryl group, heteroaryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, heteroaryl fused with an aryl or heteroaryl group,
\u2003wherein one or more of the aryl andor one or more of the heteroaryl in the above-noted definitions for R2 can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, \u2014CN, \u2014OR5, \u2014SR5, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014NR5R6, \u2014C(O)NR5R6, CF3, alkyl, aryl and OCF3;
R3 is selected from the group consisting of H, halogen, \u2014NR5R6, \u2014OR6, \u2014SR6, \u2014C(O)N(R5R6), alkyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl,
\u2003wherein each of said alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl for R3 and the heterocyclyl moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, CN, \u2014OCF3, \u2014(CR4R5)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR4R5)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7, \u2014N(R5)C(R4R5)nN(R5R6) and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R4 is H, halo or alkyl;
R5 is H, alkyl, aryl, heteroaryl, arylalkyl or cycloalkyl;
R6 is selected from the group consisting of H, Boc, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR4R5, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)NR4R5, \u2014C(O)R5, \u2014SO3H, \u2014SR5, \u2014S(O2)R7, \u2014S(O2)NR4R5, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR4R5;
or optionally (i) R5 and R10 in the moiety \u2014NR5R10, or (ii) R5 and R6 in the moiety \u2014NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of said cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups;

R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl, wherein each of said alkyl, cycloalkyl, heteroarylalkyl, aryl, heteroaryl and arylalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014OR6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7, \u2014C(\u2550N\u2014CN)\u2014NH2, \u2014C(\u2550NH)\u2014NHR5, heterocyclyl, and \u2014S(O2)R7;
R9 is selected from the group consisting of halogen, \u2014CN, \u2014NR5R10, \u2014SCN, \u2014NO2, \u2014C(O)R5, \u2014C(O2)R6, \u2014C(O)NR5R10, \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
m is 0 to 4;
n is 1 to 4; and
p is 1 to 4,
with the proviso that when R2 is phenyl, R3 is not alkyl, alkynyl or halogen, and that when R2 is aryl, R is not
and with the further proviso that when R is arylalkyl, then any heteroaryl substituent on the aryl of said arylalkyl contains at least three heteroatoms.
47. The method according to any of claims 2, 3, 4, 44, 45 or 46, wherein the disease is a proliferative disease, autoimmune disease, viral disease, fungal disease, neurologicalneurodegenerative disorder, arthritis, inflammation, anti-proliferative disease, neuronal, alopecia or cardiovascular disease.
48. The method according to claim 47, wherein the disease is a proliferative disease.
49. The method according to claim 48, wherein the proliferative disease is selected from the group consisting of: cancer of the bladder, breast, colon, kidney, liver, lung, small cell lung cancer, non-small cell lung cancer, head and neck, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, and skin, squamous cell carcinoma; leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy cell lymphoma, mantle cell lymphoma, myeloma, Burkett’s lymphoma; acute and chronic myelogenous leukemia, myelodysplastic syndrome, promyelocytic leukemia; fibrosarcoma, rhabdomyosarcoma; astrocytoma, neuroblastoma, glioma and schwannomas; melanoma, seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer and Kaposi’s sarcoma.
50. The method according to claim 48, further comprising treatment with radiation therapy.
51. The method according to claim 45, wherein said one or more anti-cancer agent is selected from the group consisting of a cytostatic agent, cisplatin, doxorubicin, taxotere, taxol, etoposide, irinotecan, camptostar, topotecan, paclitaxel, docetaxel, epothilones, tamoxifen, 5-fluorouracil, methoxtrexate, temozolomide, cyclophosphamide, SCH 66336, R115777, L778,123, BMS 214662, Iressa, Tarceva, antibodies to EGFR, Gleevec, intron, ara-C, adriamycin, cytoxan, gemcitabine, Uracil mustard, Chlormethine, Ifosfamide, Melphalan, Chlorambucil, Pipobroman, Triethylenemelamine, Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine, Streptozocin, Dacarbazine, Floxuridine, Cytarabine, 6-Mercaptopurine, 6-Thioguanine, Fludarabine phosphate, oxaliplatin, leucovirin, ELOXATIN\u2122, Pentostatine, Vinblastine, Vincristine, Vindesine, Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Teniposide 17\u03b1-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone, Fluoxymesterone, Dromostanolone propionate, Testolactone, Megestrolacetate, Methylprednisolone, Methyltestosterone, Prednisolone, Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide, Estramustine, Medroxyprogesteroneacetate, Leuprolide, Flutamide, Toremifene, goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine, Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene, Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine, Hexamethylmelamine, Avastin, herceptin, Bexxar, Velcade, Zevalin, Trisenox, Xeloda, Vinorelbine, Porfimer, Erbitux, Liposomal, Thiotepa, Altretamine, Melphalan, Trastuzumab, Lerozole, Fulvestrant, Exemestane, Fulvestrant, Ifosfomide, Rituximab, C225, Campath, Clofarabine, cladribine, aphidicolon, rituxan, sunitinib, dasatinib, tezacitabine, Sml1, fludarabine, pentostatin, triapine, didox, trimidox, amidox, 3-AP, and MDL-101,731.
52. A method of treating a cancer comprising administering a therapeutically effective amount of at least one compound of any of formulas I-VI in claim 1.
53. The method of claim 52, wherein said cancer is selected from the group consisting of: cancer of the bladder, breast, colon, kidney, liver, lung, small cell lung cancer, non-small cell lung cancer, head and neck, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, and skin, including squamous cell carcinoma;
leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy cell lymphoma, mantle cell lymphoma, myeloma and Burkett’s lymphoma;
acute and chronic myelogenous leukemia, myelodysplastic syndrome and promyelocytic leukemia;
fibrosarcoma, rhabdomyosarcoma;
head and neck, mantle cell lymphoma, myeloma;
astrocytoma, neuroblastoma, glioma and schwannomas;
melanoma, seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer and Kaposi’s sarcoma.
54. A method of treating a cancer, comprising administering to a mammal in need of such treatment
an amount of a first compound, which is a compound of formula I, or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof; and
an amount of at least one second compound, said second compound being an anti-cancer agent;
wherein the amounts of the first compound and said second compound result in a therapeutic effect,
wherein said compound of formula I is:
wherein:
R is H, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, cycloalkyl, cycloalkylalkyl, alkenylalkyl, alkynylalkyl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl (including N-oxide of said heteroaryl), \u2014(CHR5)n-aryl, \u2014(CHR5)n-heteroaryl,
\u2003wherein each of said alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R2 is selected from the group consisting of H, R9, alkyl, alkenyl, alkynyl, CF3, heterocyclyl, heterocyclylalkyl, halogen, haloalkyl, aryl, arylalkyl, heteroarylalkyl, alkynylalkyl, cycloalkyl, heteroaryl, alkyl substituted with 1-6 R9 groups which can be the same or different and are independently selected from the list of R9 shown below, aryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, aryl fused with an aryl or heteroaryl group, heteroaryl substituted with 1-3 aryl or heteroaryl groups which can be the same or different and are independently selected from phenyl, pyridyl, thiophenyl, furanyl and thiazolo groups, heteroaryl fused with an aryl or heteroaryl group,
\u2003wherein one or more of the aryl andor one or more of the heteroaryl in the above-noted definitions for R2 can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, \u2014CN, \u2014OR5, \u2014SR5, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014NR5R6, \u2014C(O)NR5R6, CF3, alkyl, aryl and OCF3;
R3 is selected from the group consisting of H, halogen, \u2014NR5R6, \u2014OR6, \u2014SR6, \u2014C(O)N(R5R6), alkyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl,
\u2003wherein each of said alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl for R3 and the heterocyclyl moieties whose structures are shown immediately above for R3 can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, CN, \u2014OCF3, \u2014(CR4R5)pOR5, \u2014OR5, \u2014NR5R6, \u2014(CR4R5)pNR5R6, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R6, \u2014SR6, \u2014S(O2)R6, \u2014S(O2)NR5R6, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7, \u2014N(R5)C(R4R5)nN(R5R6) and \u2014N(R5)C(O)NR5R6, with the proviso that no carbon adjacent to a nitrogen atom on a heterocyclyl ring carries a \u2014OR5 moiety;
R4 is H, halo or alkyl;
R5 is H, alkyl, aryl, heteroaryl, arylalkyl or cycloalkyl;
R6 is selected from the group consisting of H, Boc, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)R5, \u2014C(O)NR5R10, \u2014SO3H, \u2014SR10, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
R10 is selected from the group consisting of H, alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, wherein each of said alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, heterocyclylalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR4R5, \u2014C(R4R5)p\u2014R9, \u2014N(R5)Boc, \u2014(CR4R5)pOR5, \u2014C(O2)R5, \u2014C(O)NR4R5, \u2014C(O)R5, \u2014SO3H, \u2014SR5, \u2014S(O2)R7, \u2014S(O2)NR4R5, \u2014N(R5)S(O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR4R5;
or optionally (i) R5 and R10 in the moiety \u2014NR5R10, or (ii) R5 and R6 in the moiety \u2014NR5R6, may be joined together to form a cycloalkyl or heterocyclyl moiety, with each of said cycloalkyl or heterocyclyl moiety being unsubstituted or optionally independently being substituted with one or more R9 groups;

R7 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkenyl, heteroaryl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, and heterocyclyl, wherein each of said alkyl, cycloalkyl, heteroarylalkyl, aryl, heteroaryl and arylalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF3, OCF3, CN, \u2014OR5, \u2014NR5R10, \u2014CH2OR5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014C(O)R5, \u2014SR10, \u2014S(O2)R10, \u2014S(O2)NR5R10, \u2014N(R5)S(O2)R10, \u2014N(R5)C(O)R10 and \u2014N(R5)C(O)NR5R10;
R8 is selected from the group consisting of R6, \u2014OR6, \u2014C(O)NR5R10, \u2014S(O2)NR5R10, \u2014C(O)R7, \u2014C(\u2550N\u2014CN)\u2014NH2, \u2014C(\u2550NH)\u2014NHR5, heterocyclyl, and \u2014S(O2)R7;
R9 is selected from the group consisting of halogen, \u2014CN, \u2014NR5R10, \u2014SCN, \u2014NO2, \u2014C(O)R5, \u2014C(O2)R5, \u2014C(O)NR5R10, \u2014OR6, \u2014SR6, \u2014S(O2)R7, \u2014S(O2)NR5R10, \u2014N(R5)S (O2)R7, \u2014N(R5)C(O)R7 and \u2014N(R5)C(O)NR5R10;
m is 0 to 4;
n is 1 to 4; and
p is 1 to 4,
with the proviso that when R2 is phenyl, R3 is not alkyl, alkynyl or halogen, and that when R2 is aryl, R is not
and with the further proviso that when R is arylalkyl, then any heteroaryl substituent on the aryl of said arylalkyl contains at least three heteroatoms.
55. The method of claim 5, further comprising treatment with radiation therapy.
56. The method of claim 54, wherein said anti-cancer agent is selected from the group consisting of a cytostatic agent, cisplatin, doxorubicin, taxotere, taxol, etoposide, irinotecan, camptostar, topotecan, paclitaxel, docetaxel, epothilones, tamoxifen, 5-fluorouracil, methoxtrexate, temozolomide, cyclophosphamide, SCH 66336, R115777, L778,123, BMS 214662, Iressa, Tarceva, antibodies to EGFR, Gleevec, intron, ara-C, adriamycin, cytoxan, gemcitabine, Uracil mustard, Chlormethine, Ifosfamide, Melphalan, Chlorambucil, Pipobroman, Triethylenemelamine, Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine, Streptozocin, Dacarbazine, Floxuridine, Cytarabine, 6-Mercaptopurine, 6-Thioguanine, Fludarabine phosphate, oxaliplatin, leucovirin, ELOXATIN\u2122, Pentostatine, Vinblastine, Vincristine, Vindesine, Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Teniposide 17\u03b1-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone, Fluoxymesterone, Dromostanolone propionate, Testolactone, Megestrolacetate, Methylprednisolone, Methyltestosterone, Prednisolone, Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide, Estramustine, Medroxyprogesteroneacetate, Leu prolide, Flutamide, Toremifene, goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine, Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene, Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine, Hexamethylmelamine, Avastin, herceptin, Bexxar, Velcade, Zevalin, Trisenox, Xeloda, Vinorelbine, Porfimer, Erbitux, Liposomal, Thiotepa, Altretamine, Melphalan, Trastuzumab, Lerozole, Fulvestrant, Exemestane, Fulvestrant, Ifosfomide, Rituximab, C225, Campath, Clofarabine, cladribine, aphidicolon, rituxan, sunitinib, dasatinib, tezacitabine, Sml1, fludarabine, pentostatin, triapine, didox, trimidox, amidox, 3-AP, and MDL-101,731.
57. A method of inhibiting activity of a Checkpoint kinase, the method comprising administering a therapeutically effective amount of at least one compound, or a pharmaceutically acceptable salt, solvate, ester or prodrug of the compound to a patient in need thereof, the compound being selected from the group consisting of:
58. A method of treating, or slowing the progression of, a disease by inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising in combination (i) at least one pharmaceutically acceptable carrier and (ii) at least one compound or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof, wherein the compound is selected from the group consisting of:
59. A method of treating a proliferative disease, comprising administering to a mammal in need of such treatment
an amount of a first compound, or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof; and
an amount of at least one second compound, said second compound being an anti-cancer agent;
wherein the amounts of the first compound and said second compound result in a therapeutic effect,
wherein said first compound is selected from the group consisting of:
60. The method of claim 59, further comprising treatment with radiation therapy.
61. The method of claim 59, wherein said anti-cancer agent is selected from the group consisting of a cytostatic agent, cisplatin, doxorubicin, taxotere, taxol, etoposide, irinotecan, camptostar, topotecan, paclitaxel, docetaxel, epothilones, tamoxifen, 5-fluorouracil, methoxtrexate, temozolomide, cyclophosphamide, SCH 66336, R115777, L778,123, BMS 214662, Iressa, Tarceva, antibodies to EGFR, Gleevec, intron, ara-C, adriamycin, cytoxan, gemcitabine, Uracil mustard, Chlormethine, Ifosfamide, Melphalan, Chlorambucil, Pipobroman, Triethylenemelamine, Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine, Streptozocin, Dacarbazine, Floxuridine, Cytarabine, 6-Mercaptopurine, 6-Thioguanine, Fludarabine phosphate, oxaliplatin, leucovirin, ELOXATIN\u2122, Pentostatine, Vinblastine, Vincristine, Vindesine, Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Teniposide 17\u03b1-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone, Fluoxymesterone, Dromostanolone propionate, Testolactone, Megestrolacetate, Methylprednisolone, Methyltestosterone, Prednisolone, Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide, Estramustine, Medroxyprogesteroneacetate, Leuprolide, Flutamide, Toremifene, goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine, Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene, Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine, Hexamethylmelamine, Avastin, herceptin, Bexxar, Velcade, Zevalin, Trisenox, Xeloda, Vinorelbine, Porfimer, Erbitux, Liposomal, Thiotepa, Altretamine, Melphalan, Trastuzumab, Lerozole, Fulvestrant, Exemestane, Fulvestrant, Ifosfomide, Rituximab, C225, Campath, Clofarabine, cladribine, aphidicolon, rituxan, sunitinib, dasatinib, tezacitabine, Sml1, fludarabine, pentostatin, triapine, didox, trimidox, amidox, 3-AP, and MDL-101,731.
62. A method of treating, or slowing the progression of, a proliferative disease in a patient, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising in combination (i) at least one pharmaceutically acceptable carrier and (ii) at least one compound or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof, wherein said compound is selected from the group consisting of:
63. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
64. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
65. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
66 A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
67. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
68. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
69. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
70. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
71. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
72. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
73. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
74. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
75. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
76. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
77. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
78. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
79. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
80. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
81. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
82. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
83. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
84. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
85. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
86. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
87. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
88. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
89. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
90. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
91. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
92. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
93. A method of inhibiting a Checkpoint kinase, comprising administering a therapeutically effective amount of a compound of formula:
94. A compound exhibiting CHK-1 inhibition which is at least five-fold said compound’s CDK2 inhibition.
95. A compound exhibiting CHK-1 inhibition which is at least ten-fold said compound’s CDK2 inhibition.
96. A compound exhibiting CHK-1 inhibition which is at least fifty-fold said compound’s CDK2 inhibition.
97. A pyrazolopyrimidine compound exhibiting CHK-1 inhibition which is at least five-fold said compound’s CDK2 inhibition.
98. A pyrazolopyrimidine compound exhibiting CHK-1 inhibition which is at least ten-fold said compound’s CDK2 inhibition.
99. A pyrazolopyrimidine compound exhibiting CHK-1 inhibition which is at least fifty-fold said compound’s CDK2 inhibition.