Compounds useful for inhibiting chk1
OwnerKathleen S. Keegan, Edward A. Kesicki +4inventors
InventorsKathleen S. Keegan, Edward A. Kesicki, John Joseph Gaudino, Adam Wade Cook, Scott Douglas Cowen, Laurence Edward Burgess
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Abstract
Aryl- and heteroaryl-substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.
Claims2
1-30. (canceled)
A method of treating a cancer selected from the group consisting of a colorectal cancer, a breast cancer, a leukemia, a melanoma, a renal cell carcinoma, an ovarian cancer, a lung carcinoma, a cervical cancer, a colon cancer, and a prostate cancer which comprises administering to a patient in need thereof a therapeutically effective amount of a compound having a formula
- wherein:
- Y′ is O or S;
- W′ is
- optionally substituted with from one to four substituents selected from the group consisting of C1-6alkyl, aryl, N(R7)2, OR7, N3, CN, C(O)R7, C1-3alkylenearyl, C1-3alkyleneN(R2)2, halo, and
- Z′ is selected from the group consisting of:
- wherein
- Q′ is OR7;
- J′ is selected from the group consisting of CR8, NR8, O, and S;
- K′ is selected from the group consisting of CR9, NR9, O, and S;
- L′ is selected from the group consisting of CR10, NR10, O, and S;
- M′ is selected from the group consisting of CR11, NR11, O, and S;
- and provided when Z′ is a six-membered ring J′, K′, L′, and M′ cannot be O or S;
- wherein:
- R7 is C1-3alkyleneC3-8heterocycloalkyl;
- R8, R9, and R10 are each independently selected from the group consisting of hydrogen, halo, optionally substituted C1-6alkyl, C2-6alkenyl, OCF3, NO2, CN, NC, N(R7)2, OR7, CO2R7, C(O)N(R7)2, C(O)R7, N(R13)C(O)R7, N(R13)C(O)OR7, N(R7)C(O)OR7, N(R7)C(O)C1-3alkyleneC(O)R7, N(R7)C(O)C1-3alkyleneC(O)OR7, N(R7)C(O)C1-3alkyleneOR7, N(R7)C(O)C1-3alkyleneNHC(O)OR7, N(R7)C(O)C1-3alkyleneSO2NR7, CF3, C1-3alkyleneN(R12)SO2aryl, C1-3alkyleneN(R12)SO2heteroaryl, C1-3alkyleneOC1-3alkylenearyl, C1-3alkyleneN(R12)C1-3alkylenearyl, C1-3alkyleneN(R12)C1-3alkyleneheteroaryl, C1-3alkyleneN(R12)C(O)R7, C1-3alkyleneN(R12)C(O)C1-3alkyleneOR2, C1-3alkyleneN(R12)C(O)aryl, C1-3alkyleneN(R12)C(O)C1-3alkyleneN(R12)2, C1-3alkyleneN(R12)C(O)heteroaryl, C1-3alkyleneOR7, and SR7, wherein R7 is as defined above;
- R11 is selected from the group consisting of hydrogen, optionally substituted C1-6alkyl, and halo;
- R12 is selected from the group consisting of hydrogen, C1-6alkyl, cycloalkyl, aryl, heteroaryl, C1-3alkylenearyl, and SO2C1-6alkyl, or two R12 groups are taken together to form an optionally substituted 3- to 6-membered ring;
- and
- R13 is hydrogen;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.