Compounds useful for inhibiting Chk1

A method of sensitizing cells in an individual undergoing a chemotherapeutic or radiotherapeutic treatment for a medical condition, comprising administering a therapeutically effective amount of a compound of formula (I) in combination with a therapeutically effective amount of a chemotherapeutic agent, a radiotherapeutic agent, or a mixture thereof to the individual, said compound of formula (I) having a structure

• wherein X1 is —O—, —S—, —CH2—, or —N(R1)—;
• X2 is —O—, —S—, or —N(R1)—;
• Y is O or S;
• W is
• Z is
• wherein Z is optionally substituted with one to four substituents represented by R2, and W is are optionally substituted with one to three substituents represented by R5;
• R1 is selected from the group consisting of hydro, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and aryl;
• R2 is selected from the group consisting of halo, optionally substituted C1-6alkyl, C2-6alkenyl, OCF3, NO2, CN, NC, N(R3)2, OR3, C2R3, C(O)N(R3)2, C(O)R3, N(R1)C(O)R3, N(R1)C(O)OR3, N(R3)C(O)OR3, N(R3)C(O)C1-3alkyleneC(O)R3, N(R3)C(O)C1-3alkyleneC(O)OR3, N(R3)C(O)C1-3alkyleneOR3, N(R3)C(O)C1-3alkyleneNHC(O)OR3, N(R3)C(O)C1-3alkyleneSO2NR3, C1-3alkyleneOR3, and SR3;
• R3 is selected from the group consisting of hydro, C1-6alkyl, C2-6alkenyl, cycloalkyl, aryl, heteroaryl, SO2R4, C1-6alkyl substituted with one or more of halo, hydroxy, aryl, heteroaryl, heterocycloalkyl, N(R4)2, and SO2R4, C1-3alkylenearyl, C1-3alkyleneheteroaryl, C1-3alkyleneC3-8heterocycloalkyl, C1-3alkyleneSO2aryl, optionally substituted C1-3alkyleneN(R4)2, OCF3, C1-3alkyleneN(R4)3+, C3-8heterocycloalkyl, and CH(C1-3alkyleneN(R4)2)2, or two R3 groups are taken together to form an optionally substituted 3- to 6-membered aliphatic ring;
• R4 is selected from the group consisting of hydro, C1-6alkyl, cycloalkyl, aryl, heteroaryl, C1-3-alkylenearyl, and SO2C1-6alkyl, or two R4 groups are taken together to form an optionally substituted 3- to 6-membered ring;
• R5 is selected from the group consisting of C1-6alkyl, aryl, N(R3)2, OR3, halo, N3, CN, C1-3alkylenearyl, C1-3alkyleneN(R3)2, C(O)R3, and
• or pharmaceutically acceptable salts, or prodrugs, or solvates thereof.

A compound having a formula

• wherein Y′ is O or S;
• W′ is
• optionally substituted with from one to three 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,
• and halo;
• Z′ is:
• wherein:
• Q′ is selected from the group consisting of OR7, SR71, and N(R7)2;
• J′ is CR8;
• K′ is CR9;
• L′ is CR10;
• M′ is CR11;
• wherein:
• R7, independently, is selected from the group consisting of hydro, C1-6alkyl, C2-6alkenyl, cycloalkyl, aryl, heteroaryl, SO2R12, C1-6alkyl substituted with one or more of halo, hydroxy, aryl, heteroaryl, heterocycloalkyl, N(R12)2, and SO2R12, C1-3alkylenearyl, C1-3alkyleneheteroaryl, C1-3alkyleneC3-8heterocycloalkyl, C1-3alkyleneSO2aryl, optionally substituted C1-3alkyleneN(R12)2, OCF3, C1-3alkyleneN(R12)3+, C3-8heterocycloalkyl, and CH(C1-3alkyleneN(R12)2)2, or two R7 groups are taken together to form an optionally substituted 3- to 6-membered aliphatic ring;
• R8, R9, and R10 are each independently selected from the group consisting of hydro, 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)C1-3 alkyleneC(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 hydro, optionally substituted C1-6alkyl, and halo;
• R12 is selected from the group consisting of hydro, 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 selected from the group consisting of hydro, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and aryl;
• provided that when Q′ OCH3, at least one of R8, R9, and R10 is different from hydro, CH3, OCH3, and halo,
• or pharmaceutically acceptable salts, or prodrugs, or solvates thereof.

A compound having a structure

• wherein R27 and R28 are
• R27
• R28
• H
• H
• H
• CH3
• H
• H
• H
• H
• H
• or
• wherein R29 is
• R29

A compound selected from the group consisting of:

• N-(2-dimethylamino-1-phenyl-ethyl)-3-methoxy-4-[3-(5-methyl-pyrazin-2-yl)-ureido]-benzamine;
• N-(1-aza-bicyclo[2.2.2]oct-3-yl)-3-methoxy-4-[3-(5-methyl-pyrazin-2-yl)-ureido]-benzamide;
• N-(3-R-1-cyclohexylmethyl-pyrrolidin-3-yl)-3-methoxy-4-[3-(5-methyl-pyrazin-2-yl)-ureido]-benzamide;
• 1-[2-(2-dimethylamino-ethoxy)-5-methyl-phenyl]-3-pyrazin-2-yl-urea;
• 1-[2-(3-dimethylamino-propoxy)-5-methyl-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-(5-methyl-pyrazin-2-yl)-3-[5-methyl-2-(pyridin-3-ylmethoxy)-phenyl]-urea;
• 1-[2-(2-dimethylamino-1-dimethylaminomethyl-ethoxy)-5-methyl-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-methyl-2-(2-S-1-methyl-pyrrolidin-2-ylmethoxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-{5-methyl-2-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-phenyl}-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-{5-methyl-2-(1-methyl-piperidin-4-yloxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-methyl-2-(3-(S)-1-methyl-piperidin-3-ylmethoxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-methyl-2-(3-(R)-1-methyl-piperidin-3-ylmethoxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-methyl-2-(1-methyl-piperidin-2-ylmethoxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-methyl-2-(1-methyl-piperidin-3-yloxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-methyl-2-piperidin-3-ylmethoxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-fluoro-2-(1-methyl-piperidin-3-ylmethoxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[5-fluoro-2-(1-methyl-piperidin-4-yloxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-[4-fluoro-2-(1-methyl-piperidin-4-yloxy)-phenyl]-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-(2-methoxy-4-methylaminomethyl-phenyl)-3-(5-methyl-pyrazin-2-yl)-urea;
• 1-(4-{[(furan-3-ylmethyl)-amino]-methyl}-2-methoxyphenyl)-3-(5-methyl-pyrazin-2-yl)-urea;
• and
• 1-{2-methoxy-4-[(4-methoxy-benzylamino)-methyl]-phenyl}-3-(5-methyl-pyrazin-2-yl)-urea.

A composition comprising a compound of formula (II) and a pharmaceutically acceptable carrier, said compound of formula (II) having a formula

• wherein Y′ is O or S;
• W′ is
• optionally substituted with from one to three substituents selected from the group consisting of C1-6alkyl, aryl, N(R7)2, OR7, N3, CN, C(O)R7, C1-3alkylenearyl, C1-3alkyleneN(R12)2,
• and halo;
• Z′ is
• wherein:
• Q′ is selected from the group consisting of OR7, SR7, and N(R7)2;
• J′ is CR8;
• K′ is CR9;
• L′ is CR10;
• M′ is CR11;
• wherein:
• R7, independently, is selected from the group consisting of hydro, C1-6alkyl, C2-6alkenyl, cycloalkyl, aryl, heteroaryl, SO2R12, C1-6alkyl substituted with one or more of halo, hydroxy, aryl, heteroaryl, heterocycloalkyl, N(R12)2, and SO2R12, C1-3alkylenearyl, C1-3alkyleneheteroaryl, C1-3alkyleneC3-8heterocycloalkyl, C1-3alkyleneSO2aryl, optionally substituted C1-3alkyleneN(R12)2, OCF3, C1-3alkyleneN(R12)3+, C3-8heterocycloalkyl, and CH(C1-3alkyleneN(R12)2)2, or two R7 groups are taken together to form an optionally substituted 3- to 6-membered aliphatic ring;
• R8, R9, and R10 are each independently selected from the group consisting of hydro, 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, C1-3alkyleneOR7, and SR7, wherein R7 is as defined above;
• R11 is selected from the group consisting of hydro, optionally substituted C1-6alkyl, and halo;
• R12 is selected from the group consisting of hydro, 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 selected from the group consisting of hydro, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and aryl;
• provided that when Q′ is hydro or OCH3, at least one of R8, R9, and R10 is different from hydro, CH3, OCH3, and halo,
• or pharmaceutically acceptable salts, or prodrugs, or solvates thereof.