Benzazepine derivatives as inhibitors of hyperproliferation diseases

A method of treating cancer sensitive to compounds of the following formula, in mammals in need of such treatment, comprising administering to said mammal a therapeutically effective amount of a compound of the formula:

• or a pharmaceutically acceptable salt, or hydrate thereof, wherein:
• R1 is a group having an acidic proton, particularly —CO2H, —CONHSO2R8, —CONR8(CH2)CO2H, —SO2H, —PO3H2,
• R2 is H or R1, or R1 and R2 together with the phenyl ring form
• R3 and R4 are independently selected from hydrogen, (C1-C10)alkyl, phenyl, and a 4 to 10 membred hetrocyclic group or R3 and R4 taken together with the two carbons to which they are attached form phenyl, which is optionally substituted by one or more R5 groups;
• R5 is thienyl, pyridyl, furyl, or pyrimidyl, halogen, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, (C1-C6)alkoxy, optionally substituted with from one to three fluorine atoms, (C3-C10) aryl, phenyl, —(CH2)t phenyl, —(CH2)t-(4 to 10 membered heterocyclic group), nitro, cyano, amino, —NH(C1-C6)alkyl, —N((C1-C8)alkyl)2, —S(C1-C8)alkyl, —SO(C1-C8)alkyl, —C(O)(C1-C8)alkyl, —CO(O)(C1-C8)alkyl, wherein said phenyl, aryl or heterocycle moiety may be optionally substituted with one or two substituents independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, amino and trifluoromethyl;
• W is OH or NR6R7;
• R6 and R7 are independently selected from H, (C1-C8)alkyl, (C3-C8)cycloalkyl, or R6 and R7 taken together form a six-membered saturated ring containing 5 carbon atoms and one nitrogen atom, one or more of said carbon atoms being optionally substituted with one or more substituents independently selected from (C1-C3)alkyl;
• R8 is H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, —(CH2)t(C6-C10 aryl), or —(CH2)t(4 to 10 membered heterocyclic), wherein t is an integer from 0 to 5;
• said alkyl group optionally including 1 or 2 hetero moieties selected from O, S and —N(R6)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other;
• said aryl and heterocyclic R8 groups being optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4 to 10 membered heterocyclic group;
• one or two carbon atoms in said 4 to 10 membered heterocyclic group of R8 being optionally substituted by an oxo (═O) moiety;
• the —(CH2)t— moieties of R8 optionally including a carbon-carbon double or triple bond when t is an integer from two to five;
• R8 groups being optionally substituted by one to five R9 groups;
• R9 is each independently selected from C1-C10 alkyl, C2-C10alkenyl, C2-C10alkynyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —OR10, —C(O)R11, —C(O)OR10, —NR11C(O)OR10, —OC(O)R10, —NR11SO2R10, —SO2NR10OR11, —NR11C(O)R10, —C(O)NR10R11, —NR10R11, —S(O)jR12, —SO3H, —NR10(CR11R12)tOR11, —(CH2)t(C6-C10 aryl), —SO2(CH2)t(C6-C10aryl), —S(CH2)t(C6-C10aryl), —O(CH2)t(C6-C10aryl), —(CH2)t(4 to 10 membered heterocyclic group), and —(CR11R12)mOR11, said alkyl group optionally containing one or two hetero moieties selected from O, S and —N(R8)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other;
• aryl and heterocyclic moieties of R9 being optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4 to 10 membered heterocyclic group;
• one or two carbon atoms of the heterocyclic moieties of R9 being optionally substituted by an oxo (═O) moiety;
• and the alkyl, aryl and heterocyclic moieties of R9 groups being optionally substituted by one to three substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —NR11SO2R10, —SO2NR10R11, —C(O)R10, —C(O)OR10, —OC(O)R10, —NR11C(O)R10, —C(O)NR10R11, —NR10R11, —(CR11R12)mOR11, —OR10 and R10;
• R10 is each independently selected from H, C1-C10 alkyl, —(CH2)t(C6-C10 aryl), and —(CH2)t(4 to 10 membered heterocyclic), said alkyl group optionally including one or two hetero moieties selected from O, S and —N(R6)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other;
• said aryl and heterocyclic R10 groups being optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4 to 10 membered heterocyclic group;
• the foregoing moieties of R10, with the exception of H, being optionally substituted by one to three substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —C(O)R11, —C(O)OR11, —CO(O)R11, —NR11C(O)R12, —C(O)NR11R12, —NR11R12, hydroxy, C1-C6 alkyl, and C1-C6 alkoxy;
• R11 and R12 are each independently H or C1-C6 alkyl;
• X, Y and Z are each independently selected from O, S, CH, CHR13, SO, SO2 and NR13;
• R13 is H, (C3-C8)cycloalkyl, phenyl, (C7-C8)phenylalkyl, or a 4 to 11 membered heterocyclic group optionally substituted with one or more substituents selected from halogen, hydroxy, (C1-C8)alkyl and (C1-C8)alkoxy;
• m is an integer ranging from one to five;
• t is an integer ranging from zero to five;
• and
• j is an integer ranging from zero to two.