3-(aryl or heteroaryl) methyleneindolin-2-one derivatives as inhibitors of cancer stem cell pathway kinases for the treatment of cancer

A compound of Formula I,

• or an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof,
• wherein:
• R1 is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)2Re, S(═O)2ORe, C(═O)ORd, C(═O)Ra, or C(═O)NRbRc;
• R2 is monocyclic or bicyclic heterocycle or substituted heterocycle, aryl or substituted aryl;
• R3 is hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, aryl or substituted aryl, halogen, —ORa, —C(O)Ra, —C(O)ORa, —NRaRb, S(O)2NRaRb;
• R4, R5, R6, and R7 are each independently hydrogen, halogen, cyano, nitro, trihalomethyl, OCF3, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)Re, S(═O)2Re, P(═O)2Re, S(═O)2ORe, P(═O)2ORe, NRbRc, NRbS(═O)2Re, NRbP(═O)2Re, S(═O)2NRbRc, P(═O)2NRbRc, C(═O)ORe, C(═O)Ra, C(═O)NRbRc, OC(═O)Ra, OC(═O)NRbRc, NRbC(═O)ORe, NRdC(═O)NRbRc, NRdS(═O)2NRbRc, NRdP(═O)2NRbRc, NRbC(═O)Ra, or NRbP(═O)2Re;
• T is O, S or Ra;
• U and V are each independently a carbon;
• W is N;
• X, Y, Z, and A are each independently a carbon or N, with the proviso that the ring in which X, Y, Z, and A exist is aromatic;
• with the provision that
• one of R4, R5, R6, and R7 is substituted heterocycle or substituted aryl, and
• R4, R5, R6, or R7 is absent if X, Y, Z, or A, respectively, is a heteroatom;
• wherein
• substituted heterocycle and substituted aryl in R4, R5, R6, and R7 is the following group:
• wherein:
• Q-2 is heterocycle or aryl selected from the group consisting of pyrrole, furan, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, triazole, thiadiazole, oxadiazole, pyrrolidine, piperidine, azepane, tetrahydrofuran, oxane, oxepane, indole, indolinone, indazole, benzothiazole, quinoline, quinazoline, quinoxaline, imidazopyridine, imidazopyridazine, pyrazolopyridine, pyrazolopyrimidine, and phthalazinone;
• Rn′, Rn″ and Rn′″ are each independently hydrogen, halogen, cyano, nitro, trihalomethyl, OCF3, alkyl or substituted alkyl, ORa, SRa, C(═O)Ra, C(═O)ORa, NH2, S(O)2NH2, pyrrolidinyl, piperidinyl, azepanyl, tetrahydrofuranyl, oxanyl, oxepanyl, pyranyl, phenyl, thiophenyl, pyrazinyl, pyrimidinyl, pyridazinyl, or pyridyl (said piperidinyl, pyranyl, phenyl, thiophenyl, pyrazinyl, pyrimidinyl, pyridazinyl, and pyridyl are optionally substituted with halogen, cyano, nitro, alkyl or substituted alkyl, ORa, NRbRc, C(═O)ORe, C(═O)Ra, or C(═O)NRbRc (wherein Ra is hydrogen, or alkyl or substituted alkyl, Rb and Rc are independently hydrogen, or alkyl or substituted alkyl, and Re is alkyl or substituted alkyl (substituted alkyl is optionally substituted with one or more substituent(s) selected from the group consisting of hydroxy, amino, nitro, cyano, halogen, alkoxy, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, aryl, cycloalkyl, and heterocycle));
• Ra is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl;
• Rb, Re and Rd are each independently hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, or aryl or substituted aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle or substituted heterocycle;
• and
• Re is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl.