Patent ID: 8586565
Filing Date: 2013-11-19
Classification: A61P,C07D

Abstract:
1. A method of treating an individual suffering from a disease selected from the group consisting of chronic myelogenous leukemia, acute lymphocytic leukemia, lung cancers, breast cancers, and thyroid cancer, and combinations thereof, comprising the step of administering to such individual a compound of formula Ia or a pharmaceutically acceptable salt thereof, wherein E1 is phenyl and wherein the E1 ring is substituted with one to three R16 moieties; A is selected from the group consisting of imidazolyl, and pyrazolyl; G1 is a heteroaryl taken from the group consisting of pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, triazinyl, pyridinyl, and pyrimidinyl; G4 is a heterocyclyl taken from the group consisting of oxetanyl, azetadinyl, tetrahydrofuranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, imidazolonyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, and homotropanyl; the A ring is substituted at any substitutable position with one A1 moiety, wherein A1 is selected from the group consisting of: and wherein the symbol (**) is the point of attachment to the A ring of formula Ia; and wherein the A ring is optionally substituted with one or more R2 moieties; X2 is a direct bond, wherein E1 is directly linked to the NH group of formula Ia; X3 is —O—; V, V1 and V2 are each independently O or represent two hydrogens attached to the methylene carbon to which the V, V1, and V2 is attached; each Z3 is independently and individually selected from the group consisting of H, C1-C6alkyl, branched C3-C7alkyl, C3-C8carbocyclyl, halogen, fluoroC1-C6alkyl wherein the alkyl moiety can be partially or fully fluorinated, cyano, hydroxyl, methoxy, oxo, (R3) in the event that Z3 contains an alkyl or alkylene moiety, such moieties may be further substituted by one or more C1-C6alkyl; each Z4 is independently and individually selected from the group consisting of H, C1-C6alkyl, hydroxyC2-C6alkyl, C1-C6alkoxyC2-C6alkyl, (R4) in the event that Z4 contains an alkyl or alkylene moiety, such moieties may be further substituted by one or more C1-C6alkyl; each Z6 is independently and individually selected from the group consisting of H, C1-C6alkyl, branched C3-C7alkyl, hydroxyl, hydroxyC1-C6alkyl, hydroxyC2-C6 branched alkyl, C1-C6alkoxy, C1-C6alkoxyC1-C6alkyl-, C1-C6alkoxyC2-C6 branched alkyl-, C2-C6 branched alkoxy-, C1-C6alkylthio-, (R3) each R2 is selected from the group consisting of Z3-substituted aryl, Z3-substituted G1-, Z3-substituted G4-, C1-C6alkyl, branched C3-C8alkyl, R19 substituted C3-C8-carbocyclyl, hydroxyC1-C6alkyl-, hydroxy branched C3-C6alkyl-, hydroxy substituted C3-C8-carbocyclyl-, cyanoC1-C6alkyl-, cyano substituted branched C3-C6alkyl, cyano substituted C3-C8-carbocyclyl, (R4) wherein each R3 is independently and individually selected from the group consisting of H, C1-C6alkyl, branched C3-C7alkyl, C3-C8-carbocyclyl, and Z3-substituted phenyl; each R4 is independently and individually selected from the group consisting of H, C1-C6alkyl, hydroxyC1-C6alkyl-, dihydroxyC1-C6alkyl-, C1-C6alkoxyC1-C6alkyl-, branched C3-C7alkyl-, branched hydroxyC1-C6alkyl-, branched C1-C6alkoxyC1-C6alkyl-, branched dihydroxyC2-C6alkyl-, —(CH each R5 is independently and individually selected from the group consisting of and wherein the symbol (##) is the point of attachment of the R5 moiety; each R6 is independently and individually selected from the group consisting of C1-C6alkyl, branched C3-C7alkyl, C3-C8-carbocyclyl, phenyl, G1, and G4; each R7 is independently and individually selected from the group consisting of H, C1-C6alkyl, hydroxyC2-C6alkyl-, dihydroxyC2-C6alkyl-, C2-C6alkoxyC2-C6alkyl-, branched C3-C7alkyl-, branched hydroxyC2-C6alkyl-, branched C2-C6alkoxyC2-C6alkyl-, branched dihydroxyC2-C6alkyl-, —(CH each R8 is independently and individually selected from the group consisting of C1-C6alkyl, branched C3-C7alkyl, fluoroC1-C6alkyl wherein the alkyl moiety is partially or fully fluorinated, C3-C8-carbocyclyl, Z3-substituted phenyl-, Z3-substituted phenylC1-C6alkyl-, Z3-substituted G1, Z3-substituted G1-C1-C6alkyl-, Z2-substituted G4, Z2-substituted G4-C1-C6alkyl-, OH, C1-C6alkoxy, N(R3) each R10 is independently and individually selected from the group consisting of CO each R14 is independently and respectively selected from the group consisting of H, C1-C6alkyl, branched C3-C6alkyl, and C3-C8-carbocyclyl; R16 is independently and individually selected from the group consisting of C1-C6alkyl, branched C3-C7alkyl, C3-C8-carbocyclyl, halogen, fluoroC1-C6alkyl wherein the alkyl moiety can be partially or fully fluorinated, cyano, hydroxyl, C1-C6alkoxy, fluoroC1-C6alkoxy wherein the alkyl moiety can be partially or fully fluorinated, —N(R3) each R17 is selected from the group consisting of phenyl, naphthyl, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, triazinyl, oxetanyl, azetadinyl, tetrahydrofuranyl, oxazolinyl, oxazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, azepinyl, oxepinyl, diazepinyl, pyrrolidinyl, and piperidinyl; wherein R17 can be further substituted with one or more Z2, Z3 or Z4 moieties; R19 is H or C1-C6alkyl; n is 0-6; p is 1-4; q is 2-6; r is 0 or 1; t is 1-3; and v is 1 or 2.