Imidazo 1,2A pyridine Derivatives, Pharmaceutical compositions containing same and Use thereof in Leukemia and myeloproliferative disorders, immunological and inflammatory diseases.

摘要

Item 1: a formula compound (1)or a pharmaceutically acceptable salt, or solvate, or N-oxide or stereoisomer thereof, for use in the treatment of a pathological condition or disease susceptible to improvement by inhibition of Janus kinases (JAK) where, m is 0 or an integer number of 1 to 3; Z is an oxygen atom or an NR5 group; X and Y independently represent a nitrogen atom or a -CR9 group, where at least one of X and Y represents a nitrogen atom; each of R1, R2, R3, R4 and R9 independently represents a hydrogen atom, halogen, cyano, linear or branched C1-8 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 hydroxyalkyl , C3-10 cycloalkyl, C3-10 cycloalkenyl,C3-7 c1-4-cyclopentanediol, monocyclic or multicyclic c5-14 arilo, an unorthodox group consisting of 5 to 14 members, including at least one heteroatom selected from O, s and N, an unorthodox group consisting of 5 to 14 members, including at least one heteroatom selected from O, s and N, A bicyclic group consisting of arilo or heterocyclic group of monocyclic C5-9, directly associated with a cyclopropyl or heterocyclic group of 5-9 members, in which the heterocyclic or heterocyclic group contains at least one heterocyclic atom selected from O, s, and n, An aza biocyclequilo group with up to 12 carbon atoms or an aza biocycle group with up to 12 carbon atoms,wherein the alkenyl, alkynyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclic, bicyclic, aza-bicycloalkyl and aza-bicycloalkenyl groups are unsubstituted or substituted with one or more substituents selected from the Ra substituents, and the groups alkyl are unsubstituted or substituted with one or more substituents selected from Rb; or R1, R2, R3, R4 and R9 independently represent a group -SR13, -SOR13, -S (O) 2R13, -S (O) 2NR13R14, -NR13S (O) 2R14, -NR13S (O) 2NR14, -OR13 , -C (O) OR13, -OC (O) R13, -C (O) - (CH2) n-R13, -NR13R14, -C (O) - (CH2) n-NR13R14, -NR13C (O) - (CH2) n-R14 or a group -NR13C (O) - (CH2) n-NR14R15, where each n is 0,If there are two adjacent CR9 groups, the two adjacent CR9 groups and the carbon atoms connected with them can optionally form a c5-12 group arilo, or a heterocycle, ring or heterocycle group consisting of 4 to 12 members, wherein the heterocycle and heterocycle groups have at least one member. Selected o, s and N heteromorphic atoms, among which arilo, heteromorphic, cyclopropene and heterocyclic groups are not replaced or replaced by one or more substitutes selected from halogenated atoms, one C1-6 linear tar or branched group, one single cycle or multi cycle arilo group c5-14,Heteromorphism consisting of 5 to 14 members, including at least one heteromorphic atom selected from O, s and N, or 5 to 14 members, including at least one heteromorphic atom selected from O, s and N, among which asphalt, arilo, heterocyclic and heterocyclic substitutes are not replaced by one or more 1. Halogenated atom, C1-6 hydrogen Xi group, cyanogen group, linear tar or branched substance or C1-4 halogenated tar group; R5 represents a hydrogen atom, a linear tar or C1-6 derivative group, which can be replaced by one or more substitutes selected from the hydrogen Xi group, cyanogen group, C1-4 halogenated tar, C1-4 hydroxide compound, c13-10,a phenyl group or a 6-membered saturated heterocyclic ring containing N, or R5 represents a group -S (O) 2R10, a group -S (O) 2NR10R11, -C (O) OR10, -C (O) - ( CH2) n-R10 or -C (O) - (CH2) n-NR10R11; R6 and R7 each independently represents a hydrogen atom or a C1-6 linear or branched alkyl group optionally substituted with one or more substituents selected from a hydroxy, cyano, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy group, C1-4 alkoxycarbonyl, C3-7 cycloalkyl, a phenyl group or a 6-membered N-containing heterocyclic ring; R8 represents a hydrogen atom, halogen, a cyano group, linear or branched C1-6 alkyl, C2-4 alkenyl,C2-4 alkynyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-6 alkyl C1-4 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkenyl, C5-14 monocyclic or polycyclic aryl, a heteroaryl group of 5 to 14 members containing at least one heteroatom selected from O, S and N, a 5 to 14 member heterocyclic group containing at least one heteroatom selected from O, S and N, C3-7 heterocycloalkyl ketone containing 1, 2 or 3 Nitrogen atoms, a bicyclic group containing a C5-9 monocyclic aryl or heteroaryl group directly attached to a 5- to 9-membered cycloalkyl or heterocyclic group,The heterocyclic or heterocyclic group includes at least one heterocyclic atom selected from O, s and N, one aza biocyclequilo group with a maximum of 12 carbon atoms, or one aza biocyclequinio group with a maximum of 12 carbon atoms, wherein the atoms of alquenilo, tar, halotard, hydroxy, cyclopentyl, cyclopentyl, cyclopentadienyl, etc, Arilo, heterosexual, heterosexual, heterosexual, heterosexual, isopropyl ketone, bicycle, aza bicycloquilo and aza bicycloquenilo have not been replaced or replaced by one or more selected RA, c1-4-cn tar substitutes,or C1-4-C alkyl groups (O) NR'Rö where R 'and Rö are the same or different and are selected from hydrogen atoms and C1-4 linear or branched alkyl groups and the alkyl groups are unsubstituted or are substituted with one or more substituents selected from Rb; or R8 represents a group -SR13, -SOR13, -S (O) 2R13, - S (O) 2NR13R14, -NR13S (O) 2R14, -NR13S (O) 2NR14, -OR13, -C (O) OR13, - OC (O) R13, -C (O) - (CH2) n-R13, -NR13R14, -C (O) - (CH2) n-NR13R14, -NR13C (O) - (CH2) n-R14, or - NR13C (O) - (CH2) n-NR14R15, where n is 0, 1 or 2, or R8 together with R5 and the nitrogen atom to which R5 is attached form a saturated heterocyclic group, 4 to 10 members, which contains, as heteroatoms,One or two nitrogen atoms, consisting of one C1-6 linear tar or branch group, one single cycle or multi cycle c5-14 arilo group, one heteromorphic group composed of 5 to 14 members, including at least one heteromorphic group selected from O, s and N, one heteromorphic group composed of 5 to 14 members, and at least one selected heteromorphic group. O. S and N, - so10, - C (o) - (CH2) n-r10, O-C (o) - (CH2) n-nr10r11, where each n is 0, 1 or 2, are not replaced or replaced by one or more substitutes selected from the halogenated atom, one hydrogen Xi group, cyanogen, linear tar or branch C1-6 or one C1-4 halogenated substance group.and wherein the alkyl groups are unsubstituted or substituted with one or more substituents selected from a halogen atom, a hydroxy, cyano group or a C1-4 haloalkyl group, provided that when m is zero, R8 is different from a group - SR13, -SOR13, -S (O) 2R13, -S (O) 2NR13R14, -NR13S (O) 2R14, -NR13S (O) 2NR14, -OR13, -OC (O) R13, -NR43R14, -NR13C (O ) - (CH2) n-R14 or -NR13C (O) - (CH2) n-NR14R15, where Ra is a halogen atom, a cyano, hydroxy, linear or branched C1-6 alkyl group, wherein said alkyl group is not substituted or substituted with one or more cyano, C 1-4 haloalkyl, C 1-4 hydroxyalkyl, C 3-7 cycloalkyl or a C 3-7 cycloalkenyl groups,arilo monoc clico o polic clico C5-14 donde dicho grupo arilo est no sustituido o sustituido con uno oms sustituyentes seleccionados de un tomo de halogeno o un grupo ciano un grupo heteroarilo de 5 a 14 miembros que contiene al menos un hetero tomo seleccionado de OS -Each nr12 (nr2-r11 (or (n11-r1-r1-rn is an integer of 0 or 1 to 5, P is an integer of 1 to 3, Rb is a cyanide, hydrogen, C1-6, C1-4 halide, C1-4 hydroxy, C1-4 hydrate, c3-7 cyclopropyl or c3-7 cyclopropene group, c5-14 monocyclic or multicyclic arilo group. In these monocyclic or multicyclic arilo groups, there is no substitute selected from one or more halogen atoms or cyanide groups to replace or replace this monocyclic propene group,5 to 14 membered heteroaryl containing at least one heteroatom selected from O, S and N, wherein said heteroaryl group is unsubstituted or substituted with one or more substituents selected from a halogen atom or a cyano group, a 5-heterocyclic group to 14 members containing at least one heteroatom selected from O, S and N, a group -SR10, -SOR10, -S (O) 2R10, -S (O) 2NR10R11, -NR10S (O) 2R11, -NR10S (O ) 2NR11, -OR10, -C (O) OR10, -C (O) -CH2-OR10, -C (O) - (CH2) nO- (CH2) pR10, -C (O) - (CH2) nO- (CH2) pO-R10, -OC (O) R10, -C (O) - (CH2) n-R10, -NR10R11, -C (O) - (CH2) n-NR10R11, -R10C (O) - ( CH2) n-NR11R12, -C (C1-4 alkyl) 2-C (O) - (CH2) n-NR10R11, -NR10C (O) - (CH2) n-R11 or -NR10C (O) - (CH2) n-NR11R12,Each n is an integer of 0 or 1 to 5, and P is an integer of 1 to 3; each R10, R11 and R12 independently represents a hydrogen atom, a cyanide, linear tar or C1-6 derivative, C1-4 halide, C1-6 hydroxy compound, C1-4 halocarbon, c3-7 cyclopropyl compound, phenyl, A group of - (hydroxy) C1-4 - (phenyl),-C (o) - (phenyl),A heterocyclic group consisting of 5 to 6 members, 1, 2, 3 or 4 heterocyclic atoms selected from n or s, 5 to 6 heterocyclic groups, 1, 2 or 3 heterocyclic atoms selected from oxygen and nitroso benzene, 1, 2 or 3 heterocyclic groups composed of 1, 2 or 3 nitrogens, and a two periodic group.