Macrocyclic compounds as inhibitors of viral Replication, Pharmaceutical compositions containing them and their use in the treatment of Viral Infections.

摘要

ILO, c2-6 alquenilo, C1-6 alcoxi, hidroxi-c1-6 acquilo, C1-6 optional tar, replaced by haen, containing 5 fluorocarbons in various functions, C1-6 alcoxi optional alternative general formula (1) - (19),And compounds, including FA compounds below 5 fluorination; or R21 is pyridyl Dan, pyridyl Dan, RMA, including a compound of mepirazi Nile, Tianjin, furan, sulfuryl hydrazide, oxazolilo, which can be used for treating infertility, phenyl or sulfuryl; and R22 is C1-6 tar, C3 flash memory compound, Including infectious monocyclopentadiol 7, c4-10 propyl propyl tar, all of which are optional substitutes for hepatitis C virus, and three times of treatment of fibrosis with halide, cyanide, nitric acid and hydroxyl,C1-6 liver. Claim 1: A compound characterized in that it has the formula (1): wherein Q is an aalkyl optionally substituted with up to 5 fluoro, or phenyl. Claim 200: A central caranillo compound that is selected from the remains of formulas (2) where the central ring can be jaundred because it has the formula (14) where Q is a central ring that is selected from those substituted or substituted with H, halo , cyano, nitro, hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C4-10 os of formulas (11) where the central ring can alkylcycloalkyl, C2-6 alkenyl, C1-6 alkoxy, be unsubstituted or substituted with H, halo, cyano, idroxy C1-6 alkyl, C1-6 alkyl,Or an oxy, Cilo, Mino, hydrocarbon, carboxilo,Cyclopentadiene, cyclopentadiene, sulfur, sulfur oxide, sulfur, amino group, epoxicopropylene, epoxicopropylene or ethylene oxide, epoxicopropylene, leasing, cyclopropenyl acrylonitrile, or q is R1-R2, wherein R1 earboxi, carbide, cyclopentadiene spiral, epoxicopropylene, C1-6 spiral cyclopropene Tar, C3-7 cyclopropene, C4-10 cyclopropene, phenyl, pyridine, pyridine, pyridine, pyridine,o ciclohexilo espiroc clico o Q es R1-R2 donde R1 es C1-6 alquilo C3-7 cicloalquilo C4-10 alqu piridazina pirrol furano tiofeno tiazol oxazol imidazol isoxazol pirazol isotiazol naftililcicloalquilo fenilo piridina pirazina pirimio quinolina isoquinolina quinoxalina benzotiazdina piridazina pirrol furano tiofeno tiazol ol each optionally substituted with haso, C3-7 cycloalkyl, C4-10 alkylcycloalkyl, C2ta three NR6R7, halo, cyano, nitro, hydroxy, C1-6 to -6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, or C1-6 alkyl optionally substituted with up to 5 alkyl, C3-7 cycloalkyl, C4-10 alkylcycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl fluoro, C1-6 alkoxy optionally substituted with it, C1-6 alkyl optionally substituted with hasthasta 5 fluoro; and R2 is H, phenyl, pyridine, pyrazine, 5-fluoro, or C1-6 optionally substituted alkoxy, pyrimidine, pyridazine, pyrrole, furan, thiophene with up to 5 fluoro; and R2 is H, phenyl, pyridine, no, thiazole, oxazole, imidazole, isoxazole, pyrazole,ipirazine, pyrimidine, pyridazine, pyrrole, furan, sothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indtiofen, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, quinoline, naphthyl, benzimine, quinoline , each optionally substituted with up to three NR6R7, halo, cyano, nitro, hydruinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each optionally sustoxy, C1-6 alkyl, C3-7 cycloalkyl, C4-10 alkylcycloalkyl, C2- 6 alkenyl, C1-6 alkoxy, hydroxy substituted with up to three NR6R7, halo, cyano, nitro, hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C4-10 alq-C1-6 alkyl,C1-6 alkyl optionally substituted with up to 5 fluoro, or C1-6 alkoxy optionally alkylcycloalkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, C1-6 alkyl optionally substituted with up to 5 fluoro; R4 is H, C1-6 alkylated with up to 5 fluoro, or C1-6 alkoxy optional, C3-7 cycloalkyl, C4-10 alkylcycloalkyl, phenyl, or benzyl, said phenyl or benzyl substituted with up to 5 fluoro; R4 is H, C1-6 alkyl, C3-7 cycloalkyl, C4-10 alkylcycloalkyl substituted by up to three halo, cyano, nitro, hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C4-10 or, phenyl, or benzyl, said phenyl or benzyl optatalkylcycloalkyl, C2-6 alkenyl, C1-6 alkoxy,Hively substituted by up to three halo, cyano, nitro, hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C4-idroxy-C1-6 alkyl, C1-6 alkyl optionally substituted with up to 5 fluoro, or C1-6 alkoxy optativ10 alkylcycloalkyl , C2-6 alkenyl, C1-6 alkoxy, hydroxy-C1-6 alkyl, C1-6 alkyl optionally substituted with up to 5 fluoro; R5 is H, C1- substituted with up to 5 fluoro, or C1-6 alkoxy opta6 alkyl, C (O) NR6R7, C (S) NR6R7, C (O) R8, C (O) OR8, S (O) 2R8, or (CO) CHR21NH (CO) R22; R6 and R7 are each uniquely substituted with up to 5 fluoro; R5 is C1-6 alkyl, C (O) NR6R7, C (S) NR6R7, C (O) R8, C (O) OR8, or independently H, C1-6 alkyl, C3-7 cicS (O) 2R8 , or (CO) CHR21NH (CO) R22;R6 and R7 are each unloalkyl, C4-10 alkylcycloalkyl, or phenyl, said phenyl optionally substituted by up to three or independently H, C1-6 alkyl, C3-7 cyclo, cyano, nitro, hydroxy, C1-6 alkyl, C3 -7 cycloalkyl, C4-10 alkylcycloalkyl, or phenyl, said phenyl optionally substituted by up to three chloalkyl, C4-10 alkylcycloalkyl, C2-6 alkenihalo, cyano, nitro, hydroxy, C1-6 alkyl, C3-7 cyclo, hydroxy-C1 -6 alkyl, C1-6 alkyl optionally substituted with up to 5 fluoro, or C1-6 alkoxy opcloalkyl, C4-10 alkylcycloalkyl, C2-6 alkenatively substituted with up to 5 fluoro; or R6 and lo, hydroxy-C1-6 alkyl,C1-6 can be optionally replaced by C1-6 tar with no more than 5 fluorination, or C1-6 alcoxi compressive 7, which is used with N and is combined with N, which is temporarily replaced by a substance with no more than 5 fluorination; or R6 and formed Indian forest, pyridinol, pyridinediol, pyridinediol, picolinate or morphine alcohol; R8 is C1-6 tar, which is combined with N, is combined with N, and is combined with P c3-7 cyclopentyl glycol, C4-10.c4-10.acquilcoalquilo, todoro formula indolilo, pirrolidini, piperiazinilo, O morfolinil; R8 is C1-6 tar, and halogen, cyanogen, nitrate, hydroxyl, c-3-7 cycloquilo, c4-10 quilcoalquilo can be used instead of 1-6 alcoxi, all of which are optional substitutes, O phenyl;or R8 is C6 or 10 aryl which is optionally substituted by up to three halo, cyano and three times with halo, cyano, nitro, hydroxy, Cno, nitro, hydroxy, C1-6 alkyl, C3-7 cycloalkyl1-6 alkoxy, or phenyl ; or R8 is C6 or 10 aryl than that, C4-10 alkylcycloalkyl, C2-6 alkenyl, C1-6 optionally substituted by up to three halo, cyano, nitro, hydroxy, C1-6 alkyl, C3-7 cycloalkylalkoxy, C1-6 hydroxy alkyl, C1-6 optional alkyl, C4-10 alkylcycloalkyl, C2-6 alkenyl, C1-6 substituted with up to 5 fluoro, or C1-6 alkoxy optionally substituted with up to 5 fluoro; or Ralcoxi, hydroxy-C1-6 alkyl,C1-6 optional C1-6 tar 8 is a C1-6 tar, which is replaced by a substance below 5 fluorination, or by a substance 5 fluorination, or by a substance 5 fluorination; or R8 is a C1-6 tetrahydrogen ring structure, which can optionally be replaced by hasourano through a tetrahydrofuran ring structure C3 or C4; R8 is a large teapot ring composed of five fluorine groups, or R8 is a tetrahydrazine ring connected by the combined cation position of tetrahydrofuran ring C3 or C4, or R8 is a large teapot ring composed of tetrahydropyridin ring, which is a toluenediamide connected by the C4 position of anila-c (o) NHS (o) 2r9,where R9 is C1-6 alkyl, C3-7l tetrapiranyl; And it is COOR9, where R9 is C1-6 to the cycloalkyl, or C4-10 alkylcycloalkyl, all of which are optionally substituted between a chyl; or Y is a sulfonimide of the formula -C (O) NHS (O) 2R9, where R9 is C1-3 alkyl, C3-7 cycloalkyl three times with halo, cyano, nitro, hydroxy, C1-6yl, or phenyl which is optionally substituted by alkoxy, or phenyl; or R9 is C6 or 10 aryl which is ophasta two halo, cyano, nitro, hydroxy, C1-3 alkyl substituted by up to three halo, cyano, or, C3-7 cycloalkyl, or C1-3 alkoxy, or Y is a nitro acid , hydroxy, C1-6 alkyl, C3-7 cycloalkyl, C4-10 alkylcycloalkyl, C2-6 alkenyl, C1-6 carboxylic aldo;P = 0 or 1; V and W are selected from O, s or NH respectively; Cox line, C1-6 tar or C1-6 tar selected from script represent an additional double-layer combination, replaced by C1-6 alcox with no more than 5 fluorination;R21 is a C1-6 tar, c3-7 cyclopropylsulfonate, c4-10 heterogeneous substitute, with a maximum of 5 fluorination; or R9 quilcoalquilo, all of which are optional C1-6 tar, with a maximum of 5 fluorination group, nr6r7, nr1ar1b, O (CO) Oh; or 1-3 to 3 times with halogen, cyanogen, nitric acid, hydrocarbon, C1-6 alcox, C1-6 or 9 light substitutes. This is an alternative heteroaromatic ring with up to 5 fluorinated or phenyl substituted