Tiadiazoles receptor ligands as CXC and CC Chemokine; Pharmaceutical compositions containing as the active ingredient and Use thereof in the preparation of medicines.

摘要

Currently, thiadiazepine is called the adhesive of CXC and CC chemotherapy receivers. These compounds help to treat various diseases caused by chemotherapy, such as cancer, angioplasty, eye vascular disease, lung disease, multiple sclerosis, rheumatoid arthritis, skeletitis and stroke. A formula compound (1a) is used to cause ischemic injury by repulsion, pain (such as acute pain, acute and chronic inflammatory pain, and neuralgia). Claim 1: a compound of formula (1a) and a salt acceptable for the same agent,where: A is selected from the group of formulas (2) where the preceding rings of said groups A are substituted with 1 to 6 substituents, each independently selected from the group consisting of R9 groups (formulas 3) in which or both anterior rings of said groups A are substituted with 1 to 6 substituents each independently selected from the group consisting of R9 groups (formulas 4) where the above phenyl rings of said groups A are substituted with 1 to 3 substituents each independently selected from the group consisting of R9 groups; (formulas 5) and B is selected from the group consisting of (formulas 6),n is 0 to 6; p is 1 to 5; X is O, NR18 or S; Z s 1 to 3; R2 is selected from the group consisting of: H, OH, -C (O) OH, -SH, -SO2NR13R14, -NHC (O) R13, -NHSO2NR13R14, -NHSO2R13, -NR13R14, - C (O) NR13R14, - C (O) NHOR13, -C (O) NR13OH, -S (O2) OH, -OC (O) R13, an unsubstituted heterocyclic acid functional group and a substituted heterocyclic acid functional group; wherein there are 1 to 6 substituents in said substituted heterocyclic acid functional group, where each substituent is independently selected from the group consisting of: R9 groups; each R3 and R4 is independently selected from the group consisting of H, cyano, halogen, alkyl, alkoxy,cycloalkyl substituted with 1 to 4 alkyl groups where each alkyl group is independently selected, unsubstituted cycloalkyl, cycloalkyl substituted with 1 to 4 alkyl groups, -OH, -CF3, -OCF3, -NO2, -C (O) R13, -C (O) OR13, -C (O) NHR17, -C (O) NR13R14, - SO (t) NR13R14, -SO (t) R13, -C (O) NR13OR14, unsubstituted or substituted aryl, unsubstituted heteroaryl or substituted formulas (7),Among them, there are 1-6 substitutes in the replaced arilo, each of which is selected from a separate R9 group consisting of: R9 group, 1-6 substitutes in the replaced heterogeneous group, each of which is selected from a separate group consisting of R9 group; O R3 and R4 combine with C atom and b-phenyl (a compound (formula 6)),They form a combined formula ring (8), in which Z1 or Z2 is a saturated heterocycle that has not been replaced or replaced (preferably a heterocycle of 4 to 7 members),Among them, the Z1 or Z2 ring optionally includes an extra heteromorphic atom selected from the group, which is composed of O, s and N18; there are 1 to 3 substitutes of Z1 or Z2, each of which is located in the,independently selected from the group consisting of: alkyl, aryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, arylalkyl, fluoralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, amino, - C (O) OR15, -C (O) NR15R16, -SOtNR15R16 , -C (O) R15, -SO2R15 with the proviso that R15 is not H, -NHC (O) NR15R16, -NHC (O) OR15, halogen and a heterocycloalkenyl group; each R5 and R6 are the same or different and are independently selected from the group consisting of: H, halogen, alkyl, alkoxy, CF3, -OCF3, -NO2, -C (O) R13, -C (O) OR13, -C (O) NR13R14, -SO (t) NR13R14, -C (O) NR13OR14, cyano,a. Arilo that is not replaced or replaced and a heterosexual group that is not replaced or replaced; in these groups, there are 1 to 6 replacement arilo, each of which is selected independently from the following groups: Where there are 1 to 6 alternatives, each of which is selected from a separate group consisting of R9; each R7 and R8 is selected from a separate group consisting of H, unreplaced or substituted bitumen, unreplaced or substituted arilo, Alien not replaced or replaced, alien not replaced or replaced, alien not replaced or replaced,There are no substituted or replaced cycloquinolones, no substituted or replaced cycloquinolones, co2r13, conr13r14, asphalt, alquinio and cycloquinolene; among these substitutes, R7 and R8 of one or more substitutes are selected independently from the following categories: -R13 (E) - nr13r14 (f) - NO2 (g) - CN (H) - so2r13, I) - if (either party) 3, each party is independently selected, (J) - if (arilo) 3, each party is independently selected, (k) (R13) 2r14si, each R13 (L) - co2r13, m) - C (o) nr13r14, n) - so2n13r14, O) - so2r13, P) - OC (o) R13,(q) OC (o) nr13r14, R) - n13c (o) R14, y (s) - n13co2r14 (fluorotar is a non limiting example of a halogenated tar group);R8a is selected from a group consisting of H, asphalt, cyclopentanediol a n d cyclopentanediol; each R9 is independently selected from a group consisting of: (a) R13, (b) halogen, (c) CF3, (d) - cor13, (E) - or13, f) - nr13r14, g) - NO2, H) - C N, I) - so2r13, J) - so2n13r14, K) - n13cor14, l) - conr13r14, m) - nr13r14, n) - cor13, (o) Or R-Nhso2nr13r14, - nhso2r13, - C (o) nr13r14, - C (o) nr13, - OC (o) R13 and cyanogen; R12 is selected from H-C (o) R13, not replaced or replaced by arilo, not replaced or replaced by alien arilalquilo, not replaced or replaced by cyclododecane, replaced or replaced by asphalt In this case, there are 1 to 6 substitutes in R12 group, each of which is selected independently from the following groups: R9 group; each of R13 and R14 group is selected independently from the following groups:Unreplaced or substituted tar, unreplaced or substituted cyanopropyl compounds, unreplaced or substituted arilo, unreplaced or substituted heterosexual, unreplaced or substituted heterosexual 1. Not replaced or replaced Cycas (Cycas) tequila, not replaced or replaced aperiodically, not replaced or replaced fluorojoules, not replaced or replaced aperiodicallyAmong these R13 and R14 alternatives, there are 1 to 5 alternatives, each of which is selected separately from the following categories: pitch-cf3-oh, Alcoy, arilo, arilalquilo, fluorotar, cyclopentanediol, cyclopentadienyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl Halogen, - NHC (o) n15r16 and - so2r15, provided R15 is not h; and, for the substituted cyano methyl ion and the substituted cyano hcyclohexane, the C atom attached to the cyano group is also not connected with the C atom, provided that the alternatives selected from group C include: - Oh, alcox, - n (R40) 2,Halogen y-nhc (o) n15r16; or R13 and R14 are combined with n groups in N group to form a saturated heterocycle which is not replaced or replaced, and the heterocycle can selectively contain an additional heteroatom selected from O.S and nr18 groups; There are 1 to 3 substitutes in the substituted R13 and R14 converters, each of which is independently selected from the following categories: CN, tar, cyanopropyl compound, arilo, hidroxi, oxyhydrogen compound, alcoxi, arilalquilo, fluorotar, cyclopentadienyl, cyandiallyl, cyclopropyl methanol, isopropyl sulfonylpropyl ester, CYCLOPROPYLENE allyl propyl propyl propyl propyl ester, isopropylene allyl propyl ester, Heteromorph, amino, propyl (o) or15,-C (o) n15r16, - sotnr15r16, - C (o) R15, - so2r15 (if R15 is not h),-NHC (O) NR15R16 -NHC (O) OR15 hal geno y un grupo heterocicloalquenilo y con la condici n de que el tomo de C al cual est unido el grupo ciano no tenga que estar tambi n unido al dicho tomo de C un sustituyente Each R19 and R20 is selected from a separate category consisting of asphalt, ash and heterogeneity; R30 is selected from a category consisting of cyclopropene CN -, NO2, or so2r15, provided that R15 should not be h; and each R31 is selected from a separate category consisting of: a. Arilo that is not replaced or replaced, ariarilo that is not replaced or replaced, cyclomequine that is not replaced or replaced;Among these R31 alternatives, there are 1 to 6 alternatives, each of which is selected separately from the following groups: