Compounds as modulators of the thrombopoietin receptor activity, Pharmaceutical compositions containing them and uses in hematopoietic diseases.

摘要

Item 1: a compound whose characteristic is the response formula (1),(2)(3)(4)(5)this is it.or a salt acceptable for pharmaceutical, ester, amide or prodrug use thereof, wherein: R1 is selected from H, halogen, OR14, NO2, CN, NR14R15, an optionally substituted C1-6 alkyl, an optionally substituted C1-6 haloalkyl , an optionally substituted C1-6 heteroalkyl, CO2R14, CONR14R15, SO3R14, SO2NR14R15 and a carboxylic acid bioiso ester; each R2 is independently selected from H, halogen, OR14, NR14R15, an optionally substituted C1-6 alkyl, an optionally substituted C1-6 haloalkyl, and an optionally substituted C1-6 heteroalkyl; R3 and R4 are independently selected from H, an optionally substituted C1-6 alkyl,an optionally substituted C1-6 haloalkyl, and an optionally substituted C1-6 heteroalkyl; R5 is selected from H, halogen, OR14, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, and C1-6 haloheteroalkyl; R6 is selected from an optionally substituted C1-10 alkyl, an optionally substituted C1-10 haloalkyl, and an optionally substituted C1-10 heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is selected from (CH2) mR18, C (O) NHR18, C ::: CR18, CR3 = CR4R18, and CR3 = R18; R7 is selected from CO2R14, CONR14R15, SO3R14, SO2NR14R15 and a carboxylic acid bioiso ester;Each R8 and R9 shall be selected from the following substances respectively: H, R16, n16r17, a selective alternative C1-6 tar, a selective alternative C1-6 halide, a selective alternative C1-6 heterogeneous tar; (CH2) mr18, and a non-existent C1-6; (or 8 and R9 constitute a selective alternative oil; O R8 and R9 combine to form an alternative C3-8 ring; R10 is selected from h, halogenated, oxo, or16, nr16r17, sr16, an alternative C1-6 tar, an alternative C1-6 halide and an alternative C1-6 alien tar; R11 is selected from h, halogenated, or14, nr14r15 and sr14;or R11 and R4 join to form an optionally substituted heterocycle; R 12 is selected from H, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, and C 1-6 haloheteroalkyl; R13 is selected from H, halogen, CN, NO2, CO2R14, S (O) mR14, C1-4 alkyl, C1-4 haloalkyl, C1-4 heteroalkyl, C1-4 haloheteroalkyl; R14 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, and C1-6 heterohaloalkyl; R15 is selected from H, SO2R19, C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, and C1-6 heterohaloalkyl; R16 and R17 are each independently selected from H, an optionally substituted C1-6 alkyl, an optionally substituted C1-6 haloalkyl,One kind of alternative C1-6 and (CH2) mr18, or one kind of R16 and R17, one kind of alternative c2-6 and one kind of R16 and R17, while the other R16 and R17 are not, or R16 and R17 combine to form an alternative C3-8 ring; R18 is selected from a selective single ring or double ring aromatic ring system, which can optionally contain one or more heteroatoms and optionally fuse with a non aromatic heterocycle or carbon thyroid. When R18 contains non aromatic heterocycle or carbon thyroid, the position of the alliance can be Non aromatic thyroid or aromatic ring system; R19 is selected from h,C1-3 tar, c1-3 halide, and an alternative arilo; D is a single or double ring aromatic ring system, which can optionally contain one or more heteroatoms, and can optionally combine with heterocyclic or non aromatic carbon; E is a single ring or double ring aromatic ring system, which can optionally contain one or more heteroatoms, which can optionally combine with heteromorphic or non aromatic carbon thyroid; L is NH or does not exist; q is a single ring or double ring aromatic ring system, which can optionally contain one or more heteroatoms, It can be combined with non aromatic thyroid or heterosexual, or selected from O, Nr4, cr3r4,1. W is selected from O, Nr4, cr3r4, CO and nonexistence; X is n or Cr5; it is a 1-4 atom spacing, consisting of one or more groups selected from optional C1-6 tar, optional C1-6 isomerized tar, optional alternative phenyl and optional alternative isomer; Z is selected from the following two options: missing, the space between the alternative C6-10 arilo and the alternative c1-8 alien arilo is 2-5 atoms, each of which can be combined with the alternative heterocyclic or non aromatic carbocyclo,And a 1-5 atom selection spacing, between the selective replacement of C1-6 tar, the selective replacement of C1-6 isomerized tar and the selective replacement of C1-6 halogenated tar, each alternative combined with the selective replacement of arilo C6-10; m is 0, 1, 2 or 3; n is 0 or 1; each optional replacement group has been replaced. It has not been replaced or replaced by one or more independently selected groups: asphalt, ISO asphalt, halo tar, ISO halo tar, epoxy, arilo, arilalquilo, ISO propene, aromatic heterocycle, hydroxy, ariloxi, mercato, hydrocarbon, ariltio, cyanogen, halogen, carbide, hydrogen sulfide, o-carbamillo, n-carbamillo,O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanate, thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, = O, = S, amino, and protected derivatives of amino groups; with the proviso that if Y is oriented as shown in the remainder (7) in the compounds of formulas (1) or (2) to form a dihydropyrazolinine, then (i) D is not naphthyl if X is N and W is NH; (ii) D is not phenyl if X is CH, W is NH, Z is phenyl, and R10 or R11 is - (CH2) 0-6OH, (iii) R11-D-R10 is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl , and (iv) U is not NH; also with the proviso that if X is N and W is NH, then D is not phenyl;Moreover, if x is n and W is NH in compound (3) or (6) of the formula,R6, R10, and R11 do not contain functions of carbonic acid, acylamine, ester or sulfuric acid, or bioisotopes of carbonates.