发明名称 KINASE INHIBITORS BASED UPON N-ALKYL PYRAZOLES
摘要 Compounds are of formula (I):;;The compounds have antiinflammatory activity (e.g., through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.
申请公布号 US2016039797(A1) 申请公布日期 2016.02.11
申请号 US201414781844 申请日期 2014.04.01
申请人 TOPIVERT PHARMA LIMITED ;RESPIVERT LIMITED 发明人 FYFE Matthew Colin Thor
分类号 C07D403/12;A61K31/4439;C07D401/12;A61K31/5377;A61K31/506 主分类号 C07D403/12
代理机构 代理人
主权项 1. A compound of formula I, wherein Ak represents C1-4 alkyl;R1 represents trimethylsilyl, C2-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, phenyl, Het1 or Het2, which latter seven groups are optionally substituted by one or more substituents selected from the group consisting of C1-2 alkyl, halo, hydroxy, and C1-2 alkoxy;R2 and R3, together with the C-atoms to which they are attached, form a fused phenyl or pyridyl ring, which latter two rings are optionally substituted by one or more substituents selected from the group consisting of C1-3 alkyl, C1-3 haloalkyl, cyano and halo,or one of R2 and R3 represents H, halo, cyano, C1-3 alkyl or C1-3 haloalkyl and the other independently represents halo, cyano, C1-3 alkyl or C1-3 haloalkyl,or R2 and R3 together combine to form C3-5 alkylene or C3-5 alkenylene, which latter two groups are optionally substituted by one or more substituents selected from the group consisting of C1-3 alkyl, C1-3 haloalkyl, cyano and halo;X1 represents N or CH;X2 and X3 both represent CRZ or one of X2 and X3 represents N and the other represents CRZ;RZ represents H, halo, cyano, C1-3 alkyl or C1-3 alkoxy, which latter two groups are optionally substituted by one or more halo atoms;R4 represents -Q1-[CH2(CH2)0-1CH2—O]1-12—CH2(CH2)0-1CH2—R6a,-Q2-C(R6c)(R6d)—[C1-5 alkylene]-R6a or—S(O)nR6b;R5 represents C1-3 alkoxy or C1-3 alkyl, which latter two groups are optionally substituted by one or more halo atoms, or R5 represents H, cyano, halo or C2-3 alkynyl;R6a represents OR7a or N(R7b)R7c;R6b represents C1-8 alkyl, C3-8 cycloalkyl, phenyl, Het1 or Het2, which latter five groups are optionally substituted by one or more substituents selected from the group consisting of hydroxyl, C1-3 alkyl and C1-3 alkoxy;R6c and R6d independently represent H or methyl;R7a to R7c independently represent H or C1-4 alkyl optionally substituted by one or more halo atoms, or R7b and R7c, together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic and which heterocyclic group contains one N atom (the atom to which R7b and R7c are attached) and, optionally, one or more further heteroatoms selected from O, S and N, and which heterocyclic group is optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, oxo, C1-4 alkyl and C1-4 alkoxy;Q1 and Q2 independently represent C(O)NH, O or S(O)p;n and p independently represent 0, 1 or 2,Het1 represents 5- or 6-membered heterocyclic group that is fully aromatic, which group contains one or more heteroatoms selected from the group consisting of N, O and S; andHet2 represents a 4- to 7-membered heterocyclic group that is fully saturated or partially unsaturated, which group contains one or more heteroatoms selected from the group consisting of N, O and S; or a pharmaceutically acceptable salt, solvate or isotopic derivative thereof.
地址 London GB