发明名称 Fused Tricyclic Imidazole Derivatives As Modulators of TNF Activity
摘要 A series of substituted fused tricyclic imidazole derivatives, in particular dihydro-1H-pyrano[4′,3′:4,5]imidazo[1,2-a]pyridine, 1,2,3,4-tetrahydroimidazo[1,2-a:5,4-c′]dipyridine, dihydro-1H-pyrano[3′,4′:4,5]imidazo[1,2-a]pyridine and tetrahydro-6H-cyclohepta[4,5]imidazo[1,2-a]pyridine, and analogues thereof, being potent modulators of human TNF activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
申请公布号 US2016304530(A1) 申请公布日期 2016.10.20
申请号 US201415101798 申请日期 2014.12.08
申请人 UCB BIOPHARMA SPRL 发明人 Alexander Rikki Peter;Brown Julien Alistair;Deligny Michael;Heer Jag Paul;Jackson Victoria Elizabeth;Jadot Sophie;Kroeplien Boris;Mac Coss Malcolm;Sabnis Yogesh Anil;Swinnen Dominique Louis Léon;Van Houtvin Nathalie;Zhu Zhaoning
分类号 C07D491/147;C07D471/04;C07D471/14 主分类号 C07D491/147
代理机构 代理人
主权项 1. A compound represented by formula (I) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, or a glucuronide derivative thereof, or a co-crystal thereof, wherein n represents an integer equal to 1 or 2;Y represents C3-7 cycloalkyl, aryl, C3-7 heterocycloalkyl or heteroaryl, any of which groups may be optionally substituted by one or more substituents;X and Z represent independently a heteroatom; carbonyl, —S(O)—, —S(O)2—, —S(O)(N—Rd), —NC(O)Rd, —N(CO)—ORd, —NS(O)2Rd or —N(Rd); or an optionally substituted straight or branched C1-4 alkylene chain;R1 and R2 independently represent hydrogen, halogen, cyano, nitro, hydroxy, trifluoromethyl, trifluoromethoxy, —ORa, —SRa, —SORa, —SO2Ra, —SF5, —NRbRc, —NRcCORd, —NRcCO2Rd, —NHCONRbRc, —NRcSO2Re, —N(SO2Re)2, —NHSO2NRbRc, —CORd, —CO2Rd, —CONRbRc, —CON(ORa)Rb, —SO2NRbRc or —S(O)(N—Rd)Ra; or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, C3-7 heterocycloalkenyl, C4-9 heterobicycloalkyl, heteroaryl, heteroaryl(C1-6)alkyl, (C3-7)heterocycloalkyl(C1-6)alkyl-aryl-, heteroaryl(C3-7)heterocycloalkyl-, (C3-7)cycloalkyl-heteroaryl-, (C3-7)cycloalkyl(C1-6)alkyl-heteroaryl-, (C4-7)cycloalkenyl-heteroaryl-, (C4-9)bicycloalkyl-heteroaryl-, (C4-9)bicycloalkenyl-heteroaryl-, (C3-7)heterocycloalkyl-heteroaryl-, (C3-7)heterocycloalkyl(C1-6)alkyl-heteroaryl-, (C3-7)heterocycloalkenyl-heteroaryl-, (C4-9)heterobicycloalkyl-heteroaryl-, heteroaryl-aryl- or (C4-9)spiroheterocycloalkyl-heteroaryl-, any of which groups may be optionally substituted by one or more substituents;R3 and R4 independently represents hydrogen, halogen, cyano, nitro, hydroxy, trifluoromethyl, trifluoromethoxy or —ORa; or C1-6 alkyl optionally substituted by one or more substituents;R5a and R5b independently represent hydrogen, hydroxy, halogen, trifluoromethyl, cyano; —NRbRc, —NRcC(O)Rd, —(CO)NRcRd, —NHS(O)2Re, —S—Ra, —(SO)—Ra, —S(O)2Ra, —S(O)(N—Rd), —S(O)2(N—Rd), —ORa, —C(O)—ORd, or —O(CO)—Rd—; or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents; or R5a and R5b when taken together with the carbon to which they are attached represent a carbonyl, thiocarbonyl or —C═N—OH; andR6 independently represent hydrogen, hydroxy, halogen, trifluoromethyl, cyano; —NRbRc, —NRcC(O)Rd, —(CO)NRcRd, —NHS(O)2Re, —S—Ra, —(SO)—Ra, —S(O)2Ra, —S(O)(N—Rd), —S(O)2(N—Rd), —ORa, —C(O)—ORd, or —O(CO)—Rd—; or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents; or R6 and Y together with the carbon to which they are attached form a C3-7 cycloalkyl or C3-7 heterocycloalkyl, optionally substituted with one or more substituents; andRa represents C1-6 alkyl, aryl, aryl(C1-6)alkyl, C3-7 cycloalkyl, C3-7 heterocycloalkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents;Rb and Rc independently represent hydrogen or trifluoromethyl; or C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted by one or more substituents; or Rb and Rc, when taken together with the nitrogen atom to which they are both attached, represent azetidin-1-yl, pyrrolidin-1-yl, oxazolidin-3-yl, isoxazolidin-2-yl, thiazolidin-3-yl, isothiazolidin-2-yl, piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, piperazin-1-yl, homopiperidin-1-yl, homomorpholin-4-yl, homopiperazin-1-yl, (imino)(oxo)thiazinan-4-yl, (oxo)thiazinan-4-yl or (dioxo)thiazinan-4-yl, any of which groups may be optionally substituted by one or more substituents; andRd represents hydrogen; or C1-6 alkyl, C3-7 cycloalkyl, aryl, C3-7 heterocycloalkyl or heteroaryl, any of which groups may be optionally substituted by one or more substituents; andRe represents C1-6 alkyl, aryl or heteroaryl, any of which groups may be optionally substituted by one or more substituents.
地址 Brussels BE