US 11,912,721 B2
Fused pentacyclic imidazole derivatives
Teresa De Haro Garcia, Slough (GB); Michael Deligny, Brussels (BE); Jag Paul Heer, Slough (GB); Joanna Rachel Quincey, Slough (GB); Mengyang Xuan, Slough (GB); Zhaoning Zhu, Slough (GB); Daniel Christopher Brookings, Slough (GB); Mark Daniel Calmiano, Slough (GB); Yves Evrard, Brussels (BE); Martin Clive Hutchings, Slough (GB); James Andrew Johnson, Slough (GB); Sophie Jadot, Brussels (BE); Jean Keyaerts, Brussels (BE); Malcolm MacCoss, Seabrook Island, SC (US); Matthew Duncan Selby, Slough (GB); Michael Alan Shaw, Slough (GB); Dominique Louis Leon Swinnen, Brussels (BE); Laurent Schio, Paris (FR); Yann Foricher, Paris (FR); and Bruno Filoche-Romme, Paris (FR)
Assigned to UCB Biopharma SRL, Brussels (BE); and Sanofi, Paris (FR)
Filed by UCB Biopharma SRL, Brussels (BE); and Sanofi, Paris (FR)
Filed on Nov. 24, 2020, as Appl. No. 17/102,790.
Application 16/220,847 is a division of application No. 15/513,357, granted, now 10,202,405, issued on Feb. 12, 2019, previously published as PCT/EP2015/072868, filed on Oct. 2, 2015.
Application 17/102,790 is a continuation of application No. 16/220,847, filed on Dec. 14, 2018, granted, now 10,906,919.
Claims priority of application No. 14290299 (EP), filed on Oct. 3, 2014; application No. 15162641 (EP), filed on Apr. 7, 2015; and application No. 15171036 (EP), filed on Jun. 8, 2015.
Prior Publication US 2021/0155637 A1, May 27, 2021
Int. Cl. C07D 519/00 (2006.01); C07D 491/08 (2006.01); C07D 487/08 (2006.01); C07D 491/18 (2006.01); C07D 495/08 (2006.01); C07D 471/18 (2006.01); C07D 487/18 (2006.01); C07D 493/18 (2006.01); C07D 495/18 (2006.01); C07D 513/18 (2006.01); C07F 7/18 (2006.01); A61K 31/4184 (2006.01); A61K 31/506 (2006.01); A61K 31/55 (2006.01)
CPC C07D 519/00 (2013.01) [A61K 31/4184 (2013.01); A61K 31/506 (2013.01); A61K 31/55 (2013.01); C07D 471/18 (2013.01); C07D 487/08 (2013.01); C07D 487/18 (2013.01); C07D 491/08 (2013.01); C07D 491/18 (2013.01); C07D 493/18 (2013.01); C07D 495/08 (2013.01); C07D 495/18 (2013.01); C07D 513/18 (2013.01); C07F 7/1804 (2013.01)] 16 Claims
 
1. A compound represented by formula (IB), or an N-oxide thereof, or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein
—X-Q- represents —O—, —O—C(O)—, —O—C(CH—CN)—, —S—, —SO—, —SO2—; or —N(Rg)—, —N(Rf)—CO, —N(Rf)—SO2—, —O—CH2—, —CH2—S—, —CH2—SO—, —CH2—SO2—, —N(Rg)—CH2—, —N(Rf)—C(S)—, —N═S(O)(CH3)—, —O—C(═CH2)— or —S(═N—CN)—, any of which groups may be optionally substituted by one or more substituents selected from fluoro, methyl, carboxy, trifluoromethyl, methylcarbonyl, deuterated methyl, ethoxycarbonyl, hydroxyisopropyl, and hydroxymethyl;
Z represents methylene;
R1 represents halogen or cyano; or aryl, heteroaryl, (C3-7)cycloalkyl-heteroaryl, (C3-7)heterocycloalkyl-heteroaryl, (C4-9)heterobicycloalkyl-heteroaryl, (C3-7)heterocycloalkyl, (C3-7)heterocycloalkenyl, or (C3-7)heterocycloalkenyl-aryl, any of which groups may be optionally substituted by one or more substituents selected from halogen, cyano, cyano(C1-6)alkyl, C1-6 alkyl, difluoromethyl, trifluoromethyl, hydroxy, (hydroxy)(C1-6)alkyl, amino, (amino)(C1-6) alkyl, C1-6 alkoxy, (C1-6) alkoxy(C1-6)alkyl, C2-6 alkylcarbonyl, C2-6 alkoxycarbonyl, (C2-6) alkoxycarbonyl-amino-C1-6 alkyl, phosphate(C1-6)alkyl, C1-6 alkylthio, C1-6 alkylsulphonyl, oxo, (C1-6)alkylsulphoximinyl, (C1-6)alkylsulphinyl-amino-, di(C1-6)alkylamino (C1-6)alkyl, (C2-6)alkylcarbonylamino(C1-6)alkyl, di(C1-6)alkenylamino (C1-6)alkyl, (C2-6)alkylcarbonylamino(C1-6)alkyl, C1-6 alkylsulphonyl-amino-C1-6 alkyl, tetrahydrofuranyl, sulphate(C1-6)alkyl, and carboxy-(C1-6)alkyl-carbonyloxy-(C1-6)alkyl;
R2 represents hydrogen or halogen;
R3 and R4 independently represent hydrogen, halogen or trifluoromethyl; or C1-6 alkyl;
R5 represents halogen, —ORa, difluoromethoxy or trifluoromethoxy;
R6 represents hydrogen, halogen or trifluoromethyl;
R7 represents hydrogen or trifluoromethyl;
R8 represents hydrogen, halogen or trifluoromethyl;
R12 represents C1-6 alkyl;
Ra represents C1-6 alkyl;
Rf represents hydrogen; or C1-6 alkyl, which group may be optionally substituted by one or more substituents selected from halogen or C1-6 alkyl; and
Rg represents hydrogen; or C1-6 alkyl, —CO—(C1-6)alkyl, —SO2—(C1-6)alkyl, —CO—(C3-7)heterocycloalkyl, —SO2—(C3-7)cycloalkyl, —SO2-aryl, —SO2-heteroaryl, heteroaryl or (C2-6)alkoxycarbonyl, any of which groups may be optionally substituted by one or more substituents selected from halogen or C1-6 alkyl.