US 11,052,076 B2
Spirocyclic indolines as IL-17 modulators
Gareth Neil Brace, Abingdon (GB); Rose Elizabeth Chappell, Abingdon (GB); Hervé Jean Claude Deboves, Abingdon (GB); Anne Marie Foley, Slough (GB); Gregory Foulkes, Abingdon (GB); Elizabeth Pearl Jones, Bracknell (GB); Fabien Claude Lecomte, Slough (GB); Joanna Rachel Quincey, Slough (GB); Monika-Sarah Elisabeth Dorothea Schulze, Slough (GB); Matthew Duncan Selby, Slough (GB); Adam Peter Smalley, Slough (GB); Richard David Taylor, Slough (GB); Robert James Townsend, Abingdon (GB); and Zhaoning Zhu, Slough (GB)
Assigned to UCB Biopharma SRL, Brussels (BE)
Appl. No. 16/619,573
Filed by UCB BIOPHARMA SRL, Brussels (BE)
PCT Filed Jun. 12, 2018, PCT No. PCT/EP2018/065558
§ 371(c)(1), (2) Date Dec. 5, 2019,
PCT Pub. No. WO2018/229079, PCT Pub. Date Dec. 20, 2018.
Claims priority of application No. 1709456 (GB), filed on Jun. 14, 2017.
Prior Publication US 2020/0138797 A1, May 7, 2020
Int. Cl. C07D 471/10 (2006.01); C07D 487/10 (2006.01); C07D 495/10 (2006.01); C07D 491/20 (2006.01); A61K 31/4439 (2006.01); A61K 31/407 (2006.01); A61K 31/4155 (2006.01); A61K 31/4192 (2006.01); A61K 31/4196 (2006.01); A61K 31/422 (2006.01); A61K 31/427 (2006.01); A61K 31/433 (2006.01); A61K 31/437 (2006.01); A61K 31/501 (2006.01); A61K 31/502 (2006.01); A61K 31/506 (2006.01); C07D 491/107 (2006.01); C07D 519/00 (2006.01)
CPC A61K 31/4439 (2013.01) [A61K 31/407 (2013.01); A61K 31/4155 (2013.01); A61K 31/4192 (2013.01); A61K 31/4196 (2013.01); A61K 31/422 (2013.01); A61K 31/427 (2013.01); A61K 31/433 (2013.01); A61K 31/437 (2013.01); A61K 31/501 (2013.01); A61K 31/502 (2013.01); A61K 31/506 (2013.01); C07D 471/10 (2013.01); C07D 487/10 (2013.01); C07D 491/107 (2013.01); C07D 491/20 (2013.01); C07D 495/10 (2013.01); C07D 519/00 (2013.01)] 14 Claims
 
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein
ring A represents C3-9 cycloalkyl, C3-7 heterocycloalkyl or C4-9 heterobicycloalkyl, any of which groups may be optionally substituted by one or more substituents;
B represents C—R2 or N;
D represents C—R3 or N;
E represents C—R4 or N;
R0 represents hydrogen or C1-6 alkyl;
R1 represents —CORa;
Ra represents —CH(R5)N(H)C(O)R6, —CH(R5)N(H)S(O)2R6, —C(═CR5aR5b)N(H)C(O)R6, —CH(R5)R7, —CH(R5)N(H)R7 or —CH(R5)C(O)N(H)R7;
R2 represents hydrogen, halogen, cyano, C1-6 alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxy, C1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C1-6 alkyl-sulphinyl or C1-6 alkylsulphonyl;
R3 represents hydrogen, halogen, cyano, C1-6 alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxy, C1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C1-6 alkyl-sulphinyl or C1-6 alkylsulphonyl;
R4 represents hydrogen, halogen, cyano, C1-6 alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxy, C1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C1-6 alkyl-sulphinyl or C1-6 alkylsulphonyl;
R5 represents hydrogen; or R5 represents C1-5 alkyl, C3-9 cycloalkyl, C3-9 cyclo-alkyl(C1-5)alkyl, C4-9 bicycloalkyl, C4-9 bicycloalkyl(C1-5)alkyl, C5-9 spirocycloalkyl, C5-9 spirocycloalkyl(C1-5)alkyl, C9-11 tricycloalkyl, C9-11 tricycloalkyl(C1-5)alkyl, aryl, aryl-(C1-5)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-5)alkyl, heteroaryl or heteroaryl(C1-5)alkyl, any of which groups may be optionally substituted by one or more substituents;
R5a represents C3-7 cycloalkyl, C4-9 bicycloalkyl, aryl, C3-7 heterocycloalkyl or heteroaryl, any of which groups may be optionally substituted by one or more substituents; and
R5b represents hydrogen or C1-6 alkyl; or
R5a and R5b, when taken together with the carbon atom to which they are both attached, represent C3-7 cycloalkyl, C4-9 bicycloalkyl or C3-7 heterocycloalkyl, any of which groups may be optionally substituted by one or more substituents;
R6 represents —NR6aR6b or —OR6c; or R6 represents C1-9 alkyl, C3-9 cycloalkyl, C3-9 cycloalkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl-(C1-6)alkyl, heteroaryl, heteroaryl(C1-6)alkyl or spiro[(C3-7)heterocycloalkyl][heteroaryl], any of which groups may be optionally substituted by one or more substituents;
R6a represents hydrogen; or R6a represents C1-6 alkyl, C3-7 cycloalkyl, C3-7 cyclo-alkyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl(C1-6)-alkyl, heteroaryl, heteroaryl(C1-6)alkyl or spiro[(C3-7)heterocycloalkyl][heteroaryl], any of which groups may be optionally substituted by one or more substituents;
R6b represents hydrogen or C1-6 alkyl;
R6c represents 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; and
R7 represents aryl, heteroaryl or spiro[(C3-7)heterocycloalkyl][heteroaryl], any of which groups may be optionally substituted by one or more substituents.