US 11,708,366 B2
Heteroaryl substituted spiropiperidinyl derivatives and pharmaceutical uses thereof
Mallesh Bushaboina, Bengaluru (IN); Xin Chen, Lexington, MA (US); Atwood Kim Cheung, Arlington, MA (US); Andrew James Culshaw, Norfolk (GB); Timothy Brian Hurley, Boston, MA (US); Nancy Labbe-Giguere, Arlington, MA (US); Wolfgang Miltz, Allschwil (CH); David Orain, Hesingue (FR); Tajesh Patel, Westford, MA (US); Srinivasan Rajagopalan, Bengaluru (IN); Till Roehn, Zurich (CH); David Andrew Sandham, Concord, MA (US); Gebhard Thoma, Lörrach (DE); Ritesh Bhanudasji Tichkule, Cambridge, MA (US); and Rudolf Wälchli, Basel (CH)
Assigned to Novartis AG, Basel (CH)
Filed by Novartis AG, Basel (CH)
Filed on Aug. 12, 2021, as Appl. No. 17/400,458.
Claims priority of application No. 20191191 (EP), filed on Aug. 14, 2020.
Prior Publication US 2022/0048909 A1, Feb. 17, 2022
Int. Cl. C07D 471/10 (2006.01); A61K 31/438 (2006.01); A61K 45/06 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/10 (2013.01) [A61K 45/06 (2013.01); C07D 519/00 (2013.01)] 27 Claims
 
1. A compound of Formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is phenyl optionally substituted with one or more halo substituents;
R2 is H or fluoro;
X1 is CH2 or O;
R4 is a mono or bicyclic heteroaryl, optionally substituted with one or more R3 substituents;
each R3 is independently selected from C6-10aryl, benzyl, C1-6 alkyl, C3-7 cycloalkoxy, hydroxyC1-6alkyl, C1-6alkoxyC1-6alkyl, halo, haloC1-6alkyl, OR5, CN, C(O)OC1-6alkyl, OH, C3-7cycloalkyl, O3-7cycloalkenyl, 5- to 10 membered heteroaryl, 4-10 membered heterocyclyl, —C(O)NH2, and NRaRb, wherein Ra and Rb are independently H, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-6alkyl or halo C1-6alkyl;
wherein said aryl, heterocyclyl, heteroaryl, C3-7cycloalkyl, C3-7cycloalkenyl, C3-7cycloalkoxy are further optionally substituted with one or more substituents independently selected from OH, CN, C3-7cycloalkyl, C3-7cycloalkoxy, NH2, C1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, hydroxyC1-6alkyl, —S—C1-6alkyl; —S-(haloC1-6alkyl), halo, haloC1-6alkyl, —C(O)—C1-6alkyl, phenyl optionally further substituted with halo; and heteroaryl optionally substituted with halo, C1-6alkyl, haloC1-6alkyl or C3-7 cycloalkyl;
R5 is C1-6alkyl, haloC1-6alkyl, hydroxyC1-6alkyl, alkoxyC1-6alkyl, C3-7cycloalkyl, C3-7cycloalkenyl, C3-7cycloalkylC1-6alkyl, phenyl, benzyl, 4-10 membered heterocyclyl, 5-10 membered heteroaryl;
wherein phenyl, heterocyclyl and C3-7cycloakyl, C3-7cycloalkylC1-6alkyl is optionally substituted by one or more substituents selected from C1-6alkyl, C1-6alkoxy, halo, phenyl optionally further substituted with halo; heterocyclyl optionally further substituted with C1-6alkyl or haloC1-6alkyl;
with the proviso that when R2 is F, then X1 is CH2.