US 12,122,761 B2
2-azaspiro[3.4]octane derivatives as M4 agonists
Amy Calhoun, Cambridge, MA (US); Xin Chen, Lexington, MA (US); Kevin Matthew Gardinier, Arlington, MA (US); Edward Charles Hall, Boston, MA (US); Keith Jendza, Boston, MA (US); Nancy Labbe-Giguere, Arlington, MA (US); James Neef, Stow, MA (US); Daniel Steven Palacios, Cambridge, MA (US); Ming Qian, Watertown, MA (US); Michael David Shultz, Lexington, MA (US); Christopher G. Thomson, Herts (GB); Kate Yaping Wang, Boxborough, MA (US); and Fan Yang, West Roxbury, MA (US)
Assigned to Novartis AG, Basel (CH)
Filed by NOVARTIS AG, Basel (CH)
Filed on Dec. 6, 2022, as Appl. No. 18/062,356.
Application 18/062,356 is a continuation of application No. 17/065,360, filed on Oct. 7, 2020, granted, now 11,548,865.
Claims priority of provisional application 62/912,980, filed on Oct. 9, 2019.
Prior Publication US 2023/0212139 A1, Jul. 6, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/04 (2006.01); A61K 45/06 (2006.01)
CPC C07D 401/04 (2013.01) [A61K 45/06 (2013.01)] 25 Claims
 
1. A method for the treatment of psychosis comprising administration of a therapeutically effective amount of a compound according to Formula (I) or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the compound according to Formula (I) is

OG Complex Work Unit Chemistry
wherein
R1 is halogen or hydrogen;
R2 is halogen or hydrogen;
R3 is
C1-6 alkyl, said alkyl is optionally substituted with one or two substituents independently selected from the group consisting of 4 to 6-membered heterocycloalkyl and —OH,
5 to 6-membered heteroaryl,
3 to 6-membered cycloalkyl, said cycloalkyl is optionally substituted with one —OH,
5 to 6-membered heterocycloalkyl, said heterocycloalkyl is optionally substituted with one —OH, or
—OR4;
R4 is
—CF3,
—CF2H,
C1-6 alkyl, said alkyl is optionally substituted with one or two R6,
3 to 6-membered cycloalkyl,
4 to 7-membered heterocycloalkyl, said heterocycloalkyl is optionally substituted with one R6,
5 to 6-membered heteroaryl, or
R4 is one of the following groups:

OG Complex Work Unit Chemistry
R5 is halogen or hydrogen;
each R6 is
independently halogen,
—OH,
—CF3,
—CF2H,
cyano,
—OCF3,
—OCH3,
—O-heterocycloalkyl,
C1-C4 alkyl,
4 to 7-membered heterocycloalkyl, said heterocycloalkyl is optionally substituted with one or two substituents independently selected from the group consisting of halogen, —OH, and C1-3 alkyl,
5 to 6-membered heteroaryl, said heteroaryl is optionally substituted with one or two C1-3 alkyl,
3 to 6-membered cycloalkyl, said cycloalkyl is optionally substituted with one —CF3, or
each of R6 is independently one of the following groups:

OG Complex Work Unit Chemistry
R7 is
a 5 to 6-membered heteroaryl, said heteroaryl is optionally substituted with one substituent selected from the group consisting of C1-C6 alkyl, —CF3, and halogen, or C(O)R8; and
R8 is
3 to 6-membered cycloalkyl, said cycloalkyl is optionally substituted with one halogen, or
4 to 6-membered heterocycloalkyl.