US 11,851,425 B2
Combination treatments comprising administration of 1H-pyrazolo[4,3-B]pyridines
Jan Kehler, Lyngby (DK); Karsten Juhl, Greve (DK); Mauro Marigo, Skovlunde (DK); Paulo Jorge Vieira Vital, København V (DK); Mikkel Jessing, Frederiksberg (DK); Morten Langgård, Glostrup (DK); Lars Kyhn Rasmussen, Vanløse (DK); and Carl Martin Sebastian Clementson, Valby (DK)
Assigned to H. Lundbeck A/S, Valby (DK)
Appl. No. 16/772,612
Filed by H. Lundbeck A/S, Valby (DK)
PCT Filed Dec. 12, 2018, PCT No. PCT/EP2018/084434
§ 371(c)(1), (2) Date Oct. 27, 2020,
PCT Pub. No. WO2019/115567, PCT Pub. Date Jun. 20, 2019.
Claims priority of application No. PA201700711 (DK), filed on Dec. 14, 2017.
Prior Publication US 2020/0385372 A1, Dec. 10, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); C07D 413/14 (2006.01); C07D 401/14 (2006.01); C07D 407/14 (2006.01); C07D 409/14 (2006.01)
CPC C07D 413/14 (2013.01) [C07D 401/14 (2013.01); C07D 407/14 (2013.01); C07D 409/14 (2013.01)] 15 Claims
 
1. A composition or kit comprising:
1) A first compound according to formula (I)

OG Complex Work Unit Chemistry
wherein
L is selected from the group consisting of NH, CH2, S and O;
R1 is selected from the group consisting of hydrogen, linear or branched C1-C5 alkyl, C1-C5 fluoroalkyl and saturated monocyclic C3-C5 cycloalkyl;
R2 is selected from the group consisting of linear or branched C1-C8 alkyl, saturated monocyclic C3-C8 cycloalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl; all of which can be optionally substituted one or more times with one or more substituents selected from the group consisting of methyl, fluorine, hydroxy, cyano and methoxy;
R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl all of which can be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 fluoroalkoxy and C1-C3 alkoxy; or
R3 is methyl substituted with a 5-membered heteroaryl which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 fluoroalkoxy and C1-C3 alkoxy; or
R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl all of which can be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 fluoroalkoxy and C1-C3 alkoxy; or
R3 is ethyl substituted with a 5-membered heteroaryl which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 fluoroalkoxy and C1-C3 alkoxy; or
L is CH2 and R3 is NH which is substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl all of which can be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 fluoroalkoxy and C1-C3 alkoxy; or
L is CH2 and R3 is NH which is substituted with a 5-membered heteroaryl which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 fluoroalkoxy and C1-C3 alkoxy;
R4 is phenyl, pyridinyl or pyridonyl all of which can be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 deutereoalkyl, C1-C3 fluoroalkoxy, cyclopropyloxy, C1-C3 alkoxy, C1-C3 deutereoalkoxy and —N-R5R6 wherein R5 and R6 are each independently selected from H, C1-C3 alkyl and C1-C3 deutereoalkyl; or
R4 is a 5-membered heteroaryl which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 deutereoalkyl, C1-C3 fluoroalkoxy, cyclopropyloxy, C1-C3 alkoxy, C1-C3 deutereoalkoxy and —N-R5R6 wherein R5 and R6 are each independently selected from H, C1-C3 alkyl and C1-C3 deutereoalkyl; or
R4 is a 4, 5 or 6 membered saturated heterocycle all of which can be optionally substituted with one or more substituents selected from oxo, C1-C4 alkyl and C1-C4 fluoroalkyl;
or a pharmaceutically acceptable salt thereof, and
2) A second compound, which compound is selected from a compound useful in active or passive Aβ peptide immunotherapy, an NMDA receptor antagonist, an acetylcholine esterase inhibitor, a BACE inhibitor, a 5-HT6 receptor antagonist, an antiepileptic, an anti-inflammatory drug or an anti-N3-pGlu Abeta monoclonal antibody;
wherein the composition or kit is for use in the treatment of a neurodegenerative and/or cognitive disorder.