US 12,358,910 B2
Heteroaromatic compounds as Vanin inhibitors
Cedrickx Godbout, Attenweiler (DE); Martin Thomas Fleck, Munich (DE); and Hannes Fiepko Koolman, Biberach an der Riss (DE)
Assigned to Boehringer Ingelheim International GmbH, Ingelheim am Rhein (DE)
Appl. No. 17/299,164
Filed by Boehringer Ingelheim International GmbH, Ingelheim am Rhein (DE)
PCT Filed Dec. 2, 2019, PCT No. PCT/EP2019/083262
§ 371(c)(1), (2) Date Jun. 2, 2021,
PCT Pub. No. WO2020/114949, PCT Pub. Date Jun. 11, 2020.
Claims priority of application No. 18209727 (EP), filed on Dec. 3, 2018.
Prior Publication US 2022/0041592 A1, Feb. 10, 2022
Int. Cl. C07D 471/04 (2006.01); A61K 31/4365 (2006.01); A61K 31/437 (2006.01); A61K 31/4439 (2006.01); A61K 31/444 (2006.01); A61K 31/4709 (2006.01); A61K 31/519 (2006.01); A61K 45/06 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 495/04 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 31/4365 (2013.01); A61K 31/437 (2013.01); A61K 31/4439 (2013.01); A61K 31/444 (2013.01); A61K 31/4709 (2013.01); A61K 31/519 (2013.01); A61K 45/06 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 495/04 (2013.01)] 14 Claims
 
1. A compound of the formula I,

OG Complex Work Unit Chemistry
wherein
R1 denotes naphthalenyl substituted with R1.1 and R1.2 or
8-10 membered heteroaryl containing 1 to 3 heteroatoms selected from the group consisting of S, N and O substituted with R1.1 and R1.2,
R1.1 is selected from the group consisting of H, C1-4-alkyl, C1-2-alkyl-O—, CF3, C3-5-cycloalkyl, H2N—, Br, Cl and F;
R1.2 is selected from the group consisting of H, C1-4-alkyl, CF3, H2N—, Br, Cl and F;
wherein the alkyl of R1.1 and R1.2 are each independently optionally substituted by 1-3 F-atoms
R2 and R3 are independently from each other selected from the group consisting of H and methyl,
R4 denotes R4.1R4.2N— or NC;
or
R4 denotes a group of formula R4.a

OG Complex Work Unit Chemistry
wherein the asterisk (*) denotes the point of attachment of the R4a group to the pyrrolidinyl ring of the compound of formula I, wherein
X denotes CH2 or O;
R4.1 is selected from the group consisting of C1-4-alkyl-CO—, 6-membered heteroaryl containing 1-2 N-atoms, C3-5-cycloalkyl-CO— substituted by R4.1.1 and R4.1.2, Phenyl-CO— optionally substituted by 1-2 halogen atoms, C1-4-alkyl- or CH3—O— and 5 to 6 membered heteroaryl-CO-optionally substituted by C1-4-alkyl- or CH3—O—,
wherein
R4.1.1, R4.1.2 independently from each other are selected from the group consisting of H, —CH3, F, and —CN;
R4.2 denotes H or C1-3-alkyl, and
R5 denotes H or methyl;
or a pharmaceutically acceptable salt thereof.