US 11,858,927 B2
Protein kinase MKK4 inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death
Bent Praefke, Tübingen (DE); Philip Klövekorn, Pliezhausen (DE); Roland Selig, Ulm (DE); Wolfgang Albrecht, Ulm (DE); and Stefan Laufer, Tübingen (DE)
Assigned to HepaRegeniX GmbH, Tuebingen (DE)
Appl. No. 16/965,912
Filed by HEPAREGENIX GMBH, Tuebingen (DE)
PCT Filed Jan. 30, 2019, PCT No. PCT/EP2019/052213
§ 371(c)(1), (2) Date Jul. 29, 2020,
PCT Pub. No. WO2019/149738, PCT Pub. Date Aug. 8, 2019.
Claims priority of application No. 18154454 (EP), filed on Jan. 31, 2018; and application No. 18183692 (EP), filed on Jul. 16, 2018.
Prior Publication US 2021/0078995 A1, Mar. 18, 2021
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 19 Claims
 
1. A compound having formula (Ic) or a pharmaceutically acceptable salt, solvate, or optical isomer thereof,

OG Complex Work Unit Chemistry
wherein the variables in formula (Ic) have the meanings as follows:
R1 is H, alkyl or heterocycloalkyl having 4 to 5 ring carbon atoms and 1 or 2 heteroatoms independently selected from 0, NH or N-alkyl;
Rw is —NR10SO2R12 or —N═S(═O)R10NR10R10;
Rx is F;
Ry is F;
R4 is
H,
halogen, or
alkyl;
R5 is a heteroaromatic 5- or 6-membered monocyclic or heteroaromatic 9- or 10-membered bicyclic group having 1, 2 or 3 heteroatoms independently selected from O, N and S which group is optionally substituted with 1 or 2 groups independently selected from alkyl,
haloalkyl,
alkoxy,
—NR10R10,
halogen,
—NR10-cycloalkyl,
tetrazolyl,
—O-alkylene-NR10R10,
—NR10-alkylene-Oalkyl,
—CN,
—CONR10R10,
—COOR10)
alkylSO(═NR10)—,
—CONR10—O-alkylene-OH,
—CONR10—O-alkylene-O-alkyl,
morpholinyl,
piperazinyl,
oxadiazolyl and
phenylcarbonyl;
R6 is H, or alkyl;
R10 at each occurrence independently is H, alkyl, phenyl which is optionally substituted with hydroxyl or alkoxy or is phenylalkyl wherein the phenyl group is optionally substituted with halogen; and
R12 is H, alkyl, phenylalkyl, or —NR10R10.