US 12,264,158 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)
Filed by HEPAREGENIX GMBH, Tuebingen (DE)
Filed on Nov. 8, 2023, as Appl. No. 18/388,084.
Application 18/388,084 is a continuation of application No. 16/965,912, granted, now 11,858,927, previously published as PCT/EP2019/052213, filed on Jan. 30, 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 2024/0116931 A1, Apr. 11, 2024
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 7 Claims
 
1. A compound having formula (Ie) or a pharmaceutically acceptable salt, solvate or optical isomer thereof,

OG Complex Work Unit Chemistry
wherein the variables in formula (Ie) have the meanings as follows:
Rw is —NR10SO2R12;
Rx, Ry, Rz are selected from:
a) Rx is F, Ry is F and Rz is H; and
b) Rx is F, Ry is F and Rz is F;
R1 is H, alkyl or heterocycloalkyl having 4 to 5 ring carbon atoms and 1 or 2 heteroatoms independently selected from O, NH or N-alkyl;
R4 is H or alkyl;
R5 is phenyl which is optionally substituted with 1, 2 or 3 groups independently selected from
alkyl,
hydroxy,
halogen,
haloalkyl,
alkylsulfonyl,
alkylSO (═NR10)—,
alkylsulfonyl-NR10—,
—NR10R10,
R10R10NSO2—,
R10R11NSO2—,
alkyl-C(═O)—NR10SO2—,
R10R11N (C═O)—,
alkoxy,
—OCH2O-(methylenedioxy attached in neighboring positions to the phenyl ring),
—OCH2CH2O-(ethylenedioxy attached in neighboring positions to the phenyl ring),
—NO2,
—COOR10,
—COOR14,
R10R10N(C═O)—,
tetrazolyl,
alkylSO (═NR10)—,
—CONR10—O-alkylene-OH, and
—CONR10—O-alkylene-O-alkyl, or
R6 is H, or alkyl;
R10 at each occurrence independently is H or alkyl;
R11 is alkyl which is substituted with 1, 2 or 3 hydroxy groups;
R12 is H, C1-C6 alkyl or phenyl-C1-C6 alkyl; and
R14 is alkyl which is substituted with 1 or 2 groups independently selected from —NR10R10, hydroxy or alkoxy.