MKK4 PROTEIN KINASE INHIBITORS FOR STIMULATION OF LIVER REGENERATION OR REDUCTION OR PREVENTION OF HEPATOCYTE DEATH Russian patent published in 2023 - IPC C07D405/04 C07D471/04 A61K31/437 A61P1/16 A61P19/02 A61P25/00 

FIELD: biotechnology.

SUBSTANCE: invention relates to pyrazolo-pyridine compounds, namely to a compound of the formula (Ic) or its pharmaceutically acceptable salt or optical isomer. In the formula (Ic), R¹ is H; R^W is -NR¹⁰SO₂R¹²; R^x is F; R^y is F; R⁴ is H; R⁵ is phenyl substituted with 1, 2, or 3 groups independently selected from C₁-C₆ alkyl, hydroxy, halogen, C₁-C₆ halogen alkyl, C₁-C₆ alkyl sulfonyl, C₁-C₆ alkyl-SO(=NR¹⁰)-, C₁-C₆ alkyl sulfonyl-NR¹⁰-, -NR¹⁰R¹⁰, R¹⁰R¹⁰NSO₂-, R¹⁰R¹¹N(C=O)-, C₁-C₆ alkoxy, -OCH₂CH₂O- (ethylenedioxy attached in neighboring positions to a phenyl ring), -NO₂, -COOR¹⁰, R¹⁰R¹⁰N(C=O)-, and tetrazolyl, or R⁵ is pyridyl, pyridyl substituted with -COOR¹⁰, or pyrimidinyl substituted with CF₃; R⁶ is H; R¹⁰, in each case, is independently H or C₁-C₆ alkyl; R¹¹ is alkyl, which is substituted with 1 or 2 hydroxy groups; and R¹² is C₁-C₆ alkyl, phenylC₁-C₆ alkyl, or -NR¹⁰R¹⁰. A compound selected from a group of individual compounds, a pharmaceutical composition, the use of a compound, and a method for selective inhibition of MKK4 protein kinase compared to JNK1 and MKK7 protein kinases or stimulation of liver regeneration or prevention of hepatocyte death are also proposed.

EFFECT: proposed compounds inhibit mitogen-activated protein kinase-kinase 4 (hereinafter – MKK4) and, in particular, selectively inhibit MKK4 compared to JNK1 and MKK7 protein kinases; compounds are useful for stimulation of liver regeneration or reduction or prevention of hepatocyte death.

(Ic)

10 cl, 8 tbl, 97 ex