Granted Patent B2

US 12,559,473 · App. 18/651,572 · Granted Feb 24, 2026

Inventors: Ulrich Bothe (Berlin, DE); Holger Siebeneicher (Berlin, DE); Nicole Schmidt (Berlin, DE); Reinhard Nubbemeyer (Berlin, DE); Ulf Bömer (Glienicke, DE); Judith Günther (Berlin, DE); Holger Steuber (Berlin, DE); Martin Lange (Berlin, DE); Christian Stegmann (Berlin, DE); Andreas Sutter (Berlin, DE); Alexandra Rausch (Berlin, DE); Christian Friedrich (Brandenburg, DE); Peter Hauff (Berlin, DE)

Assignee: BAYER PHARMA AKTIENGESELLSCHAFT

C07D401/12A61K31/4439A61P19/02C07D405/14C07F7/1804

Abstract

Claims (57)

1 . A method for treating an inflammatory skin disorder in an animal in need thereof, comprising administering to the animal an effective amount of a compound of formula (I):

wherein:

R 1 is C 1 -C 6 -alkyl, wherein the C 1 -C 6 -alkyl group is monosubstituted with an R 7 SO 2 or R 7 SO group, or

wherein the C 1 -C 6 -alkyl group is polysubstituted with at least one of an R 7 SO 2 group or R 7 SO group, and one or more additional substituents selected from the group consisting of halogen, hydroxyl, an unsubstituted or mono- or poly-halogen substituted C 3 -C 6 -cycloalkyl, an R 6 group, and an R 8 O group;

R 2 and R 3 always have the same definition and are both either hydrogen or C 1 -C 6 -alkyl;

R 4 is halogen, cyano, an unsubstituted or a singly or multiply, identically or differently substituted C 1 -C 6 -alkyl or an unsubstituted or a singly or multiply, identically or differently substituted C 3 -C 6 -cycloalkyl, and the substituents are selected from the group consisting of halogen and hydroxyl;

R 5 is hydrogen, halogen or an unsubstituted or mono- or poly-halogen-substituted C 1 -C 6 -alkyl;

R 6 is an unsubstituted or mono- or di-methyl-substituted monocyclic saturated heterocycle having 4 to 6 ring atoms, which contains a heteroatom or a heterogroup from the group of O, S, SO and SO 2 ;

R 7 is C 1 -C 6 -alkyl, where the C 1 -C 6 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen, hydroxyl or C 3 -C 6 -cycloalkyl;

or R 7 is C 3 -C 6 -cycloalkyl; and

R 8 is C 1 -C 6 -alkyl, where the C 1 -C 6 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen,

or a diastereomer, an enantiomer, a salt, a solvate, or a solvate of the salt thereof.

2 . The method according to claim 1 , wherein:

R 1 is C 1 -C 6 -alkyl, wherein the C 1 -C 6 -alkyl group is monosubstituted with an R 7 SO 2 group or an R 7 SO group, or

wherein the C 1 -C 6 -alkyl group is polysubstituted with at least one of an R 7 SO 2 group or an R 7 SO group, and one or more additional substituents selected from the group consisting of fluorine, hydroxyl, an R 6 group, and an R 8 O group;

R 2 and R 3 always have the same definition and are both either hydrogen or C 1 -C 3 -alkyl;

R 4 is halogen, cyano or C 1 -C 3 -alkyl, wherein the C 1 -C 3 -alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen or hydroxyl;

R 5 is hydrogen, fluorine, chlorine or C 1 -C 3 -alkyl;

R 6 is oxetanyl or tetrahydrofuranyl;

R 7 is C 1 -C 4 -alkyl, wherein the C 1 -C 4 -alkyl group is unsubstituted or monosubstituted by hydroxyl or by cyclopropyl or substituted by three fluorine atoms, and

R 8 is an unsubstituted C 1 -C 4 -alkyl group or a tri-fluorine-substituted C 1 -C 4 -alkyl group.

3 . The method according to claim 1 , wherein R 4 is difluoromethyl, trifluoromethyl or methyl.

4 . The method according to claim 1 , wherein R 5 is hydrogen or fluorine.

5 . The method according to claim 1 , wherein R 2 and R 3 are both either hydrogen or methyl.

6 . The method according to claim 2 , wherein

R 1 is C 2 -C 6 -alkyl, wherein the C 2 -C 6 -alkyl group is monosubstituted by an R 7 SO 2 group;

R 2 and R 3 always have the same definition and are both either hydrogen or methyl;

R 4 is an unsubstituted or mono- or poly-halogen-substituted C 1 -C 3 -alkyl group or a C 1 -C 3 -alkyl group substituted by one hydroxyl group or a C 1 -C 3 -alkyl group substituted by one hydroxyl group and three fluorine atoms;

R 5 is hydrogen, fluorine or C 1 -C 3 -alkyl, and

R 7 is C 1 -C 3 -alkyl.

7 . The method according to claim 6 , wherein

R 1 is a methyl-SO 2 -substituted C 2 -C 4 -alkyl group;

R 2 and R 3 always have the same definition and are both either hydrogen or methyl;

R 4 is selected from the group consisting of methyl, ethyl, trifluoro-C 1 -C 3 -alkyl, difluoro-C 1 -C 3 -alkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxypropan-2-yl and 2,2,2-trifluoro-1-hydroxyethyl, and

R 5 is hydrogen, fluorine or methyl.

8 . The method according to claim 7 , wherein

R 1 is 2-(methylsulphonyl)ethyl or 3-(methylsulphonyl)propyl;

R 2 and R 3 are both either methyl or hydrogen;

R 4 is difluoromethyl, trifluoromethyl or methyl; and

R 5 is hydrogen or fluorine.

9 . The method according to claim 8 , wherein

R 1 is 3-(methylsulphonyl)propyl or 2-(methylsulphonyl)ethyl;

R 2 and R 3 are both methyl;

R 4 is difluoromethyl or trifluoromethyl; and

R 5 is hydrogen.

10 . The method according to claim 8 , wherein

R 1 is 3-(methylsulphonyl)propyl or 2-(methylsulphonyl)ethyl;

R 2 and R 3 are both methyl;

R 4 is methyl; and

R 5 is fluorine, wherein R 5 is in the ortho position to R 4 .

11 . The method according to claim 1 , wherein the compound is:

or a metabolite, a salt, a solvate, a solvate of the salt thereof.

12 . The method according to claim 1 , wherein the compound is:

or a salt thereof.

13 . The method according to claim 1 , wherein the compound is administered to the animal in a dosage form comprising at least one pharmaceutically suitable excipient.

14 . The method according to claim 11 , wherein the compound is administered to the animal in a dosage form comprising at least one pharmaceutically suitable excipient.

15 . The method according to claim 12 , wherein the compound is administered to the animal in a dosage form comprising at least one pharmaceutically suitable excipient.

Assignments (1)

Priority Claims (1)

Continuity (5)

References Cited (327)