Claims for Patent: 8,754,073

Summary for Patent: 8,754,073

Title:	Substituted piperazino-dihydrothienopyrimidines
Abstract:	Piperidinodihydrothienopyrimidines of formula 1 wherein X is SO or SO2 (preferably SO), and R1, R2, R3, and R4 may have the meanings given in the disclosure and claims, pharmacologically acceptable salts thereof, and pharmaceutical compositions containing these compounds. These piperidinodihydrothienopyrimidines are suitable for the treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system, or cancers.
Inventor(s):	Pascale Pouzet, Ralf Anderskewitz, Horst Dollinger, Dennis Fiegen, Thomas Fox, Rolf Goeggel, Christoph Hoenke, Domnic Martyres, Peter Nickolaus, Klaus Klinder
Assignee:	Boehringer Ingelheim International GmbH
Application Number:	US12/738,344
Patent Claims:	1. A compound of formula 1 wherein: X is SO or SO2, R1 is H or C1-6-alkyl, R2 is H or a group selected from C1-10-alkyl and C2-6-alkenyl, each optionally substituted by one or more groups selected from halogen and C1-3-fluoroalkyl or optionally substituted by one or more groups selected from OR2.1, COOR2.1, CONR2.2R2.3, SR2.1, SO—R2.1, SO2—R2.1, C6-10-aryl, -het, hetaryl, a mono- or bicyclic —C3-10-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, which in turn are optionally substituted by one or more groups selected from OH, halogen, OR2.1, oxo, CF3, CHF2, CH2F, C1-6-alkyl, C1-6-alkanol, C6-10-aryl, COOR2.1, CH2—NR2.2R2.3, and NR2.2R2.3, R2 is a mono- or polycyclic C3-10 cycloalkyl, optionally bridged one or more times via C1-3-alkyl groups and optionally substituted by a group selected from branched or unbranched C1-6-alkanol, C1-3-fluoroalkyl, C1-3-alkylene-OR2.1, OR2.1, COOR2.1, —SO2—NR2.2R2.3, het, —NH—CO—O—(C1-6-alkyl), —NH —CO—(C1-6-alkyl), —NH—CO—O—(C6-10-aryl), —NH—CO—(C6-10-aryl), —NH—CO—O-hetaryl, —NH—CO-hetaryl, —NH—CO—O—(C1-3-alkylene)-(C6-10-aryl), —NH—CO—(C1-3-alkylene)-(C6-10-aryl), —N(C1-3-alkyl)-CO—(C1-6-alkyl), —N(C1-3-alkyl)-CO—O—(C6-10-aryl), —N(C1-3-alkyl)-CO—(C6-10-aryl), —N(C1-3-alkyl)-CO—O-hetaryl, —N(C1-3-alkyl)-CO-hetaryl, —N(C1-3-alkyl)-CO—O—(C1-3-alkylene)-(C6-10-aryl), —N(C1-3-alkyl)-CO—(C1-3-alkylene)-(C6-10-aryl), C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C3-10 cycloalkyl, F, Cl, Br, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3, R2 is a mono- or polycyclic C6-10-aryl, optionally substituted by OH, SH, or halogen, or by one or more groups selected from OR2.1, COOR2.1, NR2.2R2.3, CH2—NR2.2R2.3, C3-10-cycloalkyl, het, C1-6-alkyl, C1-3-fluoroalkyl, CF3, CHF2, CH2F, C6-10-aryl-C1-6-alkylene, het-C1-6-alkylene, hetaryl-C1-6-alkylene, C6-10-aryl, SO2—CH3, SO2—CH2CH3, and SO2—NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, CF3, CHF2, CH2F, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3, R2 is a group selected from het and hetaryl, each optionally substituted by one or more groups selected from halogen, OH, oxo, CF3, CHF2, and CH2F, or by one or more groups selected from OR2.1, C1-3-alkylene-OR2.1, SR2.1, SO—R2.1, SO2—R2.1, COOR2.1, COR2.1, C1-6-alkanol, mono- or bicyclic C3-10-cycloalkyl, C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, het, hetaryl, C1-3-alkylene-OR2.1, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3, or NR1R2 together are a heterocyclic C4-7 ring optionally bridged, which contains 1, 2, or 3 heteroatoms selected from N, O, and S and is optionally substituted by one or more groups selected from OH, OR2.1, C1-3-alkylene-OR2.1, oxo, halogen, C1-6-alkyl, C6-10-aryl, COOR2.1, CH2—NR2.2—COO—R2.1, CH2—NR2.2—CO—R2.1, CH2—NR2.2—CO—CH2—NR2.2R2.3, CH2—NR2.2—SO2—C1-3-alkyl, CH2—NR2.2—SO2—NR2.2R2.3, CH2—NR2.2—CO—NR2.2R2.3, CO—NR2.2R2.3, CH2—NR2.2R2.3, and NR2.2R2.3, R3 is a C6-10-aryl optionally substituted by in the ortho, para, or meta position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, C1-6-alkyl, C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —C1-3-alkylene-NR2.2R2.3, NR2.2R2.3, O—R2.1, SO—R2.1, SO2—R2.1, COOR2.1, —CO—NH—(C1-6-alkylene)-hetaryl, —CO—NH-hetaryl, —CO—N(CH3)-het, —CO —N(CH3)—(C1-3-alkylene)-het, —CO—N(CH3)—(C1-3-alkylene)-hetaryl, —CO—N(C3-7-cycloalkyl)-het, —CO—NR2.2R2.3, —CO—NH—(C1-6-alkylene)-het, NR2.2—CO—R2.1, C6-10-aryl, C6-10-aryl-C1-2-alkylene, het-C1-2-alkylene, -het, —CO-het, CO—N(CH3)—C3-7-cycloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-2-alkylene, hetaryl-C1-2-alkylene, and hetaryl, each optionally substituted by one or more groups selected from OH, halogen, —C1-3-fluoroalkyl, oxo, methyl, and phenyl, R3 is a group selected from het and hetaryl, each optionally substituted by one or more groups selected from halogen, C1-3-fluoroalkyl, CN, OH, oxo, —C1-6-alkyl, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, SO—R2.1, SO2—R2.1, —O—R2.1, —COOR2.1, SO2—(CH3), SO2—(CH2—CH3), C6-10-aryl, het, C3-7-cycloalkyl, and hetaryl, each optionally substituted by one or more groups selected from OH, halogen, —C1-3-fluoroalkyl, C1-6-alkyl, C6-10-aryl, —COO(C1-3-alkyl), and O—(C1-3-alkyl), or R3 is —O—R3.1, wherein R3.1 is a group selected from —C1-6-alkyl, —C6-10-aryl, —C1-3-alkylene-C6-10-aryl, hetaryl, and het, each optionally substituted in the ortho, para, or meta position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, C1-6-alkyl, C1-3 -fluoroalkyl, CO—(C1-5-alkyl), —CO—(C1-3-fluoroalkyl), —CO—NH—(C1-6-alkylene)-hetaryl, —CO—N(C1-3-alkyl)-(C1-6-alkylene)-hetaryl, —CO—N(C1-3-alkyl)-het, —CO—N(C3-7-cycloalkyl)-het, —C1-3-alkylene-OR2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, O—R2.1; SO—R2.1, SO2—R2.1, COOH, COO—(C1-4-alkyl), —O—C1-3-alkylene-N(C1-3-alkyl)2, CO—NR2.2R2.3, NR2.2—CO—R2.1, C6-10-aryl, C6-10-aryl-C1-2-alkylene, het-C1-2-alkylene, —CO-het, het, —CO—C3-7-cycloalkyl, —CO—N(C1-3-alkyl)-C3-7-cycloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-2-alkylene, hetaryl-C1-2-alkylene, and hetaryl, each optionally substituted by 1, 2, 3, or 4 groups independently selected from F, Cl, Br, methyl, O-methyl, ethyl, O-ethyl, OH, oxo, and CF3, and R4 is H, CN, OH, CF3, CHF2, CH2F, F, methyl, ethyl, —O—(C1-3-alkyl), —C1-3-alkylene-OH, —COO(C1-3-alkyl), —CO-het, —(C1-2-alkylene)-NH—SO2—(C1-2-alkyl), —(C1-2-alkylene)-N (C1-3-alkyl)-SO2—(C1-2-alkyl), —(C1-2-alkylene)-O—(C1-2-alkylene)-C6-10-aryl, —C1-3-alkylene-O—C1-3-alkyl, —(C1-2-alkylene)-N(C1-3-alkyl)-CO—(C1-2-alkyl), —NH—CO—(C1-3-alkylene)-O—(C1-3-alkyl), —C1-3-alkylene-NH—CO—(C1-3-alkyl), —C1-3-alkylene-NH—CO—(C1-3-alkylene)-N(C1-3 -alkyl)2, —O—(C1-2-alkylene)-(C6-10-aryl), —C1-3-alkylene-NH—CO —(C1-3-alkylene)-O—(C1-3-alkyl), —CO—(C6-10-aryl), and —(C1-2-alkylene)-N(C1-3-alkyl)-CO —(C1-2-alkylene)-O—(C1-3-alkyl), wherein the aryl in the above groups of R4 are optionally substituted by one or more other groups selected from F, Cl, Br, methyl, ethyl, propyl, isopropyl, cyclopropyl, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —O-cyclopropyl, —OH, and CF3, or R3 and R4 together are a mono- or bicyclic, unsaturated, saturated, or partially saturated heterocycle, which contains 1, 2, or 3 heteroatoms selected from N, O and S, and optionally substituted by one or more groups selected from halogen, OH, oxo, C1-3-fluoroalkyl, CN, C1-6-alkyl, —O—R2.1, —COOR2.1, SO—R2.1, SO2—R2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, C6-10-aryl, C3-7-cycloalkyl, het, and hetaryl, wherein: R2.1 is H or is a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-haloalkyl, mono- or bicyclic, —C3-10-cycloalkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, het-C1-6-alkylene, C3-10-cycloalkyl-C1-6-alkylene, a mono- or bicyclic C6-10-aryl, heteroaryl, and a -het, each optionally substituted by one or more groups selected from OH, O—(C1-3-alkyl), halogen, C1-6-alkyl, and C6-10-aryl, R2.2 and R2.3 are each independently H or a group selected from C1-6-alkyl, mono- or bicyclic C3-10 cycloalkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C6-10-aryl, het, hetaryl, CO—NH2, CO—NHCH3, —CO—N(CH3)2, SO2—(C1-C2-alkyl), CO—R2.1, and COOR2.1, each optionally substituted by one or more groups selected from OH, halogen, C1-6-alkyl, C6-10-aryl, and COOR2.1, het is a three- to eleven-membered, mono- or bicyclic, saturated or partially saturated, optionally anellated or optionally bridged heterocycle which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, hetaryl is a five- to eleven-membered, mono- or bicyclic, optionally anellated heteroaryl, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and cycloalkyl is saturated or partially saturated, and pharmacologically acceptable salts thereof. 2. The compounds of formula 1 according to claim 1, wherein: X is SO or SO2, R1 is H R2 is H or C1-10-alkyl optionally substituted by one or more groups selected from halogen and C1-3-fluoroalkyl or optionally substituted by one or more groups selected from OR2.1, COOR2.1, CONR2.2R2.3, SR2.1, SO—R2.1, SO2—R2.1, phenyl, het, hetaryl, a monocyclic C3-7-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, F, Cl, Br, OR2.1, oxo, CF3, CHF2, CH2F, C1-6-alkyl, C1-6-alkanol, phenyl, COOR2.1, CH 2—NR2.2R2.3, and NR2.2R2.3, R2 is a monocyclic C3-7 cycloalkyl optionally substituted by a group selected from branched or unbranched C1-6-alkanol, C1-3-fluoroalkyl, OR2.1, C1-3 -alkylene-OR2.1, OR2.1, COOR2.1, SO2—NR2.2R2.3, -het, —NH—CO—O-(phenyl), phenyl, C1-6-alkyl, phenyl-C1-6-alkylene, -hetaryl-C1-6-alkylene, monocyclic C3-7 cycloalkyl, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, F, Cl, CF3, CHF2, CH2F, C1-6-alkyl, phenyl, and —NR2.2R2.3, R2 is a phenyl optionally substituted by OH, SH, or halogen, or by one or more groups selected from OR2.1, COOR2.1, NR2.2R2.3, CH2—NR2.2R2.3,C3-7-cycloalkyl, C3-7 heterocycle, C1-6-alkyl, C1-3-fluoroalkyl, phenyl-C1-6-alkylene, -het-C1-6-alkylene, -hetaryl-C1-6-alkylene, phenyl, SO2—CH3, SO2—CH2CH3, and SO2—NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, F, Cl, CF3, CHF2, CH2F, C1-6-alkyl, phenyl, and NR2.2R2.3, R2 is a group selected from het and hetaryl, each optionally substituted by one or more groups selected from F, Cl, OH, oxo, CF3, CHF2, and CH2F, or by one or more groups selected from OR2.1, —C1-3-alkylene-OR2.1, SR2.1, SO—R2.1, SO2—R2.1, COOR2.1, COR2.1, C1-6-alkanol, monocyclic C3-7-cycloalkyl, phenyl, C1-6-alkyl, phenyl-C1-6-alkylene, -hetaryl-C1-6-alkylene, -het, -hetaryl, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, F, Cl, CF3, CHF2, CH2F, C1-6-alkyl, phenyl, and NR2.2R2.3, or NR1R2 together are a heterocyclic C4-7 ring optionally bridged, which contains 1, 2, or 3 heteroatoms selected from N, O, and S and is optionally substituted by one or more groups selected from OH, OR2.1, C1-3-alkylene-OR2.1, oxo, F, Cl, C1-6-alkyl, phenyl, COOR2.1, CH2—NR2.2—COO—R2.1, CH2—NR2.2—CO—R2.1, CH2—NR2.2—CO—CH2—NR2.2R2.3, CH2—NR2.2—SO2—C1-3-alkyl, CH2—NR2.2—SO2—NR2.2R2.3, CH2—NR2.2—CO—NR2.2R2.3, CO—NR2.2R2.3, CH2—NR2.2R2.3, and NR2.2R2.3, R3 is a naphthalene or phenyl, each optionally substituted in the ortho, para, or meta position by one or two groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, C1-6-alkyl, C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, O—R2.1; SO—R2.1, SO2—R2.1, COOR2.1, —CO—NH—(C1-6-alkylene)-hetaryl, —CO—NH-hetaryl, —CO—N(CH3)-het, —CO—N (CH3)—(C1-3-alkylene)-het, —CO—N(CH3)—(C1-3-alkylene)-hetaryl, —CO—N(C3-7-cycloalkyl)-het, CO—NR2.2R2.3, —CO—NH—(C1-6-alkylene)-het, —NR2.2—CO—R2.1, phenyl, phenyl-C1-2-alkylene, -het-C1-2-alkylene, -het, —CO-het, CO—N(CH3) —C3-7-cycloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-2-alkylene, -hetaryl-C1-2-alkylene, and -hetaryl, each optionally substituted by one or more groups selected from OH, F, Cl, —C1-3-fluoroalkyl, oxo, methyl, and phenyl, R3 is a group selected from het and hetaryl, each optionally substituted by one or more groups selected from F, Cl, Br, C1-3-fluoroalkyl, CN, OH, oxo, —C1-6-alkyl, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, SO—R2.1, SO2—R2.1, —O—R2.1, —COOR2.1, SO2—(CH3), SO2—(CH2—CH3), phenyl, het, C3-7-cycloalkyl, and hetaryl, each optionally substituted by one or more groups selected from OH, F, Cl, Br, —C1-3-fluoroalkyl, C1-6-alkyl, phenyl, —COO(C1-3-alkyl), and O—(C1-3-alkyl), R3 is —O—R3.1, wherein R3.1 is a group selected from —C1-6-alkyl, -phenyl, —C1-3-alkylene-phenyl, hetaryl and het, each optionally substituted in the ortho, para, or meta position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, C1-6-alkyl, C1-3-fluoroalkyl, CO—(C1-5-alkyl), —CO—(C1-3-fluoroalkyl), —CO—NH—(C1-6-alkylene)-hetaryl, —CO—N(CH3)—(C1-6-alkylene)-hetaryl, —CO—N(CH3)-het, —CO—N(C3-7-cycloalkyl)-het, —C1-3-alkylene-OR2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, O—R2.1; SO—R2.1, SO2—R2.1, COOH, COO—(C1-4-alkyl), —O—C1-3-alkylene-N(C1-3-alkyl)2, CO—NR2.2R2.3, NR2.2—CO —R2.1, phenyl, phenyl-C1-2-alkylene, het-C1-2-alkylene, —CO-het, het, —CO—C3-7-cycloalkyl, —CO—N(CH3)—C3-7-cycloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-2-alkylene, hetaryl-C1-2-alkylene, and hetaryl, each optionally substituted by 1, 2, 3, or 4 groups independently selected from F, Cl, Br, methyl, O-methyl, ethyl, O-ethyl, OH, oxo, CF3, and R4 is H, CN, OH, CF3, CHF2, CH2F, F, methyl, ethyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, —C1-3-alkylene-OH, —COO(C1-3 -alkyl), —CO-het, —(C1-2-alkylene)-NH—SO2—(C1-2-alkyl), —(C1-2-alkylene)-N(CH3)—SO2—(C1-2-alkyl), —(C1-2-alkylene)-O—(C1-2-alkylene)-phenyl, —C1-3-alkylene-O—C1-3-alkyl, —(C1-2-alkylene)-N(CH3)—CO—(C1-2-alkyl), —NH—CO—(C1-3-alkylene)-O—(C1-3-alkyl), —C1-3-alkylene-NH—CO—(C1-3-alkyl), —C1-3-alkylene-NH—CO—(C1-3-alkylene)-N(C1-3-alkyl)2, —O—(C1-2-alkylene)-phenyl-C1-3-alkylene-NH—CO—(C1-3-alkylene)-O—(C1-3-alkyl), —CO-phenyl, and —(C1-2-alkylene) -N(CH3)—CO—(C1-2-alkylene)-O—(C1-3-alkyl), wherein the phenyl in the above groups of R4 are optionally substituted by one or more other groups selected from F, Cl, Br, methyl, ethyl, propyl, —O-methyl, —O-ethyl, —O-propyl, —OH, and CF3, or R3 and R4 together are a mono- or bicyclic, unsaturated, saturated or partially saturated heterocycle, which contains 1, 2, or 3 heteroatoms selected from N, O, and S, and optionally substituted by one or more groups selected from F, Cl, Br, OH, oxo, C1-3-fluoroalkyl, CN, C1-6-alkyl, —O—R2.1, —COOR2.1, SO—R2.1, SO2—R2.1, —C1-3-alkylene-NR2.2R2.3, —NR2.2R2.3, phenyl, C3-7-cycloalkyl, het, and hetaryl, wherein: R2.1 is H or a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-haloalkyl, monocyclic C3-7 cycloalkyl, phenyl-C1-6-alkylene, hetaryl-C1-6-alkylene, het-C1-6-alkylene, —C3-7-cycloalkyl-C1-6-alkylene, phenyl, hetaryl, and a het, each optionally substituted by one or more groups selected from OH, F, Cl, C1-6-alkyl, —O—(C1-3-alkyl), and phenyl, wherein R2.2 and R2.3 are each independently H or a group selected from C1-6-alkyl, monocyclic C3-7 cycloalkyl, phenyl-C1-3-alkylene, hetaryl-C1-3-alkylene, phenyl, het, hetaryl, CO—NH2, —CO—NHCH3, —CON(CH3)2, SO2—(C1-2-alkyl), CO—R2.1, and COOR2.1, each optionally substituted by one or more groups selected from OH, F, Cl, C1-6-alkyl, phenyl, and COOR2.1, het is a three- to seven-membered, monocyclic, saturated or partially saturated heterocycle or a seven- to eleven-membered, bicyclic, saturated or partially saturated heterocycle, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and hetaryl is a five- to six-membered, monocyclic, aromatic heteroaryl or a seven- to eleven-membered, bicyclic, aromatic heteroaryl, which contains in each case 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and pharmacologically acceptable salts thereof. 3. The compounds of formula 1 according to claim 1, wherein: X is SO, R1 is H, R2 is H or C1-6-alkyl optionally substituted by one or more groups selected from F, Cl, CF3, CHF2, or CH2F, or optionally substituted by one or more groups selected from OR2.1, COOR2.1, CONR2.2R2.3, SR2.1, SO—R2.1, SO2—R2.1, phenyl, het, hetaryl, a monocyclic C3-7-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, F, Cl, Br, CF3, CHF2, CH2F, OR2.1, oxo, methyl, ethyl, propyl, isopropyl, methanol, ethanol, phenyl, COOR2.1, CH2—NR2.2R2.3, and NR2.2R2.3, R2 is a monocyclic C3-7 cycloalkyl optionally substituted by a group selected from C1-2-alkanol, C1-3-fluoroalkyl, C1-3-alkylene-OR2.1, OR2.1, COOR2.1, SO2—NR2.2R2.3, -het, —NH—CO—O-(phenyl), methyl, ethyl, propyl, isopropyl, phenyl, phenyl-C1-2-alkylene, -hetaryl-C1-2-alkylene, monocyclic C3-7 cycloalkyl, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, F, Cl, CF3, CHF2, CH2F, methyl, ethyl, propyl, isopropyl, phenyl, and NR2.2R2.3, R2 is a phenyl optionally substituted by OH, SH, F, Cl, or Br, or by one or more groups selected from OR2.1, COOR2.1, NR2.2R2.3, CH2—NR2.2R2.3, monocyclic C3-7-cycloalkyl, -het, methyl, ethyl, propyl, isopropyl, CF3, CHF2, CH2F, phenyl-C1-2-alkylene, het-C1-2-alkylene, hetaryl-C1-2-alkylene, phenyl, SO2—CH3, SO2—CH2CH3, and SO2—NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, F, Cl, CF3, CHF2, CH2F, methyl, ethyl, propyl, isopropyl, phenyl, and NR2.2R2.3, R2 is a group selected from het and hetaryl, each optionally substituted by one or more groups selected from F, Cl, OH, oxo, CF3, CHF2, and CH2F, or by one or more groups selected from OR2.1, C1-3-alkylene-OR2.1, SR2.1, SO—R2.1, SO2—R2.1, COOR2.1, COR2.1, methanol, ethanol, monocyclic C3-7-cycloalkyl, phenyl, methyl, ethyl, propyl, isopropyl, phenyl-C1-2-alkylene, hetaryl-C1-2-alkylene, -het, -hetaryl, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, F, Cl, CF3, CHF2, CH2F, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl, and NR2.2R2.3, R3 is a naphthalene or phenyl, each optionally substituted in the ortho, para, or meta position by one or two groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, methyl, ethyl, propyl, isopropyl, cyclopropyl, CF3, CHF2, CH2F, —OCH3, OCH2CH3; SO2—CH3, SO—CH3, COOCH3, COOCH2CH3, —CO—NH-(methylene)-hetaryl, —CO—NH-(ethylene)-hetaryl, —CO—NH-hetaryl, —CO—N(CH3)-het, —CO—N(CH3)-(methylene)-het, —CO—N(CH3)-(ethylene)-het, —CO—N(CH3)-(methylene)-hetaryl, —CO—N(CH3)-(ethylene)-hetaryl, —CO—N (cyclopropyl)-het, CO—NH2, CONH(CH3), CON(CH3)2, —CO—NH-(methylene)-het, —CO—NH-(ethylene)-het, —NH—CO-methyl, NCH3—CO-methyl, —NH—CO-ethyl, NCH3—CO-ethyl, —NH—CO-propyl, NCH3—CO-propyl, —NH—CO-isopropyl, NCH3—CO—isopropyl, phenyl, phenyl-methylene, phenyl-ethylene, het-methylene, het-ethylene, -het, —CO-het, CO—N(CH3)-cyclopropyl, C3-7-cycloalkyl, C3-7-cycloalkyl-methylene, C3-7-cycloalkyl-ethylene, hetaryl-methylene, hetaryl-ethylene, -hetaryl, CH2—NH2, CH2—NH(CH3), CH2—N(CH3)2, —NH2, —NH(CH3), and —N(CH3)2, each optionally substituted by one or more groups selected from OH, F, Cl, —CF3, CHF2, CH2F, oxo, methyl, and phenyl, R3 is a group selected from a het and hetaryl, each optionally substituted by one or more groups selected from F, Cl, Br, CF3, CHF2, CH2F, CN, OH, oxo, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —COO-methyl, —COO-ethyl, —COO-propyl, —COO-isopropyl, SO—(CH3), SO—(CH2—CH3), SO2—(CH3), SO2—(CH2—CH3), phenyl, CH2—NH2, CH2—NH(CH3), CH2—N(CH3)2, —NH2, —NH(CH3), —N(CH3)2, het, and hetaryl, each optionally substituted by one or more groups selected from OH, F, Cl, CF3, CHF2, CH2F, methyl, ethyl, propyl, isopropyl, phenyl, —COO-methyl, —COO-ethyl, O-methyl, and O-ethyl, R3 is —O—R3.1, wherein R3.1 is a group selected from C1-3-alkyl, -phenyl, —C1-3-alkylene-phenyl, hetaryl and het, each optionally substituted in the ortho, para, or meta position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, CF3, CHF2, CH2F, CO-(methyl), CO-(ethyl), CO-(propyl), CO-(isopropyl), —CO—(CF3), —CO—NH-(methylene)-hetaryl, —CO—NH-(ethylene)-hetaryl, —CO—N(CH3)-(methylene)-hetaryl, —CO—N(CH3)-(ethylene)-hetaryl, —CO—N(CH3)-(propylene)-hetaryl, —CO—N(CH3)-(isopropylene)-hetaryl, —CO—N(CH3)-het, —CO—N(cyclopropyl)-het, —CO—N(C5-7-cycloalkyl)-het, -methylene-O-methyl, -ethylene-O-methyl, -propylene-O-methyl, -methylene-O-ethyl, -ethylene-O-ethyl, -propylene-O-ethyl, -methylene-NH2, -methylene-NHCH3, -methylene-N(CH3)2, -ethylene-NH2, -ethylene-NHCH3, -ethylene-N(CH3)2, NH2, N(CH3)2, NHCH3, —O-methyl, O-ethyl, O-propyl, O-isopropyl, O-butyl, O-isobutyl, —SO—CH3, SO-ethyl, —SO-propyl, —SO-isopropyl, SO2-methyl, —SO2-ethyl, SO2-propyl, SO2-isopropyl, COOH, COO-(methyl), COO-(ethyl), COO-(propyl), COO-(isopropyl), —O-methylene-N(methyl)2, —O-ethylene-N(methyl)2, —O-methylene-N(ethyl)2, —O—ethylene-N(ethyl)2, CO—NH2, CO—NH(CH3), CO—N(CH3)2, —NH—CO-methyl, —NCH3—CO-methyl, —NH—CO-ethyl, NCH3—CO—ethyl, phenyl, phenyl-methylene, phenyl-ethylene, het-methylene, het-ethylene, —CO-het, het, —CO—C5-7-cycloalkyl, —CO-cyclopropyl, —CO—N(CH3)—C5-7-cycloalkyl, —CO—N(CH3)-cyclopropyl, C5-7-cycloalkyl, cyclopropyl, C5-7-cycloalkyl-methylene, C5-7-cycloalkyl-ethylene, cyclopropyl-methylene, cyclopropyl-ethylene, hetaryl-methylene, hetaryl-ethylene, and hetaryl, each optionally substituted by 1, 2, 3, or 4 groups independently selected from F, Cl, Br, methyl, O-methyl, ethyl, O-ethyl, OH, oxo, and CF3, and R4 is H, CN, OH, CF3, CHF2, CH2F, F, methyl, ethyl, O-methyl, O-ethyl, -methylene-OH, -ethylene-OH, -propylene-OH, isopropylene-OH, —COO(methyl), —COO(ethyl), —COO(propyl), —COO(isopropyl), —CO-het, -(methylene)-NH—SO2-(methyl), -(methylene)-NH—SO2-(ethyl), -(ethylene)-NH—SO2-(methyl), -(ethylene)-NH —SO2-(ethyl), -(methylene)-N(CH3)—SO2-(methyl), -(methylene)-N(CH3)—SO2-(ethyl), -(ethylene)-N (CH3)—SO2-(methyl), -(ethylene)-N(CH3)—SO2-(ethyl), -(methylene)-O-(methylene)-phenyl, -(methylene)-O-(ethylene)-phenyl, -(ethylene)-O-(methylene)-phenyl, -(ethylene)-O-(ethylene)-phenyl, -methylene-O-methyl, -methylene-O-ethyl, -ethylene-O-methyl, -ethylene-O-ethyl, -(methylene)-N(CH3)—CO—(methyl), -(methylene)-N (CH3)—CO-(ethyl), -(ethylene)-N(CH3)—CO-(methyl), -(ethylene)-N (CH3)—CO-(ethyl), —NH—CO-(methylene)-O-(methyl), —NH—CO-(methylene)-O-(ethyl), —NH—CO-(ethylene)-O-(methyl), —NH—CO-(ethylene)-O-(ethyl), -methylene-NH—CO -(methyl), -methylene-NH—CO-(ethyl), -ethylene-NH—CO-(methyl), -ethylene-NH —CO-(ethyl), -methylene-NH—CO-(methylene)-N(methyl)2, -methylene-NH—CO-(ethylene)-N(methyl)2, -ethylene-NH—CO-(methylene)-N(methyl)2, -ethylene-NH—CO-(ethylene)-N(methyl)2, -methylene-NH—CO-(methylene)-O-(methyl), -methylene-NH —CO-(ethylene)-O-(methyl), -ethylene-NH—CO-(methylene)-O-(methyl), -methylene-NH—CO-(methylene)-O-(ethyl), -methylene-NH—CO-(ethylene)-O-(ethyl), -ethylene-NH —CO-(methylene)-O-(ethyl), -(methylene)-N(CH3)—CO-(methylene)-O-(methyl), -(methylene)-N(CH3) -CO-(ethylene)-O-(methyl), -(ethylene)-N(CH3)—CO-(methylene)-O-(methyl), -(methylene)-N(CH3)—CO-(methylene)-O-(ethyl), -(methylene)-N(CH3)—CO-(ethylene)-O-(ethyl), -(ethylene)-N(CH3)—CO-(methylene)-O-(ethyl), —O-(methylene)-phenyl, —O-(ethylene)-phenyl, and —CO-phenyl, wherein the phenyl in the above groups of R4 are optionally substituted by one or more other groups selected from F, Cl, Br, methyl, ethyl, propyl, —O-methyl, —O-ethyl, —O-propyl, —OH, and CF3, or R3 and R4 together are a mono- or bicyclic, unsaturated, saturated or partially saturated heterocycle, which contains 1, 2, or 3 heteroatoms selected from N, O, and S, and optionally substituted by one or more groups selected from F, Cl, Br, OH, oxo, CF3, CHF2, CH2F, CN, methyl, ethyl, propyl, isopropyl, cyclopropyl, COO-methyl, —COO-ethyl, O-methyl, O-ethyl, SO2—(CH3), SO2—(CH2CH3), SO —(CH3), SO—(CH2CH3), CH2—NH2, CH2—NH(CH3), CH2—N(CH3)2, —NH2, —NH(CH3), —N(CH3)2, phenyl, C5-7-cycloalkyl, het, and hetaryl, wherein: R2.1 is H or a group selected from methyl, ethyl, propyl, isopropyl, methanol, ethanol, monocyclic C3-7 cycloalkyl, phenyl-C1-2-alkylene, -hetaryl-C1-2-alkylene, -het-C1-2-alkylene, C3-7-cycloalkyl-C1-2-alkylene, phenyl, hetaryl, and a het, each optionally substituted by one or more groups selected from OH, F, Cl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, and phenyl, R2.2 and R2.3 are each independently H or a group selected from methyl, ethyl, propyl, isopropyl, monocyclic C3-7 cycloalkyl, phenyl-C1-3-alkylene, hetaryl-C1-3-alkylene, phenyl, -het, -hetaryl, CO—NH2, CO—NHCH3, CON(CH3)2, SO2—(C1-2-alkly), CO—R2.1, and COOR2.1, each optionally substituted by one or more groups selected from OH, F, Cl, methyl, ethyl, propyl, isopropyl, phenyl, and COOR2.1, or het is a three- to seven-membered, monocyclic, saturated or partially saturated heterocycle, which contains 1, 2, or 3 heteroatoms independently selected from N, S, or O, and hetaryl is a five- to six-membered, monocyclic, aromatic heteroaryl which contains 1, 2, or 3 heteroatoms independently selected from N, S, or O, and pharmacologically acceptable salts thereof. 4. The compounds of formula 1 according to claim 1, wherein: R2 is a group according to formula 2 wherein: R6 is OH or NH2, and R5 is a group selected from C1-4-alkyl, a five- to six-membered heteroaryl with 1, 2, or 3 heteroatoms selected from S, O, and N, and phenyl optionally substituted by one or more groups selected from OH, F, Br, OR2.1, oxo, methyl, ethyl, methanol, ethanol, phenyl, COOR2.1, CH2—NR2.2R2.3, and NR2.2R2.3, and pharmacologically acceptable salts thereof. 5. The compounds of formula 1 according to claim 4, wherein: R6 is OH or NH2, and R5 is methyl, ethyl, propyl, or isopropyl, and pharmacologically acceptable salts thereof. 6. The compound of formula 1 according to claim 1, wherein: R2 is a monocyclic three-, four-, five-, six-, or seven-membered cycloalkyl ring optionally substituted in the spiro position by a group selected from —CH2—, OR2.1, branched or unbranched C2-6-alkylene-OR2.1, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, —CF3, CHF2, CH2F, and C2-4-fluoroalkyl, wherein R2.1 is selected from methyl, ethyl, propyl, isopropyl, butyl, and isobutyl, and pharmacologically acceptable salts thereof. 7. The compound of formula 1 according to claim 1, wherein: R2 is a cyclopropyl optionally substituted by another group selected from —NH2, CH2—NH2, —NH(CH3), —N(CH3)2, methyl, ethyl, propyl, isopropyl, —NH—CO -(tert-butyl), —NH—CO—O-(tert-butyl), —N(CH3)—CO-(tert-butyl), —N(CH3)—CO—O-(tert-butyl), —CF3, —CHF2, CH2F, F, Cl, and Br, and pharmacologically acceptable salts thereof. 8. The compound of formula 1 according to claim 1, wherein: R2 is a phenyl optionally substituted in one or both meta positions by one or more groups selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, F, Cl, Br, OH, OR2.1, COOR2.1, CF3, CHF2, CH2F, NH2, NH(CH3), and N(CH3)2, wherein R2.1 is H, methyl, or ethyl, and pharmacologically acceptable salts thereof. 9. The compound of formula 1 according to claim 1, wherein: R2 is a group selected from monocyclic, saturated three-, four-, five-, six-, or seven-membered heterocycles with 1, 2, or 3 heteroatoms selected in each case from N, O, and S, each optionally substituted by one or more groups selected from fluorine, chlorine, bromine, CF3, CHF2, CH2F, OH, and oxo or by one or more groups selected from OR2.1, C1-3-alkylene-OR2.1, SR2.1, SO—R2.1, SO2—R2.1, COOR2.1, COR2.1, C1-6-alkanol, C3-10-cycloalkyl, phenyl, C1-6-alkyl, phenyl-C1-6-alkylene, C5-10-heteroaryl-C1-6-alkylene, C5-10 heterocycle, C5-10-heteroaryl, and NR2.2R2.3, each optionally substituted by one or more groups selected from OH, OR2.1, oxo, F, Cl, CF3, CHF2, CH2F, C1-6-alkyl, phenyl, and NR2.2R2.3, and pharmacologically acceptable salts thereof. 10. The compound of formula 1 according to claim 9, wherein: R2 is a group selected from a monocyclic, saturated six-membered heterocycle with a heteroatom selected from N, O, and S, each optionally substituted by one or more groups selected from F, Cl, Br, CF3, CHF2, CH2F, OH, oxo, NH2, NHCH3, N(CH3)2, methyl, ethyl, propyl, isopropyl, cyclopropyl, methoxy, and ethoxy, and pharmacologically acceptable salts thereof. 11. The compound of formula 1 according to claim 9, wherein: R2 is piperidine or tetrahydropyran, each optionally substituted by one or more groups selected from F, Cl, Br, OH, CF3, CHF2, CH2F, NH2, NHCH3, N(CH3)2, oxo, methyl, and methoxy, and pharmacologically acceptable salts thereof. 12. The compounds of formula 1 according to claim 1, wherein: R3 is a naphthalene or phenyl, each optionally substituted in any position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, methyl, ethyl, propyl, isopropyl, cyclopropyl, CF3, CHF2, CH2F, —OCH3, OCH2CH3; SO2—CH3, SO2—CH2CH3, COOCH3, and CO—O—CH2CH3, and pharmacologically acceptable salts thereof. 13. The compound of formula 1 according to claim 1, wherein: R3 is a group selected from het and hetaryl, each optionally substituted by one or more groups selected from F, Cl, Br, CF3, CHF2, CH2F, CN, OH, oxo, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, C5-7-cycloalkyl, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —COO-methyl, —COO-ethyl, —COO-propyl, —COO-isopropyl, SO2—(CH3), SO2—(CH2—CH3), SO—(CH3), SO—(CH2—CH3), phenyl, —CH2—NH2, —CH2—NHCH3, —CH2—N(CH3)2, NH2, NHCH3, N(CH3)2, het, and hetaryl, each optionally substituted by one or more groups selected from OH, F, Cl, Br, CF3, CHF2, CH2F, methyl, ethyl, propyl, isopropyl, phenyl, —COO-methyl, —COO-ethyl, —COO-propyl, —COO-isopropyl, O-methyl, O-ethyl, O-propyl, and O-isopropyl, R4 is H, CN, OH, CF3, CHF2, CH2F, F, methyl, ethyl, O-methyl, or O-ethyl, wherein: het is a three- to seven-membered, monocyclic, saturated or partially saturated heterocycle or a seven- to eleven-membered, bicyclic, anellated, saturated or partially saturated heterocycle which contains 1, 2, or 3 heteroatoms independently selected from N, S, or O, and hetaryl is a five- to six-membered, monocyclic, aromatic heteroaryl or a seven- to eleven-membered, bicyclic, anellated, aromatic heteroaryl, which contains 1, 2, or 3 heteroatoms independently selected from N, S, or O, and pharmacologically acceptable salts thereof. 14. The compound of formula 1 according to claim 13, wherein: R3 is indole, dihydroindole, quinazoline, dihydroquinazoline, tetrahydroquinazoline, benzoisoxazole, dihydrobenzoisoxazole, benzoxazine, dihydrobenzoxazine, benzothiazole, dihydrobenzothiazole, triazolopyridine, dihydrotriazolopyridine, benzofuran, dihydrobenzofuran, isobenzofuran, or dihydroisobenzofuran, each optionally substituted by one or more groups selected from F, Cl, Br, CF3, CHF2, CH2F, CN, OH, oxo, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —COO-methyl, —COO-ethyl, —COO-propyl, —COO-isopropyl, SO2—(CH3), SO2—(CH2—CH3), SO—(CH3), SO—(CH2—CH3), phenyl, —CH2—NH2, —CH2—NHCH3, —CH2—N(CH3)2, NH2, NHCH3, N(CH3)2, furanyl, and pyridinyl, each optionally substituted by one or more groups selected from OH, F, Cl, Br, CF3, CHF2, CH2F, methyl, ethyl, propyl, isopropyl, phenyl, —COO-methyl, —COO-ethyl, O-methyl, and O-ethyl, and pharmacologically acceptable salts thereof. 15. The compound of formula 1 according to claim 13, wherein: R3 is imidazole, dihydroimidazole, oxadiazole, oxadiazolidine, pyrazole, pyridine, or dihydropyrazole, each optionally substituted by one or more groups selected from F, Cl, Br, CF3, CHF2, CH2F, CN, OH, oxo, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —COO-methyl, —COO-ethyl, —COO-propyl, —COO-isopropyl, SO2—(CH3), SO2—(CH2—CH3), SO—(CH3), SO—(CH2—CH3), phenyl, —CH2—NH2, —CH2—NHCH3, —CH2—N(CH3)2, NH2, NHCH3, N(CH3)2, furanyl, and pyridinyl, each optionally substituted by one or more groups selected from OH, F, Cl, Br, CF3, CHF2, CH2F, methyl, ethyl, propyl, isopropyl, phenyl, —COO-methyl, —COO-ethyl, and O-methyl, O-ethyl, and pharmacologically acceptable salts thereof. 16. The compounds of formula 1 according to claim 1, wherein: R3 and R4 together are a mono- or bicyclic, unsaturated or partially saturated, three- to eleven-membered heterocycle which contains 1, 2, or 3 heteroatoms selected from N, O, and S, and optionally substituted by one or more groups selected from F, Cl, Br, OH, oxo, CF3, CHF2, CH2F, CN, methyl, ethyl, propyl, isopropyl, cyclopropyl, COO-methyl, —COO-ethyl, O-methyl, O-ethyl, SO2—(CH3), SO2—(CH2—CH3), SO—(CH3), SO—(CH2—CH3), phenyl, —CH2—NH2, —CH2NHCH3, —CH2—N(CH3)2, NH2, NHCH3, N(CH3)2, a saturated or partially saturated, five- to six-membered heterocycle, and a five- to six-membered heteroaryl, as well as pharmacologically acceptable salts thereof. 17. The compounds of formula 1 according to claim 16, wherein: R3 and R4 together are tetrahydroquinazoline, tetrahydrobenzoxazine, dihydroindole, or dihydroisobenzofuran, each optionally substituted by one or more groups selected from F, Cl, Br, OH, oxo, CF3, CHF2, CH2F, CN, methyl, ethyl, propyl, isopropyl, cyclopropyl, COO-methyl, —COO-ethyl, O-methyl, O-ethyl, SO2—(CH3), SO2—(CH2—CH3), phenyl, —CH2—NH2, —CH2NHCH3, —CH2—N(CH3)2, NH2, NHCH3, N(CH3)2, a saturated or partially saturated, five- to six-membered heterocycle, and a five- to six-membered heteroaryl, and pharmacologically acceptable salts thereof. 18. The compounds of formula 1 according to claim 1, wherein: R3 is —O—R3.1, wherein R3.1 is a group selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, -phenyl, -methylene-phenyl, -ethylene-phenyl, -propylene-phenyl, -isopropylene-phenyl, hetaryl, and het, each optionally substituted in the ortho, para, or meta position by one, two, or three groups independently selected from fluorine, chlorine, bromine, hydroxy, CN, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, —CF3, CHF2, CH2F, CO-(methyl), CO-(ethyl), CO-(propyl), CO-(isopropyl), CO-(butyl), CO-(isobutyl), —CO—(CF3), —CO—(CH2F), —CO—(CHF2), —CO—NH-(methylene)-hetaryl, —CO—NH-(ethylene)-hetaryl, —CO—NH-(propylene)-hetaryl, —CO—NH-(isopropylene)-hetaryl, —CO—N(CH3)—(methylene)-hetaryl, —CO—N(CH3)-(ethylene)-hetaryl, —CO—N(CH3)-(propylene)-hetaryl, —CO—N(CH3)-(isopropylene)-hetaryl, —CO—N(CH3)-het, —CO—N(C3-7-cycloalkyl)-het, -methylene-O-methyl, -ethylene-O-methyl, -methylene-O-ethyl, -ethylene-O-ethyl, -methylene-NH2, -ethylene-NH2, -methylene-NHCH3, -ethylene-NHCH3, -methylene-N(CH3)2, -ethylene-N(CH3)2, —NH2, —NHCH3, —N(CH3)2, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —SO—CH3, —SO—(CH2CH3), —SO2—CH3, —SO2—(CH2CH3), COOH, COO-(methyl), COO-(ethyl), COO-(propyl), COO-(isopropyl), —O-methylene-N(methyl)2, —O-ethylene-N(methyl)2, —O-methylene-N(ethyl)2, —O-ethylene-N(ethyl)2, CO—NH2, CO—NHCH3, CO—N(CH3)2, NH—CO-methyl, NCH3—CO-methyl, NH—CO-ethyl, N(CH3)—CO-ethyl, phenyl, phenyl-methylene, phenyl-ethylene, het-methylene, het-ethylene, —CO-het, het, —CO—C4-7-cycloalkyl, —CO-cyclopropyl, —CO—N(CH3)-cyclopropyl, —CO—N(CH3)—C4-7-cycloalkyl, C4-7-cycloalkyl, cyclopropyl, C4-7-cycloalkyl-methylene, cyclopropyl-methylene, C4-7-cycloalkyl-ethylene, cyclopropyl-ethylene, hetaryl-methylene, hetaryl-ethylene, and hetaryl, each optionally substituted by 1, 2, 3, or 4 groups independently selected from F, Cl, Br, methyl, O-methyl, ethyl, O-ethyl, OH, oxo, and CF3, and pharmacologically acceptable salts thereof. 19. The compounds of formula 1 according to claim 1, wherein: R4 is H, CN, OH, CF3, CHF2, CH2F, F, methyl, ethyl, O-methyl, O-ethyl, -methylene-OH, -ethylene-OH, -propylene-OH, isopropylene-OH, —COO(methyl), —COO(ethyl), —COO(propyl), —COO(isopropyl), —CO-het, -(methylene)-NH—SO2-(methyl), -(methylene)-NH—SO2-(ethyl), -(ethylene)-NH—SO2-(methyl), -(ethylene)-NH —SO2-(ethyl), -(methylene)-N(CH3)—SO2-(methyl), -(methylene)-N(CH3)—SO2-(ethyl), -(ethylene)-N(CH3)—SO2-(methyl), -(ethylene)-N(CH3)—SO2-(ethyl), -(methylene)-O-(methylene)-phenyl, -(methylene)-O-(ethylene)-phenyl, -(ethylene)-O-(methylene)-phenyl, -(ethylene)-O-(ethylene)-phenyl, -methylene-O-methyl, -methylene-O-ethyl, -ethylene-O-methyl, -ethylene-O-ethyl, -(methylene)-N(CH3)—CO-(methyl), -(methylene)-N(CH3)—CO-(ethyl), -(ethylene)-N(CH3)—CO-(methyl), -(ethylene) -N(CH3)—CO-(ethyl), —NH—CO-(methylene)-O-(methyl), —NH—CO-(methylene)-O-(ethyl), —NH—CO-(ethylene)-O-(methyl), —NH—CO-(ethylene)-O-(ethyl), -methylene-NH—CO-(methyl), -methylene-NH—CO-(ethyl), -ethylene-NH—CO-(methyl), -ethylene-NH—CO-(ethyl), -methylene-NH—CO-(methylene)-N(methyl)2, -methylene-NH—CO-(ethylene)-N(methyl)2, -ethylene-NH—CO-(methylene)-N(methyl)2, -ethylene-NH—CO-(ethylene)-N(methyl)2, -methylene-NH—CO-(methylene)-O-(methyl), -methylene-NH—CO-(ethylene)-O-(methyl), -ethylene-NH—CO-(methylene)-O-(methyl), -methylene-NH—CO-(methylene)-O-(ethyl), -methylene-NH—CO-(ethylene)-O-(ethyl), -ethylene-NH—CO-(methylene)-O-(ethyl), -(methylene)-N(CH3)—CO-(methylene)-O-(methyl), -(methylene)-N(CH3)—CO-(ethylene)-O-(methyl), -(ethylene)-N(CH3)—CO-(methylene)-O-(methyl), -(methylene)-N(CH3)—CO-(methylene)-O-(ethyl), -(methylene)-N(CH3)—CO-(ethylene)-O-(ethyl), -(ethylene)-N(CH3)—CO-(methylene)-O-(ethyl), —O-(methylene)-phenyl, —O-(ethylene)-phenyl, and —CO-phenyl, wherein the phenyl in the above groups of R4 are optionally substituted by one or more other groups selected from F, Cl, Br, methyl, ethyl, propyl, —O-methyl, —O-ethyl, —O-propyl, —OH, and CF3, and pharmacologically acceptable salts thereof. 20. The compounds of formula 1 according to claim 1, wherein: R3 is oxazole, imidazole, or thiazole, each optionally substituted by one, two, or three further groups independently selected from methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, OH, F, Cl, Br, CF3, phenyl, hetaryl, and C3-6-cycloalkyl, and pharmacologically acceptable salts thereof. 21. The compounds of formula 1 according to claim 1, wherein X is SO2, and pharmacologically acceptable salts thereof. 22. The compounds of formula 1 according to claim 1, wherein the compounds are selected from: and pharmacologically acceptable salts thereof. 23. A pharmaceutical formulation, comprising a compound according to formula 1 according to claim 1 and a pharmaceutical excipient. 24. A pharmaceutical formulation, comprising a compound of formula 1 according to claim 1 in combination with one or more active substances selected from betamimetics, corticosteroids, other phophodiesterase 4 inhibitors (PDE4-inhibitors), epidermal growth factor receptor inhibitors (EGFR-inhibitors), and leukotriene D4-antagonist (LTD4-antagonists), chemokine receptor 3-inhibitors (CCR3-inhibitors), inducible nitric oxide synthase inhibitors (iNOS-inhibitors), and spleen tyrosine kinase inhibitors (SYK-inhibitors). 25. The compound of formula 1 according to claim 1, wherein the compound is or a pharmaceutically acceptable salt thereof. 26. The compound of formula 1 according to claim 1, wherein the compound is or a pharmaceutically acceptable salt thereof. 27. The compound of formula 1 according to claim 1, wherein the compound is or a pharmaceutically acceptable salt thereof. 28. The compound of formula 1 according to claim 1, wherein the compound is or a pharmaceutically acceptable salt thereof. 29. The compound of formula 1 according to claim 1, wherein the compound is or a pharmaceutically acceptable salt thereof. 30. The compound of formula 1 according to claim 1, wherein the compound is or a pharmaceutically acceptable salt thereof. 31. The compound of formula 1 according to claim 1, wherein the compound is or a pharmaceutically acceptable salt thereof. 32. A method for treating idiopathic pulmonary fibrosis (IPF) in a patient comprising administering to the patient a therapeutically effective amount of the compound of formula 1 according to claim 1. 33. A method for treating chronic obstructive pulmonary disease (COPD), chronic sinusitis, asthma and ulcerative colitis in a patient comprising administering to the patient a therapeutically effective amount of the compound of formula 1 according to claim 1. 34. A method for treating depression and schizophrenia in a patient comprising administering to the patient a therapeutically effective amount of the compound of formula 1 according to claim 1.