Piperazino-dihydrothienopyrimidine derivatives

A method for treating respiratory or gastrointestinal complaints or diseases, such as inflammatory diseases of the joints, skin, or eyes, cancers, and diseases of the peripheral or central nervous system in a patient comprising administering to the patient in need thereof a therapeutically effective amount of 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, a het, a hetaryl, a mono- or bicyclic C3-10-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, each 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 mono- or poly-bridged 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, C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C3-10 cycloalkyl, 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, 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, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3,
• R2 is a group selected from a het and a 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, 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 is a heterocyclic four- to seven-membered ring optionally bridged, which contains 1, 2, or 3 heteroatoms selected from N, O, and S and 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 group selected from a mono- or bicyclic C6-10-aryl, a het, and a hetaryl, each optionally substituted by one or more groups selected from halogen, —C1-3-alkyl, cyclopropyl, —C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —OH, and —O—C1-3-alkyl,
• R4 is H, C1-6-alkyl, F, C1-3-fluoroalkyl, (C1-6-alkylene)-OH, (C1-6-alkylene)-OCH3, (C1-6-alkylene)-NH2, (C1-6-alkylene)-NH(C1-3-alkyl), or (C1-6-alkylene)-N(C1-3-alkyl)2,
• R4′ is H or F, and
• R5 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R6 and R7 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from —CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and O—(C1-3-alkyl), or
• R7 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R5 and R6 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and OCH3,
• wherein:
• R2.1 is H or a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-fluoroalkyl, 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, a hetaryl, 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, a het, a hetaryl, CO—NH2, CO—NH(CH3), CO—N(CH3)2, SO2—(C1-2-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 annelated or optionally bridged heterocyclic group, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O,
• hetaryl is a five- to ten-membered, mono- or bicyclic, optionally annelated heteroaryl, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and
• cycloalkyl is saturated or partially saturated,
• and the pharmacologically acceptable salts thereof.

A method for preventing and/or treating respiratory or pulmonary diseases which are associated with increased mucus production, inflammation and/or obstructive diseases of the respiratory tract in a patient comprising administering to the patient in need thereof a therapeutically effective amount of 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, a het, a hetaryl, a mono- or bicyclic C3-10-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, each 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 mono- or poly-bridged 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, C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C3-10 cycloalkyl, 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, 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, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3,
• R2 is a group selected from a het and a 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, 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 is a heterocyclic four- to seven-membered ring optionally bridged, which contains 1, 2, or 3 heteroatoms selected from N, O, and S and 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 group selected from a mono- or bicyclic C6-10-aryl, a het, and a hetaryl, each optionally substituted by one or more groups selected from halogen, —C1-3-alkyl, cyclopropyl, —C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —OH, and —O—C1-3-alkyl,
• R4 is H, C1-6-alkyl, F, C1-3-fluoroalkyl, (C1-6-alkylene)-OH, (C1-6-alkylene)-OCH3, (C1-6-alkylene)-NH2, (C1-6-alkylene)-NH(C1-3-alkyl), or (C1-6-alkylene)-N(C1-3-alkyl)2,
• R4′ is H or F, and
• R5 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R6 and R7 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from —CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and O—(C1-3-alkyl), or
• R7 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R5 and R6 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and OCH3,
• wherein:
• R2.1 is H or a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-fluoroalkyl, 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, a hetaryl, 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, a het, a hetaryl, CO—NH2, CO—NH(CH3), CO—N(CH3)2, SO2—(C1-2-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 annelated or optionally bridged heterocyclic group, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O,
• hetaryl is a five- to ten-membered, mono- or bicyclic, optionally annelated heteroaryl, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and
• cycloalkyl is saturated or partially saturated,
• and the pharmacologically acceptable salts thereof.

A method for treating inflammatory and obstructive diseases such as COPD, chronic sinusitis, asthma, Crohn's disease, and ulcerative colitis in a patient comprising administering to the patient in need thereof a therapeutically effective amount of 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, a het, a hetaryl, a mono- or bicyclic C3-10-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, each 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 mono- or poly-bridged 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, C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C3-10 cycloalkyl, 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, 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, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3,
• R2 is a group selected from a het and a 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, 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 is a heterocyclic four- to seven-membered ring optionally bridged, which contains 1, 2, or 3 heteroatoms selected from N, O, and S and 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 group selected from a mono- or bicyclic C6-10-aryl, a het, and a hetaryl, each optionally substituted by one or more groups selected from halogen, —C1-3-alkyl, cyclopropyl, —C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —OH, and —O—C1-3-alkyl,
• R4 is H, C1-6-alkyl, F, C1-3-fluoroalkyl, (C1-6-alkylene)-OH, (C1-6-alkylene)-OCH3, (C1-6-alkylene)-NH2, (C1-6-alkylene)-NH(C1-3-alkyl), or (C1-6-alkylene)-N(C1-3-alkyl)2,
• R4′ is H or F, and
• R5 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R6 and R7 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from —CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and O—(C1-3-alkyl), or
• R7 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R5 and R6 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and OCH3,
• wherein:
• R2.1 is H or a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-fluoroalkyl, 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, a hetaryl, 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, a het, a hetaryl, CO—NH2, CO—NH(CH3), CO—N(CH3)2, SO2—(C1-2-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 annelated or optionally bridged heterocyclic group, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O,
• hetaryl is a five- to ten-membered, mono- or bicyclic, optionally annelated heteroaryl, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and
• cycloalkyl is saturated or partially saturated,
• and the pharmacologically acceptable salts thereof.

A method for treating inflammatory diseases of the gastrointestinal tract in a patient comprising administering to the patient in need thereof a therapeutically effective amount of 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, a het, a hetaryl, a mono- or bicyclic C3-10-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, each 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 mono- or poly-bridged 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, C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C3-10 cycloalkyl, 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, 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, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3,
• R2 is a group selected from a het and a 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, 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 is a heterocyclic four- to seven-membered ring optionally bridged, which contains 1, 2, or 3 heteroatoms selected from N, O, and S and 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 group selected from a mono- or bicyclic C6-10-aryl, a het, and a hetaryl, each optionally substituted by one or more groups selected from halogen, —C1-3-alkyl, cyclopropyl, —C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —OH, and —O—C1-3-alkyl,
• R4 is H, C1-6-alkyl, F, C1-3-fluoroalkyl, (C1-6-alkylene)-OH, (C1-6-alkylene)-OCH3, (C1-6-alkylene)-NH2, (C1-6-alkylene)-NH(C1-3-alkyl), or (C1-6-alkylene)-N(C1-3-alkyl)2,
• R4′ is H or F, and
• R5 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R6 and R7 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from —CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and O—(C1-3-alkyl), or
• R7 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R5 and R6 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and OCH3,
• wherein:
• R2.1 is H or a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-fluoroalkyl, 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, a hetaryl, 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, a het, a hetaryl, CO—NH2, CO—NH(CH3), CO—N(CH3)2, SO2—(C1-2-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 annelated or optionally bridged heterocyclic group, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O,
• hetaryl is a five- to ten-membered, mono- or bicyclic, optionally annelated heteroaryl, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and
• cycloalkyl is saturated or partially saturated,
• and the pharmacologically acceptable salts thereof.

A method for preventing and/or treating diseases of the peripheral or central nervous system such as depression, bipolar or manic depression, acute and chronic anxiety states, schizophrenia, Alzheimer's disease, Parkinson's disease, acute and chronic multiple sclerosis or acute and chronic pain as well as injury to the brain caused by stroke, hypoxia or cranio-cerebral trauma in a patient comprising administering to the patient in need thereof a therapeutically effective amount of 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, a het, a hetaryl, a mono- or bicyclic C3-10-cycloalkyl, CH2—NR2.2R2.3, and NR2.2R2.3, each 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 mono- or poly-bridged 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, C6-10-aryl, C1-6-alkyl, C6-10-aryl-C1-6-alkylene, hetaryl-C1-6-alkylene, mono- or bicyclic C3-10 cycloalkyl, 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, 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, oxo, halogen, CF3, CHF2, CH2F, C1-6-alkyl, C6-10-aryl, and NR2.2R2.3,
• R2 is a group selected from a het and a 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, 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 is a heterocyclic four- to seven-membered ring optionally bridged, which contains 1, 2, or 3 heteroatoms selected from N, O, and S and 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 group selected from a mono- or bicyclic C6-10-aryl, a het, and a hetaryl, each optionally substituted by one or more groups selected from halogen, —C1-3-alkyl, cyclopropyl, —C1-3-fluoroalkyl, —C1-3-alkylene-OR2.1, —OH, and —O—C1-3-alkyl,
• R4 is H, C1-6-alkyl, F, C1-3-fluoroalkyl, (C1-6-alkylene)-OH, (C1-6-alkylene)-OCH3, (C1-6-alkylene)-NH2, (C1-6-alkylene)-NH(C1-3-alkyl), or (C1-6-alkylene)-N(C1-3-alkyl)2,
• R4′ is H or F, and
• R5 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R6 and R7 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from —CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and O—(C1-3-alkyl), or
• R7 is H, F, C1-6-alkyl, C1-3-fluoroalkyl, C1-6-alkylene-OH, C1-6-alkylene-OCH3, C1-6-alkylene-NH2, C1-6-alkylene-NH(C1-3-alkyl), or C1-6-alkylene-N(C1-3-alkyl)2, and R5 and R6 together form a bridge selected from methylene, ethylene, and propylene, each optionally substituted by a group selected from CH3, —OH, —F, —CF3, —CHF2, —CH2F, —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2, and OCH3,
• wherein:
• R2.1 is H or a group selected from C1-6-alkyl, C1-6-alkanol, C1-3-fluoroalkyl, 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, a hetaryl, 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, a het, a hetaryl, CO—NH2, CO—NH(CH3), CO—N(CH3)2, SO2—(C1-2-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 annelated or optionally bridged heterocyclic group, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O,
• hetaryl is a five- to ten-membered, mono- or bicyclic, optionally annelated heteroaryl, which contains 1, 2, 3, or 4 heteroatoms independently selected from N, S, or O, and
• cycloalkyl is saturated or partially saturated,
• and the pharmacologically acceptable salts thereof.