ZA200502946B - Carbamic acid esters with an anticholinergic action. - Google Patents
Carbamic acid esters with an anticholinergic action. Download PDFInfo
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- ZA200502946B ZA200502946B ZA200502946A ZA200502946A ZA200502946B ZA 200502946 B ZA200502946 B ZA 200502946B ZA 200502946 A ZA200502946 A ZA 200502946A ZA 200502946 A ZA200502946 A ZA 200502946A ZA 200502946 B ZA200502946 B ZA 200502946B
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- 230000001078 anti-cholinergic effect Effects 0.000 title abstract description 4
- 229940112021 centrally acting muscle relaxants carbamic acid ester Drugs 0.000 title abstract description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 title abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 120
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 119
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 88
- 229910052736 halogen Inorganic materials 0.000 claims description 68
- 150000002367 halogens Chemical class 0.000 claims description 68
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 64
- 229910052731 fluorine Inorganic materials 0.000 claims description 64
- 239000011737 fluorine Substances 0.000 claims description 64
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 54
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 54
- 229910052794 bromium Inorganic materials 0.000 claims description 54
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 53
- 229910052801 chlorine Inorganic materials 0.000 claims description 53
- 239000000460 chlorine Chemical group 0.000 claims description 53
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 50
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 45
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 42
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 38
- -1 -OC4-Cs-alkyl Chemical group 0.000 claims description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 30
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 30
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 30
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 28
- 229920006395 saturated elastomer Polymers 0.000 claims description 24
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 21
- 239000005864 Sulphur Chemical group 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 150000004677 hydrates Chemical class 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 239000001301 oxygen Chemical group 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 21
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 150000001450 anions Chemical class 0.000 claims description 16
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 15
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 15
- SYKNUAWMBRIEKB-UHFFFAOYSA-N [Cl].[Br] Chemical compound [Cl].[Br] SYKNUAWMBRIEKB-UHFFFAOYSA-N 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- 229930192474 thiophene Chemical group 0.000 claims description 15
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- YUCFVHQCAFKDQG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH] YUCFVHQCAFKDQG-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 3
- 229910002651 NO3 Inorganic materials 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 3
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 3
- 229940095064 tartrate Drugs 0.000 claims description 3
- 239000000543 intermediate Substances 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 208000007101 Muscle Cramp Diseases 0.000 claims 2
- 208000005392 Spasm Diseases 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 2
- 239000005557 antagonist Substances 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 229940043355 kinase inhibitor Drugs 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 2
- 102000017925 CHRM3 Human genes 0.000 claims 1
- 101150060249 CHRM3 gene Proteins 0.000 claims 1
- 101100289061 Drosophila melanogaster lili gene Proteins 0.000 claims 1
- 208000005171 Dysmenorrhea Diseases 0.000 claims 1
- 206010040741 Sinus bradycardia Diseases 0.000 claims 1
- 206010062225 Urinary tract pain Diseases 0.000 claims 1
- 239000000808 adrenergic beta-agonist Substances 0.000 claims 1
- 230000003266 anti-allergic effect Effects 0.000 claims 1
- 239000000043 antiallergic agent Substances 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 230000003454 betamimetic effect Effects 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003246 corticosteroid Substances 0.000 claims 1
- 229960001334 corticosteroids Drugs 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 1
- 239000013312 porous aromatic framework Substances 0.000 claims 1
- 230000033764 rhythmic process Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 210000001635 urinary tract Anatomy 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract 2
- 150000002148 esters Chemical class 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 101000829705 Methanopyrus kandleri (strain AV19 / DSM 6324 / JCM 9639 / NBRC 100938) Thermosome subunit Proteins 0.000 description 1
- 239000013625 clathrin-independent carrier Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention relates to novel carbamic acid esters of general formula (1), in which X<-> and the groups A, R<1>, R<2>, R<3> and R<4> can be defined as cited in the claims and the description. The invention also relates to a method for producing said esters and to their use as medicaments, in particular medicaments with an anticholinergic action.
Description
» ® WO 2004/048373 PCT/EP2003/012912 82496pct
CARBAMIC ACID ESTERS WITH AN ANTICHOLINERGIC ACTION
The present invention relates to new carbamic acid esters of general formula 1 2 +R -
RN X i
NS
N
4." "N3
R R 1 wherein X - and the groups A, R1, RZ, R3 and R4 may have the meanings given in the claims and in the specification, processes for preparing them and their use as pharmaceutical compositions, particularly as pharmaceutical compositions with an anticholinergic activity.
The present invention relates to compounds of general formula 1
RZ + R! - :
A OF
N
4,7" "N\p3
R R 1 wherein
A denotes a double-bonded group selected from among \N / \ /
Cc—C C= and :
H, H, ' HH " H oo H H cHH
X- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate,
° maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate;
R'and R® which may be identical or different, denote C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of -C3-Cs-cycloalkyl, hydroxy or halogen, or
R1 and R? together denote a C;-Cs-alkylene bridge:
R®and R* which may be identical or different, denote hydrogen, or
C1-Cs-alkyl, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of hydroxy, halogen, CF3 and -OC4-C4-alkyl, or a Cz-Cs-alkenyl or C,-Cs-alkynyl group, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of hydroxy, halogen, CFs, -OC;-Cs- alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CF3 or methoxy, or
Ce-Cro-aryl, which may optionally be substituted by one or more groups selected from the group consisting of C;-C4-alkyl, hydroxy, halogen, CF3, -OC4-Cs-alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, or
Ce-Cio-aryl, which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, or
Cs-Cio-aryl-C4-C4-alkylene, which may optionally be substituted at the aryl group by one or more groups selected from the group consisting of C1-Cs-alkyl, hydroxy, halogen, CF, -OC;-
. @® y
C4-alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CF3; or methoxy, or
Ce-C1o-aryl-C1-Cy-alkylene, which is substituted at the aryl group by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF or methoxy, or
Ce-C1o-aryl-C4-Cs-alkylene, which may optionally be substituted at the alkylene group by one or more groups selected from the group consisting of C4-Cas-alkyl, hydroxy, halogen, CFs, -
OC-Cs-alkyl and phenyl, or a 5- or 6-membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C-C4-alky! hydroxy, halogen, CFs, phenyl, benzyl and -OC,-Cs-alkyl, or a 5- or 6-membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, or
C3-Ce-cycloalkyl, which may optionally be substituted by one or more groups selected from the group consisting of C1-Cs- alkyl, hydroxy, halogen, CFs, -OC,-C4-alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, or
Cs-Ce-cycloalkyl, which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, or
' a group of formula
IC
B wherein B denotes -CH,, -NH, -S or -O-, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-Cs-alkyl, hydroxy, halogen,
CFs and -OC+-Cs-alkyl, or a group of formula one
B' wherein B' denotes CH or N, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-Cs-alkyl, hydroxy, halogen, CF3 and -
OC,-C4-alkyl, or a group of formula
CLT
B wherein B denotes -CH,, -NH, -S or -O-, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-C4-alkyl, hydroxy, halogen,
CFs and -OC;-Cs-alkyl, or 3 a group of formula
R'
LI
B wherein B denotes -CH,, -NH, -S or -O-,
R' may represent hydrogen, hydroxy, methyl, hydroxymethyl, ethyl, -CF3, CHF; or halogen, and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-C4-alkyl, hydroxy, halogen,
CF3 and -OC4-Cs-alkyl, or
R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-C4-alkyl hydroxy, halogen, CF3, phenyl, benzyl and -OC4-C4-alkyl, or
R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.
Preferred are compounds of general formula 1 wherein
A denotes a double-bonded group selected from among \, =<’ ) / \ / and ;
HH Hw 5H Hcp, H
X- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of chloride, bromide, methanesulphonate and p-toluenesulphonate, preferably bromide;
R'and R® which may be identical or different, denote C;-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of C3-Cs-cycloalkyl, hydroxy, or fluorine, or
R' and R? together denote a C3-Cs-alkylene bridge;
i C y
R®and R* which may be identical or different, denote hydrogen, or
C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine, CF and methoxy, or a phenyl or naphthyl group which may optionally be substituted by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CFs; or methoxy, or a phenyl or naphthyl group which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CFs; or methoxy, or a benzyl or phenylethyl group which may optionally be substituted at the phenyl ring by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methy!, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or a benzyl or phenylethyl group which is substituted at the phenyl ring by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CFs or methoxy, or a benzyl! or phenylethyl group which may optionally be substituted at the alkylene bridge by one or two, preferably one group selected from the group consisting of methyl, ethyl,
PY ; 7 hydroxy, fluorine, chlorine, bromine, CFs, methoxy and phenyl, or a 5- or 6- membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, phenyl, benzyl and methoxy, or a 5- or 6- membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CF3; or methoxy, or a cyclopentyl or cyclohexyl group which may optionally be substituted by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CF3; or methoxy, or a cyclopentyl or cyclohexyl group which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CF; or methoxy, or a group of formula
LI nn =
B wherein B denotes - CHz, -NH, -S or -O-, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or a group of formula one
B' wherein B' denotes CH or N, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or a group of formula
SNS
B wherein B denotes -CHg, -NH, -S or -O-, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or a group of formula
R'
CLIC
B wherein B denotes -CHy, -NH, -S or -O-,
R' may represent hydrogen, hydroxy, methyl, hydroxymethyl, ethyl, -CF3, CHF; or fluorine, and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or
R?*and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, phenyl, CFs or methoxy, or
R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur, which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CFs or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.
Particularly preferred are compounds of general formula 1 wherein
A denotes a double-bonded group selected from among
NS ~ ) / \ / and ;
HH 4 5H H ch, H
X- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of chloride, bromide, methanesulphonate and p-toluenesulphonate, preferably bromide;
R' and R*> which may be identical or different, denote a methyl or ethyl group which may optionally be substituted by cyclopropyl, hydroxy or fluorine, or
R' and R? together denote a C3-Cq4-alkylene bridge;
° ’
R® denotes hydrogen or C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CFj;
R* denotes C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or
CFs;
R* denotes a phenyl group which may optionally be substituted by one or two, preferably one group selected from the group consisting of furyl, thienyl, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or
R* denotes a benzyl group which may optionally be substituted at the phenyl ring by one, two or three, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy, furyl, thienyl and phenyl, or
R* denotes a benzyl group which may optionally be substituted at the methylene bridge by one, two or three, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy and phenyl, or
R* denotes a group of formula one
B' wherein B' denotes CH, which may optionally be mono- or disubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.
® )
Also of particular interest are compounds of general formula 1 wherein
A denotes a double-bonded group selected from among %, ~’ \ / \ / , and
H H H o H H ch, H
X- denotes an anion with a single negative charge selected from the group consisting of chloride, bromide, methanesulphonate and p-toluenesulphonate, preferably bromide;
R'and R? which may be identical or different, denote a methyl or ethyl! group which may optionally be substituted by cyclopropyl, hydroxy or fluorine, or
R' and R? together denote a C3-Cy-alkylene bridge;
R® denotes hydrogen or C;-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CF;
R* denotes C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or
CFs;
R* denotes a phenyl group which may optionally be substituted by phenyl, which may optionally be mono- or disubstituted by methyl, fluorine, hydroxy or CF3, or
R* denotes a benzyl group which may optionally be substituted at the phenyl ring by one or two, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, CF, and phenyl, or
R* denotes a benzyl! group which may optionally be monosubstituted at the methylene bridge by phenyl, or
R* denotes a group of formula
® ; 12
Ori
N BT NF wherein B' denotes CH, which may optionally be mono- or disubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.
Of the abovementioned compounds of general formula 1 particular importance is attached to those wherein X - denotes bromide or methanesulphonate, most preferably bromide, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.
Also particularly preferred according to the invention are those of the abovementioned compounds of formula 1 wherein R' and R? have the same meaning and denote methyl, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.
Also of particular importance according to the invention are those of the abovementioned compounds of formula 1, wherein R® denotes hydrogen or methyl, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.
Also of particular importance are all the compounds of general formula 1 wherein the group R* denotes biphenyl, benzhydryl, fluorenyl or
Claims (1)
- Co : 53 Patent Claims 1) Compounds of general formula 1 2 +R - R~N’ X ) \ ~H ToSN4." "p33 R R 1 wherein A denotes a double-bonded group selected from among \ / \ / C—C C=C and H, H, H H " H o H H cHH X- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate; R'and R> which may be identical or different, denote Ci-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of -C3-Ce-cycloalkyl, hydroxy or halogen, or R1 and R2 together denote a Cs-Cs-alkylene bridge: R®and R* which may be identical or different, denote hydrogen, or C1-Cs-alkyl, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of hydroxy, halogen, CFs and -OC;-Cs-alkyl, orCe 54 ® a C-Cs-alkenyl or C,-Cs-alkynyi group, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of hydroxy, halogen, CFs, -OC4-C4- alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, orCe-Co-aryl, which may optionally be substituted by one or more groups selected from the group consisting of C4-Cs-alkyl, hydroxy, halogen, CFs, -OC1-Cs-alky!, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, orCs-Cio-aryl, which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, orCe-C1o-aryl-C1-Cy-alkylene, which may optionally be substituted at the aryl group by one or more groups selected from the group consisting of C4-Cs-alkyl, hydroxy, halogen, CFs, -OC;- Cs-alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, orCe-Cio-aryl-Cy-C4-alkylene, which is substituted at the aryl group by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, orCe-Cio-aryl-C-Cs-alkylene, which may optionally be substituted at the alkylene group by one or more groups selected from the group consisting of C4-Cs-alkyl, hydroxy, halogen, CF3, -OC4-Cs-alkyl and phenyl, or a 5- or 6-membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and whichSE 55 may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C1-C4-alkyl hydroxy, halogen, CFs, phenyl, benzyl and -OC1-C4-alkyl, or a 5- or 6-membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF3 or methoxy, orCs-Cs-cycloalkyl, which may optionally be substituted by one or more groups selected from the group consisting of C-Cs- alkyl, hydroxy, halogen, CF3, -OC4-Cs-alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, orCs-Ces-cycloalkyl, which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF3 or methoxy, or a group of formulaCII B wherein B denotes -CHy, -NH, -S or -O-, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-C4-alkyl, hydroxy, halogen, CF3 and -OC4-C4-alkyl, or a group of formula one B' wherein B' denotes CH or N, which may optionally be mono- or polysubstituted by one or more groups selected from theCe 56 group consisting of C-C4-alkyl, hydroxy, halogen, CFs and -0C1-C4-alkyl, or a group of formula SNe B wherein B denotes -CHy, -NH, -S or -O-, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C;-Cs-alkyl, hydroxy, halogen, CFs and -OC4-C4-alkyl, or a group of formula R' CTC B wherein B denotes -CH,, -NH, -S or -O-, R' may represent hydrogen, hydroxy, methyl, hydroxymethyl, ethyl, -CF3, CHF or halogen, and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C1-Cs-alkyl, hydroxy, halogen, CF3 and -OC,4-C4-alkyl, or R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-C4-alkyl hydroxy, halogen, CFs, phenyl, benzy! and -OC4-C4-alkyl, or R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which is substituted by a 5- or 6-membered heteroaryl! ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy,Ce 57 optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.2) Compounds of general formula 1 according to claim 1,whereinA denotes a double-bonded group selected from among t= NA NA, and X H H H o H H CH, H X- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of chloride, bromide, methanesulphonate and p-toluenesulphonate, preferably bromide; R'and R? which may be identical or different, denote C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of Cs-Cs-cycloalkyl, hydroxy, or fluorine, or R' and R? together denote a C3-Cs-alkylene bridge: R®and R* which may be identical or different, denote hydrogen, or C1-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine, CF3 and methoxy, or a phenyl or naphthyl group which may optionally be substituted by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or a phenyl or naphthyl group which is substituted by a heteroary! ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CF; or methoxy, or a benzyl or phenylethyl group which may optionally be substituted at the phenyl ring by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or a benzyl or phenylethyl group which is substituted at the phenyl ring by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CFs or methoxy, or a benzyl or phenylethyl group which may optionally be substituted at the alkylene bridge by one or two, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, methoxy and phenyl, or a 5- or 6- membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, phenyl, benzyl and methoxy, or a 5- or 6- membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine andCT. 59 pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CF3 or methoxy, or a cyclopentyl or cyclohexyl group which may optionally be substituted by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, methoxy, phenyl! and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or a cyclopentyl or cyclohexyl group which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methy!|, fluorine, chlorine bromine, hydroxy, CF3 or methoxy, or a group of formulaCT B wherein B denotes - CH, -NH, -S or -O-, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CF; or methoxy, or a group of formula one B' wherein B' denotes CH or N, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or a group of formula: . : | 60 NNR wherein B denotes -CHj,, -NH, -S or -O-, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or a group of formula R' CC B wherein B denotes -CH;, -NH, -S or -O-, R' may represent hydrogen, hydroxy, methyl, hydroxymethyl, ethyl, -CF3, CHF: or fluorine, and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or R?>and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, phenyl, CFs or methoxy, or R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur, which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CFs; or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of theCT. 61 ® racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.3) Compounds of general formula 1 according to claim 1 or 2,whereinA denotes a double-bonded group selected from among t=’ 3A NA , and X H H H o H Hcp, HX- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of chloride, bromide, methanesulphonate and p-toluenesulphonate, preferably bromide;R'and R®> which may be identical or different, denote a methyl or ethyl group which may optionally be substituted by cyclopropyl, hydroxy or fluorine, or R' and R? together denote a C3-Cs-alkylene bridge;R° denotes hydrogen or Cy-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CF3;R* denotes C,-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CFs;R* denotes a phenyl group which may optionally be substituted by one or two, preferably one group selected from the group consisting of furyl, thienyl, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, orR* denotes a benzyl group which may optionally be substituted at the phenyl ring by one, two or three, preferably one group selected from the group consisting of methyl, ethyl, hydroxy,} ‘ oo 62 fluorine, chlorine, bromine, CF 3, methoxy, furyl, thienyl and phenyl, orR* denotes a benzyl group which may optionally be substituted at the methylene bridge by one, two or three, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, methoxy and phenyl, orR* denotes a group of formulaIC B' wherein B' denotes CH, which may optionally be mono- or disubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy,optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.4) Compounds of general formula 1 according to one of claims 1, 2 or 3,whereinA denotes a double-bonded group selected from among NS —’ ) / \ /and : HH + ny § H H ch, HX- denotes an anion with a single negative charge selected from the group consisting of chloride, bromide, methanesulphonate and p-toluenesulphonate, preferably bromide;R'and R?> which may be identical or different, denote a methyl or ethyl group which may optionally be substituted by cyclopropyl, hydroxy or fluorine, or R' and R? together denote a Cs-Cs-alkylene bridge;B . 63R® denotes hydrogen or C4-C;-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CF;R* denotes C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CF3;R* denotes a phenyl group which may optionally be substituted by phenyl, which may optionally be mono- or disubstituted by methyl, fluorine, hydroxy or CFs, orR* denotes a benzyl group which may optionally be substituted at the phenyl ring by one or two, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, CF, and phenyl, orR* denotes a benzyl group which may optionally be monosubstituted at the methylene bridge by phenyl, orR* denotes a group of formula one B' wherein B' denotes CH, which may optionally be mono- or disubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CF; or methoxy,optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof.5) Compounds of general formula 1 according to one of claims 1 to 4, whereinX - denotes bromide or methanesulphonate, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally inTL 64 ® the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof. 6) Compounds of general formula 1 according to one of claims 1 to 5, wherein R' and R? represent methyl, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof. 7) Compounds of general formula 1 according to one of claims 1 to 6, wherein R ® denotes hydrogen or methyl, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof. 8) Compounds of general formula 1 according to one of claims 1 to 7, wherein R* denotes biphenyl, benzhydryl, fluorenyl or biphenylmethyl, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof. 9) Compounds of general formula 1 according to one of claims 1 to 8, wherein A denotes a double-bonded group selected from among be MA we NA and ; HH HH 5H H CHHX- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of bromide and methanesulphonate, preferably bromide; R' and R? denote methyl;R? denotes hydrogen or methyl;- Do 65 R* denotes biphenyl, benzhydryl, fluorenyl or biphenyimethyl, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and hydrates thereof. 10) Use of a compound of general formula 1 according to one of claims 1 to 9 as a pharmaceutical composition. 11) Use of a compound of general formula 1 according to one of claims 1 to 9 for preparing a pharmaceutical composition for the treatment of diseases in which antagonists of the M3 receptor can develop a therapeutic benefit. 12) Use of a compound of general formula 1 according to one of claims 1 to 9 for preparing a pharmaceutical composition for the treatment of asthma, COPD, vagally induced sinus bradycardia, heart rhythm disorders, spasms in the gastrointestinal tract, spasms in the urinary tract and menstrual pain. 13) Pharmaceutical preparations, containing as active substance one or more compounds of general formula 1 according to one of claims 1 to 9 or the physiologically acceptable salts thereof optionally in combination with conventional excipients and/or carriers. 14) Pharmaceutical preparations according to claim 10, characterised in that they contain, in addition to one or more of the compounds of formula 1 , at least one other active substance which is selected from among the betamimetics, antiallergics, PAF antagonists, PDE IV inhibitors, leukotriene antagonists, p38 kinase inhibitors, EGFR kinase inhibitors and corticosteroids. 15) Intermediates of formula 4 R' N \ ~H A O° N RY” ~R3 aREE 66 wherein A denotes a double-bonded group selected from among Y, =’ \ / \ / , and ; H H H o H HCH R1 denotes C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of C3-Cs-cycloalkyl or hydroxy, or R1 denotes -Cs-Cs-alkylene-X, wherein X denotes chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate; R%®and R* which may be identical or different, denote hydrogen, or C1-Cs-alkyl, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of hydroxy, halogen, CF; and -OC4-Cs-alkyl, or a C»-Cs-alkenyl or C2-Cs-alkynyl group, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of hydroxy, halogen, CFs, -OC;-Cs- alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, or Ce-C1o-aryl, which may optionally be substituted by one or more groups selected from the group consisting of C1-C4-alkyl, hydroxy, halogen, CFs, -OC4-Cs-alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, or Cs-Cyo-aryl, which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or- Co 67 polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, orCe-C1o-ary!-C1-Cs-alkylene, which may optionally be substituted at the aryl group by one or more groups selected from the group consisting of C1-Cs-alkyl, hydroxy, halogen, CFs, -OC;- Cs-alkyl, phenyl and phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, orCe-Cio-aryl-C4-Cy-alkylene, which is substituted at the aryl group by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, orCe-Cio-aryl-C4-Cy-alkylene, which may optionally be substituted at the alkylene group by one or more groups selected from the group consisting of C4-C4-alkyl, hydroxy, halogen, CFs, -OC4-C4-alkyl and phenyl, or a 5- or 6-membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-C4-alkyl hydroxy, halogen, CFs, phenyl, benzyl and -OC-C4-alkyl, or a 5- or 6-membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, orCs-Ce-cycloalkyl, which may optionally be substituted by one or more groups selected from the group consisting of C1-Cs- alkyl, hydroxy, halogen, CFs, -OC-Cs-alkyl, phenyl andBE o 68 phenyl which may be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, or C3-Ce-cycloalkyl, which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CFs or methoxy, or a group of formula CTI B wherein B denotes -CH,, -NH, -S or -O-, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C1-C4-alkyl, hydroxy, halogen, CF3 and -OC4-Cs-alkyl, or a group of formula Ine B' wherein B' denotes CH or N, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C1-C4-alkyl, hydroxy, halogen, CFs; and -0C4-Cs-alkyl, or a group of formula SNe B wherein B denotes -CH,, -NH, -S or -O-, which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-C4-alkyl, hydroxy, halogen, CFs and -OC,-C4-alkyl, or a group of formulaCo - 69 R' LIC B wherein B denotes -CH,, -NH, -S or -O-, R' may represent hydrogen, hydroxy, methyl, hydroxymethyl, ethyl, -CFs;, CHF or halogen, and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C-C4-alkyl, hydroxy, halogen, CFs and -OC4-C4-alkyl, or R® and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two mare heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono- or polysubstituted by one or more groups selected from the group consisting of C4-Cs-alkyl hydroxy, halogen, CFs, phenyl, benzyl and -OC1-C4-alkyl, or R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which is substituted by a 5- or 6-membered heteroaryl ring, which may optionally be mono- or polysubstituted by methyl, halogen, hydroxy, CF; or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the acid addition salts, solvates and hydrates thereof, with the proviso that ifA denotesNN / c=C H HR' denotes methyl and rR? denotes hydrogen,R* cannot denote phenyl, pentafluorophenyl, 2-chloro-4- trifluoromethyl-phenyl, 3-chloro-4-methoxyphenyl or cyclopentyl;and with the proviso that if. a. 70 A denotes H po H R' denotes methyl and R® denotes hydrogen, R* cannot denote phenyl. 16) Intermediates of formula 4 according to claim 15, wherein A denotes a double-bonded group selected from among % =’ \ / \ / , and X H H H o H H chi, H R! denotes C;-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of C3-Cs-cycloalkyl, hydroxy or fluorine, or R’ denotes C3-C4-alkylene-X, wherein X may represent chloride, bromide, methanesulphonate or p-toluenesulphonate; R®and R* which may be identical or different, denote hydrogen, or C1-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine, CF; and methoxy, or a phenyl or naphthyl group which may optionally be substituted by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CF; or methoxy, or a phenyl or naphthyl group which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may y Lo 71 optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CFs or methoxy, or a benzyl or phenylethyl group which may optionally be substituted at the phenyl ring by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or a benzyl or phenylethyl group which is substituted at the phenyl ring by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CF; or methoxy, or a benzyl or phenylethyl group which may optionally be substituted at the alkylene bridge by one or two, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, methoxy and phenyl, or a 5- or 6- membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, phenyl, benzyl and methoxy, or a 5- or 6-membered saturated or unsaturated ring which may contain one, two or three heteroatoms selected from the: group consisting of nitrogen, oxygen or sulphur and which is substituted by a heteroaryl! ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CFs or methoxy, orTo . 72 a cyclopentyl or cyclohexyl group which may optionally be substituted by one, two or three groups selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CFs, methoxy, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or a cyclopentyl or cyclohexyl group which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CF3 or methoxy, or a group of formula CI B wherein B denotes -CHy, -NH, -S or -O-, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CF3 or methoxy, or a group of formula one B' wherein B' denotes CH or N, which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or a group of formula SNe B wherein B denotes -CH, -NH, -S or -O-, which may optionally be mono-, di- or trisubstituted by one or more groups selected~ . 73 ® from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or a group of formula R' Sie CT, wherein B denotes -CH,, -NH, -S or -O-, R' may represent hydrogen, hydroxy, methyl, hydroxymethyl, ethyl, -CF3, CHF; or fluorine, and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, or R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur and which may optionally be mono-, di- or trisubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, phenyl, CF; or methoxy, or R®and R* together with the nitrogen atom form a 5- or 6-membered saturated or unsaturated heterocyclic ring which may optionally contain one or two more heteroatoms selected from the group consisting of nitrogen, oxygen or sulphur, which is substituted by a heteroaryl ring selected from the group consisting of furan, thiophene, pyrrole, imidazole, pyridine and pyrimidine, which may optionally be mono- or disubstituted by methyl, fluorine, chlorine bromine, hydroxy, CF3 or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the acid addition salts, solvates and hydrates thereof, with the proviso that if A denotes\ / C=C H H R! denotes methyl and R® denotes hydrogen, R* cannot represent phenyl, 2-chloro-4-trifluoromethyi- phenyl, 3-chloro-4-methoxyphenyl or cyclopentyl; and with the proviso that if A denotes H o H R' denotes methyl and R® denotes hydrogen, R* cannot represent phenyl.17) Intermediates of formula 4 according to claim 15 or 16,whereinA denotes a double-bonded group selected from among b1 =’ \ / \ / , and X H H H o H H CH,HR! denotes a methyl or ethyl group which may optionally be substituted by cyclopropyl, hydroxy or fluorine, orR' denotes C3-Cs-alkylene-X, wherein X may represent chloride, bromide, methanesulphonate or p-toluenesulphonate;R3 denotes hydrogen or C4-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CFs;R* denotes C;-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CF; orT ; 75 4 R* denotes a phenyl group which may optionally be substituted by one or two, preferably one group selected from the group consisting of furyl, thienyl, phenyl and phenyl which may be mono-, di- or trisubstituted by methyl, fluorine, chiorine, bromine, hydroxy, CF3 or methoxy, or R* denotes a benzyl group which may optionally be substituted at the phenyl ring by one, two or three, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF3, methoxy, furyl, thienyl and phenyl, or R* denotes a benzyl! group which may optionally be substituted at the methylene bridge by one, two or three, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, chlorine, bromine, CF 3, methoxy and phenyl, or R* denotes a group of formula LILI B' wherein B' denotes CH, which may optionally be mono- or disubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CFs or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the acid addition salts, solvates and hydrates thereof, with the proviso that if A denotes Nn / \ / C=C or H H H o H R' denotes methyl and R® denotes hydrogen, R* cannot represent phenyl.n a 7618) Intermediates of formula 4 according to one of claims 15, 16 or 17,whereinA denotes a double-bonded group selected from among 6 Ae NA, and X H H H o H H CH,HR' which may be identical or different, denotes a methyl or ethyl group which may optionally be substituted by cyclopropy!, hydroxy or fluorine, orR! denotes Cs-Cs-alkylene-X, where X denotes chloride, bromide, methanesulphonate and p-toluenesulphonate;R® denotes hydrogen or C1-Cs-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CF3;R* denotes C1-Cz-alkyl, which may optionally be substituted by a group selected from the group consisting of hydroxy, fluorine or CFs, orR* denotes a phenyl group which may optionally be substituted by phenyl, which may optionally be mono- or disubstituted by methyl, fluorine, hydroxy or CF3, orR* denotes a benzyl group which may optionally be substituted at the phenyl ring by one or two, preferably one group selected from the group consisting of methyl, ethyl, hydroxy, fluorine, CF3, and phenyl, orR* denotes a benzyl group which may optionally be monosubstituted by phenyl at the methylene bridge, orR* denotes a group of formula one B' wherein B' denotes CH, which may optionally be mono- or disubstituted by one or more groups selected from the group consisting of methyl, fluorine, chlorine, bromine, hydroxy, CF; or methoxy, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the acid addition salts, solvates and hydrates thereof, with the proviso that if A denotes \N / ) / C= or H H H o H R! denotes methyl and R® denotes hydrogen, R* cannot represent phenyl. 19) Intermediates of formula 4 according to one of claims 15 to 18, wherein A denotes a double-bonded group selected from among 3 =’ \ / \ / , and X H H H o H H ch, H R' denotes methyl; R3 denotes hydrogen or methyl: R* denotes biphenyl, benzhydryl, fluoreny! or biphenylmethyl, optionally in the form of the individual enantiomers or diastereomers, mixtures of the enantiomers or diastereomers and optionally in the form of the racemates, and optionally in the form of the acid addition salts, solvates and hydrates thereof.
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| DE10255040A DE10255040A1 (en) | 2002-11-26 | 2002-11-26 | New carbamic acid esters with anticholinergic activity |
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| ZA200502946B true ZA200502946B (en) | 2005-11-23 |
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| US7358244B2 (en) | 2003-05-28 | 2008-04-15 | Theravance, Inc. | Azabicycloalkane compounds |
| TW200534855A (en) * | 2004-01-13 | 2005-11-01 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| US20080287487A1 (en) * | 2004-06-30 | 2008-11-20 | Anthony William James Cooper | Muscarinic Acetylcholine Receptor Antagonists |
| WO2006055503A2 (en) * | 2004-11-15 | 2006-05-26 | Glaxo Group Limited | Novel m3 muscarinic acetylcholine receptor antagonists |
| WO2007007282A2 (en) * | 2005-07-11 | 2007-01-18 | Ranbaxy Laboratories Limited | Azabicyclo derivatives as muscarinic receptor antagonists |
| WO2007068929A1 (en) * | 2005-12-16 | 2007-06-21 | Argenta Discovery Ltd. | Cyclic amine derivatives and their uses |
| JP5293192B2 (en) | 2007-02-09 | 2013-09-18 | アステラス製薬株式会社 | Aza-bridged ring compounds |
| CA3128468A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce dux4 and downstream gene expression for the treatment of fshd |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| WO2019096226A1 (en) | 2017-11-16 | 2019-05-23 | Chengdu Easton Biopharmaceuticals Co., Ltd. | Pasylated vegfr/pdgfr fusion proteins and their use in therapy |
| US20200308168A1 (en) | 2017-12-04 | 2020-10-01 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Fluorophenyl substituted muscarinic receptor ligands with selectivity for m3 over m2 |
| KR20220001259A (en) | 2020-06-29 | 2022-01-05 | (주)아모레퍼시픽 | Surface-treated inorganic particles, manufacturing method of the same, dispersion solution of the same and cosmetic composition comprising the same |
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| BE759460A (en) * | 1969-11-26 | 1971-05-26 | Knoll Ag | NEW CARBAMATES AND THEIR PREPARATION PROCESS |
| GB8600978D0 (en) * | 1986-01-16 | 1986-02-19 | Beecham Group Plc | Compounds |
| IT1228293B (en) * | 1989-02-06 | 1991-06-07 | Angeli Inst Spa | BENZODERIVATES OF HETEROCYCLIC COMPOUNDS CONTAINING NITROGEN. |
| DE4108393A1 (en) * | 1991-03-15 | 1992-09-17 | Boehringer Ingelheim Kg | NEW ESTERS BI-AND TRICYCLIC AMINO ALCOHOLS, THEIR PREPARATION AND THEIR USE IN MEDICINAL PRODUCTS |
| WO1995006635A1 (en) * | 1993-09-02 | 1995-03-09 | Yamanouchi Pharmaceutical Co., Ltd. | Carbamate derivative and medicine containing the same |
| WO1995021820A1 (en) * | 1994-02-10 | 1995-08-17 | Yamanouchi Pharmaceutical Co., Ltd. | Novel carbamate derivative and medicinal composition containing the same |
| ATE466862T1 (en) * | 1996-03-20 | 2010-05-15 | Univ Wake Forest Health Sciences | SIGMA-2 RECEPTORS AS BIOMARKERS OF TUMOR CELL PROLIFERATION |
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| PL376638A1 (en) | 2006-01-09 |
| HRP20050465A2 (en) | 2006-10-31 |
| ECSP055803A (en) | 2005-08-11 |
| ES2304538T3 (en) | 2008-10-16 |
| EP1567526B1 (en) | 2008-04-16 |
| CA2507110C (en) | 2012-07-10 |
| RS20050384A (en) | 2007-12-31 |
| KR20050086821A (en) | 2005-08-30 |
| NO20053089L (en) | 2005-06-23 |
| AU2003289880A1 (en) | 2004-06-18 |
| JP4754829B2 (en) | 2011-08-24 |
| BR0316549A (en) | 2005-10-04 |
| MXPA05005443A (en) | 2005-08-03 |
| DE10255040A1 (en) | 2004-06-03 |
| CA2507110A1 (en) | 2004-06-10 |
| UA81649C2 (en) | 2008-01-25 |
| EA200500775A1 (en) | 2005-12-29 |
| DE50309655D1 (en) | 2008-05-29 |
| JP2006514010A (en) | 2006-04-27 |
| EP1567526A1 (en) | 2005-08-31 |
| ATE392424T1 (en) | 2008-05-15 |
| CN1717408A (en) | 2006-01-04 |
| WO2004048373A1 (en) | 2004-06-10 |
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