ZA200402060B - Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors. - Google Patents
Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors. Download PDFInfo
- Publication number
- ZA200402060B ZA200402060B ZA200402060A ZA200402060A ZA200402060B ZA 200402060 B ZA200402060 B ZA 200402060B ZA 200402060 A ZA200402060 A ZA 200402060A ZA 200402060 A ZA200402060 A ZA 200402060A ZA 200402060 B ZA200402060 B ZA 200402060B
- Authority
- ZA
- South Africa
- Prior art keywords
- methoxy
- oct
- azabicyclo
- propyn
- phenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 22
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 title description 5
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title description 2
- 150000008584 quinuclidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 99
- -1 cyano, hydroxy Chemical group 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 20
- 229910000085 borane Inorganic materials 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 238000003786 synthesis reaction Methods 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 239000000543 intermediate Substances 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- LPUCHTNHUHOTRY-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)ethanamine Chemical compound C1CC2C(C(N)C)CC1C2 LPUCHTNHUHOTRY-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
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- 210000003169 central nervous system Anatomy 0.000 claims description 5
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
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- RTMQZXMBCBMCJK-ZMFCMNQTSA-N 1-(2-fluoropyridin-3-yl)-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenylprop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C(=NC=CC=1)F)C1=CC=CC=C1 RTMQZXMBCBMCJK-ZMFCMNQTSA-N 0.000 claims description 2
- DVSLSPWSCJLOGG-BPGUCPLFSA-N 1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylhept-1-yn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(CCCC)C1=CC=CC=C1 DVSLSPWSCJLOGG-BPGUCPLFSA-N 0.000 claims description 2
- XTZFWAQEYOYZPT-GFOWMXPYSA-N 1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-5,5-dimethyl-3-thiophen-2-ylhex-1-yn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(CC(C)(C)C)C1=CC=CS1 XTZFWAQEYOYZPT-GFOWMXPYSA-N 0.000 claims description 2
- YQDAZCGHMNYZMU-WTQRLHSKSA-N 1-cycloheptyl-1-(2-fluoropyridin-3-yl)-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]prop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C(=NC=CC=1)F)C1CCCCCC1 YQDAZCGHMNYZMU-WTQRLHSKSA-N 0.000 claims description 2
- VBKBVALDNMYEBZ-UHFFFAOYSA-N 1-cyclohexyl-3-(3-methoxy-1-azabicyclo[2.2.2]octan-3-yl)-1-phenylprop-2-yn-1-ol Chemical compound C1N(CC2)CCC2C1(OC)C#CC(O)(C=1C=CC=CC=1)C1CCCCC1 VBKBVALDNMYEBZ-UHFFFAOYSA-N 0.000 claims description 2
- KGGLWTNSVNKIRD-VQCQRNETSA-N 3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenyl-1-pyrimidin-5-ylprop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C=NC=NC=1)C1=CC=CC=C1 KGGLWTNSVNKIRD-VQCQRNETSA-N 0.000 claims description 2
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- 206010036018 Pollakiuria Diseases 0.000 claims description 2
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- VBKBVALDNMYEBZ-PKTZIBPZSA-N (1r)-1-cyclohexyl-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenylprop-2-yn-1-ol Chemical compound C1([C@](O)(C#C[C@@]2(C3CCN(CC3)C2)OC)C=2C=CC=CC=2)CCCCC1 VBKBVALDNMYEBZ-PKTZIBPZSA-N 0.000 claims 1
- YVSSRNVDYCUSLE-WTQRLHSKSA-N (3r)-3-(3-cyclohexyl-3-fluoro-3-phenylprop-1-ynyl)-3-methoxy-1-azabicyclo[2.2.2]octane Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(F)(C=1C=CC=CC=1)C1CCCCC1 YVSSRNVDYCUSLE-WTQRLHSKSA-N 0.000 claims 1
- LTFTWJYRQNTCHI-UHFFFAOYSA-N -1-Hexyn-3-ol Natural products CCCC(O)C#C LTFTWJYRQNTCHI-UHFFFAOYSA-N 0.000 claims 1
- ROGNPHYAHLESSZ-FOIFJWKZSA-N 1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-3-phenyloct-1-yn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(CCCCC)C1=CC=CC=C1 ROGNPHYAHLESSZ-FOIFJWKZSA-N 0.000 claims 1
- WUMIJQZPHGJALC-UHFFFAOYSA-N 3-(3-methoxy-1-azabicyclo[2.2.2]octan-3-yl)-1,1-diphenylprop-2-yn-1-ol Chemical compound C1N(CC2)CCC2C1(OC)C#CC(O)(C=1C=CC=CC=1)C1=CC=CC=C1 WUMIJQZPHGJALC-UHFFFAOYSA-N 0.000 claims 1
- 241000006460 Cyana Species 0.000 claims 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- 125000006267 biphenyl group Chemical group 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 15
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
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- 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 description 5
- 239000002253 acid Substances 0.000 description 5
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
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- 230000009466 transformation Effects 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
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- 125000003368 amide group Chemical group 0.000 description 4
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- 238000013375 chromatographic separation Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
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- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
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- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical class C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 3
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 2
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- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
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- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- BOYNGGAGOZVINO-UHFFFAOYSA-N phenyl(8-thiabicyclo[3.2.1]octan-3-yl)methanone Chemical compound C1C(S2)CCC2CC1C(=O)C1=CC=CC=C1 BOYNGGAGOZVINO-UHFFFAOYSA-N 0.000 description 1
- UEOGIEBMJRBYIC-UHFFFAOYSA-N phenyl(thian-4-yl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1CCSCC1 UEOGIEBMJRBYIC-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
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- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
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- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- WJXREUZUPGMAII-UHFFFAOYSA-N sulfurazidic acid Chemical compound OS(=O)(=O)N=[N+]=[N-] WJXREUZUPGMAII-UHFFFAOYSA-N 0.000 description 1
- ITLCXSHKUNNAHG-UHFFFAOYSA-N tert-butyl 4-benzoylpiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)C1=CC=CC=C1 ITLCXSHKUNNAHG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
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- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 1
- 229960004045 tolterodine Drugs 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
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- 210000001186 vagus nerve Anatomy 0.000 description 1
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01124727 | 2001-10-17 |
Publications (1)
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|---|---|
| ZA200402060B true ZA200402060B (en) | 2005-03-15 |
Family
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Family Applications (1)
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| ZA200402060A ZA200402060B (en) | 2001-10-17 | 2004-03-15 | Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors. |
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| JP (1) | JP2005512974A (bg) |
| KR (1) | KR20050030169A (bg) |
| CN (1) | CN1571787A (bg) |
| BG (1) | BG108683A (bg) |
| BR (1) | BR0212983A (bg) |
| CA (1) | CA2462980A1 (bg) |
| CZ (1) | CZ2004501A3 (bg) |
| HU (1) | HUP0401849A3 (bg) |
| IL (1) | IL160896A0 (bg) |
| IS (1) | IS7186A (bg) |
| MX (1) | MXPA04002983A (bg) |
| NO (1) | NO20042023L (bg) |
| NZ (1) | NZ532283A (bg) |
| PL (1) | PL370087A1 (bg) |
| RU (1) | RU2004110717A (bg) |
| WO (1) | WO2003033495A1 (bg) |
| ZA (1) | ZA200402060B (bg) |
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| EP1506205B1 (en) | 2002-05-07 | 2008-07-16 | Neurosearch A/S | Novel azacyclic ethynyl derivatives |
| MXPA05000434A (es) | 2002-07-08 | 2005-04-19 | Ranbaxy Lab Ltd | Derivados de hexano [3.1.0] azabiciclo 3,6-disustituido utiles como antagonistas de receptor muscarinico. |
| WO2004089898A1 (en) | 2003-04-09 | 2004-10-21 | Ranbaxy Laboratories Limited | Substituted azabicyclo hexane derivatives as muscarinic receptor antagonists |
| CN100436414C (zh) | 2003-04-11 | 2008-11-26 | 兰贝克赛实验室有限公司 | 作为毒蕈碱受体拮抗剂的氮杂双环衍生物 |
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| AR048573A1 (es) * | 2003-07-17 | 2006-05-10 | Glaxo Group Ltd | Compuesto de 8-azoniabiciclo[3.2.1]octano sustituido en la posicion 3, composicion farmceutica que lo comprende y su uso para preparar esta ultima |
| PE20050250A1 (es) * | 2003-07-17 | 2005-04-08 | Glaxo Group Ltd | Antagonistas de los receptores muscarinicos de la acetilcolina |
| SI1677795T1 (sl) * | 2003-10-14 | 2011-04-29 | Glaxo Group Ltd | Antagonisti muskarinskega acetilholinskega receptorja |
| TW200528448A (en) * | 2003-10-17 | 2005-09-01 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| AR046225A1 (es) * | 2003-11-04 | 2005-11-30 | Glaxo Group Ltd | Compuesto de 8-azoniabiciclo(3.2.1)octano, composicion farmaceutica para el tratamiento de enfermedades mediadas por receptores de acetilcolina muscarinicos que lo comprende y uso del compuesto para preparar dicha composicion |
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| ES2239546B1 (es) * | 2004-03-15 | 2006-12-01 | Almirall Prodesfarma, S.A. | Nuevos esteres de quinuclidina cuaternizados. |
| MY144753A (en) | 2004-04-27 | 2011-10-31 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| EP1747219A4 (en) * | 2004-05-13 | 2010-05-26 | Glaxo Group Ltd | Antagonists of muscarinic acetylcholine receptor |
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| WO2007016639A2 (en) * | 2005-08-02 | 2007-02-08 | Glaxo Group Limited | M3 muscarinic acetylcholine receptor antagonists |
| JP2009504768A (ja) * | 2005-08-18 | 2009-02-05 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
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| US20100112061A1 (en) * | 2006-12-13 | 2010-05-06 | William Baker | Monophosphates as Mutual Prodrugs of Muscarinic Receptor Antagonists and Beta-Agonists for the Treatment of COPD And Chronic Bronchitis |
| JP2010515729A (ja) | 2007-01-10 | 2010-05-13 | アイアールエム・リミテッド・ライアビリティ・カンパニー | チャネル活性化プロテアーゼ阻害剤としての化合物および組成物 |
| WO2008096094A1 (en) * | 2007-02-06 | 2008-08-14 | Argenta Discovery Ltd. | Bicyclor[2.2.1]hept-7-ylamine derivatives as muscarinic m3 receptor modulators |
| RU2446166C2 (ru) * | 2007-04-24 | 2012-03-27 | Солвей Фармасьютикалс Б.В. | Гетероциклические соединения, имеющие сродство к мускариновым рецепторам |
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| US20110294835A1 (en) | 2008-05-15 | 2011-12-01 | The Board Of Trustees Of The University Of Illinois | Muscarinic Agonists as Cognitive Enhancers |
| CN102112130A (zh) | 2008-06-10 | 2011-06-29 | 诺瓦提斯公司 | 作为上皮钠通道阻滞剂的吡嗪衍生物 |
| WO2009152392A2 (en) * | 2008-06-11 | 2009-12-17 | University Of Toledo | Muscarinic agonists for neurological disorders and methods of making the same |
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| EP2813227A1 (en) | 2009-10-22 | 2014-12-17 | Vertex Pharmaceuticals Incorporated | Compositions for treatment of cystic fibrosis and other chronic diseases |
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| JP5808826B2 (ja) | 2011-02-23 | 2015-11-10 | インテリカイン， エルエルシー | 複素環化合物およびその使用 |
| CA2828219A1 (en) | 2011-02-25 | 2012-08-30 | Irm Llc | Pyrazolo [1,5-a] pyridines as trk inhibitors |
| WO2012149524A1 (en) | 2011-04-29 | 2012-11-01 | The University Of Toledo | Muscarinic agonists as enhancers of working memory and cognitive flexibility |
| UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
| CA2848809A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6-substituted 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyradines as c-met tyrosine kinase |
| JP5886433B2 (ja) | 2011-09-16 | 2016-03-16 | ノバルティス アーゲー | 嚢胞性線維症処置のためのヘテロ環式化合物 |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
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| EP2793893A4 (en) | 2011-11-23 | 2015-07-08 | Intellikine Llc | IMPROVED TREATMENT REGIMES USING MTOR INHIBITORS |
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| CN105246482A (zh) | 2013-03-15 | 2016-01-13 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
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| EA033571B1 (ru) | 2014-04-24 | 2019-11-06 | Novartis Ag | Производные пиразина в качестве ингибиторов фосфатидилинозитол 3-киназы |
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| CN106518840B (zh) * | 2016-11-17 | 2019-03-01 | 山东铂源药业有限公司 | 一种2-氯噻吩-5-甲酸的合成方法 |
| MX2021015133A (es) | 2019-06-10 | 2022-01-24 | Novartis Ag | Derivado de piridina y pirazina para el tratamiento de la fibrosis quistica, enfermedad pulmonar obstructiva cronica y bronquiectasia. |
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Family Cites Families (13)
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| US4644003A (en) * | 1985-04-03 | 1987-02-17 | Research Corporation | 3-quinuclidinol esters, useful as antagonists of muscarinic acetylcholine receptors |
| IE922270A1 (en) * | 1991-07-26 | 1993-01-27 | Akzo Nv | Pyrazole derivatives |
| GB9127279D0 (en) * | 1991-12-23 | 1992-02-19 | Ici Plc | Heterocyclic derivatives |
| GB9216721D0 (en) | 1992-08-06 | 1992-09-23 | Ici Plc | Therapeutic heterocyclic derivatives |
| GB9218334D0 (en) | 1992-08-28 | 1992-10-14 | Ici Plc | Heterocyclic compounds |
| US5384462A (en) | 1992-12-08 | 1995-01-24 | Levitt; Roy C. | Process and apparatus for localizing a source of charged particles using an electric field |
| GB9226573D0 (en) * | 1992-12-21 | 1993-02-17 | Ici Plc | Heterocyclic compounds |
| JPH08134067A (ja) | 1994-11-11 | 1996-05-28 | Yamanouchi Pharmaceut Co Ltd | キヌクリジン誘導体 |
| PL322083A1 (en) * | 1995-03-02 | 1998-01-05 | Yamanouchi Pharma Co Ltd | Novel derivative of quinuklidine, incorporating a tricyclic system of condensed heteronuclei |
| EP1217001B1 (en) * | 1999-09-28 | 2005-12-07 | Eisai Co., Ltd. | Quinuclidine compounds and drugs containing the same as the active ingredient |
| GB0004887D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| EP1375496B1 (en) | 2001-03-27 | 2007-07-04 | Eisai R&D Management Co., Ltd. | N-aryl-substituted cyclic amine derivative and medicine containing the same as active ingredient |
| NZ532283A (en) * | 2001-10-17 | 2005-06-24 | Ucb S | Quinuclidine derivatives, processes for preparing them and their uses as m2 and/or m3 muscarinic receptor inhibitors |
-
2002
- 2002-09-23 NZ NZ532283A patent/NZ532283A/en unknown
- 2002-09-23 JP JP2003536234A patent/JP2005512974A/ja active Pending
- 2002-09-23 CZ CZ2004501A patent/CZ2004501A3/cs unknown
- 2002-09-23 CA CA002462980A patent/CA2462980A1/en not_active Abandoned
- 2002-09-23 EP EP02772337A patent/EP1438309A1/en not_active Withdrawn
- 2002-09-23 IL IL16089602A patent/IL160896A0/xx unknown
- 2002-09-23 BR BR0212983-3A patent/BR0212983A/pt not_active IP Right Cessation
- 2002-09-23 WO PCT/EP2002/010644 patent/WO2003033495A1/en active IP Right Grant
- 2002-09-23 KR KR1020047005658A patent/KR20050030169A/ko not_active Application Discontinuation
- 2002-09-23 HU HU0401849A patent/HUP0401849A3/hu unknown
- 2002-09-23 PL PL02370087A patent/PL370087A1/xx not_active Application Discontinuation
- 2002-09-23 CN CNA028206037A patent/CN1571787A/zh active Pending
- 2002-09-23 US US10/490,436 patent/US7361668B2/en not_active Expired - Fee Related
- 2002-09-23 RU RU2004110717/04A patent/RU2004110717A/ru not_active Application Discontinuation
-
2004
- 2004-03-15 ZA ZA200402060A patent/ZA200402060B/en unknown
- 2004-03-18 IS IS7186A patent/IS7186A/is unknown
- 2004-03-30 MX MXPA04002983A patent/MXPA04002983A/es unknown
- 2004-04-15 BG BG108683A patent/BG108683A/bg unknown
- 2004-05-14 NO NO20042023A patent/NO20042023L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL370087A1 (en) | 2005-05-16 |
| IL160896A0 (en) | 2004-08-31 |
| CN1571787A (zh) | 2005-01-26 |
| WO2003033495A1 (en) | 2003-04-24 |
| BG108683A (bg) | 2005-04-30 |
| RU2004110717A (ru) | 2005-10-20 |
| HUP0401849A3 (en) | 2007-05-02 |
| US7361668B2 (en) | 2008-04-22 |
| NO20042023L (no) | 2004-05-14 |
| CZ2004501A3 (cs) | 2004-09-15 |
| HUP0401849A2 (hu) | 2004-12-28 |
| EP1438309A1 (en) | 2004-07-21 |
| JP2005512974A (ja) | 2005-05-12 |
| CA2462980A1 (en) | 2003-04-24 |
| IS7186A (is) | 2004-03-18 |
| US20050020660A1 (en) | 2005-01-27 |
| KR20050030169A (ko) | 2005-03-29 |
| BR0212983A (pt) | 2004-10-13 |
| MXPA04002983A (es) | 2004-07-15 |
| NZ532283A (en) | 2005-06-24 |
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