JP4030040B2 - キヌクリジン誘導体およびそれらのムスカリンm3レセプターリガンドとしての使用 - Google Patents
キヌクリジン誘導体およびそれらのムスカリンm3レセプターリガンドとしての使用 Download PDFInfo
- Publication number
- JP4030040B2 JP4030040B2 JP2001509727A JP2001509727A JP4030040B2 JP 4030040 B2 JP4030040 B2 JP 4030040B2 JP 2001509727 A JP2001509727 A JP 2001509727A JP 2001509727 A JP2001509727 A JP 2001509727A JP 4030040 B2 JP4030040 B2 JP 4030040B2
- Authority
- JP
- Japan
- Prior art keywords
- azoniabicyclo
- octane
- hydroxy
- nmr
- dmso
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000008584 quinuclidines Chemical class 0.000 title description 3
- 102000007202 Muscarinic M3 Receptor Human genes 0.000 title 1
- 108010008405 Muscarinic M3 Receptor Proteins 0.000 title 1
- 239000003446 ligand Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 342
- 239000000203 mixture Substances 0.000 claims abstract description 52
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 150000001450 anions Chemical class 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 232
- -1 xanthene-9-carbonyloxy Chemical group 0.000 claims description 100
- 238000004519 manufacturing process Methods 0.000 claims description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 208000006673 asthma Diseases 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 5
- 206010006451 bronchitis Diseases 0.000 claims description 5
- 208000007451 chronic bronchitis Diseases 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 206010039083 rhinitis Diseases 0.000 claims description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 5
- 206010066091 Bronchial Hyperreactivity Diseases 0.000 claims description 4
- 230000036427 bronchial hyperreactivity Effects 0.000 claims description 4
- 206010048994 Bladder spasm Diseases 0.000 claims description 3
- 206010063057 Cystitis noninfective Diseases 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
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- UQOFGTXDASPNLL-XHNCKOQMSA-N Muscarine Chemical compound C[C@@H]1O[C@H](C[N+](C)(C)C)C[C@H]1O UQOFGTXDASPNLL-XHNCKOQMSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical group OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 201000003139 chronic cystitis Diseases 0.000 claims description 3
- 206010009887 colitis Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 230000001631 hypertensive effect Effects 0.000 claims description 3
- 208000002551 irritable bowel syndrome Diseases 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
- 230000027939 micturition Effects 0.000 claims description 3
- 230000003551 muscarinic effect Effects 0.000 claims description 3
- 230000001272 neurogenic effect Effects 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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 2
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 claims description 2
- 206010029279 Neurogenic bladder Diseases 0.000 claims description 2
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 2
- NZEQHVXFILCVRD-CLBCXVIASA-N [(2r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCCOC1=CC=CC=C1 NZEQHVXFILCVRD-CLBCXVIASA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 208000007784 diverticulitis Diseases 0.000 claims description 2
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical group NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims 1
- 241001149724 Cololabis adocetus Species 0.000 claims 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical group O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- XLAKJQPTOJHYDR-QTQXQZBYSA-M aclidinium bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1 XLAKJQPTOJHYDR-QTQXQZBYSA-M 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 239000001530 fumaric acid Substances 0.000 claims 1
- 229940071870 hydroiodic acid Drugs 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 239000001630 malic acid Substances 0.000 claims 1
- 235000011090 malic acid Nutrition 0.000 claims 1
- 229960002510 mandelic acid Drugs 0.000 claims 1
- 229910017604 nitric acid Inorganic materials 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- 210000002700 urine Anatomy 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 5
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 abstract description 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 abstract description 2
- 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 abstract 1
- ASMXXROZKSBQIH-UHFFFAOYSA-N [1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C=1C=CSC=1C(C=1SC=CC=1)(O)C(=O)OC(C(CC1)CC2)C[N+]21CCCOC1=CC=CC=C1 ASMXXROZKSBQIH-UHFFFAOYSA-N 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 320
- 238000005160 1H NMR spectroscopy Methods 0.000 description 184
- 230000008569 process Effects 0.000 description 158
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 85
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- 239000000243 solution Substances 0.000 description 29
- 238000002360 preparation method Methods 0.000 description 27
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- IVLICPVPXWEGCA-ZETCQYMHSA-N (3r)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@@H](O)CN1CC2 IVLICPVPXWEGCA-ZETCQYMHSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 6
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 208000023504 respiratory system disease Diseases 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- 208000014001 urinary system disease Diseases 0.000 description 5
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 125000002723 alicyclic group Chemical group 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 3
- XLHUBROMZOAQMV-UHFFFAOYSA-N 1,4-benzosemiquinone Chemical group [O]C1=CC=C(O)C=C1 XLHUBROMZOAQMV-UHFFFAOYSA-N 0.000 description 3
- 208000009079 Bronchial Spasm Diseases 0.000 description 3
- 208000014181 Bronchial disease Diseases 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000007941 film coated tablet Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RQRSQXFVRUWISR-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-4-ol Chemical compound C1CN2CCC1(O)CC2 RQRSQXFVRUWISR-UHFFFAOYSA-N 0.000 description 2
- YYXNXGQEMYTJDE-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-4-yl 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C1CN(CC2)CCC12OC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 YYXNXGQEMYTJDE-UHFFFAOYSA-N 0.000 description 2
- VIKSKCIJBNEIKG-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-4-yl 2-oxo-2-thiophen-2-ylacetate Chemical compound C1CN(CC2)CCC12OC(=O)C(=O)C1=CC=CS1 VIKSKCIJBNEIKG-UHFFFAOYSA-N 0.000 description 2
- WRDWRFQPCQESHV-UHFFFAOYSA-N 2-(furan-2-yl)-2-hydroxy-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(O)(C(=O)O)C1=CC=CO1 WRDWRFQPCQESHV-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- GIWRVUADKUVEGU-UHFFFAOYSA-N 2-oxo-2-thiophen-2-ylacetic acid Chemical compound OC(=O)C(=O)C1=CC=CS1 GIWRVUADKUVEGU-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- VZFUCHSFHOYXIS-UHFFFAOYSA-N Cycloheptanecarboxylic acid Chemical compound OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- VZCLCKQUGUCPTO-NFVORSKWSA-N [(2r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2,2-diphenylacetate Chemical compound C([C@H]1OC(=O)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(CC2)CC[N+]12CCCOC1=CC=CC=C1 VZCLCKQUGUCPTO-NFVORSKWSA-N 0.000 description 2
- GQTUXLIYPJWLRD-WTJPCUSZSA-N [(2r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-(furan-2-yl)-2-hydroxy-2-phenylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2OC=CC=2)C=2C=CC=CC=2)C(CC2)CC[N+]12CCCOC1=CC=CC=C1 GQTUXLIYPJWLRD-WTJPCUSZSA-N 0.000 description 2
- WOPPGGGGQFNBFL-FQEVSTJZSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2,2-diphenylpropanoate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(C)(C=1C=CC=CC=1)C1=CC=CC=C1 WOPPGGGGQFNBFL-FQEVSTJZSA-N 0.000 description 2
- NENRZCSTZIWMEU-NSHDSACASA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-(furan-2-yl)-2-oxoacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(=O)C1=CC=CO1 NENRZCSTZIWMEU-NSHDSACASA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 238000004080 punching Methods 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- FSNYTEYOTCTPSO-ZETCQYMHSA-N (2s)-1-azabicyclo[2.2.2]octan-2-ol Chemical compound C1CN2[C@@H](O)CC1CC2 FSNYTEYOTCTPSO-ZETCQYMHSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- CFDXNDOROWMXIV-UHFFFAOYSA-N 1-(3-chloropropoxy)naphthalene Chemical compound C1=CC=C2C(OCCCCl)=CC=CC2=C1 CFDXNDOROWMXIV-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- DSNGLKATJGBVIX-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptan-4-ol Chemical compound C1CN2CCC1(O)C2 DSNGLKATJGBVIX-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- NMGODFWGUBLTTA-UHFFFAOYSA-N 3-amino-1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)N(N)C(=O)NC2=C1 NMGODFWGUBLTTA-UHFFFAOYSA-N 0.000 description 1
- NIDWUZTTXGJFNN-UHFFFAOYSA-N 3-bromopropoxybenzene Chemical compound BrCCCOC1=CC=CC=C1 NIDWUZTTXGJFNN-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical class C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- HAMMHSUBQYOIFQ-UHFFFAOYSA-N 9,10-dihydroanthracene-9-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)C3=CC=CC=C3CC2=C1 HAMMHSUBQYOIFQ-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- YLSVSNYPDKQJJE-LWCCLMHTSA-M C(C1=CC=CC=C1)OCC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.[Br-] Chemical compound C(C1=CC=CC=C1)OCC[N+]12C[C@@H](C(CC1)CC2)OC(C(C=2SC=CC2)(C=2SC=CC2)O)=O.[Br-] YLSVSNYPDKQJJE-LWCCLMHTSA-M 0.000 description 1
- RUSKZRGOPVRKKG-RZVKIGGTSA-M C1(=CC=CC=C1)C(C(=O)O[C@H]1C[N+]2(CCC1CC2)CCCOC2=CC=CC=C2)(C)C2=CC=CC=C2.[Br-] Chemical compound C1(=CC=CC=C1)C(C(=O)O[C@H]1C[N+]2(CCC1CC2)CCCOC2=CC=CC=C2)(C)C2=CC=CC=C2.[Br-] RUSKZRGOPVRKKG-RZVKIGGTSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- JNXDFEVPFOOPCK-JUGXAVIMSA-N FC1=CC=C(C=C1)C(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C2=CC=CC=C2)(O)C2=CC=C(C=C2)F Chemical compound FC1=CC=C(C=C1)C(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C2=CC=CC=C2)(O)C2=CC=C(C=C2)F JNXDFEVPFOOPCK-JUGXAVIMSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- DCVHZPQZXJYOSC-AWEZNQCLSA-N O([C@@H]1C2CCN(CC2)C1)C(=O)C1CCCCCC1 Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C1CCCCCC1 DCVHZPQZXJYOSC-AWEZNQCLSA-N 0.000 description 1
- WVSLILWGBHCSMD-PNXYCFKJSA-M OC(C(=O)O[C@H]1C[N+]2(CCC1CC2)CCCOC2=CC=CC=C2)(C=2SC=CC2)C2=CC=CC=C2.[Br-] Chemical compound OC(C(=O)O[C@H]1C[N+]2(CCC1CC2)CCCOC2=CC=CC=C2)(C=2SC=CC2)C2=CC=CC=C2.[Br-] WVSLILWGBHCSMD-PNXYCFKJSA-M 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010040741 Sinus bradycardia Diseases 0.000 description 1
- 208000012931 Urologic disease Diseases 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- MXNUYDSBSNZSHB-HDVAYDHISA-N [(2R)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-(furan-2-yl)-2-hydroxy-2-phenylacetate Chemical compound O1C(=CC=C1)C(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C1=CC=CC=C1)(C1=CC=CC=C1)O MXNUYDSBSNZSHB-HDVAYDHISA-N 0.000 description 1
- XCUJQGVPEATBCH-OAQORGFKSA-N [(2R)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-(furan-2-yl)-2-hydroxy-2-thiophen-2-ylacetate Chemical compound O1C(=CC=C1)C(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C1=CC=CC=C1)(C=1SC=CC=1)O XCUJQGVPEATBCH-OAQORGFKSA-N 0.000 description 1
- OGGCONASXMHGDY-QCWHMEMVSA-N [(2R)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-bis(4-methylphenyl)acetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C1=CC=CC=C1)(C1=CC=C(C=C1)C)C1=CC=C(C=C1)C OGGCONASXMHGDY-QCWHMEMVSA-N 0.000 description 1
- KVEIZUGMFBPVHD-BFTQCOBVSA-N [(2R)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C2=CC=CC=C2)(C2=CSC=C2)C2=CSC=C2 KVEIZUGMFBPVHD-BFTQCOBVSA-N 0.000 description 1
- QXMLBUMHVSKFLO-BFTQCOBVSA-N [(2R)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C2=CC=CC=C2)(C=2SC=CC2)C=2SC=CC2 QXMLBUMHVSKFLO-BFTQCOBVSA-N 0.000 description 1
- QQZLYDBTHLPMAQ-GRHBHRITSA-N [(2R)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9,10-dihydroanthracene-9-carboxylate Chemical compound C1=CC=CC=2CC3=CC=CC=C3C(C1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)C(C)C1=CC=CC=C1 QQZLYDBTHLPMAQ-GRHBHRITSA-N 0.000 description 1
- KVLGKPLAROETMS-CXSPSCEVSA-N [(2R)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2,2-dithiophen-2-ylacetate Chemical compound S1C(=CC=C1)C(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCOC2=CC=CC=C2)C=2SC=CC2 KVLGKPLAROETMS-CXSPSCEVSA-N 0.000 description 1
- XYEKORMBDUWHEX-ZTICKOJLSA-N [(2R)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-(furan-2-yl)-2-hydroxy-2-thiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCOc1ccccc1)CC2)(c1ccco1)c1cccs1 XYEKORMBDUWHEX-ZTICKOJLSA-N 0.000 description 1
- MSJOMBPJYBWHIE-CXSPSCEVSA-N [(2R)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCOc1ccccc1)CC2)(c1ccsc1)c1ccsc1 MSJOMBPJYBWHIE-CXSPSCEVSA-N 0.000 description 1
- YCKHNJZDIYMCGS-CXSPSCEVSA-N [(2R)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCOC1=CC=CC=C1 YCKHNJZDIYMCGS-CXSPSCEVSA-N 0.000 description 1
- XYTFPHCAFNKRAP-CSLSLHETSA-N [(2R)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyxanthene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2OC=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCOC1=CC=CC=C1 XYTFPHCAFNKRAP-CSLSLHETSA-N 0.000 description 1
- XCEQEBAIISLVFC-RVSWETABSA-N [(2R)-1-(2-thiophen-2-ylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyxanthene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2OC=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCC=1SC=CC=1 XCEQEBAIISLVFC-RVSWETABSA-N 0.000 description 1
- LMVKXMMGQIZWKA-KBEAHSEHSA-N [(2R)-1-(3-anilinopropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCNC1=CC=CC=C1)(C=1SC=CC=1)C=1SC=CC=1 LMVKXMMGQIZWKA-KBEAHSEHSA-N 0.000 description 1
- XHTMHHASZXLTTB-YGVWRKSZSA-N [(2R)-1-(3-naphthalen-1-yloxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCOc1cccc3ccccc13)CC2)(c1cccs1)c1cccs1 XHTMHHASZXLTTB-YGVWRKSZSA-N 0.000 description 1
- QVJACSKVTBNRMZ-YGVWRKSZSA-N [(2R)-1-(3-naphthalen-2-yloxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCOc1ccc3ccccc3c1)CC2)(c1cccs1)c1cccs1 QVJACSKVTBNRMZ-YGVWRKSZSA-N 0.000 description 1
- UNODHYRYJRKFAD-MWJDUVRESA-N [(2R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2,2-bis(4-fluorophenyl)-2-hydroxyacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCOc1ccccc1)CC2)(c1ccc(F)cc1)c1ccc(F)cc1 UNODHYRYJRKFAD-MWJDUVRESA-N 0.000 description 1
- XRVIROXSETXCQM-KJUSFPLJSA-N [(2R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2,2-diphenylpropanoate Chemical compound C1(=CC=CC=C1)C(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCOC1=CC=CC=C1)(C)C1=CC=CC=C1 XRVIROXSETXCQM-KJUSFPLJSA-N 0.000 description 1
- UAAZZFCQPNAHOC-CLBCXVIASA-N [(2R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2,2-dithiophen-2-ylacetate Chemical compound O=C(O[C@@H]1CC2CC[N+]1(CCCOc1ccccc1)CC2)C(c1cccs1)c1cccs1 UAAZZFCQPNAHOC-CLBCXVIASA-N 0.000 description 1
- RTVRYZFXXPZMJP-SRCXMTRWSA-N [(2R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-bis(4-methylphenyl)acetate Chemical compound Cc1ccc(cc1)C(O)(C(=O)O[C@@H]1CC2CC[N+]1(CCCOc1ccccc1)CC2)c1ccc(C)cc1 RTVRYZFXXPZMJP-SRCXMTRWSA-N 0.000 description 1
- SCHFYHBKAZKRDC-JGEGOWRNSA-N [(2R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9,10-dihydroanthracene-9-carboxylate Chemical compound O=C(O[C@@H]1CC2CC[N+]1(CCCOc1ccccc1)CC2)C1c2ccccc2Cc2ccccc12 SCHFYHBKAZKRDC-JGEGOWRNSA-N 0.000 description 1
- HKHNSBQVQRJJAC-DSYMUFTKSA-N [(2R)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCc1ccccc1)CC2)(c1ccsc1)c1ccsc1 HKHNSBQVQRJJAC-DSYMUFTKSA-N 0.000 description 1
- VODWPMTYFBHONZ-DSYMUFTKSA-N [(2R)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCc1ccccc1)CC2)(c1cccs1)c1cccs1 VODWPMTYFBHONZ-DSYMUFTKSA-N 0.000 description 1
- GKXDZPNAGTZFFU-ZCVRLNQYSA-N [(2R)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyfluorene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2C=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCC1=CC=CC=C1 GKXDZPNAGTZFFU-ZCVRLNQYSA-N 0.000 description 1
- MQJKQGCRJVBOBM-ZCVRLNQYSA-N [(2R)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyxanthene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2OC=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCC1=CC=CC=C1 MQJKQGCRJVBOBM-ZCVRLNQYSA-N 0.000 description 1
- PFXGEDUCWGKPAM-CLBCXVIASA-N [(2R)-1-(3-phenylsulfanylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCSc1ccccc1)CC2)(c1cccs1)c1cccs1 PFXGEDUCWGKPAM-CLBCXVIASA-N 0.000 description 1
- DDOWMDYBTXBYAJ-MAGGMQRZSA-N [(2R)-1-(3-pyrrol-1-ylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCN1C=CC=C1)(C=1SC=CC=1)C=1SC=CC=1 DDOWMDYBTXBYAJ-MAGGMQRZSA-N 0.000 description 1
- NDVJUVSRQZBTTG-NCCPMLBXSA-N [(2R)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyxanthene-9-carboxylate Chemical compound OC1(C(=O)O[C@@H]2CC3CC[N+]2(CCCc2cccs2)CC3)c2ccccc2Oc2ccccc12 NDVJUVSRQZBTTG-NCCPMLBXSA-N 0.000 description 1
- RTHHTRQPXKGRMK-MCSXIPJESA-N [(2R)-1-(4-oxo-4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCC(C1=CC=CC=C1)=O)(C=1SC=CC=1)C=1SC=CC=1 RTHHTRQPXKGRMK-MCSXIPJESA-N 0.000 description 1
- BVYZETAIAIAJJX-GRELRLAZSA-N [(2R)-1-(4-oxo-4-thiophen-2-ylbutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCCC(=O)C1=CC=CS1 BVYZETAIAIAJJX-GRELRLAZSA-N 0.000 description 1
- WCWXQFXCSWXHHZ-ZUYJMMGOSA-N [(2R)-1-(4-phenoxybutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCCOc1ccccc1)CC2)(c1ccsc1)c1ccsc1 WCWXQFXCSWXHHZ-ZUYJMMGOSA-N 0.000 description 1
- ZTCVQTWPJAKIIR-ZUYJMMGOSA-N [(2R)-1-(4-phenoxybutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCCOc1ccccc1)CC2)(c1cccs1)c1cccs1 ZTCVQTWPJAKIIR-ZUYJMMGOSA-N 0.000 description 1
- QDJOXRZCSMRIFS-JGEGOWRNSA-N [(2R)-1-(4-phenoxybutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyfluorene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2C=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCCOC1=CC=CC=C1 QDJOXRZCSMRIFS-JGEGOWRNSA-N 0.000 description 1
- XUERTQZDLAPXIG-JGEGOWRNSA-N [(2R)-1-(4-phenoxybutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyxanthene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2OC=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCCOC1=CC=CC=C1 XUERTQZDLAPXIG-JGEGOWRNSA-N 0.000 description 1
- LSNYVHHDXWLSIN-PBYFFWLKSA-N [(2R)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCCC1=CC=CC=C1)(C1=CSC=C1)C1=CSC=C1 LSNYVHHDXWLSIN-PBYFFWLKSA-N 0.000 description 1
- LMOLILDWDBNGOU-UIDYKCEHSA-N [(2R)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyfluorene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2C=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCCC1=CC=CC=C1 LMOLILDWDBNGOU-UIDYKCEHSA-N 0.000 description 1
- NJHOLHZLIVDODO-UIDYKCEHSA-N [(2R)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 9-hydroxyxanthene-9-carboxylate Chemical compound OC1(C2=CC=CC=C2OC=2C=CC=CC1=2)C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCCC1=CC=CC=C1 NJHOLHZLIVDODO-UIDYKCEHSA-N 0.000 description 1
- BIRASVXDZLYBGL-VSGCJZCHSA-N [(2R)-1-[3-(1-methylimidazol-2-yl)sulfanylpropyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCSC=2N(C=CN2)C)(C=2SC=CC2)C=2SC=CC2 BIRASVXDZLYBGL-VSGCJZCHSA-N 0.000 description 1
- SHGDJRLVBFSZNK-CKRRMXRSSA-N [(2R)-1-[3-(2,4,6-trimethylphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCOC2=C(C=C(C=C2C)C)C)(C=2SC=CC2)C=2SC=CC2 SHGDJRLVBFSZNK-CKRRMXRSSA-N 0.000 description 1
- UBGKLWFFIUWEDK-NZQYTBKXSA-O [(2R)-1-[3-(2-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound Oc1ccccc1OCCC[N+]12CCC(CC1)C[C@H]2OC(=O)C(O)(c1cccs1)c1cccs1 UBGKLWFFIUWEDK-NZQYTBKXSA-O 0.000 description 1
- BYVONKIWMVLFCL-ZUYJMMGOSA-N [(2R)-1-[3-(2-methylphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound Cc1ccccc1OCCC[N+]12CCC(CC1)C[C@H]2OC(=O)C(O)(c1cccs1)c1cccs1 BYVONKIWMVLFCL-ZUYJMMGOSA-N 0.000 description 1
- NEMFSGSYLFNWDU-NZQYTBKXSA-O [(2R)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC1=CC=CC(OCCC[N+]23CCC(CC2)C[C@H]3OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)=C1 NEMFSGSYLFNWDU-NZQYTBKXSA-O 0.000 description 1
- IIQXFDXGVIWBNC-MCSXIPJESA-N [(2R)-1-[3-(3-methoxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound COc1cccc(OCCC[N+]23CCC(CC2)C[C@H]3OC(=O)C(O)(c2cccs2)c2cccs2)c1 IIQXFDXGVIWBNC-MCSXIPJESA-N 0.000 description 1
- QGXAZODHTKSUTL-YTPQQOOLSA-N [(2R)-1-[3-(3-nitrophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCOc1cccc(c1)[N+]([O-])=O)CC2)(c1cccs1)c1cccs1 QGXAZODHTKSUTL-YTPQQOOLSA-N 0.000 description 1
- FJLZBMUKZKSJBA-NZQYTBKXSA-O [(2R)-1-[3-(4-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C1=CC(O)=CC=C1OCCC[N+]1([C@@H](C2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)CCC2CC1 FJLZBMUKZKSJBA-NZQYTBKXSA-O 0.000 description 1
- HAZODLQCNYVYRF-YTPQQOOLSA-N [(2R)-1-[3-(4-nitrophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCOc1ccc(cc1)[N+]([O-])=O)CC2)(c1cccs1)c1cccs1 HAZODLQCNYVYRF-YTPQQOOLSA-N 0.000 description 1
- HKAWDLAEKTYSQE-YGVWRKSZSA-N [(2R)-1-[3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@@H]1CC2CC[N+]1(CCCOc1ccc3CCCCc3c1)CC2)(c1cccs1)c1cccs1 HKAWDLAEKTYSQE-YGVWRKSZSA-N 0.000 description 1
- MHTSEAIDVZWYED-UGGZBGRQSA-N [(2R)-1-[3-(N-methylanilino)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCN(C1=CC=CC=C1)C)(C=1SC=CC=1)C=1SC=CC=1 MHTSEAIDVZWYED-UGGZBGRQSA-N 0.000 description 1
- LBVFLKFOMAGTJD-MCSXIPJESA-N [(2R)-1-[3-[2-(hydroxymethyl)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OCc1ccccc1OCCC[N+]12CCC(CC1)C[C@H]2OC(=O)C(O)(c1cccs1)c1cccs1 LBVFLKFOMAGTJD-MCSXIPJESA-N 0.000 description 1
- AJZAUFUOZOJRFK-MCSXIPJESA-N [(2R)-1-[3-[3-(hydroxymethyl)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OCc1cccc(OCCC[N+]23CCC(CC2)C[C@H]3OC(=O)C(O)(c2cccs2)c2cccs2)c1 AJZAUFUOZOJRFK-MCSXIPJESA-N 0.000 description 1
- DMPGLQAJZVUSTM-KFQUYWJNSA-N [(2R)-1-[3-[3-(trifluoromethyl)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCOC1=CC(=CC=C1)C(F)(F)F)(C=1SC=CC=1)C=1SC=CC=1 DMPGLQAJZVUSTM-KFQUYWJNSA-N 0.000 description 1
- KTYMNUVVFMPZAV-MCSXIPJESA-N [(2R)-1-[3-[4-(hydroxymethyl)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound OCc1ccc(OCCC[N+]23CCC(CC2)C[C@H]3OC(=O)C(O)(c2cccs2)c2cccs2)cc1 KTYMNUVVFMPZAV-MCSXIPJESA-N 0.000 description 1
- FKCBVTSGMHXSRL-KHJLETBISA-N [(2r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-(furan-2-yl)-2-hydroxy-2-phenylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2OC=CC=2)C=2C=CC=CC=2)C(CC2)CC[N+]12CCOC1=CC=CC=C1 FKCBVTSGMHXSRL-KHJLETBISA-N 0.000 description 1
- CUGDKAOYRQVMRL-SSSUMRQXSA-N [(2r)-1-(2-thiophen-2-ylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound C([C@H]1OC(=O)C(O)(C2=CSC=C2)C2=CSC=C2)C(CC2)CC[N+]12CCC1=CC=CS1 CUGDKAOYRQVMRL-SSSUMRQXSA-N 0.000 description 1
- UPTCOTAMZGEDSW-SSSUMRQXSA-N [(2r)-1-(2-thiophen-2-ylethyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCC1=CC=CS1 UPTCOTAMZGEDSW-SSSUMRQXSA-N 0.000 description 1
- WTKMWYQOVGXZBL-CLBCXVIASA-N [(2r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound C([C@H]1OC(=O)C(O)(C2=CSC=C2)C2=CSC=C2)C(CC2)CC[N+]12CCCOC1=CC=CC=C1 WTKMWYQOVGXZBL-CLBCXVIASA-N 0.000 description 1
- YYXQHWCBZPYSGB-NFVORSKWSA-N [(2r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)C(CC2)CC[N+]12CCCOC1=CC=CC=C1 YYXQHWCBZPYSGB-NFVORSKWSA-N 0.000 description 1
- CTJCHBXUUVLZGJ-WOVMLBJDSA-N [(2r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCCC1=CC=CS1 CTJCHBXUUVLZGJ-WOVMLBJDSA-N 0.000 description 1
- WQJGXIQFDHCVTN-PBYFFWLKSA-N [(2r)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCCCC1=CC=CC=C1 WQJGXIQFDHCVTN-PBYFFWLKSA-N 0.000 description 1
- RYLRKJPKDIDJQE-MCSXIPJESA-N [(2r)-1-[3-(4-methoxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C1=CC(OC)=CC=C1OCCC[N+]1([C@@H](C2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)CCC2CC1 RYLRKJPKDIDJQE-MCSXIPJESA-N 0.000 description 1
- GUARHEPRQTXFTK-IEPGKUISSA-N [(2r)-1-[6-(4-phenylbutoxy)hexyl]-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCCCCCOCCCCC1=CC=CC=C1 GUARHEPRQTXFTK-IEPGKUISSA-N 0.000 description 1
- NZEQHVXFILCVRD-OTBAGVBSSA-N [(2s)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-2-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H]1OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)C(CC2)CC[N+]12CCCOC1=CC=CC=C1 NZEQHVXFILCVRD-OTBAGVBSSA-N 0.000 description 1
- AODUMGUMFGRDRE-SJBAUBOLSA-M [(3R)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate bromide Chemical compound OC(C(=O)O[C@H]1C[N+]2(CCC1CC2)CCCC=2SC=CC2)(C=2SC=CC2)C=2SC=CC2.[Br-] AODUMGUMFGRDRE-SJBAUBOLSA-M 0.000 description 1
- LIVFOVVBZGGJFD-AWEZNQCLSA-N [(3R)-1-azabicyclo[2.2.2]octan-3-yl] cyclohept-4-ene-1-carboxylate Chemical compound O=C(O[C@H]1CN2CCC1CC2)C1CCC=CCC1 LIVFOVVBZGGJFD-AWEZNQCLSA-N 0.000 description 1
- NETKUYSZWVBUQE-ZVOVCPRUSA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCOCC1=CC=CC=C1 NETKUYSZWVBUQE-ZVOVCPRUSA-N 0.000 description 1
- UAUSTCLJJODBIH-VITNCHFBSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2,2-bis(furan-2-yl)-2-hydroxyacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3OC=CC=3)C=3OC=CC=3)[N+]21CCCOC1=CC=CC=C1 UAUSTCLJJODBIH-VITNCHFBSA-N 0.000 description 1
- ZPUIFOBXUIMYGP-YMVPHMABSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2,2-dithiophen-2-ylpropanoate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(C)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1 ZPUIFOBXUIMYGP-YMVPHMABSA-N 0.000 description 1
- IYWRNILAOARDKA-WDVLHWPLSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-(furan-2-yl)-2-hydroxy-2-thiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3OC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1 IYWRNILAOARDKA-WDVLHWPLSA-N 0.000 description 1
- SMCLERNDEYAHHL-WJOQIKPCSA-M [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 SMCLERNDEYAHHL-WJOQIKPCSA-M 0.000 description 1
- WZXRPTLWADRYET-GYNTZMJKSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 6,11-dihydro-5h-dibenzo[1,2-a:1',2'-e][7]annulene-11-carboxylate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C3C4=CC=CC=C4CCC4=CC=CC=C43)[N+]21CCCOC1=CC=CC=C1 WZXRPTLWADRYET-GYNTZMJKSA-N 0.000 description 1
- QFOWZIANZZMDKR-CBQRAPNFSA-N [(3r)-1-(3-phenylmethoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOCC1=CC=CC=C1 QFOWZIANZZMDKR-CBQRAPNFSA-N 0.000 description 1
- USKNUYDOJZZWSC-VONVOUFKSA-N [(3r)-1-[3-(1,3-benzothiazol-2-yloxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2SC3=CC=CC=C3N=2)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 USKNUYDOJZZWSC-VONVOUFKSA-N 0.000 description 1
- QEXWJULWOZTIGD-WJUMYPGWSA-N [(3r)-1-[3-(2,4-difluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=C(F)C=C1F QEXWJULWOZTIGD-WJUMYPGWSA-N 0.000 description 1
- VUBTVAJZRQUMAG-JZETWELJSA-N [(3r)-1-[3-(2,4-difluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 9-methylfluorene-9-carboxylate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C3(C)C4=CC=CC=C4C4=CC=CC=C43)[N+]21CCCOC1=CC=C(F)C=C1F VUBTVAJZRQUMAG-JZETWELJSA-N 0.000 description 1
- RHVNLHKKXWNLHB-LGCWNYSLSA-O [(3r)-1-[3-(2-carbamoylphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound NC(=O)C1=CC=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)CCC2CC1 RHVNLHKKXWNLHB-LGCWNYSLSA-O 0.000 description 1
- MBYLOEWSZFYCBU-JKLGZZSBSA-N [(3r)-1-[3-(2-chlorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1Cl MBYLOEWSZFYCBU-JKLGZZSBSA-N 0.000 description 1
- ZMYATJJAGNSEED-JWALKRTLSA-N [(3r)-1-[3-(2-tert-butyl-6-methylphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound CC1=CC=CC(C(C)(C)C)=C1OCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)CCC2CC1 ZMYATJJAGNSEED-JWALKRTLSA-N 0.000 description 1
- HVUYZXPDGVAYIH-ICFHYRHXSA-N [(3r)-1-[3-(3-cyanophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC(C#N)=C1 HVUYZXPDGVAYIH-ICFHYRHXSA-N 0.000 description 1
- VCAGNOUEEGLZFM-SLRLHWDHSA-O [(3r)-1-[3-(4-acetamidophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C1=CC(NC(=O)C)=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)CCC2CC1 VCAGNOUEEGLZFM-SLRLHWDHSA-O 0.000 description 1
- JSCPTYQCJKZVJX-ICFHYRHXSA-N [(3r)-1-[3-(4-cyanophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=C(C#N)C=C1 JSCPTYQCJKZVJX-ICFHYRHXSA-N 0.000 description 1
- WGVMNUVUUCHNMA-JZWOKSBVSA-N [(3r)-1-[3-(4-fluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-di(thiophen-3-yl)acetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C3=CSC=C3)C3=CSC=C3)[N+]21CCCOC1=CC=C(F)C=C1 WGVMNUVUUCHNMA-JZWOKSBVSA-N 0.000 description 1
- SQYXFUZHRVSBFP-JKLGZZSBSA-N [(3r)-1-[3-(4-fluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=C(F)C=C1 SQYXFUZHRVSBFP-JKLGZZSBSA-N 0.000 description 1
- GOQZLTZVGNWQNP-QIJSRAMZSA-N [(3r)-1-[3-(4-fluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 9-hydroxyxanthene-9-carboxylate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C3(O)C4=CC=CC=C4OC4=CC=CC=C43)[N+]21CCCOC1=CC=C(F)C=C1 GOQZLTZVGNWQNP-QIJSRAMZSA-N 0.000 description 1
- LIBPBHTXCSZAHE-SLRLHWDHSA-N [(3r)-1-[3-[3-(dimethylamino)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound CN(C)C1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)=C1 LIBPBHTXCSZAHE-SLRLHWDHSA-N 0.000 description 1
- MYLRUMTYZFICQR-LPHOPBHVSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] (2r)-2-hydroxy-2-phenyl-2-thiophen-2-ylacetate Chemical compound C1([C@@](C(=O)O[C@@H]2C3CCN(CC3)C2)(O)C=2C=CC=CC=2)=CC=CS1 MYLRUMTYZFICQR-LPHOPBHVSA-N 0.000 description 1
- MYLRUMTYZFICQR-QFBILLFUSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] (2s)-2-hydroxy-2-phenyl-2-thiophen-2-ylacetate Chemical compound C1([C@](C(=O)O[C@@H]2C3CCN(CC3)C2)(O)C=2C=CC=CC=2)=CC=CS1 MYLRUMTYZFICQR-QFBILLFUSA-N 0.000 description 1
- HOSIJIINLUWTDR-ZDUSSCGKSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2,2-bis(furan-2-yl)-2-hydroxyacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1OC=CC=1)C1=CC=CO1 HOSIJIINLUWTDR-ZDUSSCGKSA-N 0.000 description 1
- KKEWMOSHVGOQOG-UCFFOFKASA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-(furan-2-yl)-2-hydroxy-2-phenylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CO1 KKEWMOSHVGOQOG-UCFFOFKASA-N 0.000 description 1
- YQPNKRDRENWYPM-CWQZNGJJSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-(furan-2-yl)-2-hydroxy-2-thiophen-2-ylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CO1 YQPNKRDRENWYPM-CWQZNGJJSA-N 0.000 description 1
- GYDFTKNRHZMENP-ZDUSSCGKSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 GYDFTKNRHZMENP-ZDUSSCGKSA-N 0.000 description 1
- MYLRUMTYZFICQR-UCFFOFKASA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2-phenyl-2-thiophen-2-ylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CS1 MYLRUMTYZFICQR-UCFFOFKASA-N 0.000 description 1
- RZYBPZPILUXNNH-JTQLQIEISA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-oxo-2-thiophen-2-ylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(=O)C1=CC=CS1 RZYBPZPILUXNNH-JTQLQIEISA-N 0.000 description 1
- DCVFVRXNLHLACD-FQEVSTJZSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 9,10-dihydroanthracene-9-carboxylate Chemical compound C12=CC=CC=C2CC2=CC=CC=C2C1C(=O)O[C@@H]1C(CC2)CCN2C1 DCVFVRXNLHLACD-FQEVSTJZSA-N 0.000 description 1
- CGXUXXWCFRCLCU-UHFFFAOYSA-N [1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-4-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C1CC(OC(=O)C(O)(C=2SC=CC=2)C=2SC=CC=2)(CC2)CC[N+]12C(C)C1=CC=CC=C1 CGXUXXWCFRCLCU-UHFFFAOYSA-N 0.000 description 1
- MTYDMUSNAYECGU-UHFFFAOYSA-N [1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-4-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C=1C=CSC=1C(C=1SC=CC=1)(O)C(=O)OC(CC1)(CC2)CC[N+]21CCCOC1=CC=CC=C1 MTYDMUSNAYECGU-UHFFFAOYSA-N 0.000 description 1
- PWFARANTDRNLBZ-MSZWFKHVSA-M [O-]C(=O)C(F)(F)F.OC(C(=O)O[C@H]1C[N+]2(CCCOc3ccccc3)CCC1CC2)(c1ccsc1)c1ccsc1 Chemical compound [O-]C(=O)C(F)(F)F.OC(C(=O)O[C@H]1C[N+]2(CCCOc3ccccc3)CCC1CC2)(c1ccsc1)c1ccsc1 PWFARANTDRNLBZ-MSZWFKHVSA-M 0.000 description 1
- NDYUJGPKQFPCSF-CBTJMOJFSA-M [O-]C(=O)C(F)(F)F.OC(C(=O)O[C@H]1C[N+]2(CCCn3cccc3)CCC1CC2)(c1cccs1)c1cccs1 Chemical compound [O-]C(=O)C(F)(F)F.OC(C(=O)O[C@H]1C[N+]2(CCCn3cccc3)CCC1CC2)(c1cccs1)c1cccs1 NDYUJGPKQFPCSF-CBTJMOJFSA-M 0.000 description 1
- GRGKPKAOUPDYLO-YDSHNTAWSA-M [O-]C(=O)C(F)(F)F.OC(C(=O)O[C@H]1C[N+]2(CCc3cccs3)CCC1CC2)(c1cccs1)c1cccs1 Chemical compound [O-]C(=O)C(F)(F)F.OC(C(=O)O[C@H]1C[N+]2(CCc3cccs3)CCC1CC2)(c1cccs1)c1cccs1 GRGKPKAOUPDYLO-YDSHNTAWSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000001022 anti-muscarinic effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- MVALBWJIVQGSGK-UHFFFAOYSA-N cyclohept-4-ene-1-carboxylic acid Chemical compound OC(=O)C1CCC=CCC1 MVALBWJIVQGSGK-UHFFFAOYSA-N 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 150000002461 imidazolidines Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- KCTBOHUTRYYLJA-UHFFFAOYSA-N lithium;2h-furan-2-ide Chemical compound [Li+].C=1C=[C-]OC=1 KCTBOHUTRYYLJA-UHFFFAOYSA-N 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- HTJPDOPKPWUNBX-UHFFFAOYSA-M magnesium;2h-thiophen-2-ide;bromide Chemical compound [Mg+2].[Br-].C=1C=[C-]SC=1 HTJPDOPKPWUNBX-UHFFFAOYSA-M 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- RMOZPQBMCDJIHD-UHFFFAOYSA-N methyl 2-(furan-2-yl)-2-hydroxy-2-phenylacetate Chemical compound C=1C=CC=CC=1C(O)(C(=O)OC)C1=CC=CO1 RMOZPQBMCDJIHD-UHFFFAOYSA-N 0.000 description 1
- LFOWCAJGTMPZNO-FWTYFRHFSA-N methyl 3-[3-[(2R)-2-(2-hydroxy-2,2-dithiophen-2-ylacetyl)oxy-1-azoniabicyclo[2.2.2]octan-1-yl]propoxy]benzoate Chemical compound OC(C(=O)O[C@H]1[N+]2(CCC(C1)CC2)CCCOC2=CC(=CC=C2)C(=O)OC)(C=2SC=CC2)C=2SC=CC2 LFOWCAJGTMPZNO-FWTYFRHFSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- UANSQQFYKHHDJM-KRWDZBQOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(N[C@@H]3C4CCN(CC4)C3)=O)=CC=CC2=C1 UANSQQFYKHHDJM-KRWDZBQOSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 206010029446 nocturia Diseases 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 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
- 229920000075 poly(4-vinylpyridine) Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 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
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical class OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- A61P1/12—Antidiarrhoeals
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
- A61P11/14—Antitussive agents
-
- 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
-
- 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
- A61P13/06—Anti-spasmodics
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES9901580 | 1999-07-14 | ||
ES009901580A ES2165768B1 (es) | 1999-07-14 | 1999-07-14 | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
PCT/EP2000/006469 WO2001004118A2 (en) | 1999-07-14 | 2000-07-07 | Quinuclidine derivatives and their use as muscarinic m3 receptor ligands |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2005203365A Division JP4951217B2 (ja) | 1999-07-14 | 2005-07-12 | キヌクリジン誘導体およびそれらのムスカリンm3レセプターリガンドとしての使用 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2003504368A JP2003504368A (ja) | 2003-02-04 |
JP2003504368A5 JP2003504368A5 (US20050276830A1-20051215-C00018.png) | 2006-01-05 |
JP4030040B2 true JP4030040B2 (ja) | 2008-01-09 |
Family
ID=8309225
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2001509727A Expired - Lifetime JP4030040B2 (ja) | 1999-07-14 | 2000-07-07 | キヌクリジン誘導体およびそれらのムスカリンm3レセプターリガンドとしての使用 |
JP2005203365A Expired - Fee Related JP4951217B2 (ja) | 1999-07-14 | 2005-07-12 | キヌクリジン誘導体およびそれらのムスカリンm3レセプターリガンドとしての使用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2005203365A Expired - Fee Related JP4951217B2 (ja) | 1999-07-14 | 2005-07-12 | キヌクリジン誘導体およびそれらのムスカリンm3レセプターリガンドとしての使用 |
Country Status (39)
Families Citing this family (219)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2165768B1 (es) * | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
US7214687B2 (en) | 1999-07-14 | 2007-05-08 | Almirall Ag | Quinuclidine derivatives and medicinal compositions containing the same |
AR028948A1 (es) * | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
US20040077605A1 (en) * | 2001-06-20 | 2004-04-22 | Salvati Mark E. | Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function |
US6858593B2 (en) | 2000-08-05 | 2005-02-22 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
GB0019172D0 (en) | 2000-08-05 | 2000-09-27 | Glaxo Group Ltd | Novel compounds |
US6750210B2 (en) | 2000-08-05 | 2004-06-15 | Smithkline Beecham Corporation | Formulation containing novel anti-inflammatory androstane derivative |
US6777400B2 (en) | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
US6787532B2 (en) | 2000-08-05 | 2004-09-07 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivatives |
US6858596B2 (en) | 2000-08-05 | 2005-02-22 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivative |
US6777399B2 (en) | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
US6759398B2 (en) | 2000-08-05 | 2004-07-06 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative |
JP4445704B2 (ja) | 2000-12-22 | 2010-04-07 | アルミラル・ソシエダッド・アノニマ | キヌクリジンカルバメート誘導体およびm3アンダゴニストとしてのそれらの使用 |
UA75626C2 (en) * | 2000-12-28 | 2006-05-15 | Almirall Prodesfarma Ag | Quinuclidine derivatives and medicinal compositions containing the same |
UA77656C2 (en) | 2001-04-07 | 2007-01-15 | Glaxo Group Ltd | S-fluoromethyl ester of 6-alpha, 9-alpha-difluoro-17-alpha-[(2-furanylcarbonyl)oxy]-11-beta-hydroxy-16- alpha-methyl-3-oxoandrosta-1,4-dien-17-beta-carbothioacid as anti-inflammatory agent |
KR100912324B1 (ko) | 2001-09-14 | 2009-08-14 | 글락소 그룹 리미티드 | 호흡기 질환 치료용 펜에탄올아민 유도체 |
CN1832948B (zh) | 2001-12-20 | 2011-06-15 | 基耶西药品股份公司 | 1-烷基-1-氮*双环[2.2.2]辛烷氨基甲酸酯衍生物及其用作蕈毒碱受体拮抗剂的用途 |
DE10203753A1 (de) * | 2002-01-31 | 2003-08-14 | Boehringer Ingelheim Pharma | Neue Xanthencarbonsäureester, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel |
US7405224B2 (en) | 2002-01-31 | 2008-07-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthenecarboxylates, processes for preparing them, and their use as pharmaceutical compositions |
GB0202635D0 (en) * | 2002-02-05 | 2002-03-20 | Glaxo Wellcome Mfg Pte Ltd | Formulation containing novel anti-inflammatory androstane derivative |
ES2206021B1 (es) * | 2002-04-16 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de pirrolidinio. |
GB2389530B (en) | 2002-06-14 | 2007-01-10 | Cipla Ltd | Pharmaceutical compositions |
ES2203327B1 (es) | 2002-06-21 | 2005-06-16 | Almirall Prodesfarma, S.A. | Nuevos carbamatos de quinuclidina y composiciones farmaceuticas que los contienen. |
ES2204295B1 (es) * | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
TW200410951A (en) * | 2002-08-06 | 2004-07-01 | Glaxo Group Ltd | M3 muscarinic acetylcholine receptor antagonists |
TW200800953A (en) | 2002-10-30 | 2008-01-01 | Theravance Inc | Intermediates for preparing substituted 4-amino-1-(pyridylmethyl) piperidine |
WO2004056810A1 (en) * | 2002-12-23 | 2004-07-08 | Ranbaxy Laboratories Limited | Xanthine derivatives as muscarinic receptor antagonists |
GB0303396D0 (en) | 2003-02-14 | 2003-03-19 | Glaxo Group Ltd | Medicinal compounds |
AR044519A1 (es) | 2003-05-02 | 2005-09-14 | Novartis Ag | Derivados de piridin-tiazol amina y de pirimidin-tiazol amina |
AR044134A1 (es) * | 2003-05-02 | 2005-08-24 | Novartis Ag | Derivados de quinuclidina, metodo de preparacion y composiciones farmaceuticas. |
CN100445281C (zh) * | 2003-05-02 | 2008-12-24 | 诺瓦提斯公司 | 与毒蕈碱性m3受体结合的奎宁环衍生物 |
US7358244B2 (en) | 2003-05-28 | 2008-04-15 | Theravance, Inc. | Azabicycloalkane compounds |
GB0316290D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Novel compounds |
WO2005007645A1 (en) | 2003-07-11 | 2005-01-27 | Theravance, Inc. | Substituted 4-amino-1-benzylpiperidine compounds |
TW200519109A (en) * | 2003-07-17 | 2005-06-16 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
AR045913A1 (es) * | 2003-07-17 | 2005-11-16 | Glaxo Group Ltd | Derivados olefinicos de 8-azabiciclo[3,2,1]octanos como antagonistas de receptores muscarinicos de acetilcolina |
TW200519108A (en) * | 2003-07-17 | 2005-06-16 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
GB0317374D0 (en) | 2003-07-24 | 2003-08-27 | Glaxo Group Ltd | Medicament dispenser |
AU2004262902B2 (en) * | 2003-07-29 | 2009-07-30 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising betamimetics and an anticholinergic |
AU2004262901B2 (en) * | 2003-07-29 | 2010-05-13 | Boehringer Ingelheim International Gmbh | Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation |
US20050026886A1 (en) * | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a PDE IV inhibitor |
US20050026887A1 (en) * | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a steroid |
US20050026948A1 (en) * | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a betamimetic |
CA2534125A1 (en) * | 2003-07-29 | 2005-02-17 | Boehringer Ingelheim International Gmbh | Medicaments comprising pde iv inhibitors and an anticholinergic for treating respiratory disorders |
US20050025718A1 (en) * | 2003-07-31 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a betamimetic |
JP2007500676A (ja) * | 2003-07-31 | 2007-01-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗コリン作用薬とベータ受容体刺激薬を含む吸入用薬剤 |
AR046103A1 (es) * | 2003-10-14 | 2005-11-23 | Glaxo Group Ltd | Compuesto de 8-azoniabiciclo [3.2.1] octano,composicion farmaceutica para el tratamiento de enfermedades mediadas por receptores de acetilcolina muscarinicos y uso del compuesto para preparar dicha composicion |
MXPA06004242A (es) * | 2003-10-17 | 2006-06-28 | Glaxo Group Ltd | Antagonistas del receptor muscarinico de la acetilcolina. |
PE20050489A1 (es) * | 2003-11-04 | 2005-09-02 | Glaxo Group Ltd | Antagonistas de receptores de acetilcolina muscarinicos |
GB0329182D0 (en) | 2003-12-17 | 2004-01-21 | Glaxo Group Ltd | Chemical compounds |
GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
WO2005087236A1 (en) * | 2004-03-11 | 2005-09-22 | Glaxo Group Limited | Novel m3 muscarinic acetylcholine receptor antagonists |
ES2239546B1 (es) * | 2004-03-15 | 2006-12-01 | Almirall Prodesfarma, S.A. | Nuevos esteres de quinuclidina cuaternizados. |
JP2007529513A (ja) | 2004-03-17 | 2007-10-25 | グラクソ グループ リミテッド | M3ムスカリン性アセチルコリン受容体アンタゴニスト |
MY144753A (en) | 2004-04-27 | 2011-10-31 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
WO2005112644A2 (en) * | 2004-05-13 | 2005-12-01 | Glaxo Group Limited | Muscarinic acetylcholine receptor antagonists |
AR049384A1 (es) | 2004-05-24 | 2006-07-26 | Glaxo Group Ltd | Derivados de purina |
SI1905451T1 (sl) * | 2004-05-31 | 2010-05-31 | Almirall Sa | Kombinacije ki obsegajo antimuskarinska sredstvain kortikosteroide |
ES2257152B1 (es) * | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos. |
US20080319002A1 (en) * | 2004-06-16 | 2008-12-25 | Ranbaxy Laboratories Limited | Xanthine Derivatives a Useful as Muscarinic Receptor Antagonists |
TWI307630B (en) | 2004-07-01 | 2009-03-21 | Glaxo Group Ltd | Immunoglobulins |
GB0418045D0 (en) | 2004-08-12 | 2004-09-15 | Glaxo Group Ltd | Compounds |
GB0418278D0 (en) | 2004-08-16 | 2004-09-15 | Glaxo Group Ltd | Medicament dispenser |
GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
GB0424284D0 (en) * | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
US7579335B2 (en) | 2005-01-10 | 2009-08-25 | Glaxo Group Limited | Androstane 17α-carbonate derivatives for use in the treatment of allergic and inflammatory conditions |
CA2600636A1 (en) * | 2005-03-09 | 2006-09-14 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions based on anticholinergics and pde 5-inhibitors |
AR053346A1 (es) | 2005-03-25 | 2007-05-02 | Glaxo Group Ltd | Compuesto derivado de 8h -pirido (2,3-d) pirimidin -7 ona 2,4,8- trisustituida composicion farmaceutica y uso para preparar una composicion para tratamiento y profilxis de una enfermedad mediada por la quinasa csbp/ rk/p38 |
WO2006105401A2 (en) | 2005-03-30 | 2006-10-05 | Schering Corporation | Medicaments and methods combining an anticholinergic, a corticosteroid, and a long acting beta agonist |
GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
WO2007016650A2 (en) * | 2005-08-02 | 2007-02-08 | Glaxo Group Limited | M3 muscarinic acetylcholine receptor antagonists |
TW200738634A (en) * | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
EP1937267A4 (en) * | 2005-08-02 | 2009-08-26 | Glaxo Group Ltd | M3-MUSCARIN ACETYLCHOLIN RECEPTOR ANTAGONISTS |
JP2009504624A (ja) | 2005-08-08 | 2009-02-05 | アージェンタ ディスカバリー リミテッド | ビシクロ[2.2.1]ヘプタ−7−イルアミン誘導体およびその使用 |
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 |
TW200744612A (en) * | 2005-08-26 | 2007-12-16 | Astrazeneca Ab | New combination |
KR20080049113A (ko) | 2005-10-21 | 2008-06-03 | 노파르티스 아게 | Il-13에 대항한 인간 항체 및 치료적 용도 |
AR058109A1 (es) | 2005-12-20 | 2008-01-23 | Glaxo Group Ltd | Acido 3 - (4 - {[4 -(4 -{[3 - (3, 3 - dimetil - 1 - piperidinil)propil]oxi}fenil) - 1 - piperidinil]carbonil} - 1 - naftalenil)propanoico como antagonistas de los receptotres de histamina h1/h3, composiciones farmaceuticas que los contienen y su uso en la preparacion de medicamentos para el tratamie |
EP1978955A1 (en) * | 2006-01-06 | 2008-10-15 | Boehringer Ingelheim International GmbH | New pharmaceutical compositions based on anticholinergics and andolast |
GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
AR060536A1 (es) | 2006-04-20 | 2008-06-25 | Glaxo Group Ltd | Agonista del receptor de glucocorticoides y composiciones farmaceuticas |
ES2440317T3 (es) | 2006-04-21 | 2014-01-28 | Novartis Ag | Derivados de purina para su uso como agonistas del receptor de adenosina A2A |
GB0611587D0 (en) | 2006-06-12 | 2006-07-19 | Glaxo Group Ltd | Novel compounds |
WO2008008021A1 (en) * | 2006-07-14 | 2008-01-17 | Astrazeneca Ab | Inhalation system and delivery device for the administration of a drug in the form of dry powder. |
MX2009000475A (es) | 2006-07-19 | 2009-07-10 | Astrazeneca Ab | Nuevos compuestos de espiropiperidina triciclicos, su sintesis y sus usos como moduladores de la actividad de los receptores de quimioquinas. |
ES2298049B1 (es) * | 2006-07-21 | 2009-10-20 | Laboratorios Almirall S.A. | Procedimiento para fabricar bromuro de 3(r)-(2-hidroxi-2,2-ditien-2-ilacetoxi)-1-(3-fenoxipropil)-1-azoniabiciclo (2.2.2) octano. |
ATE502943T1 (de) | 2006-09-29 | 2011-04-15 | Novartis Ag | Pyrazolopyrimidine als pi3k-lipidkinasehemmer |
TW200825084A (en) | 2006-11-14 | 2008-06-16 | Astrazeneca Ab | New compounds 521 |
GB0622827D0 (en) | 2006-11-15 | 2006-12-27 | Glaxo Group Ltd | Sheet driver for use in a drug dispenser |
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 |
MX2009007476A (es) | 2007-01-10 | 2009-07-22 | Irm Llc | Compuestos y composiciones como inhibidores de proteasa activadora de canal. |
GB0702456D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | New combination |
NZ578473A (en) * | 2007-02-21 | 2011-10-28 | Almirall Sa | Aclinidium for use in respiratory disease |
PE20081889A1 (es) | 2007-03-23 | 2009-03-05 | Smithkline Beecham Corp | Indol carboxamidas como inhibidores de ikk2 |
PE20090733A1 (es) | 2007-05-07 | 2009-07-17 | Novartis Ag | Derivados de pirazina como bloqueadores de los canales de sodio epitelial |
CN101796026B (zh) * | 2007-09-07 | 2013-10-23 | 施万制药 | 可用作毒蕈碱受体拮抗剂的含胍化合物 |
CA2608561A1 (en) * | 2007-10-29 | 2009-04-29 | Carl Paluszkiewicz | Motorcycle wind deflector accessory support |
KR101578235B1 (ko) | 2007-12-10 | 2015-12-16 | 노파르티스 아게 | 유기 화합물 |
EP2222637A1 (en) | 2007-12-14 | 2010-09-01 | Theravance, Inc. | Amidine-containing compounds useful as muscarinic receptor antagonists |
WO2009087224A1 (en) | 2008-01-11 | 2009-07-16 | Novartis Ag | Pyrimidines as kinase inhibitors |
EP2080508A1 (en) * | 2008-01-15 | 2009-07-22 | CHIESI FARMACEUTICI S.p.A. | Dry powder formulation comprising an anticholinergic drug |
US20100055045A1 (en) | 2008-02-26 | 2010-03-04 | William Gerhart | Method and system for the treatment of chronic obstructive pulmonary disease with nebulized anticholinergic administrations |
CA2716936C (en) * | 2008-02-26 | 2018-06-05 | Elevation Pharmaceuticals, Inc. | Method and system for the treatment of chronic obstructive pulmonary disease with nebulized anticholinergic administrations |
EP2100599A1 (en) † | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
US8268834B2 (en) | 2008-03-19 | 2012-09-18 | Novartis Ag | Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme |
GB0808707D0 (en) * | 2008-05-13 | 2008-06-18 | Argenta Discovery Ltd | New compounds 275 |
AU2008356409B2 (en) | 2008-05-13 | 2012-01-19 | Astrazeneca Ab | Quinuclidine derivatives as muscarinic M3 receptor antagonists |
US20110160249A1 (en) | 2008-05-23 | 2011-06-30 | Schaab Kevin Murray | 5-lipoxygenase-activating protein inhibitor |
BRPI0912103A2 (pt) | 2008-05-27 | 2021-04-20 | Astrazeneca Ab | derivados de fenoxipiridinilamida e seu uso no tratamento de estados de doenças mediados por pde4 |
US20090326004A1 (en) | 2008-06-03 | 2009-12-31 | Ranbaxy Laboratories Limited | Muscarinic receptor antagonists |
EP2280946B1 (en) | 2008-06-05 | 2016-02-10 | Glaxo Group Limited | 4-carboxamide indazole derivatives useful as inhibitors of p13-kinases |
KR20110040818A (ko) | 2008-06-10 | 2011-04-20 | 노파르티스 아게 | 상피 나트륨 채널 차단제로서의 피라진 유도체 |
US8263623B2 (en) | 2008-07-11 | 2012-09-11 | Pfizer Inc. | Triazol derivatives useful for the treatment of diseases |
EP2154136A1 (en) * | 2008-08-08 | 2010-02-17 | CHIESI FARMACEUTICI S.p.A. | Quinuclidine carbonate derivatives and medicinal compositions thereof |
SI2391366T1 (sl) | 2009-01-29 | 2013-01-31 | Novartis Ag | Substituirani benzimidazoli za zdravljenje astrocitomov |
WO2010094643A1 (en) | 2009-02-17 | 2010-08-26 | Glaxo Group Limited | Quinoline derivatives and their uses for rhinitis and urticaria |
WO2010102958A1 (en) | 2009-03-09 | 2010-09-16 | Glaxo Group Limited | 4-oxadiazol-2 -yl- indazoles as inhibitors of p13 kinases |
JP2012520257A (ja) | 2009-03-10 | 2012-09-06 | グラクソ グループ リミテッド | Ikk2阻害剤としてのインドール誘導体 |
WO2010106016A1 (en) | 2009-03-17 | 2010-09-23 | Glaxo Group Limited | Pyrimidine derivatives used as itk inhibitors |
JP2012520685A (ja) | 2009-03-19 | 2012-09-10 | メルク・シャープ・エンド・ドーム・コーポレイション | 低分子干渉核酸(siNA)を用いたGATA結合タンパク質3(GATA3)遺伝子発現のRNA干渉媒介性阻害 |
US20120016010A1 (en) | 2009-03-19 | 2012-01-19 | Merck Sharp & Dohme Corp | RNA Interference Mediated Inhibition of BTB and CNC Homology 1, Basic Leucine Zipper Transcription Factor 1 (BACH1) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
EP2411517A2 (en) | 2009-03-27 | 2012-02-01 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF THE INTERCELLULAR ADHESION MOLECULE 1 (ICAM-1)GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
EP2411516A1 (en) | 2009-03-27 | 2012-02-01 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF APOPTOSIS SIGNAL-REGULATING KINASE 1 (ASK1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US20120004281A1 (en) | 2009-03-27 | 2012-01-05 | Merck Sharp & Dohme Corp | RNA Interference Mediated Inhibition of the Nerve Growth Factor Beta Chain (NGFB) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
KR101290893B1 (ko) | 2009-04-09 | 2013-07-29 | 노파르티스 아게 | 피롤리디늄 염의 제조 방법 |
US20100273744A1 (en) | 2009-04-24 | 2010-10-28 | Paul Martin Gore | Compounds |
WO2010122088A1 (en) | 2009-04-24 | 2010-10-28 | Glaxo Group Limited | Pyrazole and triazole carboxamides as crac channel inhibitors |
PL2424864T3 (pl) | 2009-04-30 | 2015-05-29 | Glaxo Group Ltd | Podstawione oksazolami indazole jako inhibitory kinazy pi3 |
US8815258B2 (en) | 2009-05-29 | 2014-08-26 | Pearl Therapeutics, Inc. | Compositions, methods and systems for respiratory delivery of two or more active agents |
RU2580315C3 (ru) | 2009-05-29 | 2021-06-18 | Перл Терапьютикс, Инк. | Композиции для респираторной доставки активных веществ и связанные с ними способы и системы |
GB0910537D0 (en) | 2009-06-18 | 2009-07-29 | Ivax Pharmaceuticals Ireland | Inhaler |
US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
CA2770873A1 (en) | 2009-08-12 | 2011-02-17 | Novartis Ag | Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation |
SG178454A1 (en) | 2009-08-17 | 2012-03-29 | Intellikine Inc | Heterocyclic compounds and uses thereof |
IN2012DN01453A (US20050276830A1-20051215-C00018.png) | 2009-08-20 | 2015-06-05 | Novartis Ag | |
EP2490687A1 (en) | 2009-10-22 | 2012-08-29 | Vertex Pharmaceuticals Incorporated | Compositions for treatment of cystic fibrosis and other chronic diseases |
GB0919465D0 (en) | 2009-11-06 | 2009-12-23 | Norton Healthcare Ltd | Airflow adaptor for a breath-actuated dry powder inhaler |
WO2011067365A1 (en) | 2009-12-03 | 2011-06-09 | Glaxo Group Limited | Benzpyrazole derivatives as inhibitors of p13 kinases |
JP2013512880A (ja) | 2009-12-03 | 2013-04-18 | グラクソ グループ リミテッド | Pi3−キナーゼ阻害剤としてのインダゾール誘導体 |
EP2507226A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Novel compounds |
WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
WO2011110575A1 (en) | 2010-03-11 | 2011-09-15 | Glaxo Group Limited | Derivatives of 2-[2-(benzo- or pyrido-) thiazolylamino]-6-aminopyridine, useful in the treatment of respiratoric, allergic or inflammatory diseases |
US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
GB201007203D0 (en) | 2010-04-29 | 2010-06-16 | Glaxo Group Ltd | Novel compounds |
PL2614058T3 (pl) | 2010-09-08 | 2015-12-31 | Glaxosmithkline Ip Dev Ltd | Polimorfy i sole n-[5-[4-(5-{[(2r,6s)-2,6-dimetylo-4-morfolinylo]-metylo}-1,3-oksazol-2-ilo)-1h-indazol-6-ilo]-2-(metyloksy)-3-pirydynylo]metanosulfonamidu |
WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
WO2012035055A1 (en) | 2010-09-17 | 2012-03-22 | Glaxo Group Limited | Novel compounds |
US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
GB201016912D0 (en) | 2010-10-07 | 2010-11-24 | Astrazeneca Ab | Novel combination |
US9149462B2 (en) | 2010-10-21 | 2015-10-06 | Glaxo Group Limited | Pyrazole compounds acting against allergic, inflammatory and immune disorders |
US9156791B2 (en) | 2010-10-21 | 2015-10-13 | Glaxo Group Limited | Pyrazole compounds acting against allergic, immune and inflammatory conditions |
GB201018124D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Polymorphs and salts |
US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
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 |
MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
EP2683716A1 (en) | 2011-03-11 | 2014-01-15 | Glaxo Group Limited | Pyrido[3,4-b]pyrazine derivatives as syk inhibitors |
GB201104153D0 (en) | 2011-03-11 | 2011-04-27 | Glaxo Group Ltd | Novel compounds |
EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
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 |
CN103946221B (zh) | 2011-09-16 | 2016-08-03 | 诺华股份有限公司 | 用于治疗囊性纤维化的杂环化合物 |
WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
EP2755652B1 (en) | 2011-09-16 | 2021-06-02 | Novartis AG | N-substituted heterocyclyl carboxamides |
CA2856803A1 (en) | 2011-11-23 | 2013-05-30 | Intellikine, Llc | Enhanced treatment regimens using mtor inhibitors |
US10513737B2 (en) | 2011-12-13 | 2019-12-24 | Decipher Biosciences, Inc. | Cancer diagnostics using non-coding transcripts |
US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
EP3964513A1 (en) | 2012-04-03 | 2022-03-09 | Novartis AG | Combination products with tyrosine kinase inhibitors and their use |
EP2666465A1 (en) * | 2012-05-25 | 2013-11-27 | Almirall, S.A. | Novel dosage and formulation |
EP2928880B1 (en) * | 2012-12-05 | 2018-02-14 | Chiesi Farmaceutici S.p.A. | Phenylethylpyridine derivatives as pde4-inhibitors and muscarinic receptor antagonists |
ES2917879T3 (es) | 2012-12-17 | 2022-07-12 | Almirall Sa | Nuevo uso de aclidinio |
US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
WO2014151147A1 (en) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
SG11201507286QA (en) | 2013-03-15 | 2015-10-29 | Pearl Therapeutics Inc | Methods and systems for conditioning of particulate crystalline materials |
BR112016000629B1 (pt) * | 2013-07-13 | 2023-10-31 | Beijing Showby Pharmaceutical Co., Ltd. | Compostos de quinina e isômeros ópticos, método de preparação e utilização médica dos mesmos |
KR20160060100A (ko) | 2013-09-22 | 2016-05-27 | 칼리토르 사이언시즈, 엘엘씨 | 치환된 아미노피리미딘 화합물 및 이용 방법 |
WO2015055690A1 (en) | 2013-10-17 | 2015-04-23 | Glaxosmithkline Intellectual Property Development Limited | Pi3k inhibitor for treatment of respiratory disease |
WO2015055691A1 (en) | 2013-10-17 | 2015-04-23 | Glaxosmithkline Intellectual Property Development Limited | Pi3k inhibitor for treatment of respiratory disease |
CZ306791B6 (cs) | 2013-10-29 | 2017-07-12 | Zentiva, K.S. | Průmyslově využitelný způsob přípravy aklidinium bromidu o vysoké čistotě |
TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Mdm2抑制劑與BRAF抑制劑之組合及其用途 |
CN103755698A (zh) * | 2014-01-06 | 2014-04-30 | 万特制药(海南)有限公司 | 一锅法制备阿地溴铵的工艺 |
CN103755699A (zh) * | 2014-01-06 | 2014-04-30 | 万特制药(海南)有限公司 | 一种2-羟基-2,2-二噻吩-2-基乙酸-1-氮杂二环[2,2,2]辛-3(r)-基酯制备方法 |
CZ2014188A3 (cs) | 2014-03-26 | 2015-10-07 | Zentiva, K.S. | Nové formy aclidinium chloridu a způsob jejich přípravy |
US9399637B2 (en) | 2014-03-28 | 2016-07-26 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
CN106458966B (zh) | 2014-04-24 | 2019-05-07 | 诺华股份有限公司 | 作为磷脂酰肌醇3-激酶抑制剂的吡嗪衍生物 |
BR112016024533A8 (pt) | 2014-04-24 | 2021-03-30 | Novartis Ag | derivados de amino pirazina como inibidores de fosfatidilinositol 3-cinase ou sal, seu uso, e composição e combinação farmacêuticas |
PL3134396T3 (pl) | 2014-04-24 | 2020-04-30 | Novartis Ag | Pochodne aminopirydyny jako inhibitory 3-kinazy fosfatydyloinozytolu |
CN107072976A (zh) | 2014-05-12 | 2017-08-18 | 葛兰素史克知识产权第二有限公司 | 用于治疗传染性疾病的包含Danirixin的药物组合物 |
WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
AU2015294889B2 (en) | 2014-07-31 | 2018-03-15 | Novartis Ag | Combination therapy |
AU2016227080B2 (en) * | 2015-03-02 | 2019-10-03 | Ltt Bio-Pharma Co., Ltd. | Quinuclidine derivative |
PT108370B (pt) * | 2015-03-30 | 2018-10-25 | Hovione Farm S A | Processo de preparação de brometo de aclidínio |
WO2016162878A1 (en) * | 2015-04-04 | 2016-10-13 | Harman Finochem Limited | An advantageous process for preparing 1-azoniabicyclo[2.2.2]octane,3-[(hydroxydi-2-thienylacetyl)oxy]-1-(3¬phenoxypropyl)-, bromide, (3r)- and its novel crystalline form-i |
CZ2015257A3 (cs) | 2015-04-16 | 2016-10-26 | Zentiva, K.S. | Způsob pro zmenšování velikosti částic bromidu [(3R)-1-(3-fenoxypropyl)chinuklidin-1-ium-3-yl] 2-hydroxy-2,2-bis(2-thienyl)acetátu |
CN105085355B (zh) * | 2015-06-25 | 2017-11-14 | 御盛隆堂药业有限责任公司 | 一种取代的吡咯烷羧酸酯类化合物及其制备方法和应用 |
JP2018527362A (ja) | 2015-09-11 | 2018-09-20 | サンシャイン・レイク・ファーマ・カンパニー・リミテッドSunshine Lake Pharma Co.,Ltd. | 置換されたヘテロアリール化合物および使用方法 |
GB201602527D0 (en) | 2016-02-12 | 2016-03-30 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
US20190161480A1 (en) | 2016-08-08 | 2019-05-30 | Glaxosmithkline Intellectual Property Development Limited | Chemical Compounds |
WO2018094392A1 (en) | 2016-11-21 | 2018-05-24 | Lupin Inc. | Medicament dispenser |
GB201700727D0 (en) | 2017-01-16 | 2017-03-01 | Teva Pharma | Inhalers and airflow adaptors therefor |
GB201706102D0 (en) | 2017-04-18 | 2017-05-31 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
GB201712081D0 (en) | 2017-07-27 | 2017-09-13 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
US20190076607A1 (en) | 2017-09-13 | 2019-03-14 | Lupin Atlantis Holdings Sa | Inhaler and mesh for an inhaler |
US10683297B2 (en) | 2017-11-19 | 2020-06-16 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
WO2019129801A1 (en) | 2017-12-28 | 2019-07-04 | Linnea S.A. | Process for the purification of methyl-2,2-dithienylglycolate |
US10751339B2 (en) | 2018-01-20 | 2020-08-25 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
WO2020058823A1 (en) | 2018-09-17 | 2020-03-26 | Lupin, Inc. | Dose indicator assembly for a medicament dispenser |
AU2020290094B2 (en) | 2019-06-10 | 2024-01-18 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF, COPD, and bronchiectasis |
UY38860A (es) | 2019-08-28 | 2021-02-26 | Novartis Ag | Derivados de 1,3–fenil heteroarilo sustituidos, composiciones para su uso en el tratamiento de enfermedades y formas cristalinas |
TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗tslp抗體治療炎性或阻塞性氣道疾病之方法 |
WO2021195353A1 (en) | 2020-03-25 | 2021-09-30 | Lupin Inc. | Multi-carrier medicament dispensers |
WO2021191875A1 (en) | 2020-03-26 | 2021-09-30 | Glaxosmithkline Intellectual Property Development Limited | Cathepsin inhibitors for preventing or treating viral infections |
EP4185997A1 (en) | 2020-07-23 | 2023-05-31 | Lupin Inc. | Dose counter assemblies for medicament dispensers |
Family Cites Families (182)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3091570A (en) | 1960-08-08 | 1963-05-28 | Lakeside Lab Inc | Antidepressant: 3-pyrrolidyl glycolates |
GB1219606A (en) | 1968-07-15 | 1971-01-20 | Rech S Et D Applic Scient Soge | Quinuclidinol derivatives and preparation thereof |
FR2414044A1 (fr) | 1978-01-10 | 1979-08-03 | Pharmindustrie | Nouveaux derives d'aza-1 bicyclo(2,2,2) octane, utilisables comme medicaments |
IT7920688V0 (it) | 1979-02-05 | 1979-02-05 | Chiesi Paolo Parma | Inalatore per sostanze medicamentose pulverulente, con combinata funzione di dosatore. |
IT1116047B (it) | 1979-04-27 | 1986-02-10 | Sigma Tau Ind Farmaceuti | Dispositivo per la rapida inalazione di farmaci in polvere da parte di persone sofferenti di asma |
EP0069715B1 (en) | 1981-07-08 | 1986-11-05 | Aktiebolaget Draco | Powder inhalator |
FR2539135B1 (fr) | 1983-01-11 | 1986-02-28 | Essilor Int | Hydrogels de polyurethane et procede de fabrication |
US4570630A (en) | 1983-08-03 | 1986-02-18 | Miles Laboratories, Inc. | Medicament inhalation device |
GB8334494D0 (en) | 1983-12-24 | 1984-02-01 | Tanabe Seiyaku Co | Carbostyril derivatives |
GB8613811D0 (en) | 1986-06-06 | 1986-07-09 | Phares Pharm Res Nv | Composition & method |
FI69963C (fi) | 1984-10-04 | 1986-09-12 | Orion Yhtymae Oy | Doseringsanordning |
US4675326A (en) * | 1985-05-08 | 1987-06-23 | Gabriel Amitai | Bisquaternary antidotes |
US4855290A (en) | 1985-05-10 | 1989-08-08 | State Of Israel, Represented By Prime Minister's Office, Israel Institute For Biological Research | Derivatives of quinuclidine |
GB8718345D0 (en) * | 1987-08-03 | 1987-09-09 | Fordonal Sa | N-substituted benzamides |
US4843074A (en) | 1988-05-17 | 1989-06-27 | Marion Laboratories, Inc. | 1-azabicyclo[2.2.2]octan-3-yl 2-aryl-3-azacyclo-2-hydroxypropionates and their quaternary salts |
DE3927170A1 (de) | 1989-08-17 | 1991-02-21 | Boehringer Ingelheim Kg | Inhalator |
US5290815A (en) | 1989-09-07 | 1994-03-01 | Glaxo Group Limited | Treatment of inflammation and allergy |
US5610163A (en) | 1989-09-16 | 1997-03-11 | Boehringer Ingelheim Gmbh | Esters of thienyl carboxylic acids and amino alcohols and their quaternization products |
DE3931041C2 (de) | 1989-09-16 | 2000-04-06 | Boehringer Ingelheim Kg | Ester von Thienylcarbonsäuren mit Aminoalkoholen, ihre Quaternierungsprodukte, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
GB8923590D0 (en) * | 1989-10-19 | 1989-12-06 | Pfizer Ltd | Antimuscarinic bronchodilators |
IT1237118B (it) | 1989-10-27 | 1993-05-18 | Miat Spa | Inalatore multidose per farmaci in polvere. |
GB9001635D0 (en) | 1990-01-24 | 1990-03-21 | Ganderton David | Aerosol carriers |
US5201308A (en) | 1990-02-14 | 1993-04-13 | Newhouse Michael T | Powder inhaler |
GB9004781D0 (en) | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
SG45171A1 (en) | 1990-03-21 | 1998-01-16 | Boehringer Ingelheim Int | Atomising devices and methods |
GB9015522D0 (en) | 1990-07-13 | 1990-08-29 | Braithwaite Philip W | Inhaler |
WO1992003175A1 (en) | 1990-08-11 | 1992-03-05 | Fisons Plc | Inhalation device |
DE4027391A1 (de) | 1990-08-30 | 1992-03-12 | Boehringer Ingelheim Kg | Treibgasfreies inhalationsgeraet |
US5507281A (en) | 1990-08-30 | 1996-04-16 | Boehringer Ingelheim Kg | Device for initiating a mechanical switching operation in synchronism with the breathing |
JPH0725756B2 (ja) | 1990-09-06 | 1995-03-22 | ファイザー・インコーポレーテッド | 抗ムスカリン性気管支拡張剤 |
US5091528A (en) | 1990-09-12 | 1992-02-25 | Allergan, Inc. | 6- or 7- (2-imino-2-imidazolidine)-1,4-benzoxazines as α adrenergic agents |
ATE164525T1 (de) | 1990-09-26 | 1998-04-15 | Pharmachemie Bv | Inhalator mit einem reservoir für mehrere dosierte inhalationsmittel, mit transportvorrichtung und mit wirbelkammer |
GB9026025D0 (en) | 1990-11-29 | 1991-01-16 | Boehringer Ingelheim Kg | Inhalation device |
US5290539A (en) | 1990-12-21 | 1994-03-01 | Minnesota Mining And Manufacturing Company | Device for delivering an aerosol |
US5263480A (en) | 1991-02-01 | 1993-11-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
EP0504112A3 (en) | 1991-03-14 | 1993-04-21 | Ciba-Geigy Ag | Pharmaceutical aerosol formulations |
DE4108393A1 (de) | 1991-03-15 | 1992-09-17 | Boehringer Ingelheim Kg | Neue ester bi- und tricyclischer aminoalkohole, ihre herstellung und ihre verwendung in arzneimitteln |
AU650953B2 (en) | 1991-03-21 | 1994-07-07 | Novartis Ag | Inhaler |
US6299863B1 (en) | 1992-04-03 | 2001-10-09 | Sepracor Inc. | Aerosol formulations containing micronized optically pure (R,R) formoterol for bronchodilating therapy |
GB9119705D0 (en) | 1991-09-14 | 1991-10-30 | Pfizer Ltd | Therapeutic compounds |
DE4239402A1 (de) | 1992-11-24 | 1994-05-26 | Bayer Ag | Pulverinhalator |
ATE177941T1 (de) | 1992-12-09 | 1999-04-15 | Boehringer Ingelheim Pharma | Stabilisierte medizinische aerosollösungen |
RU2111020C1 (ru) | 1992-12-18 | 1998-05-20 | Шеринг Корпорейшн | Ингалятор для порошковых лекарств |
WO1995021820A1 (fr) | 1994-02-10 | 1995-08-17 | Yamanouchi Pharmaceutical Co., Ltd. | Nouveau derive du carbamate et composition correspondante |
GB9404945D0 (en) | 1994-03-15 | 1994-04-27 | Glaxo Group Ltd | Pharmaceutical composition |
US5569447A (en) * | 1994-04-19 | 1996-10-29 | The United States Of America Represented By The Secretary Department Of Health And Human Services | Stannylated 3-quinuclidinyl benzilates and methods of preparing radiohalogenated derivatives |
JP3545414B2 (ja) | 1994-07-29 | 2004-07-21 | ミネソタ マイニング アンド マニュファクチャリング カンパニー | 架橋結合された粘弾性高分子材料に硬化可能なシロップ |
GB9426252D0 (en) | 1994-12-24 | 1995-02-22 | Glaxo Group Ltd | Pharmaceutical composition |
NO2005012I1 (no) | 1994-12-28 | 2005-06-06 | Debio Rech Pharma Sa | Triptorelin og farmasoytisk akseptable salter derav |
US5585115A (en) | 1995-01-09 | 1996-12-17 | Edward H. Mendell Co., Inc. | Pharmaceutical excipient having improved compressability |
GB9501841D0 (en) | 1995-01-31 | 1995-03-22 | Co Ordinated Drug Dev | Improvements in and relating to carrier particles for use in dry powder inhalers |
EP1366777B1 (en) | 1995-04-14 | 2005-06-15 | SmithKline Beecham Corporation | Metered dose inhaler for salmeterol |
IL122494A (en) | 1995-06-21 | 2001-08-08 | Asta Medica Ag | A cartridge for pharmaceutical powder with a measuring device and an integral inhaler for powdered medicines |
WO1997001337A1 (en) | 1995-06-29 | 1997-01-16 | Mcneil-Ppc, Inc. | The combination of topical nasal antihistamines and topical nasal steroids |
DE19528145A1 (de) | 1995-08-01 | 1997-02-06 | Boehringer Ingelheim Kg | Neue Arzneimittel und ihre Verwendung |
DE19536902A1 (de) | 1995-10-04 | 1997-04-10 | Boehringer Ingelheim Int | Vorrichtung zur Hochdruckerzeugung in einem Fluid in Miniaturausführung |
US5846983A (en) | 1996-02-09 | 1998-12-08 | Mayo Foundation For Medical Education And Research | Colonic delivery of nicotine to treat inflammatory bowel disease |
US5824669A (en) | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
US6150415A (en) | 1996-08-13 | 2000-11-21 | The Regents Of The University Of California | Epoxide hydrolase complexes and methods therewith |
US5885834A (en) | 1996-09-30 | 1999-03-23 | Epstein; Paul M. | Antisense oligodeoxynucleotide against phosphodiesterase |
SE9603669D0 (sv) | 1996-10-08 | 1996-10-08 | Astra Ab | New combination |
FR2756739B1 (fr) * | 1996-12-05 | 2000-04-28 | Astra Ab | Nouvelle formulation de budesonide |
US6495167B2 (en) | 1997-03-20 | 2002-12-17 | Schering Corporation | Preparation of powder agglomerates |
GB9807232D0 (en) | 1998-04-03 | 1998-06-03 | Univ Cardiff | Aerosol composition |
US6423298B2 (en) | 1998-06-18 | 2002-07-23 | Boehringer Ingelheim Pharmaceuticals, Inc. | Pharmaceutical formulations for aerosols with two or more active substances |
KR100600423B1 (ko) | 1998-06-18 | 2006-07-13 | 베링거 인겔하임 파마슈티칼즈, 인코포레이티드 | 2개 이상의 활성 물질을 포함하는 연무질 약제학적 제형 |
ITMI981671A1 (it) | 1998-07-21 | 2000-01-21 | Zambon Spa | Derivati ftalazinici inibitori della fosfodisterasi 4 |
ATE234604T1 (de) | 1998-08-04 | 2003-04-15 | Jago Res Ag | Medizinische aerosolformulierungen |
US5962505A (en) | 1998-08-31 | 1999-10-05 | Bobrove; Arthur M. | Method for treating hot flashes in humans |
DE19847968A1 (de) | 1998-10-17 | 2000-04-20 | Boehringer Ingelheim Pharma | Verschlußkappe und Behälter als Zweikammer-Kartusche für Vernebler zur Erzeugung von Aerosolen |
GB9902689D0 (en) | 1999-02-08 | 1999-03-31 | Novartis Ag | Organic compounds |
DE19921693A1 (de) | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika |
US20040002548A1 (en) | 1999-05-12 | 2004-01-01 | Boehringer Ingelheim Pharma Kg | Medicament compositions containing anticholinergically-effective compounds and betamimetics |
US7214687B2 (en) * | 1999-07-14 | 2007-05-08 | Almirall Ag | Quinuclidine derivatives and medicinal compositions containing the same |
ES2165768B1 (es) * | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
SE9902935D0 (sv) | 1999-08-18 | 1999-08-18 | Astra Pharma Prod | Pharmaceutical compositions |
GB9928311D0 (en) | 1999-11-30 | 2000-01-26 | Novartis Ag | Organic compounds |
US6410563B1 (en) | 1999-12-22 | 2002-06-25 | Merck Frosst Canada & Co. | Substituted 8-arylquinoline phosphodiesterase-4 inhibitors |
FR2803378B1 (fr) | 1999-12-29 | 2004-03-19 | Valeo Climatisation | Echangeur de chaleur a tubes a plusieurs canaux, en particulier pour vehicule automobile |
WO2001054728A1 (en) | 2000-01-28 | 2001-08-02 | Asahi Kasei Kabushiki Kaisha | NOVEL REMEDIES WITH THE USE OF β3 AGONIST |
AU2700301A (en) | 2000-01-31 | 2001-08-14 | Pfizer Products Inc. | Pyrimidine carboxamides useful as inhibitors of pde4 isozymes |
US6924292B2 (en) | 2000-03-23 | 2005-08-02 | Takeda Chemical Industries, Ltd. | Furoisoquinoline derivatives, process for producing the same and use thereof |
GB0008485D0 (en) | 2000-04-07 | 2000-05-24 | Glaxo Group Ltd | Pharmaceutical compositions |
GB0009605D0 (en) | 2000-04-18 | 2000-06-07 | Glaxo Group Ltd | Medicaments |
GB0009592D0 (en) | 2000-04-18 | 2000-06-07 | Glaxo Group Ltd | Respiratory combinations |
GB0009606D0 (en) | 2000-04-18 | 2000-06-07 | Glaxo Group Ltd | Therapeutic combinations |
GB0009583D0 (en) | 2000-04-18 | 2000-06-07 | Glaxo Group Ltd | Respiratory formulations |
US6777132B2 (en) | 2000-04-27 | 2004-08-17 | Valence Technology, Inc. | Alkali/transition metal halo—and hydroxy-phosphates and related electrode active materials |
GB0012261D0 (en) | 2000-05-19 | 2000-07-12 | Astrazeneca Ab | Novel process |
SK286694B6 (sk) | 2000-05-22 | 2009-03-05 | Chiesi Farmaceutici S.P.A. | Aerosólový farmaceutický prostriedok |
US20020052312A1 (en) | 2000-05-30 | 2002-05-02 | Reiss Theodore F. | Combination therapy of chronic obstructive pulmonary disease using muscarinic receptor antagonists |
AR029984A1 (es) | 2000-07-27 | 2003-07-23 | Smithkline Beecham Corp | Metodo para reducir las exacerbaciones asociadas copd ambito |
US6706726B2 (en) | 2000-10-14 | 2004-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics which may be used as medicaments as well as processes for preparing them |
US6852728B2 (en) | 2000-10-14 | 2005-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics, processes for preparing them, and pharmaceutical compositions containing them |
US6608054B2 (en) | 2001-03-20 | 2003-08-19 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics and endothelin antagonists |
US20020193393A1 (en) | 2001-03-07 | 2002-12-19 | Michel Pairet | Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors |
WO2002036106A2 (de) | 2000-10-31 | 2002-05-10 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue arzneimittelkompositionen auf der basis von anticholingergika und corticosteroiden |
US7776315B2 (en) | 2000-10-31 | 2010-08-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and additional active ingredients |
US20020151541A1 (en) | 2000-10-31 | 2002-10-17 | Michel Pairet | Pharmaceutical compositions containing tiotropium salts and antihistamines and their use |
US20020183292A1 (en) | 2000-10-31 | 2002-12-05 | Michel Pairet | Pharmaceutical compositions based on anticholinergics and corticosteroids |
US20020137764A1 (en) | 2000-10-31 | 2002-09-26 | Karin Drechsel | Inhalable formulation of a solution containing a tiotropium salt |
US20030158196A1 (en) | 2002-02-16 | 2003-08-21 | Boehringer Ingelheim Pharma Gmbh Co. Kg | Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors |
DE10062712A1 (de) | 2000-12-15 | 2002-06-20 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika und Corticosteroiden |
US20020122773A1 (en) | 2000-12-20 | 2002-09-05 | Michel Pairet | Pharmaceutical compositions based on anticholinergics and dopamine agonists |
US6620438B2 (en) | 2001-03-08 | 2003-09-16 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics and NK1-receptor antagonists |
DE10110772A1 (de) | 2001-03-07 | 2002-09-12 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika und PDE-IV-Inhibitoren |
DE10056104A1 (de) | 2000-11-13 | 2002-05-23 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Tiotropiumsalzen und Salzen des Salmeterols |
US20020193392A1 (en) | 2000-11-13 | 2002-12-19 | Christel Schmelzer | Pharmaceutical compositions based on tiotropium salts of salts of salmeterol |
US20100310477A1 (en) | 2000-11-28 | 2010-12-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg. | Pharmaceutical compositions based on anticholingerics and additional active ingredients |
JP4445704B2 (ja) | 2000-12-22 | 2010-04-07 | アルミラル・ソシエダッド・アノニマ | キヌクリジンカルバメート誘導体およびm3アンダゴニストとしてのそれらの使用 |
UA75626C2 (en) | 2000-12-28 | 2006-05-15 | Almirall Prodesfarma Ag | Quinuclidine derivatives and medicinal compositions containing the same |
US20020189610A1 (en) | 2001-02-01 | 2002-12-19 | Karl-Heinz Bozung | Pharmaceutical compositions containing an ipratropium salt and a betamimetic |
DE10104370A1 (de) | 2001-02-01 | 2002-08-08 | Boehringer Ingelheim Pharma | Arzneimittelkompositionen mit geringeren Nebenwirkungen |
DE10104367A1 (de) | 2001-02-01 | 2002-08-08 | Boehringer Ingelheim Pharma | Betamimetika enthaltende Arzneimittelkompositionen mit geringeren Nebenwirkungen |
US20020179087A1 (en) | 2001-02-01 | 2002-12-05 | Karl-Heinz Bozung | Pharmaceutical compositions containing an oxitropium salt and a betamimetic |
GB0103630D0 (en) | 2001-02-14 | 2001-03-28 | Glaxo Group Ltd | Chemical compounds |
US6667344B2 (en) | 2001-04-17 | 2003-12-23 | Dey, L.P. | Bronchodilating compositions and methods |
US20030216329A1 (en) | 2001-04-24 | 2003-11-20 | Robinson Cynthia B. | Composition, formulations & kit for treatment of respiratory & lung disease with dehydroepiandrosterone(s) steroid & an anti-muscarinic agent(s) |
MXPA03010791A (es) | 2001-05-25 | 2004-03-02 | Boehringer Ingelheim Pharma | Combinacion de inhibidor de pde4 y tiotropio a sus derivados para tratamiento de enfermedades obstructivas de vias respiratorias y de otras enfermedades inflamatorias. |
JP2005508861A (ja) | 2001-05-25 | 2005-04-07 | ファイザー・インク | 閉塞性気管疾患の治療のためのpde4阻害剤及び抗コリン性剤の組み合わせ物 |
GB0115181D0 (en) | 2001-06-20 | 2001-08-15 | Glaxo Group Ltd | Novel use |
DE10129703A1 (de) | 2001-06-22 | 2003-01-02 | Sofotec Gmbh & Co Kg | Zerstäubungssystem für eine Pulvermischung und Verfahren für Trockenpulverinhalatoren |
DE10130371A1 (de) | 2001-06-23 | 2003-01-02 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika, Corticosteroiden und Betamimetika |
US20030018019A1 (en) * | 2001-06-23 | 2003-01-23 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics |
GB0118373D0 (en) | 2001-07-27 | 2001-09-19 | Glaxo Group Ltd | Novel therapeutic method |
CA2459493C (en) | 2001-09-14 | 2011-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | New pharmaceutical compositions for inhalation |
US6919325B2 (en) | 2001-09-14 | 2005-07-19 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions containing tiotropium salts and low-solubility salmeterol salts |
US6680345B2 (en) | 2001-09-14 | 2004-01-20 | Boehringer Ingelheim Pharma Kg | Salicylic acid salts of salmeterol |
US6653323B2 (en) | 2001-11-13 | 2003-11-25 | Theravance, Inc. | Aryl aniline β2 adrenergic receptor agonists |
US6974803B2 (en) | 2001-12-06 | 2005-12-13 | Pfizer Inc | Pharmaceutical combination |
DE10202940A1 (de) | 2002-01-24 | 2003-07-31 | Sofotec Gmbh & Co Kg | Patrone für einen Pulverinhalator |
US6790856B2 (en) | 2002-01-31 | 2004-09-14 | Boehringer Ingelheim Pharma Kg | Fluorenecarboxylic acid esters, process for the manufacture thereof, and use thereof as medicaments |
GB0202635D0 (en) | 2002-02-05 | 2002-03-20 | Glaxo Wellcome Mfg Pte Ltd | Formulation containing novel anti-inflammatory androstane derivative |
PT3494995T (pt) | 2002-03-01 | 2020-03-30 | Chiesi Farm Spa | Formulação superfina de formoterol |
US6756508B2 (en) | 2002-03-04 | 2004-06-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Cinnamic acid salts, processes for their preparation, and their use as medicaments |
DE10216429A1 (de) | 2002-04-12 | 2003-10-23 | Boehringer Ingelheim Pharma | Arzneimittel enthaltend Steroide und ein neues Anticholinergikum |
DE10216333A1 (de) | 2002-04-13 | 2003-10-30 | Boehringer Ingelheim Pharma | Neue Carbonsäureester mit anticholonerger Wirksamkeit, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel |
US7094788B2 (en) | 2002-04-13 | 2006-08-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Esters of hydroxyl-substituted nitrogen heterocycles, processes for the preparation thereof as well as the use thereof as pharmaceutical compositions |
ES2206021B1 (es) | 2002-04-16 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de pirrolidinio. |
ES2195785B1 (es) | 2002-05-16 | 2005-03-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
ES2369216T3 (es) | 2002-05-17 | 2011-11-28 | Novartis Pharma Ag | Composición farmacéutica que comprende un inhibidor de renina, un bloqueador del canal de calcio y un diurético. |
ES2204295B1 (es) | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
US20040058950A1 (en) | 2002-07-09 | 2004-03-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors |
GB0230045D0 (en) | 2002-12-23 | 2003-01-29 | Glaxo Group Ltd | Compounds |
ES2211315B1 (es) | 2002-11-12 | 2005-10-16 | Almirall Prodesfarma, S.A. | Nuevos compuestos triciclicos. |
CA2506949A1 (en) | 2002-11-27 | 2004-06-10 | Altana Pharma Ag | Pde4 and pde3/4 inhibitors for use in the treatment of cachexia |
ES2211344B1 (es) | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
PE20040950A1 (es) | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
DE10307759B3 (de) | 2003-02-19 | 2004-11-18 | Schering Ag | Trimere makrocyclisch substituierte Benzolderivate, deren Herstellung und Verwendung als Kontrastmittel sowie diese enthaltende pharmazeutische Mittel |
EP1452179A1 (en) | 2003-02-27 | 2004-09-01 | CHIESI FARMACEUTICI S.p.A. | Novel medicament combination of a highly potent long-lasting beta2-agonist and a corticosteroid |
US20040184995A1 (en) | 2003-03-17 | 2004-09-23 | Yamanouchi Pharmaceutical Co., Ltd. | Novel dry powder inhalation for lung-delivery and manufacturing method thereof |
PT1610787E (pt) | 2003-03-28 | 2008-04-23 | Nycomed Gmbh | Associação sinérgica compreendendo roflumilast e um agente anticolinérgico seleccionado de sais de tiotrópio para o tratamento de doenças respiratórias |
CA2519682A1 (en) | 2003-03-28 | 2004-10-07 | Altana Pharma Ag | Synergistic combination comprising roflumilast and an anticholinergic agent selected from ipratropium, oxitropium and tiotropium salts for the treatment of respiratory diseases |
AU2004262901B2 (en) | 2003-07-29 | 2010-05-13 | Boehringer Ingelheim International Gmbh | Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation |
AU2004262902B2 (en) | 2003-07-29 | 2009-07-30 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising betamimetics and an anticholinergic |
CA2534125A1 (en) | 2003-07-29 | 2005-02-17 | Boehringer Ingelheim International Gmbh | Medicaments comprising pde iv inhibitors and an anticholinergic for treating respiratory disorders |
US20050026948A1 (en) | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a betamimetic |
US20050026886A1 (en) | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a PDE IV inhibitor |
US20050026887A1 (en) | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a steroid |
JP2007500676A (ja) | 2003-07-31 | 2007-01-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗コリン作用薬とベータ受容体刺激薬を含む吸入用薬剤 |
US20050025718A1 (en) | 2003-07-31 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a betamimetic |
DE10347994A1 (de) | 2003-10-15 | 2005-06-16 | Pari GmbH Spezialisten für effektive Inhalation | Wässrige Aerosol-Zubereitung |
ES2232306B1 (es) | 2003-11-10 | 2006-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
PT1713473E (pt) | 2004-02-06 | 2013-05-13 | Meda Pharma Gmbh & Co Kg | Combinação de anticolinérgicos e glucocorticóides para o tratamento a longo prazo de asma e copd |
RU2438660C2 (ru) | 2004-02-06 | 2012-01-10 | Меда Фарма Гмбх Унд Ко. Кг | Комбинация и фармацевтический препарат для лечения воспалительных и обструктивных заболеваний дыхательных путей |
SI1713471T1 (sl) | 2004-02-06 | 2012-07-31 | Meda Pharma Gmbh & Co Kg | Kombinacija antiholinergikov in inhibitorjev fosfodiesteraze tipa za zdravljenje respiratornih bolezni |
US7712077B2 (en) * | 2004-02-27 | 2010-05-04 | International Business Machines Corporation | Method and system for instantiating components conforming to the “COM” specification in custom contexts |
ES2239546B1 (es) | 2004-03-15 | 2006-12-01 | Almirall Prodesfarma, S.A. | Nuevos esteres de quinuclidina cuaternizados. |
DE102004016179A1 (de) | 2004-03-30 | 2005-10-20 | Boehringer Ingelheim Pharma | Verbindungen zur Behandlung von proliferativen Prozessen |
ES2257152B1 (es) | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos. |
SI1905451T1 (sl) | 2004-05-31 | 2010-05-31 | Almirall Sa | Kombinacije ki obsegajo antimuskarinska sredstvain kortikosteroide |
WO2006105401A2 (en) | 2005-03-30 | 2006-10-05 | Schering Corporation | Medicaments and methods combining an anticholinergic, a corticosteroid, and a long acting beta agonist |
ES2298049B1 (es) | 2006-07-21 | 2009-10-20 | Laboratorios Almirall S.A. | Procedimiento para fabricar bromuro de 3(r)-(2-hidroxi-2,2-ditien-2-ilacetoxi)-1-(3-fenoxipropil)-1-azoniabiciclo (2.2.2) octano. |
GB0702457D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | New combination 666 |
WO2008102128A2 (en) | 2007-02-19 | 2008-08-28 | Cipla Limited | Pharmaceutical combinations of at least two bronchodilators or of a bronchodilator with a corticosteroid |
NZ578473A (en) | 2007-02-21 | 2011-10-28 | Almirall Sa | Aclinidium for use in respiratory disease |
CN101688789B (zh) | 2007-07-03 | 2011-08-03 | Nxp股份有限公司 | 传感器系统 |
EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
EP2666465A1 (en) | 2012-05-25 | 2013-11-27 | Almirall, S.A. | Novel dosage and formulation |
ES2917879T3 (es) | 2012-12-17 | 2022-07-12 | Almirall Sa | Nuevo uso de aclidinio |
-
1999
- 1999-07-14 ES ES009901580A patent/ES2165768B1/es not_active Expired - Fee Related
-
2000
- 2000-07-07 IL IL14753300A patent/IL147533A0/xx active Protection Beyond IP Right Term
- 2000-07-07 AT AT00951361T patent/ATE235492T1/de active
- 2000-07-07 DK DK00951361.5T patent/DK1200431T6/en active
- 2000-07-07 JP JP2001509727A patent/JP4030040B2/ja not_active Expired - Lifetime
- 2000-07-07 CA CA2381165A patent/CA2381165C/en not_active Expired - Lifetime
- 2000-07-07 KR KR1020027000479A patent/KR100773844B1/ko not_active IP Right Cessation
- 2000-07-07 EP EP00951361.5A patent/EP1200431B3/en not_active Expired - Lifetime
- 2000-07-07 TR TR2002/00768T patent/TR200200768T2/xx unknown
- 2000-07-07 CN CNB2006100068921A patent/CN100451018C/zh not_active Expired - Lifetime
- 2000-07-07 RU RU2002103605A patent/RU2264401C3/ru active Protection Beyond IP Right Term
- 2000-07-07 CN CNB008127549A patent/CN1272334C/zh not_active Expired - Lifetime
- 2000-07-07 EE EEP200200017A patent/EE04915B3/et active Protection Beyond IP Right Term
- 2000-07-07 KR KR1020067027730A patent/KR100854315B1/ko active Protection Beyond IP Right Term
- 2000-07-07 DE DE60001840A patent/DE60001840D1/de not_active Expired - Lifetime
- 2000-07-07 UA UA2002010323A patent/UA73509C2/uk unknown
- 2000-07-07 PL PL357160A patent/PL204024B1/pl not_active IP Right Cessation
- 2000-07-07 PT PT00951361T patent/PT1200431E/pt unknown
- 2000-07-07 ES ES951361T patent/ES2193098T7/es active Active
- 2000-07-07 CZ CZ2002-121A patent/CZ304292B6/cs unknown
- 2000-07-07 BR BRPI0012434A patent/BRPI0012434B8/pt not_active IP Right Cessation
- 2000-07-07 SK SK43-2002A patent/SK287480B6/sk not_active IP Right Cessation
- 2000-07-07 SI SI200030108T patent/SI1200431T1/xx unknown
- 2000-07-07 HU HU0202100A patent/HU228594B1/hu active Protection Beyond IP Right Term
- 2000-07-07 DE DE60001840.7T patent/DE60001840T4/de not_active Expired - Lifetime
- 2000-07-07 KR KR1020067027733A patent/KR100854321B1/ko not_active IP Right Cessation
- 2000-07-07 WO PCT/EP2000/006469 patent/WO2001004118A2/en active IP Right Grant
- 2000-07-11 PE PE2000000691A patent/PE20010397A1/es not_active IP Right Cessation
- 2000-07-12 TW TW089113865A patent/TWI284644B/zh active
- 2000-07-12 EG EG20000907A patent/EG24066A/xx active
- 2000-07-12 MY MYPI20003178 patent/MY126959A/en unknown
- 2000-07-13 AR ARP000103613A patent/AR029760A1/es active IP Right Grant
- 2000-07-13 CO CO00052873A patent/CO5200759A1/es active IP Right Grant
- 2000-07-14 UY UY26244A patent/UY26244A1/es unknown
-
2002
- 2002-01-10 ZA ZA200200232A patent/ZA200200232B/xx unknown
- 2002-01-14 BG BG106301A patent/BG65565B1/bg unknown
- 2002-01-14 US US10/047,464 patent/US6750226B2/en not_active Expired - Lifetime
- 2002-01-14 NO NO20020180A patent/NO329484B3/no not_active IP Right Cessation
- 2002-05-29 HK HK02103992A patent/HK1042487B/xx not_active IP Right Cessation
-
2003
- 2003-12-17 US US10/740,264 patent/US7109210B2/en not_active Expired - Fee Related
-
2005
- 2005-04-28 US US11/116,777 patent/US7078412B2/en not_active Expired - Lifetime
- 2005-05-18 AU AU2005202144A patent/AU2005202144B2/en active Active
- 2005-07-06 RU RU2005121162/04A patent/RU2306312C2/ru active
- 2005-07-12 JP JP2005203365A patent/JP4951217B2/ja not_active Expired - Fee Related
-
2006
- 2006-01-03 US US11/325,059 patent/US7196098B2/en not_active Expired - Lifetime
- 2006-12-08 US US11/636,181 patent/US7358260B2/en not_active Expired - Fee Related
-
2008
- 2008-03-07 US US12/074,929 patent/US7750023B2/en not_active Expired - Fee Related
-
2010
- 2010-05-26 US US12/787,772 patent/US7897617B2/en not_active Expired - Fee Related
-
2011
- 2011-01-21 US US13/011,131 patent/US8129405B2/en not_active Expired - Fee Related
- 2011-07-08 UY UY0001033494A patent/UY33494A/es not_active Application Discontinuation
-
2012
- 2012-01-20 US US13/354,873 patent/US8513279B2/en not_active Expired - Fee Related
-
2013
- 2013-01-03 BE BE2013C001C patent/BE2013C001I2/fr unknown
- 2013-01-07 CY CY2013001C patent/CY2013001I1/el unknown
- 2013-01-08 FR FR13C0001C patent/FR13C0001I2/fr active Active
- 2013-01-16 LU LU92132C patent/LU92132I2/fr unknown
- 2013-01-18 NO NO2013002C patent/NO2013002I2/no unknown
- 2013-07-11 US US13/939,742 patent/US8802699B2/en not_active Expired - Fee Related
-
2014
- 2014-06-20 US US14/311,102 patent/US9056100B2/en not_active Expired - Fee Related
-
2015
- 2015-05-14 US US14/712,866 patent/US9333195B2/en not_active Expired - Fee Related
-
2016
- 2016-02-09 US US15/019,009 patent/USRE46417E1/en active Active
- 2016-04-09 US US15/095,036 patent/US9687478B2/en not_active Expired - Fee Related
-
2017
- 2017-05-19 US US15/599,646 patent/US10034867B2/en not_active Expired - Fee Related
-
2018
- 2018-07-25 US US16/045,333 patent/US10588895B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4030040B2 (ja) | キヌクリジン誘導体およびそれらのムスカリンm3レセプターリガンドとしての使用 | |
US20060106055A1 (en) | Novel quinuclidine derivatives and medicinal compositions containing the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050222 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050318 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20050519 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20050519 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20050520 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20050519 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050712 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20070403 |
|
A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20070522 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070529 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070829 |
|
TRDD | Decision of grant or rejection written | ||
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20070829 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20071002 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20071012 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4030040 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101026 Year of fee payment: 3 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101026 Year of fee payment: 3 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101026 Year of fee payment: 3 |
|
S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101026 Year of fee payment: 3 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111026 Year of fee payment: 4 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111026 Year of fee payment: 4 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121026 Year of fee payment: 5 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121026 Year of fee payment: 5 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131026 Year of fee payment: 6 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R153 | Grant of patent term extension |
Free format text: JAPANESE INTERMEDIATE CODE: R153 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |