ZA200402060B - Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors. - Google Patents
Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors. Download PDFInfo
- Publication number
- ZA200402060B ZA200402060B ZA200402060A ZA200402060A ZA200402060B ZA 200402060 B ZA200402060 B ZA 200402060B ZA 200402060 A ZA200402060 A ZA 200402060A ZA 200402060 A ZA200402060 A ZA 200402060A ZA 200402060 B ZA200402060 B ZA 200402060B
- Authority
- ZA
- South Africa
- Prior art keywords
- methoxy
- oct
- azabicyclo
- propyn
- phenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 22
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 title description 5
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title description 2
- 150000008584 quinuclidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 99
- -1 cyano, hydroxy Chemical group 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 20
- 229910000085 borane Inorganic materials 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 238000003786 synthesis reaction Methods 0.000 claims description 17
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 239000000543 intermediate Substances 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- LPUCHTNHUHOTRY-UHFFFAOYSA-N 1-(3-bicyclo[2.2.1]heptanyl)ethanamine Chemical compound C1CC2C(C(N)C)CC1C2 LPUCHTNHUHOTRY-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 208000026723 Urinary tract disease Diseases 0.000 claims description 3
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 230000019771 cognition Effects 0.000 claims description 3
- 230000004064 dysfunction Effects 0.000 claims description 3
- 230000035611 feeding Effects 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 230000033001 locomotion Effects 0.000 claims description 3
- 230000007257 malfunction Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000033764 rhythmic process Effects 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 208000014001 urinary system disease Diseases 0.000 claims description 3
- RTMQZXMBCBMCJK-ZMFCMNQTSA-N 1-(2-fluoropyridin-3-yl)-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenylprop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C(=NC=CC=1)F)C1=CC=CC=C1 RTMQZXMBCBMCJK-ZMFCMNQTSA-N 0.000 claims description 2
- DVSLSPWSCJLOGG-BPGUCPLFSA-N 1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylhept-1-yn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(CCCC)C1=CC=CC=C1 DVSLSPWSCJLOGG-BPGUCPLFSA-N 0.000 claims description 2
- XTZFWAQEYOYZPT-GFOWMXPYSA-N 1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-5,5-dimethyl-3-thiophen-2-ylhex-1-yn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(CC(C)(C)C)C1=CC=CS1 XTZFWAQEYOYZPT-GFOWMXPYSA-N 0.000 claims description 2
- YQDAZCGHMNYZMU-WTQRLHSKSA-N 1-cycloheptyl-1-(2-fluoropyridin-3-yl)-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]prop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C(=NC=CC=1)F)C1CCCCCC1 YQDAZCGHMNYZMU-WTQRLHSKSA-N 0.000 claims description 2
- VBKBVALDNMYEBZ-UHFFFAOYSA-N 1-cyclohexyl-3-(3-methoxy-1-azabicyclo[2.2.2]octan-3-yl)-1-phenylprop-2-yn-1-ol Chemical compound C1N(CC2)CCC2C1(OC)C#CC(O)(C=1C=CC=CC=1)C1CCCCC1 VBKBVALDNMYEBZ-UHFFFAOYSA-N 0.000 claims description 2
- KGGLWTNSVNKIRD-VQCQRNETSA-N 3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenyl-1-pyrimidin-5-ylprop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C=NC=NC=1)C1=CC=CC=C1 KGGLWTNSVNKIRD-VQCQRNETSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 claims description 2
- 206010029279 Neurogenic bladder Diseases 0.000 claims description 2
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 2
- 206010036018 Pollakiuria Diseases 0.000 claims description 2
- 208000029162 bladder disease Diseases 0.000 claims description 2
- 201000003146 cystitis Diseases 0.000 claims description 2
- 230000001272 neurogenic effect Effects 0.000 claims description 2
- 208000020629 overactive bladder Diseases 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- OIVUQKJVYIDTLN-DNQXCXABSA-N (1r)-1-cycloheptyl-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenylprop-2-yn-1-ol Chemical compound C1([C@](O)(C#C[C@@]2(C3CCN(CC3)C2)OC)C=2C=CC=CC=2)CCCCCC1 OIVUQKJVYIDTLN-DNQXCXABSA-N 0.000 claims 1
- VBKBVALDNMYEBZ-PKTZIBPZSA-N (1r)-1-cyclohexyl-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenylprop-2-yn-1-ol Chemical compound C1([C@](O)(C#C[C@@]2(C3CCN(CC3)C2)OC)C=2C=CC=CC=2)CCCCC1 VBKBVALDNMYEBZ-PKTZIBPZSA-N 0.000 claims 1
- YVSSRNVDYCUSLE-WTQRLHSKSA-N (3r)-3-(3-cyclohexyl-3-fluoro-3-phenylprop-1-ynyl)-3-methoxy-1-azabicyclo[2.2.2]octane Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(F)(C=1C=CC=CC=1)C1CCCCC1 YVSSRNVDYCUSLE-WTQRLHSKSA-N 0.000 claims 1
- LTFTWJYRQNTCHI-UHFFFAOYSA-N -1-Hexyn-3-ol Natural products CCCC(O)C#C LTFTWJYRQNTCHI-UHFFFAOYSA-N 0.000 claims 1
- ROGNPHYAHLESSZ-FOIFJWKZSA-N 1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-3-phenyloct-1-yn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(CCCCC)C1=CC=CC=C1 ROGNPHYAHLESSZ-FOIFJWKZSA-N 0.000 claims 1
- WUMIJQZPHGJALC-UHFFFAOYSA-N 3-(3-methoxy-1-azabicyclo[2.2.2]octan-3-yl)-1,1-diphenylprop-2-yn-1-ol Chemical compound C1N(CC2)CCC2C1(OC)C#CC(O)(C=1C=CC=CC=1)C1=CC=CC=C1 WUMIJQZPHGJALC-UHFFFAOYSA-N 0.000 claims 1
- 241000006460 Cyana Species 0.000 claims 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- 125000006267 biphenyl group Chemical group 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 15
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 6
- 125000003396 thiol group Chemical class [H]S* 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- 125000003368 amide group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000013375 chromatographic separation Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical class C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- FDDUSKQHAMLTFD-UHFFFAOYSA-N 3-(3,3-diphenylbut-1-ynyl)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1N(CC2)CCC2C1(O)C#CC(C)(C=1C=CC=CC=1)C1=CC=CC=C1 FDDUSKQHAMLTFD-UHFFFAOYSA-N 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000036983 biotransformation Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 238000010511 deprotection reaction Methods 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- FWLKYEAOOIPJRL-UHFFFAOYSA-N prop-1-yn-1-ol Chemical compound CC#CO FWLKYEAOOIPJRL-UHFFFAOYSA-N 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- IQLLFLWYARVSRO-UHFFFAOYSA-N (1-methylsulfonylpiperidin-4-yl)-phenylmethanone Chemical compound C1CN(S(=O)(=O)C)CCC1C(=O)C1=CC=CC=C1 IQLLFLWYARVSRO-UHFFFAOYSA-N 0.000 description 1
- ZGBSEJYQXDWFRF-YADHBBJMSA-N (1r)-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenyl-1-pyridin-3-ylprop-2-yn-1-ol Chemical compound C1([C@@](O)(C#C[C@@]2(C3CCN(CC3)C2)OC)C=2C=NC=CC=2)=CC=CC=C1 ZGBSEJYQXDWFRF-YADHBBJMSA-N 0.000 description 1
- YJBHJKVXJQIMAC-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxan-5-yl)-phenylmethanone Chemical compound C1OC(C)(C)OCC1C(=O)C1=CC=CC=C1 YJBHJKVXJQIMAC-UHFFFAOYSA-N 0.000 description 1
- ITZVOIDWSIZQDH-UHFFFAOYSA-N (3-ethynyl-1-azabicyclo[2.2.2]octan-3-yl) acetate Chemical compound C1CC2C(OC(=O)C)(C#C)CN1CC2 ITZVOIDWSIZQDH-UHFFFAOYSA-N 0.000 description 1
- VQAUUYLFOFGJQS-LLVKDONJSA-N (3r)-3-ethoxy-3-ethynyl-1-azabicyclo[2.2.2]octane Chemical compound C1CC2[C@@](OCC)(C#C)CN1CC2 VQAUUYLFOFGJQS-LLVKDONJSA-N 0.000 description 1
- FHLOPMBXJJTAFW-SNVBAGLBSA-N (3r)-3-ethynyl-3-methoxy-1-azabicyclo[2.2.2]octane Chemical compound C1CC2[C@@](OC)(C#C)CN1CC2 FHLOPMBXJJTAFW-SNVBAGLBSA-N 0.000 description 1
- IDXWWAQGKJJZJB-MRXNPFEDSA-N (3r)-3-ethynyl-3-phenylmethoxy-1-azabicyclo[2.2.2]octane Chemical compound O([C@]1(C2CCN(CC2)C1)C#C)CC1=CC=CC=C1 IDXWWAQGKJJZJB-MRXNPFEDSA-N 0.000 description 1
- BXVNSQLOFLRZOI-UHFFFAOYSA-N (4-fluorophenyl)-(2-fluoropyridin-3-yl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=CN=C1F BXVNSQLOFLRZOI-UHFFFAOYSA-N 0.000 description 1
- WNEVRSJPSKDNJK-UHFFFAOYSA-N (5-chlorothiophen-2-yl)-pyridin-2-ylmethanone Chemical compound S1C(Cl)=CC=C1C(=O)C1=CC=CC=N1 WNEVRSJPSKDNJK-UHFFFAOYSA-N 0.000 description 1
- ZAZCXXBTDSZITA-UHFFFAOYSA-N (6-fluoropyridin-3-yl)-phenylmethanone Chemical compound C1=NC(F)=CC=C1C(=O)C1=CC=CC=C1 ZAZCXXBTDSZITA-UHFFFAOYSA-N 0.000 description 1
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- SLYGFLPIVMPYBY-ZMFCMNQTSA-N 1-(4-fluorophenyl)-1-(6-fluoropyridin-3-yl)-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]prop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C=NC(F)=CC=1)C1=CC=C(F)C=C1 SLYGFLPIVMPYBY-ZMFCMNQTSA-N 0.000 description 1
- FJXLZNSVOSVTPH-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-2-one Chemical compound C1CN2C(=O)CC1CC2 FJXLZNSVOSVTPH-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- MTAUYQIIHXMBJZ-VQCQRNETSA-N 1-cyclobutyl-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenylprop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C=CC=CC=1)C1CCC1 MTAUYQIIHXMBJZ-VQCQRNETSA-N 0.000 description 1
- OIVUQKJVYIDTLN-MIHMCVIASA-N 1-cycloheptyl-3-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1-phenylprop-2-yn-1-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1C=CC=CC=1)C1CCCCCC1 OIVUQKJVYIDTLN-MIHMCVIASA-N 0.000 description 1
- IALPDUYLUXQPFV-UHFFFAOYSA-N 1-cycloheptyl-3-trimethylsilylprop-2-yn-1-one Chemical compound C[Si](C)(C)C#CC(=O)C1CCCCCC1 IALPDUYLUXQPFV-UHFFFAOYSA-N 0.000 description 1
- ZKLDXQNWYGDYPW-UHFFFAOYSA-N 1-cyclohexyl-3-(3-fluoro-1-azabicyclo[2.2.2]octan-3-yl)-1-phenylprop-2-yn-1-ol Chemical compound C1N(CC2)CCC2C1(F)C#CC(O)(C=1C=CC=CC=1)C1CCCCC1 ZKLDXQNWYGDYPW-UHFFFAOYSA-N 0.000 description 1
- MAQUXXCSNFMDJZ-BPGUCPLFSA-N 1-cyclopentyl-4-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-2-thiophen-2-ylbut-3-yn-2-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C=1SC=CC=1)CC1CCCC1 MAQUXXCSNFMDJZ-BPGUCPLFSA-N 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 0.000 description 1
- 125000006055 1-methyl-4-pentenyl group Chemical group 0.000 description 1
- 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- AHMVRMJZWFHRKP-UHFFFAOYSA-N 2,2-diphenylbut-3-ynenitrile Chemical compound C=1C=CC=CC=1C(C#N)(C#C)C1=CC=CC=C1 AHMVRMJZWFHRKP-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- ISSJSIPEFNADGV-UHFFFAOYSA-N 2-cyclopentyl-1-thiophen-2-ylethanone Chemical compound C=1C=CSC=1C(=O)CC1CCCC1 ISSJSIPEFNADGV-UHFFFAOYSA-N 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 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 1
- KJPQMLQHYWZYKW-UHFFFAOYSA-N 3,4-dibromo-2,2-diphenylbutanenitrile Chemical compound C=1C=CC=CC=1C(C#N)(C(Br)CBr)C1=CC=CC=C1 KJPQMLQHYWZYKW-UHFFFAOYSA-N 0.000 description 1
- AIDJUBJDYKFNRW-UHFFFAOYSA-N 3,5,5-trimethyl-1-thiophen-2-ylhexan-1-one Chemical compound CC(C)(C)CC(C)CC(=O)C1=CC=CS1 AIDJUBJDYKFNRW-UHFFFAOYSA-N 0.000 description 1
- JZBPAABWDQDOMS-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.2]octan-3-yl)-1,1-diphenylprop-2-yn-1-ol Chemical compound C1N(CC2)CCC2C1C#CC(O)(C=1C=CC=CC=1)C1=CC=CC=C1 JZBPAABWDQDOMS-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
- IUFMSNOFDSOXRE-OZAIVSQSSA-N 3-cycloheptyl-1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-5-trimethylsilylpenta-1,4-diyn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C#C[Si](C)(C)C)C1CCCCCC1 IUFMSNOFDSOXRE-OZAIVSQSSA-N 0.000 description 1
- IXRHDIWQVSTHFW-UHFFFAOYSA-N 3-ethynyl-3-fluoro-1-azabicyclo[2.2.2]octane Chemical compound C1CC2C(F)(C#C)CN1CC2 IXRHDIWQVSTHFW-UHFFFAOYSA-N 0.000 description 1
- 125000006046 3-methyl-1-pentenyl group Chemical group 0.000 description 1
- XTIXFYYUEQNZTQ-UHFFFAOYSA-N 4-(3-hydroxy-1-azabicyclo[2.2.2]octan-3-yl)-2,2-diphenylbut-3-ynenitrile Chemical compound C1N(CC2)CCC2C1(O)C#CC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 XTIXFYYUEQNZTQ-UHFFFAOYSA-N 0.000 description 1
- AKZBLJKZHURCTC-ZMFCMNQTSA-N 4-ethyl-1-[(3r)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylhex-1-yn-3-ol Chemical compound C([C@@]1(C2CCN(CC2)C1)OC)#CC(O)(C(CC)CC)C1=CC=CC=C1 AKZBLJKZHURCTC-ZMFCMNQTSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- XIQVNETUBQGFHX-UHFFFAOYSA-N Ditropan Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCC#CCN(CC)CC)C1CCCCC1 XIQVNETUBQGFHX-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010052402 Gastrointestinal hypermotility Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010029458 Nodal arrhythmia Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010040741 Sinus bradycardia Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- ITZVOIDWSIZQDH-LLVKDONJSA-N [(3r)-3-ethynyl-1-azabicyclo[2.2.2]octan-3-yl] acetate Chemical compound C1CC2[C@@](OC(=O)C)(C#C)CN1CC2 ITZVOIDWSIZQDH-LLVKDONJSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000006323 alkenyl amino group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000005136 alkenylsulfinyl group Chemical group 0.000 description 1
- 125000005137 alkenylsulfonyl group Chemical group 0.000 description 1
- 125000005108 alkenylthio group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000006319 alkynyl amino group Chemical group 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 125000005134 alkynylsulfinyl group Chemical group 0.000 description 1
- 125000005139 alkynylsulfonyl group Chemical group 0.000 description 1
- 125000005109 alkynylthio group Chemical group 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 206010006451 bronchitis Diseases 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
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- VZSXFJPZOCRDPW-UHFFFAOYSA-N carbanide;trioxorhenium Chemical compound [CH3-].O=[Re](=O)=O VZSXFJPZOCRDPW-UHFFFAOYSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 125000002946 cyanobenzyl group Chemical group 0.000 description 1
- JUFVVUQDXNEDAV-UHFFFAOYSA-N cyclobutyl(pyridin-2-yl)methanone Chemical compound C=1C=CC=NC=1C(=O)C1CCC1 JUFVVUQDXNEDAV-UHFFFAOYSA-N 0.000 description 1
- MTERFNLZFBTPMM-UHFFFAOYSA-N cyclohept-4-en-1-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1CCC=CCC1 MTERFNLZFBTPMM-UHFFFAOYSA-N 0.000 description 1
- VPQBBXIDNIZJLP-UHFFFAOYSA-N cycloheptyl(pyridin-3-yl)methanone Chemical compound C=1C=CN=CC=1C(=O)C1CCCCCC1 VPQBBXIDNIZJLP-UHFFFAOYSA-N 0.000 description 1
- ZHZGVOGFAHAODV-UHFFFAOYSA-N cycloheptyl(pyrimidin-5-yl)methanone Chemical compound C=1N=CN=CC=1C(=O)C1CCCCCC1 ZHZGVOGFAHAODV-UHFFFAOYSA-N 0.000 description 1
- QVHSYDSOMSIYSV-UHFFFAOYSA-N cycloheptyl(thiophen-2-yl)methanone Chemical compound C=1C=CSC=1C(=O)C1CCCCCC1 QVHSYDSOMSIYSV-UHFFFAOYSA-N 0.000 description 1
- HRHWFVYTHBOJHN-UHFFFAOYSA-N cycloheptyl-(1-methylpyrrol-2-yl)methanone Chemical compound CN1C=CC=C1C(=O)C1CCCCCC1 HRHWFVYTHBOJHN-UHFFFAOYSA-N 0.000 description 1
- GIBQKCNYJDHRKY-UHFFFAOYSA-N cycloheptyl-(2-fluoropyridin-3-yl)methanone Chemical compound FC1=NC=CC=C1C(=O)C1CCCCCC1 GIBQKCNYJDHRKY-UHFFFAOYSA-N 0.000 description 1
- NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 208000007784 diverticulitis Diseases 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000004031 fumaroyl group Chemical group C(\C=C\C(=O)*)(=O)* 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000006277 halobenzyl group Chemical group 0.000 description 1
- 125000004470 heterocyclooxy group Chemical group 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical class C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 208000018936 intestinal hypermotility Diseases 0.000 description 1
- 230000037036 intestinal hypermotility Effects 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- 230000003551 muscarinic effect Effects 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
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 125000003355 oxamoyl group Chemical group C(C(=O)N)(=O)* 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 229960005434 oxybutynin Drugs 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- BOYNGGAGOZVINO-UHFFFAOYSA-N phenyl(8-thiabicyclo[3.2.1]octan-3-yl)methanone Chemical compound C1C(S2)CCC2CC1C(=O)C1=CC=CC=C1 BOYNGGAGOZVINO-UHFFFAOYSA-N 0.000 description 1
- UEOGIEBMJRBYIC-UHFFFAOYSA-N phenyl(thian-4-yl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1CCSCC1 UEOGIEBMJRBYIC-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- WJXREUZUPGMAII-UHFFFAOYSA-N sulfurazidic acid Chemical compound OS(=O)(=O)N=[N+]=[N-] WJXREUZUPGMAII-UHFFFAOYSA-N 0.000 description 1
- ITLCXSHKUNNAHG-UHFFFAOYSA-N tert-butyl 4-benzoylpiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)C1=CC=CC=C1 ITLCXSHKUNNAHG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 1
- 229960004045 tolterodine Drugs 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01124727 | 2001-10-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200402060B true ZA200402060B (en) | 2005-03-15 |
Family
ID=8178984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200402060A ZA200402060B (en) | 2001-10-17 | 2004-03-15 | Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7361668B2 (fr) |
| EP (1) | EP1438309A1 (fr) |
| JP (1) | JP2005512974A (fr) |
| KR (1) | KR20050030169A (fr) |
| CN (1) | CN1571787A (fr) |
| BG (1) | BG108683A (fr) |
| BR (1) | BR0212983A (fr) |
| CA (1) | CA2462980A1 (fr) |
| CZ (1) | CZ2004501A3 (fr) |
| HU (1) | HUP0401849A3 (fr) |
| IL (1) | IL160896A0 (fr) |
| IS (1) | IS7186A (fr) |
| MX (1) | MXPA04002983A (fr) |
| NO (1) | NO20042023L (fr) |
| NZ (1) | NZ532283A (fr) |
| PL (1) | PL370087A1 (fr) |
| RU (1) | RU2004110717A (fr) |
| WO (1) | WO2003033495A1 (fr) |
| ZA (1) | ZA200402060B (fr) |
Families Citing this family (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL160896A0 (en) * | 2001-10-17 | 2004-08-31 | Ucb Sa | Quinuclidine derivatives, processes for preparing them and their uses as m2 and/or m3 muscarinic receptor inhibitors |
| DE60322212D1 (de) | 2002-05-07 | 2008-08-28 | Neurosearch As | Neue azacyclische ethinylderivate |
| JP2006502985A (ja) | 2002-07-08 | 2006-01-26 | ランバクシー ラボラトリーズ リミテッド | ムスカリン性受容体拮抗剤として有用な３，６−二置換アザビシクロ［３．１．０］ヘキサン誘導体 |
| WO2004089898A1 (fr) | 2003-04-09 | 2004-10-21 | Ranbaxy Laboratories Limited | Derives d'azabicyclo hexane substitues en tant qu'antagonistes de recepteurs muscariniques |
| NZ542952A (en) | 2003-04-11 | 2008-11-28 | Ranbaxy Lab Ltd | Azabicyclo derivatives as muscarinic receptor antagonists |
| TW200519106A (en) | 2003-05-02 | 2005-06-16 | Novartis Ag | Organic compounds |
| PE20050250A1 (es) * | 2003-07-17 | 2005-04-08 | Glaxo Group Ltd | Antagonistas de los receptores muscarinicos de la acetilcolina |
| TW200519109A (en) * | 2003-07-17 | 2005-06-16 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| UY28417A1 (es) * | 2003-07-17 | 2005-02-28 | Glaxo Group Ltd | Antagonistas de los receptores muscarinicos de la acetilcolina |
| 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 |
| AR046114A1 (es) * | 2003-10-17 | 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 |
| TW200524577A (en) * | 2003-11-04 | 2005-08-01 | Glaxo Group Ltd | Muscarinic acetylcholine receptor antagonists |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| JP2007528420A (ja) * | 2004-03-11 | 2007-10-11 | グラクソ グループ リミテッド | 新規ｍ３ムスカリン性アセチルコリン受容体アンタゴニスト |
| ES2239546B1 (es) * | 2004-03-15 | 2006-12-01 | Almirall Prodesfarma, S.A. | Nuevos esteres de quinuclidina cuaternizados. |
| UY28871A1 (es) | 2004-04-27 | 2005-11-30 | Glaxo Group Ltd | Antagonistas del receptor de acetilcolina muscarinico |
| EP1747219A4 (fr) * | 2004-05-13 | 2010-05-26 | Glaxo Group Ltd | Domaine de l'invention antagonistes récepteurs d'acétyle choline muscarinique |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| JP2009503101A (ja) * | 2005-08-02 | 2009-01-29 | 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 |
| JP2009503099A (ja) * | 2005-08-02 | 2009-01-29 | 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 |
| 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 |
| EP2532679B1 (fr) | 2005-10-21 | 2017-04-12 | Novartis AG | Anticorps humains dirigés contre l'IL -13 et utilisations thérapeutiques |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| SI2013211T1 (sl) | 2006-04-21 | 2012-07-31 | Novartis Ag | Purinski derivati za uporabo kot agonisti receptorja adenozina A A |
| CN101516885A (zh) | 2006-09-29 | 2009-08-26 | 诺瓦提斯公司 | 作为pi3k脂质激酶抑制剂的吡唑并嘧啶类化合物 |
| 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 |
| PT2104535E (pt) | 2007-01-10 | 2011-03-31 | Irm Llc | Compostos e composições como inibidores da protease de activação de canal |
| WO2008096094A1 (fr) * | 2007-02-06 | 2008-08-14 | Argenta Discovery Ltd. | Dérivés de bicyclor[2.2.1]hept-7-ylamine utile comme modulateur du récepteur m3 muscarinique |
| CA2682994A1 (fr) * | 2007-04-24 | 2008-10-30 | Solvay Pharmaceuticals B.V. | Composes heterocycliques presentant une affinite pour les recepteurs muscariniques |
| BRPI0811562A2 (pt) | 2007-05-07 | 2014-12-09 | Novartis Ag | Compostos orgânicos |
| ES2602331T3 (es) | 2007-12-10 | 2017-02-20 | Novartis Ag | Pirazin-carboxamidas de tipo amilorida como bloqueantes de ENaC |
| EA201001129A1 (ru) | 2008-01-11 | 2011-02-28 | Новартис Аг | Пиримидины в качестве ингибиторов киназы |
| US8268834B2 (en) | 2008-03-19 | 2012-09-18 | Novartis Ag | Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme |
| US20110294835A1 (en) | 2008-05-15 | 2011-12-01 | The Board Of Trustees Of The University Of Illinois | Muscarinic Agonists as Cognitive Enhancers |
| ES2535736T3 (es) | 2008-06-10 | 2015-05-14 | Novartis Ag | Derivados de pirazina como bloqueadores de los canales de sodio epitelial |
| WO2009152392A2 (fr) * | 2008-06-11 | 2009-12-17 | University Of Toledo | Agonistes muscariniques pour troubles neurologiques et procédés pour les préparer |
| ES2396023T3 (es) | 2009-01-29 | 2013-02-18 | Novartis Ag | Bencimidazoles sustituidos para el tratamiento de astrocitomas |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| MX2012001838A (es) | 2009-08-12 | 2012-02-29 | Novartis Ag | Compuestos de hidrazona heterociclico y sus usos para tratar cancer e inflamacion. |
| AU2010284254B2 (en) | 2009-08-17 | 2015-09-17 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
| JP5775871B2 (ja) | 2009-08-20 | 2015-09-09 | ノバルティス アーゲー | ヘテロ環式オキシム化合物 |
| US20110098311A1 (en) | 2009-10-22 | 2011-04-28 | Vertex Pharmaceuticals Incorported | Compositions for treatment of cystic fibrosis and other chronic diseases |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| WO2012034095A1 (fr) | 2010-09-09 | 2012-03-15 | Irm Llc | Composés et compositions comme inhibiteurs de trk |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| JP2014505088A (ja) | 2011-02-10 | 2014-02-27 | ノバルティス アーゲー | Ｃ−ＭＥＴチロシンキナーゼ阻害剤としての［１，２，４］トリアゾロ［４，３−ｂ］ピリダジン化合物 |
| WO2012116237A2 (fr) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Composés hétérocycliques et leurs utilisations |
| CN103492384B (zh) | 2011-02-25 | 2016-05-11 | 诺华股份有限公司 | 作为trk抑制剂的化合物和组合物 |
| WO2012149524A1 (fr) | 2011-04-29 | 2012-11-01 | The University Of Toledo | Agonistes muscariniques en tant qu'agents d'amélioration de la mémoire de travail et de la flexibilité cognitive |
| US8883819B2 (en) | 2011-09-01 | 2014-11-11 | Irm Llc | Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension |
| BR112014006223A8 (pt) | 2011-09-15 | 2018-01-09 | Novartis Ag | 3-(quinolin-6-iltio)-[1,2,4-triazol[4,3-a] piradinas 6-substituídas, seus usos, composições farmacêuticas, e combinação |
| JP5886433B2 (ja) | 2011-09-16 | 2016-03-16 | ノバルティス アーゲー | 嚢胞性線維症処置のためのヘテロ環式化合物 |
| JP6165733B2 (ja) | 2011-09-16 | 2017-07-19 | ノバルティス アーゲー | Ｎ−置換ヘテロシクリルカルボキサミド類 |
| WO2013038381A1 (fr) | 2011-09-16 | 2013-03-21 | Novartis Ag | Dérivés d'amide pyridine/pyrazine |
| WO2013038378A1 (fr) | 2011-09-16 | 2013-03-21 | Novartis Ag | Dérivés pyridinamides |
| WO2013038373A1 (fr) | 2011-09-16 | 2013-03-21 | Novartis Ag | Dérivés pyrimidinamides |
| US20130209543A1 (en) | 2011-11-23 | 2013-08-15 | Intellikine Llc | Enhanced treatment regimens using mtor inhibitors |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| CN104245701A (zh) | 2012-04-03 | 2014-12-24 | 诺华有限公司 | 有酪氨酸激酶抑制剂的组合产品和其应用 |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| EP2968340A4 (fr) | 2013-03-15 | 2016-08-10 | Intellikine Llc | Combinaison d'inhibiteurs de kinase et ses utilisations |
| 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 |
| US10112926B2 (en) | 2014-04-24 | 2018-10-30 | Novartis Ag | Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors |
| EP3134395B1 (fr) | 2014-04-24 | 2018-01-31 | Novartis AG | Dérivés de pyrazine utilisables en tant qu'inhibiteurs de la phosphatidylinositol 3-kinase |
| AU2014391608A1 (en) | 2014-04-24 | 2016-10-27 | Novartis Ag | Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| WO2016011658A1 (fr) | 2014-07-25 | 2016-01-28 | Novartis Ag | Polythérapie |
| CA2954862A1 (fr) | 2014-07-31 | 2016-02-04 | Novartis Ag | Polytherapie |
| CN106518840B (zh) * | 2016-11-17 | 2019-03-01 | 山东铂源药业有限公司 | 一种2-氯噻吩-5-甲酸的合成方法 |
| US20200383960A1 (en) | 2019-06-10 | 2020-12-10 | Novartis Ag | Pyridine and Pyrazine derivative for the Treatment of CF, COPD, and Bronchiectasis |
| JP2022547427A (ja) | 2019-08-28 | 2022-11-14 | ノバルティス アーゲー | 置換１，３－フェニルヘテロアリール誘導体及び疾患の治療におけるその使用 |
| 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 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4644003A (en) * | 1985-04-03 | 1987-02-17 | Research Corporation | 3-quinuclidinol esters, useful as antagonists of muscarinic acetylcholine receptors |
| IE922270A1 (en) * | 1991-07-26 | 1993-01-27 | Akzo Nv | Pyrazole derivatives |
| GB9127279D0 (en) * | 1991-12-23 | 1992-02-19 | Ici Plc | Heterocyclic derivatives |
| GB9216721D0 (en) | 1992-08-06 | 1992-09-23 | Ici Plc | Therapeutic heterocyclic derivatives |
| GB9218334D0 (en) * | 1992-08-28 | 1992-10-14 | Ici Plc | Heterocyclic compounds |
| US5384462A (en) * | 1992-12-08 | 1995-01-24 | Levitt; Roy C. | Process and apparatus for localizing a source of charged particles using an electric field |
| GB9226573D0 (en) * | 1992-12-21 | 1993-02-17 | Ici Plc | Heterocyclic compounds |
| JPH08134067A (ja) | 1994-11-11 | 1996-05-28 | Yamanouchi Pharmaceut Co Ltd | キヌクリジン誘導体 |
| US5830902A (en) * | 1995-03-02 | 1998-11-03 | Yamanouchi Pharmaceutical Co., Ltd. | Quinuclidine derivative having tricyclic hetero condensed ring |
| JP4206212B2 (ja) * | 1999-09-28 | 2009-01-07 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キヌクリジン化合物およびそれを有効成分として含有する医薬 |
| GB0004887D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| US7112593B2 (en) | 2001-03-27 | 2006-09-26 | Eisai Co., Ltd. | N-aryl-substituted cyclic amine derivative and medicine containing the same as active ingredient |
| IL160896A0 (en) * | 2001-10-17 | 2004-08-31 | Ucb Sa | Quinuclidine derivatives, processes for preparing them and their uses as m2 and/or m3 muscarinic receptor inhibitors |
-
2002
- 2002-09-23 IL IL16089602A patent/IL160896A0/xx unknown
- 2002-09-23 US US10/490,436 patent/US7361668B2/en not_active Expired - Fee Related
- 2002-09-23 PL PL02370087A patent/PL370087A1/xx not_active Application Discontinuation
- 2002-09-23 WO PCT/EP2002/010644 patent/WO2003033495A1/fr active IP Right Grant
- 2002-09-23 BR BR0212983-3A patent/BR0212983A/pt not_active IP Right Cessation
- 2002-09-23 NZ NZ532283A patent/NZ532283A/en unknown
- 2002-09-23 CA CA002462980A patent/CA2462980A1/fr not_active Abandoned
- 2002-09-23 EP EP02772337A patent/EP1438309A1/fr not_active Withdrawn
- 2002-09-23 KR KR1020047005658A patent/KR20050030169A/ko not_active Application Discontinuation
- 2002-09-23 HU HU0401849A patent/HUP0401849A3/hu unknown
- 2002-09-23 CN CNA028206037A patent/CN1571787A/zh active Pending
- 2002-09-23 CZ CZ2004501A patent/CZ2004501A3/cs unknown
- 2002-09-23 RU RU2004110717/04A patent/RU2004110717A/ru not_active Application Discontinuation
- 2002-09-23 JP JP2003536234A patent/JP2005512974A/ja active Pending
-
2004
- 2004-03-15 ZA ZA200402060A patent/ZA200402060B/en unknown
- 2004-03-18 IS IS7186A patent/IS7186A/is unknown
- 2004-03-30 MX MXPA04002983A patent/MXPA04002983A/es unknown
- 2004-04-15 BG BG108683A patent/BG108683A/xx unknown
- 2004-05-14 NO NO20042023A patent/NO20042023L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0401849A2 (hu) | 2004-12-28 |
| US7361668B2 (en) | 2008-04-22 |
| PL370087A1 (en) | 2005-05-16 |
| HUP0401849A3 (en) | 2007-05-02 |
| JP2005512974A (ja) | 2005-05-12 |
| WO2003033495A1 (fr) | 2003-04-24 |
| RU2004110717A (ru) | 2005-10-20 |
| BG108683A (en) | 2005-04-30 |
| CN1571787A (zh) | 2005-01-26 |
| EP1438309A1 (fr) | 2004-07-21 |
| CA2462980A1 (fr) | 2003-04-24 |
| MXPA04002983A (es) | 2004-07-15 |
| IL160896A0 (en) | 2004-08-31 |
| CZ2004501A3 (cs) | 2004-09-15 |
| BR0212983A (pt) | 2004-10-13 |
| NO20042023L (no) | 2004-05-14 |
| KR20050030169A (ko) | 2005-03-29 |
| NZ532283A (en) | 2005-06-24 |
| US20050020660A1 (en) | 2005-01-27 |
| IS7186A (is) | 2004-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200402060B (en) | Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors. | |
| EP0665843B1 (fr) | Quinuclidines substituees utiles comme antagonistes de la substance p | |
| AU624402B2 (en) | Memory enhancing-r-n-(1-azabicyclo(2.2.2)oct-3-yl) benzamides and thiobenzamides | |
| JPH0784466B2 (ja) | 老年痴呆の治療に有用なオキサジアゾ−ル類 | |
| JPH09500904A (ja) | ジアザビシクロニューロキニンアンタゴニスト | |
| US20080214600A1 (en) | Quaternized Quinuclidine Esters | |
| BRPI0507065B1 (pt) | derivados de quinolina, composição que os compreende, seu processo de preparação e seu uso como inibidores micobacterianos | |
| JPH01221378A (ja) | 新規化合物、その製法及びそれを含む医薬組成物 | |
| JPH04217660A (ja) | アザビシクロおよびアザシクロオキシムおよびアミンコリン作働剤 | |
| US7087596B2 (en) | 2-oxo-piperidinyl- and 2-oxo-azepanyl alkanoic acid derivatives for the treatment of epilepsy and other neurological disorders | |
| JPH02104529A (ja) | Ｓ―ｎ―（１―アザビシクロ〔２．２．２〕オクト―３イル）ベンズアミド類及びチオベンズアミド類を有効成分とする抗精神分裂病及び／又は抗精神病薬 | |
| US5206246A (en) | Anxiolytic-R-n(1-azabicyclo[2.2.2]oct-3-yl) benzamides and thiobenzamides | |
| JP2778832B2 (ja) | Ｇａｂａ−ｂアンタゴニストとしての２−置換モルホリンおよびチオモルホリン誘導体 | |
| AU754739B2 (en) | Novel basic derivatives of benz(e)isoindol-1-ones and pyrrolo(3,4-c)quinolin-1-ones with 5-HT3-antagonistic activity, their preparation and their therapeutic use | |
| JP4813357B2 (ja) | Ｎ−ビアリールアミド化合物 | |
| AU618027B2 (en) | Anxiolytic-r-n-(1-azabicyclo(2.2.2)oct-3-yl) benzamides and thiobenzamides | |
| JPH02275851A (ja) | 炭化水素置換ピロリジノン類 | |
| EP0763535A1 (fr) | Dérivés de pipéridinylméthyloxazolidin-2-one, leur préparation et leur utilisation comme composés pharmacologiques actifs sur le système nerveux central | |
| AU2002337126A1 (en) | Quinuclidine derivatives, processes for preparing them and their uses as M2 and/or M3 muscarinic receptor inhibitors | |
| WO2006029549A1 (fr) | Composes de quinuclidine a groupe ammonium quaternaire, procede d'elaboration et utilisation comme agents de blocage de l'acetycholine | |
| US5837711A (en) | Substituted quinuclidines as substance P antagonists | |
| JPH02247183A (ja) | ヘテロ環スピロ化合物 | |
| CA2862008A1 (fr) | Esters de quinuclidine et d'acide 1-azaheterocyclylacetique utilises comme agents antimuscariniques, procede pour leur preparation et compositions medicinales correspondantes |