JP2005538187A - 新規キヌクリジン誘導体及びその使用方法 - Google Patents
新規キヌクリジン誘導体及びその使用方法 Download PDFInfo
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- JP2005538187A JP2005538187A JP2005502013A JP2005502013A JP2005538187A JP 2005538187 A JP2005538187 A JP 2005538187A JP 2005502013 A JP2005502013 A JP 2005502013A JP 2005502013 A JP2005502013 A JP 2005502013A JP 2005538187 A JP2005538187 A JP 2005538187A
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- Prior art keywords
- alkoxy
- alkyl
- octane
- aza
- bicyclo
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- 238000000034 method Methods 0.000 title claims abstract description 71
- 150000008584 quinuclidines Chemical class 0.000 title abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 100
- 150000001875 compounds Chemical class 0.000 claims abstract description 86
- 201000010099 disease Diseases 0.000 claims abstract description 57
- 208000035475 disorder Diseases 0.000 claims abstract description 43
- 239000000126 substance Substances 0.000 claims abstract description 13
- 208000002193 Pain Diseases 0.000 claims abstract description 11
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 11
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims abstract description 9
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 7
- 230000016160 smooth muscle contraction Effects 0.000 claims abstract description 7
- -1 cycloalkoxy-alkoxy Chemical group 0.000 claims description 149
- 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 claims description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 39
- 125000002950 monocyclic group Chemical group 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- 125000003367 polycyclic group Chemical group 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000002837 carbocyclic group Chemical group 0.000 claims description 31
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 27
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 26
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 23
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 23
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 22
- 150000001408 amides Chemical class 0.000 claims description 20
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 11
- 102000005962 receptors Human genes 0.000 claims description 11
- 108020003175 receptors Proteins 0.000 claims description 11
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
- 238000004132 cross linking Methods 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- UYDJFXWILYZAEM-UHFFFAOYSA-N 3-(6-bromopyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound N1=NC(Br)=CC=C1OC1C(CC2)CCN2C1 UYDJFXWILYZAEM-UHFFFAOYSA-N 0.000 claims description 7
- 125000003118 aryl group Chemical class 0.000 claims description 7
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 6
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 6
- SURCGQGDUADKBL-UHFFFAOYSA-N 2-(2-hydroxyethylamino)-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(NCCO)C2=O)=O)=C3C2=CC=CC3=C1 SURCGQGDUADKBL-UHFFFAOYSA-N 0.000 claims description 6
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 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 claims description 6
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 6
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- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 6
- 125000003828 azulenyl group Chemical group 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 229960002715 nicotine Drugs 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 claims description 5
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 5
- 125000004522 1,3,4-thiadiazol-5-yl group Chemical group S1C=NN=C1* 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- FHBQJQOZXLTNAR-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.2]octan-3-yloxy)-1,2-benzothiazole Chemical compound C1=CC=C2C(OC3C4CCN(C3)CC4)=NSC2=C1 FHBQJQOZXLTNAR-UHFFFAOYSA-N 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 5
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 5
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 5
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 5
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 5
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 5
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 5
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 4
- LRQZHEAZRKGYRO-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)quinoline Chemical compound C1=CC=CC2=NC(OC3C4CCN(C3)CC4)=CC=C21 LRQZHEAZRKGYRO-UHFFFAOYSA-N 0.000 claims description 4
- RPAIFTHNSMJQGX-UHFFFAOYSA-M 2-(1-azabicyclo[2.2.2]octan-3-yloxy)quinoxaline;carbanylium;iodide Chemical compound [CH3+].[I-].C1=CC=CC2=NC(OC3C4CCN(C3)CC4)=CN=C21 RPAIFTHNSMJQGX-UHFFFAOYSA-M 0.000 claims description 4
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 208000032841 Bulimia Diseases 0.000 claims description 4
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 4
- 206010012735 Diarrhoea Diseases 0.000 claims description 4
- 208000012661 Dyskinesia Diseases 0.000 claims description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
- 229910005965 SO 2 Inorganic materials 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
- 230000006735 deficit Effects 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 125000004515 1,2,4-thiadiazol-3-yl group Chemical group S1N=C(N=C1)* 0.000 claims description 3
- BXENYFDBSRHICB-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-3-chloroquinoxaline Chemical compound C1N(CC2)CCC2C1OC1=NC2=CC=CC=C2N=C1Cl BXENYFDBSRHICB-UHFFFAOYSA-N 0.000 claims description 3
- VSKHAHUONMJJFL-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-bromo-1,3-thiazole Chemical compound S1C(Br)=CN=C1OC1C(CC2)CCN2C1 VSKHAHUONMJJFL-UHFFFAOYSA-N 0.000 claims description 3
- NVYFUUNOOKTHMV-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)quinoxaline Chemical compound C1=CC=CC2=NC(OC3C4CCN(C3)CC4)=CN=C21 NVYFUUNOOKTHMV-UHFFFAOYSA-N 0.000 claims description 3
- ISTQAMKJXZTCAM-UHFFFAOYSA-N 3-(3-phenylphenoxy)-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(C=1)=CC=CC=1C1=CC=CC=C1 ISTQAMKJXZTCAM-UHFFFAOYSA-N 0.000 claims description 3
- PFRYGKATQCVDFW-UHFFFAOYSA-N 3-[(4-phenylphenyl)methoxy]-1-azabicyclo[2.2.2]octane Chemical compound C1N(CC2)CCC2C1OCC(C=C1)=CC=C1C1=CC=CC=C1 PFRYGKATQCVDFW-UHFFFAOYSA-N 0.000 claims description 3
- ZTVUBKRSTBDFBC-UHFFFAOYSA-N 3-dibenzofuran-2-yloxy-1-azabicyclo[2.2.2]octane Chemical group C1=CC=C2C3=CC(OC4C5CCN(C4)CC5)=CC=C3OC2=C1 ZTVUBKRSTBDFBC-UHFFFAOYSA-N 0.000 claims description 3
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 3
- 208000028698 Cognitive impairment Diseases 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 208000028017 Psychotic disease Diseases 0.000 claims description 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 208000013403 hyperactivity Diseases 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 3
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
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- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
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- 201000000980 schizophrenia Diseases 0.000 claims description 3
- FIDMJKLFOPNZTL-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yloxy)benzotriazole Chemical compound N1=NC2=CC=CC=C2N1OC(C1)C2CCN1CC2 FIDMJKLFOPNZTL-UHFFFAOYSA-N 0.000 claims description 2
- COPKZPSRVDULIN-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-1,3-benzothiazole Chemical compound C1=CC=C2SC(OC3C4CCN(C3)CC4)=NC2=C1 COPKZPSRVDULIN-UHFFFAOYSA-N 0.000 claims description 2
- ONZZUKINKMKNFG-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-1,3-benzoxazole Chemical compound C1=CC=C2OC(OC3C4CCN(C3)CC4)=NC2=C1 ONZZUKINKMKNFG-UHFFFAOYSA-N 0.000 claims description 2
- VWUNUDCRVBDVAE-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C(OC3C4CCN(CC4)C3)=NC2=C1 VWUNUDCRVBDVAE-UHFFFAOYSA-N 0.000 claims description 2
- YGRYEAVJUADRGH-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-3-methoxyquinoxaline Chemical compound C1N(CC2)CCC2C1OC1=NC2=CC=CC=C2N=C1OC YGRYEAVJUADRGH-UHFFFAOYSA-N 0.000 claims description 2
- BWNSGMZYAPFBRL-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-(2,4-difluorophenyl)-1,3-thiazole Chemical compound FC1=CC(F)=CC=C1C(S1)=CN=C1OC1C(CC2)CCN2C1 BWNSGMZYAPFBRL-UHFFFAOYSA-N 0.000 claims description 2
- BQVJZWBRVUEZKU-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-(furan-3-yl)-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=COC=1 BQVJZWBRVUEZKU-UHFFFAOYSA-N 0.000 claims description 2
- RMCHOLPMARHFKR-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-phenyl-1,3,4-thiadiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NN=C1C1=CC=CC=C1 RMCHOLPMARHFKR-UHFFFAOYSA-N 0.000 claims description 2
- KHJZSFUHZDEQIU-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-phenyl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CC=C1 KHJZSFUHZDEQIU-UHFFFAOYSA-N 0.000 claims description 2
- PTPLMYRMZXCHSZ-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-pyridin-3-yl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CN=C1 PTPLMYRMZXCHSZ-UHFFFAOYSA-N 0.000 claims description 2
- FPVAPJYIZHSJKF-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-2-yl-1,3,4-thiadiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NN=C1C1=CC=CS1 FPVAPJYIZHSJKF-UHFFFAOYSA-N 0.000 claims description 2
- WENRZTCKEUNEMA-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-2-yl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CS1 WENRZTCKEUNEMA-UHFFFAOYSA-N 0.000 claims description 2
- GCNWMXJESTZDJB-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-3-yl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=CSC=1 GCNWMXJESTZDJB-UHFFFAOYSA-N 0.000 claims description 2
- JVLOHDNSLWPUJF-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-6-chloro-1,3-benzothiazole Chemical compound C1N(CC2)CCC2C1OC1=NC2=CC=C(Cl)C=C2S1 JVLOHDNSLWPUJF-UHFFFAOYSA-N 0.000 claims description 2
- AUVDLTULQQPZDF-UHFFFAOYSA-M 2-(1-azabicyclo[2.2.2]octan-3-yloxy)quinoline;carbanylium;iodide Chemical compound [CH3+].[I-].C1=CC=CC2=NC(OC3C4CCN(C3)CC4)=CC=C21 AUVDLTULQQPZDF-UHFFFAOYSA-M 0.000 claims description 2
- NMFVGYWXADHCBK-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-phenyl-1,2,4-thiadiazole Chemical compound C1CN(C2)CCC1C2OC(N=1)=NSC=1C1=CC=CC=C1 NMFVGYWXADHCBK-UHFFFAOYSA-N 0.000 claims description 2
- ONNLEVOYDBCRKS-UHFFFAOYSA-N 3-(2,3-dihydro-1h-inden-5-yloxy)-1-azabicyclo[2.2.2]octane Chemical compound C1N(CC2)CCC2C1OC1=CC=C2CCCC2=C1 ONNLEVOYDBCRKS-UHFFFAOYSA-N 0.000 claims description 2
- ZBDIBRKIGUGEEP-UHFFFAOYSA-N 3-(2-phenylphenoxy)-1-azabicyclo[2.2.2]octane Chemical group C1CN(C2)CCC1C2OC1=CC=CC=C1C1=CC=CC=C1 ZBDIBRKIGUGEEP-UHFFFAOYSA-N 0.000 claims description 2
- HYYHQFCZRLZVEX-UHFFFAOYSA-N 3-(3,4,5-trichlorothiophen-2-yl)oxy-1-azabicyclo[2.2.2]octane Chemical group ClC1=C(Cl)SC(OC2C3CCN(CC3)C2)=C1Cl HYYHQFCZRLZVEX-UHFFFAOYSA-N 0.000 claims description 2
- BCIOGGPNGDFPBO-UHFFFAOYSA-N 3-(4-phenylphenoxy)-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(C=C1)=CC=C1C1=CC=CC=C1 BCIOGGPNGDFPBO-UHFFFAOYSA-N 0.000 claims description 2
- OQMAYTGWZKXAME-UHFFFAOYSA-N 3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)-1-azabicyclo[2.2.2]octane Chemical compound C1N(CC2)CCC2C1OC1=CC=C(CCCC2)C2=C1 OQMAYTGWZKXAME-UHFFFAOYSA-N 0.000 claims description 2
- MCAXDSHKPBDHIW-UHFFFAOYSA-N 3-(6-chloropyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound N1=NC(Cl)=CC=C1OC1C(CC2)CCN2C1 MCAXDSHKPBDHIW-UHFFFAOYSA-N 0.000 claims description 2
- FWJYJIHEZKZYMF-UHFFFAOYSA-N 3-(6-phenylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CC=C1 FWJYJIHEZKZYMF-UHFFFAOYSA-N 0.000 claims description 2
- HMJIRHSCISEZOV-UHFFFAOYSA-N 3-(6-pyridin-3-ylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CN=C1 HMJIRHSCISEZOV-UHFFFAOYSA-N 0.000 claims description 2
- BGMCIWWSQXKNSS-UHFFFAOYSA-N 3-(6-thiophen-2-ylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CS1 BGMCIWWSQXKNSS-UHFFFAOYSA-N 0.000 claims description 2
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| US8173667B2 (en) | 2005-10-21 | 2012-05-08 | Novartis Ag | 1-aza-bicycloalkyl derivatives |
| US8236803B2 (en) | 2002-09-04 | 2012-08-07 | Novartis Ag | Aza-bicycloalkyl ethers and their use as alpha7-nAChR agonists |
| US8609662B2 (en) | 2004-07-14 | 2013-12-17 | Novartis Ag | 3-(heteroaryl-oxy)-2-alkyl-1-aza-bicycloalkyl derivatives as alpha. 7-nachr ligands for the treatment of CNS diseases |
| US8759346B2 (en) | 2005-12-16 | 2014-06-24 | Novartis Ag | Organic compounds |
| US8933090B2 (en) | 2004-06-18 | 2015-01-13 | Novartis Ag | 1-aza-bicyclo[3.3.1]nonanes |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6262265A (ja) * | 1985-09-13 | 1987-03-18 | Hitachi Ltd | 復水器自動検査補修システム |
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| GB0424564D0 (en) | 2004-11-05 | 2004-12-08 | Novartis Ag | Organic compounds |
| CA2591817A1 (en) * | 2004-12-22 | 2006-06-29 | Memory Pharmaceuticals Corporation | Nicotinic alpha-7 receptor ligands and preparation and uses thereof |
| BRPI0617534A2 (pt) * | 2005-09-23 | 2011-07-26 | Memory Pharm Corp | Composto, composição farmacêutica, método para a ativação/estimulação seletiva de receptores nicotínicos de a-7 em um paciente, método para o tratamento de um paciente que sofre de uma doença psicótica, uma doença neurodegenerativa que envolve uma disfunção do sistema colinérgico, e/ou uma condição de degeneração da memória e/ou da cognição, método para o tratamento de um paciente que sofre de demência e/ou uma outra condição com perda da memória, método para o tratamento de um paciente que sofre de degeneração da memória devida à degeneração cognitiva suave devida ao envelhecimento, mal de alzheimer, esquizofrenia, mal de parkinson, mal de huntington, mal de pick, mal de creutzfeldt-jakob, depressão, envelhecimento, trauma na cabeça, acidente vascular cerebral, hipoxia do cns, senilidade cerebral, demência de multiinfarto, hiv e/ou doença cardiovascular, método para o tratamento e/ou a prevenção da demência em um paciente com mal de alzheimer, método para o tratamento de um paciente para a retirada do álcool ou para o tratamento de um paciente com terapia anti-intoxicação, método para o tratamento de um paciente para conferir neuroproteção contra os danos associados com acidentes vasculares cerebrais e isquemia e excitotoxicidade induzida por glutamato, método para o tratamento de um paciente que sofre de vício de nicotina, dor, tontura de fuso horário, obesidade e/ou diabetes, método de indução de um paciente a parar de fumar, método para o tratamento de um paciente que sofre de degeneração cognitiva suave (mci), demência vascular (vad), declínio cognitivo associado com a idade (aacd), amnésia associada com a cirurgia de coração aberto, apreensão cardíaca, anestesia geral, déficits da memória devido à exposição a agentes anestésicos(...) |
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Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3534053A (en) * | 1967-05-24 | 1970-10-13 | American Home Prod | Quinuclidine derivatives |
| DE2502916A1 (de) * | 1974-03-05 | 1975-09-11 | Vni Chimiko Farmazewtitscheski | (chinuklidyl-3)-diaryl(heteryl) karbinole, ihre salze und verfahren zu deren herstellung |
| JPH0193585A (ja) * | 1987-08-04 | 1989-04-12 | John Wyeth & Bros Ltd | 新規エーテル化合物 |
| JPH01153662A (ja) * | 1986-12-10 | 1989-06-15 | Bayer Ag | 置換された塩基性２−アミノテトラリン類 |
| JPH0228180A (ja) * | 1988-04-01 | 1990-01-30 | Sankyo Co Ltd | カルバペネム誘導体 |
| JPH02129186A (ja) * | 1988-10-03 | 1990-05-17 | Beecham Group Plc | 新規化合物、その製法及びそれを含む医薬組成物 |
| JPH04226981A (ja) * | 1990-05-19 | 1992-08-17 | Boehringer Ingelheim Kg | 二環式の１−アザ−シクロアルカン化合物 |
| JPH0559050A (ja) * | 1991-02-01 | 1993-03-09 | Akzo Nv | ３−キヌクリジン誘導体 |
| JPH07503463A (ja) * | 1992-01-28 | 1995-04-13 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | カルシウムチャンネル拮抗薬としてのアザビシクロ化合物 |
| JPH0840999A (ja) * | 1994-08-04 | 1996-02-13 | Yamanouchi Pharmaceut Co Ltd | フルオロインダン誘導体 |
| JPH09512804A (ja) * | 1994-05-06 | 1997-12-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５−ｈｔ１ｄアンタゴニストとして有用なビフェニルカルボキシアミド類 |
| WO1999042461A1 (en) * | 1998-02-23 | 1999-08-26 | Warner-Lambert Company | Substituted quinoxaline derivatives as interleukin-8 receptor antagonists |
| JP2001514176A (ja) * | 1997-08-27 | 2001-09-11 | ファイザー・プロダクツ・インク | Ｎｏｓ阻害剤であり縮合環置換基を含む２−アミノピリジン類 |
| JP2002030084A (ja) * | 2000-07-18 | 2002-01-29 | Mitsubishi Pharma Corp | １−アザビシクロアルカン化合物およびその医薬用途 |
| WO2002044176A1 (en) * | 2000-12-01 | 2002-06-06 | Neurosearch A/S | 3-substituted quinuclidines and their use as nicotinic agonists |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5405853A (en) * | 1987-09-10 | 1995-04-11 | Merck Sharpe & Dohme Ltd. | Thiadiazoles useful in the treatment of senile dementia |
| IT1227729B (it) * | 1988-12-23 | 1991-05-06 | Savio Spa | Procedimento e dispositivo per la rimozione delle fibre deteriorate durante il riattacco del filo in un filatoio open-end |
| EP0555478A4 (en) * | 1990-08-31 | 1993-11-18 | Nippon Shinyaku Company, Limited | Pyrimidine derivative and medicine |
| US5948793A (en) * | 1992-10-09 | 1999-09-07 | Abbott Laboratories | 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling neurotransmitter release |
| US5998404A (en) * | 1994-10-24 | 1999-12-07 | Eli Lilly And Company | Heterocyclic compounds and their use |
| US5821371A (en) * | 1994-10-24 | 1998-10-13 | Eli Lilly And Comany | Heterocyclic compounds and their preparation and use |
| JPH08134067A (ja) * | 1994-11-11 | 1996-05-28 | Yamanouchi Pharmaceut Co Ltd | キヌクリジン誘導体 |
| US5512574A (en) * | 1994-12-21 | 1996-04-30 | American Home Products Corporation | Quinuclidine and azabicyclo 2.2.1! heptane pyrazinyl ethers as muscarinic agonists |
| US5852037A (en) * | 1995-11-13 | 1998-12-22 | Eli Lilly And Company | Method for treating anxiety |
| JP2000500452A (ja) * | 1995-11-13 | 2000-01-18 | イーライ・リリー・アンド・カンパニー | 不安の処置法 |
| US5763457A (en) * | 1995-11-13 | 1998-06-09 | Eli Lilly And Company | Method for treating anxiety |
| FR2754261B1 (fr) * | 1996-10-08 | 1998-10-30 | Synthelabo | Derives de quinuclidine, leur preparation et leur application en therapeutique |
| AU7871498A (en) * | 1996-12-20 | 1998-07-17 | Novo Nordisk A/S | A method of treating hypercholesterolemia and related disorders |
| FR2772378B1 (fr) * | 1997-12-12 | 2000-02-04 | Synthelabo | Derives d'imidazole, leur preparation et leur application en therapeutique |
-
2003
- 2003-08-13 RU RU2005101748/04A patent/RU2323217C2/ru not_active IP Right Cessation
- 2003-08-13 WO PCT/DK2003/000538 patent/WO2004016608A1/en not_active Ceased
- 2003-08-13 NZ NZ538058A patent/NZ538058A/en not_active IP Right Cessation
- 2003-08-13 AU AU2003250322A patent/AU2003250322B2/en not_active Ceased
- 2003-08-13 US US10/522,150 patent/US20050245567A1/en not_active Abandoned
- 2003-08-13 PL PL03375533A patent/PL375533A1/xx not_active Application Discontinuation
- 2003-08-13 AT AT03787742T patent/ATE384720T1/de not_active IP Right Cessation
- 2003-08-13 EP EP08100204A patent/EP1905771A3/en not_active Withdrawn
- 2003-08-13 CN CNB038190788A patent/CN100513406C/zh not_active Expired - Fee Related
- 2003-08-13 EP EP03787742A patent/EP1532144B1/en not_active Expired - Lifetime
- 2003-08-13 CA CA002493245A patent/CA2493245A1/en not_active Abandoned
- 2003-08-13 DE DE60318860T patent/DE60318860T2/de not_active Expired - Lifetime
- 2003-08-13 MX MXPA05001702A patent/MXPA05001702A/es active IP Right Grant
- 2003-08-13 BR BR0313153-0A patent/BR0313153A/pt not_active IP Right Cessation
- 2003-08-13 JP JP2005502013A patent/JP2005538187A/ja active Pending
- 2003-08-13 KR KR1020057002514A patent/KR20050055711A/ko not_active Ceased
-
2005
- 2005-01-12 IL IL16625405A patent/IL166254A0/xx unknown
- 2005-03-11 NO NO20051264A patent/NO20051264L/no not_active Application Discontinuation
- 2005-03-14 IS IS7742A patent/IS7742A/is unknown
-
2008
- 2008-09-08 US US12/206,302 patent/US20090005390A1/en not_active Abandoned
Patent Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3534053A (en) * | 1967-05-24 | 1970-10-13 | American Home Prod | Quinuclidine derivatives |
| DE2502916A1 (de) * | 1974-03-05 | 1975-09-11 | Vni Chimiko Farmazewtitscheski | (chinuklidyl-3)-diaryl(heteryl) karbinole, ihre salze und verfahren zu deren herstellung |
| JPH01153662A (ja) * | 1986-12-10 | 1989-06-15 | Bayer Ag | 置換された塩基性２−アミノテトラリン類 |
| JPH0193585A (ja) * | 1987-08-04 | 1989-04-12 | John Wyeth & Bros Ltd | 新規エーテル化合物 |
| JPH0228180A (ja) * | 1988-04-01 | 1990-01-30 | Sankyo Co Ltd | カルバペネム誘導体 |
| JPH02129186A (ja) * | 1988-10-03 | 1990-05-17 | Beecham Group Plc | 新規化合物、その製法及びそれを含む医薬組成物 |
| JPH04226981A (ja) * | 1990-05-19 | 1992-08-17 | Boehringer Ingelheim Kg | 二環式の１−アザ−シクロアルカン化合物 |
| JPH0559050A (ja) * | 1991-02-01 | 1993-03-09 | Akzo Nv | ３−キヌクリジン誘導体 |
| JPH07503463A (ja) * | 1992-01-28 | 1995-04-13 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | カルシウムチャンネル拮抗薬としてのアザビシクロ化合物 |
| JPH09512804A (ja) * | 1994-05-06 | 1997-12-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | ５−ｈｔ１ｄアンタゴニストとして有用なビフェニルカルボキシアミド類 |
| JPH0840999A (ja) * | 1994-08-04 | 1996-02-13 | Yamanouchi Pharmaceut Co Ltd | フルオロインダン誘導体 |
| JP2001514176A (ja) * | 1997-08-27 | 2001-09-11 | ファイザー・プロダクツ・インク | Ｎｏｓ阻害剤であり縮合環置換基を含む２−アミノピリジン類 |
| WO1999042461A1 (en) * | 1998-02-23 | 1999-08-26 | Warner-Lambert Company | Substituted quinoxaline derivatives as interleukin-8 receptor antagonists |
| JP2002030084A (ja) * | 2000-07-18 | 2002-01-29 | Mitsubishi Pharma Corp | １−アザビシクロアルカン化合物およびその医薬用途 |
| WO2002044176A1 (en) * | 2000-12-01 | 2002-06-06 | Neurosearch A/S | 3-substituted quinuclidines and their use as nicotinic agonists |
Non-Patent Citations (5)
| Title |
|---|
| JPN6009068278, Ｂｉｏｏｒｇａｎｉｃ ＆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ Ｌｅｔｔｅｒｓ, 1994, Ｖｏｌ．４， Ｎｏ．２４, ｐａｇｅｓ ２８３７−４０ * |
| JPN6009068281, Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ, 1969, Ｖｏｌ．１２， Ｎｏ．３, ｐａｇｅｓ ５２４−５２６ * |
| JPN6009068283, Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ, 1996, Ｖｏｌ．３９， Ｎｏ．１５, ｐａｇｅｓ ２９７１−２９７９ * |
| JPN6009068285, Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ, 1999, Ｖｏｌ．４２， Ｎｏ．７, ｐａｇｅｓ １３０６−１３１１ * |
| JPN6009068288, Ａｎａｌｙｔｉｃａｌ Ｂｉｏｃｈｅｍｉｓｔｒｙ, 1995, Ｖｏｌ．２２６， Ｎｏ．２, ｐａｇｅｓ ２６８−２７８ * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9012451B2 (en) | 2002-09-04 | 2015-04-21 | Novartis Ag | Aza-bicycloalkyl ethers and their use as ALPHA7-nachr agonists |
| US9849117B2 (en) | 2002-09-04 | 2017-12-26 | Novartis Ag | Aza-bicycloalkyl ethers and their use as alpha7-nachr agonists |
| US8236803B2 (en) | 2002-09-04 | 2012-08-07 | Novartis Ag | Aza-bicycloalkyl ethers and their use as alpha7-nAChR agonists |
| US9567343B2 (en) | 2002-09-04 | 2017-02-14 | Novartis Ag | Aza-bicyloalkyl ethers and their use as alpha7-nachr agonists |
| US9475811B2 (en) | 2004-06-18 | 2016-10-25 | Novartis Ag | 1-aza-bicyclo[3.3.1]nonanes |
| US8933090B2 (en) | 2004-06-18 | 2015-01-13 | Novartis Ag | 1-aza-bicyclo[3.3.1]nonanes |
| US8609662B2 (en) | 2004-07-14 | 2013-12-17 | Novartis Ag | 3-(heteroaryl-oxy)-2-alkyl-1-aza-bicycloalkyl derivatives as alpha. 7-nachr ligands for the treatment of CNS diseases |
| US9657010B2 (en) | 2004-07-14 | 2017-05-23 | Novartis Ag | Substituted quinuclidines as alpha 7-nicotinic acetylcholine receptor activity modulators |
| US8173667B2 (en) | 2005-10-21 | 2012-05-08 | Novartis Ag | 1-aza-bicycloalkyl derivatives |
| US8759346B2 (en) | 2005-12-16 | 2014-06-24 | Novartis Ag | Organic compounds |
| US8637517B2 (en) | 2005-12-16 | 2014-01-28 | Novartis Ag | Organic compounds |
| US9206181B2 (en) | 2005-12-16 | 2015-12-08 | Novartis Ag | 1-aza-bicyclo[3.3.1] non-4-yl)-[5-(1H-indol-5-yl)-heteroaryl]-amines as cholinergic ligands of the n-AChR for the treatment of psychotic and neurodegenerative disorders |
| US8048885B2 (en) | 2005-12-16 | 2011-11-01 | Novartis Ag | Organic compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1532144B1 (en) | 2008-01-23 |
| RU2323217C2 (ru) | 2008-04-27 |
| MXPA05001702A (es) | 2005-04-19 |
| CN100513406C (zh) | 2009-07-15 |
| DE60318860T2 (de) | 2008-05-21 |
| RU2005101748A (ru) | 2006-01-20 |
| IL166254A0 (en) | 2006-01-15 |
| US20050245567A1 (en) | 2005-11-03 |
| EP1532144A1 (en) | 2005-05-25 |
| AU2003250322B2 (en) | 2010-01-21 |
| DE60318860D1 (de) | 2008-03-13 |
| BR0313153A (pt) | 2005-06-28 |
| US20090005390A1 (en) | 2009-01-01 |
| CN1675205A (zh) | 2005-09-28 |
| IS7742A (is) | 2005-03-14 |
| EP1905771A2 (en) | 2008-04-02 |
| AU2003250322A1 (en) | 2004-03-03 |
| PL375533A1 (en) | 2005-11-28 |
| CA2493245A1 (en) | 2004-02-26 |
| NZ538058A (en) | 2006-11-30 |
| HK1080860A1 (zh) | 2006-05-04 |
| KR20050055711A (ko) | 2005-06-13 |
| ATE384720T1 (de) | 2008-02-15 |
| NO20051264L (no) | 2005-05-18 |
| WO2004016608A1 (en) | 2004-02-26 |
| EP1905771A3 (en) | 2008-11-26 |
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