JP2006511482A - コリン作動性受容体を活性化できる化合物 - Google Patents
コリン作動性受容体を活性化できる化合物 Download PDFInfo
- Publication number
- JP2006511482A JP2006511482A JP2004542034A JP2004542034A JP2006511482A JP 2006511482 A JP2006511482 A JP 2006511482A JP 2004542034 A JP2004542034 A JP 2004542034A JP 2004542034 A JP2004542034 A JP 2004542034A JP 2006511482 A JP2006511482 A JP 2006511482A
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- JP
- Japan
- Prior art keywords
- penten
- amine
- methyl
- pyridyl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 263
- 108010009685 Cholinergic Receptors Proteins 0.000 title description 5
- 102000034337 acetylcholine receptors Human genes 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 69
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- -1 (4E) -N-methyl-5- (5-ethoxy-3-pyridyl) -4-penten-2-amine (2S)-(4E) -N-methyl-5- (3-pyridyl) -4-penten-2-amine Chemical compound 0.000 claims description 93
- 239000000203 mixture Substances 0.000 claims description 73
- 208000015114 central nervous system disease Diseases 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 150000001412 amines Chemical class 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 208000024827 Alzheimer disease Diseases 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- IEVJOUFGBRDCNE-QLCVYAKKSA-N (e,2r)-n-methyl-5-pyridin-3-ylpent-4-en-2-amine Chemical compound CN[C@H](C)C\C=C\C1=CC=CN=C1 IEVJOUFGBRDCNE-QLCVYAKKSA-N 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- RPCVIAXDAUMJJP-HOSRBBHYSA-N (e,2r)-n-methyl-5-(5-propan-2-yloxypyridin-3-yl)pent-4-en-2-amine Chemical compound CN[C@H](C)C\C=C\C1=CN=CC(OC(C)C)=C1 RPCVIAXDAUMJJP-HOSRBBHYSA-N 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- KETAPARGUJRPEI-HWKANZROSA-N (e)-5-(5-bromopyridin-3-yl)-n-methylpent-4-en-2-amine Chemical compound CNC(C)C\C=C\C1=CN=CC(Br)=C1 KETAPARGUJRPEI-HWKANZROSA-N 0.000 claims description 12
- RPCVIAXDAUMJJP-FNORWQNLSA-N (e)-n-methyl-5-(5-propan-2-yloxypyridin-3-yl)pent-4-en-2-amine Chemical compound CNC(C)C\C=C\C1=CN=CC(OC(C)C)=C1 RPCVIAXDAUMJJP-FNORWQNLSA-N 0.000 claims description 12
- IEVJOUFGBRDCNE-ZZXKWVIFSA-N (e)-n-methyl-5-pyridin-3-ylpent-4-en-2-amine Chemical compound CNC(C)C\C=C\C1=CC=CN=C1 IEVJOUFGBRDCNE-ZZXKWVIFSA-N 0.000 claims description 12
- VZNTWLIIJWUCEP-HWKANZROSA-N (e)-n-methyl-5-pyrimidin-5-ylpent-4-en-2-amine Chemical compound CNC(C)C\C=C\C1=CN=CN=C1 VZNTWLIIJWUCEP-HWKANZROSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- XDXHBRXUPFIIRK-GQCTYLIASA-N 3-methyl-5-[(e)-4-(methylamino)pent-1-enyl]pyridin-2-amine Chemical compound CNC(C)C\C=C\C1=CN=C(N)C(C)=C1 XDXHBRXUPFIIRK-GQCTYLIASA-N 0.000 claims description 7
- 206010039966 Senile dementia Diseases 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 7
- KJZMFQZAEDAMAE-FNORWQNLSA-N (e)-5-(5-ethoxypyridin-3-yl)-n-methylpent-4-en-2-amine Chemical compound CCOC1=CN=CC(\C=C\CC(C)NC)=C1 KJZMFQZAEDAMAE-FNORWQNLSA-N 0.000 claims description 6
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 6
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 6
- 208000016620 Tourette disease Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 6
- 208000010877 cognitive disease Diseases 0.000 claims description 6
- 206010013932 dyslexia Diseases 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 208000013403 hyperactivity Diseases 0.000 claims description 6
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 208000012661 Dyskinesia Diseases 0.000 claims description 5
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 5
- 201000002832 Lewy body dementia Diseases 0.000 claims description 5
- 206010026749 Mania Diseases 0.000 claims description 5
- 206010036631 Presenile dementia Diseases 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- RPCVIAXDAUMJJP-PZBABLGHSA-N ispronicline Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC(C)C)=C1 RPCVIAXDAUMJJP-PZBABLGHSA-N 0.000 claims description 5
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 5
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910014033 C-OH Inorganic materials 0.000 claims description 3
- 229910014570 C—OH Inorganic materials 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- FPKGXWLAUMDRRC-UHFFFAOYSA-N pent-1-en-2-amine Chemical compound CCCC(N)=C FPKGXWLAUMDRRC-UHFFFAOYSA-N 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- HMFWJGFLNZUGOI-GQCTYLIASA-N 2-amino-3-methyl-5-[(e)-4-(methylamino)pent-1-enyl]-1h-pyridin-4-one Chemical compound CNC(C)C\C=C\C1=CN=C(N)C(C)=C1O HMFWJGFLNZUGOI-GQCTYLIASA-N 0.000 claims description 2
- YNSYDGJJBRDOGI-HWKANZROSA-N 3-[(e)-4-(methylamino)pent-1-enyl]-1h-pyridin-4-one Chemical compound CNC(C)C\C=C\C1=CN=CC=C1O YNSYDGJJBRDOGI-HWKANZROSA-N 0.000 claims description 2
- YNSYDGJJBRDOGI-HYYFJVDXSA-N 3-[(e,4r)-4-(methylamino)pent-1-enyl]-1h-pyridin-4-one Chemical compound CN[C@H](C)C\C=C\C1=CN=CC=C1O YNSYDGJJBRDOGI-HYYFJVDXSA-N 0.000 claims description 2
- XVZDZUKYMUYZRS-OKPNEXGHSA-N 3-[(e,4r)-4-(methylamino)pent-1-enyl]-5-propan-2-yloxy-1h-pyridin-4-one Chemical compound CN[C@H](C)C\C=C\C1=CN=CC(OC(C)C)=C1O XVZDZUKYMUYZRS-OKPNEXGHSA-N 0.000 claims description 2
- YNSYDGJJBRDOGI-SGRBOOSSSA-N 3-[(e,4s)-4-(methylamino)pent-1-enyl]-1h-pyridin-4-one Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC=C1O YNSYDGJJBRDOGI-SGRBOOSSSA-N 0.000 claims description 2
- JTEMHQVUBWRVKV-GQCTYLIASA-N 3-methoxy-5-[(e)-4-(methylamino)pent-1-enyl]-1h-pyridin-4-one Chemical compound CNC(C)C\C=C\C1=CN=CC(OC)=C1O JTEMHQVUBWRVKV-GQCTYLIASA-N 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 claims description 2
- BPIDLOWRIYHHBQ-UHFFFAOYSA-N pent-4-en-2-amine Chemical compound CC(N)CC=C BPIDLOWRIYHHBQ-UHFFFAOYSA-N 0.000 claims description 2
- VCFWBIJAXASVNG-MASHWEEQSA-N (e,2r)-5-[5-(4-chlorophenoxy)pyridin-3-yl]-n-methylpent-4-en-2-amine Chemical compound CN[C@H](C)C\C=C\C1=CN=CC(OC=2C=CC(Cl)=CC=2)=C1 VCFWBIJAXASVNG-MASHWEEQSA-N 0.000 claims 1
- WWZWUMSCNSUYTF-MASHWEEQSA-N (e,2r)-5-[5-(4-fluorophenoxy)pyridin-3-yl]-n-methylpent-4-en-2-amine Chemical compound CN[C@H](C)C\C=C\C1=CN=CC(OC=2C=CC(F)=CC=2)=C1 WWZWUMSCNSUYTF-MASHWEEQSA-N 0.000 claims 1
- AFZBPRAIJZQHRO-PRBLHWDUSA-N (e,2r)-n-methyl-5-pyrimidin-5-ylpent-4-en-2-amine;hydroiodide Chemical compound I.CN[C@H](C)C\C=C\C1=CN=CN=C1 AFZBPRAIJZQHRO-PRBLHWDUSA-N 0.000 claims 1
- IILDXAVCPGVTRJ-OWNNVSBGSA-N (e,2s)-5-(5-cyclohexyloxypyridin-3-yl)-n-methylpent-4-en-2-amine Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC2CCCCC2)=C1 IILDXAVCPGVTRJ-OWNNVSBGSA-N 0.000 claims 1
- HXZJTUDXVFHWOB-RWCYGVJQSA-N (e,2s)-5-(5-methoxypyridin-3-yl)-n-methylpent-4-en-2-amine Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC)=C1 HXZJTUDXVFHWOB-RWCYGVJQSA-N 0.000 claims 1
- AVADOTDKFKRXKV-KQIUPUNMSA-N (e,2s)-5-[5-(1h-indol-5-yloxy)pyridin-3-yl]-n-methylpent-4-en-2-amine Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC=2C=C3C=CNC3=CC=2)=C1 AVADOTDKFKRXKV-KQIUPUNMSA-N 0.000 claims 1
- WWZWUMSCNSUYTF-LQPUYASZSA-N (e,2s)-5-[5-(4-fluorophenoxy)pyridin-3-yl]-n-methylpent-4-en-2-amine Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC=2C=CC(F)=CC=2)=C1 WWZWUMSCNSUYTF-LQPUYASZSA-N 0.000 claims 1
- MVYJEPAEKWWVOZ-OWNNVSBGSA-N (e,2s)-n-methyl-5-(5-phenoxypyridin-3-yl)pent-4-en-2-amine Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC=2C=CC=CC=2)=C1 MVYJEPAEKWWVOZ-OWNNVSBGSA-N 0.000 claims 1
- PIXSVCSUXPWQTB-DUXPYHPUSA-N 3-[(e)-4-aminopent-1-enyl]-1h-pyridin-4-one Chemical compound CC(N)C\C=C\C1=CN=CC=C1O PIXSVCSUXPWQTB-DUXPYHPUSA-N 0.000 claims 1
- WMWZUQILSUHONT-DUXPYHPUSA-N 3-[(e)-4-aminopent-1-enyl]-5-bromo-1h-pyridin-4-one Chemical compound CC(N)C\C=C\C1=CN=CC(Br)=C1O WMWZUQILSUHONT-DUXPYHPUSA-N 0.000 claims 1
- PIXSVCSUXPWQTB-BYDTYLDUSA-N 3-[(e,4r)-4-aminopent-1-enyl]-1h-pyridin-4-one Chemical compound C[C@@H](N)C\C=C\C1=CN=CC=C1O PIXSVCSUXPWQTB-BYDTYLDUSA-N 0.000 claims 1
- PIXSVCSUXPWQTB-KHVHVRLGSA-N 3-[(e,4s)-4-aminopent-1-enyl]-1h-pyridin-4-one Chemical compound C[C@H](N)C\C=C\C1=CN=CC=C1O PIXSVCSUXPWQTB-KHVHVRLGSA-N 0.000 claims 1
- NOWPDELKMGMGII-RRFAQUSLSA-N 3-[5-[(e,4s)-4-(methylamino)pent-1-enyl]pyridin-3-yl]oxybenzonitrile Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC=2C=C(C=CC=2)C#N)=C1 NOWPDELKMGMGII-RRFAQUSLSA-N 0.000 claims 1
- DFZACDPSAHYHSF-FNORWQNLSA-N 3-ethoxy-5-[(e)-4-(methylamino)pent-1-enyl]-1h-pyridin-4-one Chemical compound CCOC1=CN=CC(\C=C\CC(C)NC)=C1O DFZACDPSAHYHSF-FNORWQNLSA-N 0.000 claims 1
- XGGAWFDOIDZRPI-UHFFFAOYSA-N 4,6-Dihydroxy Natural products C1=C2OCOC2=CC(C2OC(C3C(OC(O)C32)C=2C=C3OCOC3=CC=2)O)=C1 XGGAWFDOIDZRPI-UHFFFAOYSA-N 0.000 claims 1
- BXDOQSYLYHHEHO-HWKANZROSA-N 5-[(e)-4-(methylamino)pent-1-enyl]-1h-pyrimidin-6-one Chemical compound CNC(C)C\C=C\C1=CN=CN=C1O BXDOQSYLYHHEHO-HWKANZROSA-N 0.000 claims 1
- WFZOTTWUEQVHFR-DUXPYHPUSA-N 5-[(e)-4-aminopent-1-enyl]-1h-pyrimidin-6-one Chemical compound CC(N)C\C=C\C1=CN=CN=C1O WFZOTTWUEQVHFR-DUXPYHPUSA-N 0.000 claims 1
- 125000006416 CBr Chemical group BrC* 0.000 claims 1
- 125000000815 N-oxide group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001391 thioamide group Chemical group 0.000 claims 1
- 239000000651 prodrug Substances 0.000 abstract description 32
- 229940002612 prodrug Drugs 0.000 abstract description 32
- 230000003957 neurotransmitter release Effects 0.000 abstract description 18
- 150000001204 N-oxides Chemical class 0.000 abstract description 15
- 239000002207 metabolite Substances 0.000 abstract description 15
- 239000000243 solution Substances 0.000 description 120
- 239000000523 sample Substances 0.000 description 89
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- 230000000694 effects Effects 0.000 description 53
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 41
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- 238000009835 boiling Methods 0.000 description 12
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
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- ASEHPOZWQJRWAD-UHFFFAOYSA-N 3-bromo-5-propan-2-yloxypyridine Chemical compound CC(C)OC1=CN=CC(Br)=C1 ASEHPOZWQJRWAD-UHFFFAOYSA-N 0.000 description 11
- 230000003213 activating effect Effects 0.000 description 11
- 125000002252 acyl group Chemical group 0.000 description 11
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- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 11
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- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
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- 230000001568 sexual effect Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
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- 210000003568 synaptosome Anatomy 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
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- NMAOMERZNZONCN-CSKARUKUSA-N tert-butyl n-[(e)-5-(5-ethoxypyridin-3-yl)pent-4-en-2-yl]-n-methylcarbamate Chemical compound CCOC1=CN=CC(\C=C\CC(C)N(C)C(=O)OC(C)(C)C)=C1 NMAOMERZNZONCN-CSKARUKUSA-N 0.000 description 1
- PEPIRCDIOZEULJ-VQHVLOKHSA-N tert-butyl n-[(e)-5-(6-methoxypyridin-3-yl)pent-4-en-2-yl]-n-methylcarbamate Chemical compound COC1=CC=C(\C=C\CC(C)N(C)C(=O)OC(C)(C)C)C=N1 PEPIRCDIOZEULJ-VQHVLOKHSA-N 0.000 description 1
- RFHBVZLFGHWDMM-CSKARUKUSA-N tert-butyl n-methyl-n-[(e)-5-(5-propan-2-yloxypyridin-3-yl)pent-4-en-2-yl]carbamate Chemical compound CC(C)OC1=CN=CC(\C=C\CC(C)N(C)C(=O)OC(C)(C)C)=C1 RFHBVZLFGHWDMM-CSKARUKUSA-N 0.000 description 1
- PNFWHONOKRKZCD-RMKNXTFCSA-N tert-butyl n-methyl-n-[(e)-5-pyridin-3-ylpent-4-en-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N(C)C(C)C\C=C\C1=CC=CN=C1 PNFWHONOKRKZCD-RMKNXTFCSA-N 0.000 description 1
- UYAHMEHKJGGHBP-UHFFFAOYSA-N tert-butyl n-methyl-n-pent-4-en-2-ylcarbamate;tert-butyl (2-methylpropan-2-yl)oxycarbonyl carbonate Chemical compound C=CCC(C)N(C)C(=O)OC(C)(C)C.CC(C)(C)OC(=O)OC(=O)OC(C)(C)C UYAHMEHKJGGHBP-UHFFFAOYSA-N 0.000 description 1
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000008733 trauma Effects 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/263,083 US6979695B2 (en) | 1996-04-23 | 2002-10-02 | Compounds capable of activating cholinergic receptors |
| PCT/US2003/031188 WO2004031151A1 (en) | 2002-10-02 | 2003-10-01 | Compounds capable of activating cholinergic receptors |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2011051171A Division JP2011144192A (ja) | 2002-10-02 | 2011-03-09 | コリン作動性受容体を活性化できる化合物 |
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| JP2006511482A true JP2006511482A (ja) | 2006-04-06 |
| JP2006511482A5 JP2006511482A5 (enExample) | 2009-10-22 |
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| JP2011051171A Pending JP2011144192A (ja) | 2002-10-02 | 2011-03-09 | コリン作動性受容体を活性化できる化合物 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2011051171A Pending JP2011144192A (ja) | 2002-10-02 | 2011-03-09 | コリン作動性受容体を活性化できる化合物 |
Country Status (6)
| Country | Link |
|---|---|
| US (4) | US6979695B2 (enExample) |
| EP (2) | EP1556352A1 (enExample) |
| JP (2) | JP2006511482A (enExample) |
| AU (1) | AU2003282908B2 (enExample) |
| CA (1) | CA2501335C (enExample) |
| WO (1) | WO2004031151A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010516684A (ja) * | 2007-01-22 | 2010-05-20 | ターガセプト・インコーポレイテッド | メタニコチンアナログの鼻腔内、バッカル、または舌下投与 |
| JP2010535237A (ja) * | 2007-07-31 | 2010-11-18 | ターガセプト・インコーポレイテッド | (2s)−(4e)−n−メチル−5−(3−(5−イソプロポキシピリジン)イル)−4−ペンテン−2−アミンの経皮投与 |
| JP2013528601A (ja) * | 2010-05-20 | 2013-07-11 | アストラゼネカ・アクチエボラーグ | アリール置換オレフィン系アミンの新規な製造方法 |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6979695B2 (en) * | 1996-04-23 | 2005-12-27 | Targacept, Inc. | Compounds capable of activating cholinergic receptors |
| US7790757B2 (en) * | 1998-06-16 | 2010-09-07 | Targacept, Inc. | Compounds capable of activating cholinergic receptors |
| ATE442822T1 (de) * | 2004-04-02 | 2009-10-15 | Arterial Remodelling Technolog | Stentanordnung auf polymerbasis |
| US7459469B2 (en) | 2004-11-10 | 2008-12-02 | Targacept, Inc. | Hydroxybenzoate salts of metanicotine compounds |
| WO2007027729A1 (en) | 2005-08-29 | 2007-03-08 | Vertex Pharmaceuticals Incorporated | 3, 5-disubstituted pyrid-2-ones useful as inhibitors of tec family of non-receptor tyrosine kinases |
| ATE548363T1 (de) | 2005-08-29 | 2012-03-15 | Vertex Pharma | 3,5-disubstituierte pyrid-2-one, die sich als inhibitoren der tec-familie von nicht-rezeptor- tyrosinkinasen eignen |
| ES2361338T3 (es) | 2005-08-29 | 2011-06-16 | Vertex Pharmaceuticals Incorporated | Pirid-2-onas 3,5-disustituidas útiles como inhibidores de la familia tec de tirosina quinasas no ligadas a receptor. |
| TWI389889B (zh) | 2006-05-09 | 2013-03-21 | Targacept Inc | (2s)-(4e)-n-甲基-5-〔3-(5-異丙氧基吡啶)基〕-4-戊烯-2-胺之新穎多晶型 |
| EP2357174A1 (en) | 2006-05-09 | 2011-08-17 | AstraZeneca AB | Salt forms of (2S)-(4E)-N-Methyl-5-[(5-Isopropoxy)pyridin-3-yl]-4-penten-2-amine |
| WO2009018367A2 (en) * | 2007-07-31 | 2009-02-05 | Targacept, Inc. | Novel salt forms of (2s)-(4e)-n-methyl-5-[3-(5-methoxypyridin)yl]-4-penten-2-amine |
| US9463190B2 (en) | 2008-03-31 | 2016-10-11 | University Of South Florida | Methods of treating disease-induced ataxia and non-ataxic imbalance |
| US9488490B2 (en) | 2014-04-02 | 2016-11-08 | Here Global B.V. | Storing and accessing traffic data images in a limited bandwidth environment |
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| US5616716A (en) * | 1996-01-06 | 1997-04-01 | Dull; Gary M. | (3-(5-ethoxypyridin)yl)-alkenyl 1 amine compounds |
| JP2000509041A (ja) * | 1996-04-23 | 2000-07-18 | アール・ジェイ・レイノルズ・タバコ・カンパニー | 中枢神経系障害の予防及び治療のための医薬組成物 |
| WO2000075110A1 (en) * | 1999-06-07 | 2000-12-14 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
| WO2001017943A1 (en) * | 1999-09-08 | 2001-03-15 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
| JP2001512486A (ja) * | 1997-02-21 | 2001-08-21 | アール・ジェイ・レイノルズ・タバコ・カンパニー | アリール置換オレフィン型アミン化合物を含む医薬組成物 |
| JP2001520628A (ja) * | 1995-01-06 | 2001-10-30 | アール・ジェイ・レイノルズ・タバコ・カンパニー | 中枢神経系疾患の予防及び治療のための医薬組成物 |
| US20020052497A1 (en) * | 2000-03-09 | 2002-05-02 | Targacept, Inc. | Compounds capable of activating cholinergic receptors |
| JP2002518373A (ja) * | 1998-06-16 | 2002-06-25 | ターガセプト,インコーポレイテッド | アリール置換オレフィンアミンと、コリン受容体アゴニストとしてのアリール置換オレフィンアミンの使用 |
| JP2002522390A (ja) * | 1998-08-07 | 2002-07-23 | ターガセプト,インコーポレイテッド | 中枢神経系疾患の予防と治療のための医薬組成物 |
| JP2004503589A (ja) * | 2000-07-14 | 2004-02-05 | ターガセプト,インコーポレイテッド | E−メタニコチンのジアシル酒石酸塩を含有する組成物 |
| JP2004509851A (ja) * | 2000-07-14 | 2004-04-02 | ターガセプト,インコーポレイテッド | 神経疾患治療用医薬組成物 |
Family Cites Families (27)
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2010516684A (ja) * | 2007-01-22 | 2010-05-20 | ターガセプト・インコーポレイテッド | メタニコチンアナログの鼻腔内、バッカル、または舌下投与 |
| JP2014098000A (ja) * | 2007-01-22 | 2014-05-29 | Targacept Inc | メタニコチンアナログの鼻腔内、バッカル、または舌下投与 |
| JP2010535237A (ja) * | 2007-07-31 | 2010-11-18 | ターガセプト・インコーポレイテッド | (2s)−(4e)−n−メチル−5−(3−(5−イソプロポキシピリジン)イル)−4−ペンテン−2−アミンの経皮投与 |
| JP2013528601A (ja) * | 2010-05-20 | 2013-07-11 | アストラゼネカ・アクチエボラーグ | アリール置換オレフィン系アミンの新規な製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2501335C (en) | 2012-02-28 |
| CA2501335A1 (en) | 2004-04-15 |
| AU2003282908B2 (en) | 2009-05-28 |
| US20050148611A1 (en) | 2005-07-07 |
| WO2004031151A1 (en) | 2004-04-15 |
| JP2011144192A (ja) | 2011-07-28 |
| US6979695B2 (en) | 2005-12-27 |
| US20060293289A1 (en) | 2006-12-28 |
| EP2253616A1 (en) | 2010-11-24 |
| EP1556352A1 (en) | 2005-07-27 |
| US7045538B2 (en) | 2006-05-16 |
| US20100121061A1 (en) | 2010-05-13 |
| US20030125345A1 (en) | 2003-07-03 |
| AU2003282908A1 (en) | 2004-04-23 |
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