KR20080048550A - 인다졸, 벤조티아졸, 벤조이소티아졸, 벤즈이속사졸,피라졸로피리딘, 이소티아졸로피리딘, 및 이들의 제법 및용도 - Google Patents
인다졸, 벤조티아졸, 벤조이소티아졸, 벤즈이속사졸,피라졸로피리딘, 이소티아졸로피리딘, 및 이들의 제법 및용도 Download PDFInfo
- Publication number
- KR20080048550A KR20080048550A KR1020087009574A KR20087009574A KR20080048550A KR 20080048550 A KR20080048550 A KR 20080048550A KR 1020087009574 A KR1020087009574 A KR 1020087009574A KR 20087009574 A KR20087009574 A KR 20087009574A KR 20080048550 A KR20080048550 A KR 20080048550A
- Authority
- KR
- South Korea
- Prior art keywords
- carbon atoms
- alkyl
- azabicyclo
- oct
- carboxamide
- 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.)
- Ceased
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- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 title abstract description 12
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 title abstract description 7
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 title description 6
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 title description 6
- 238000002360 preparation method Methods 0.000 title description 4
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 title 1
- YJMPFOXUBAJFFA-UHFFFAOYSA-N [1,2]thiazolo[4,3-b]pyridine Chemical compound C1=CC=NC2=CSN=C21 YJMPFOXUBAJFFA-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 307
- 238000000034 method Methods 0.000 claims abstract description 155
- 239000000203 mixture Substances 0.000 claims abstract description 57
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims abstract description 42
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims abstract description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 32
- 201000010099 disease Diseases 0.000 claims abstract description 27
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 208000024891 symptom Diseases 0.000 claims abstract description 13
- 230000004064 dysfunction Effects 0.000 claims abstract description 10
- 230000004913 activation Effects 0.000 claims abstract description 9
- 230000007812 deficiency Effects 0.000 claims abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 1567
- 125000000217 alkyl group Chemical group 0.000 claims description 598
- -1 NH 2 Chemical group 0.000 claims description 309
- 125000003545 alkoxy group Chemical group 0.000 claims description 186
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 138
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 121
- 125000003342 alkenyl group Chemical group 0.000 claims description 108
- 125000000304 alkynyl group Chemical group 0.000 claims description 104
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 104
- 150000003839 salts Chemical class 0.000 claims description 101
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 97
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 95
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 93
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 72
- 125000004414 alkyl thio group Chemical group 0.000 claims description 60
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 59
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 58
- 239000012453 solvate Substances 0.000 claims description 56
- 239000012458 free base Substances 0.000 claims description 55
- 229910052760 oxygen Inorganic materials 0.000 claims description 54
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 52
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 51
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 50
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 47
- 229910052736 halogen Inorganic materials 0.000 claims description 47
- 229910052731 fluorine Inorganic materials 0.000 claims description 46
- 150000002367 halogens Chemical class 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 43
- 229920006395 saturated elastomer Polymers 0.000 claims description 43
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 229910052801 chlorine Inorganic materials 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 38
- 230000036961 partial effect Effects 0.000 claims description 38
- 125000006413 ring segment Chemical group 0.000 claims description 38
- 229910052794 bromium Inorganic materials 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 36
- 229910052740 iodine Inorganic materials 0.000 claims description 36
- 102000005962 receptors Human genes 0.000 claims description 35
- 108020003175 receptors Proteins 0.000 claims description 35
- 150000001204 N-oxides Chemical class 0.000 claims description 33
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 239000000126 substance Substances 0.000 claims description 28
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 27
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 26
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 24
- 125000002252 acyl group Chemical group 0.000 claims description 22
- 125000004423 acyloxy group Chemical group 0.000 claims description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims description 21
- 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 20
- 206010012289 Dementia Diseases 0.000 claims description 19
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 19
- 125000004434 sulfur atom Chemical group 0.000 claims description 19
- 208000010877 cognitive disease Diseases 0.000 claims description 18
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
- 206010027175 memory impairment Diseases 0.000 claims description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 15
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 14
- 208000028698 Cognitive impairment Diseases 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 13
- 208000000044 Amnesia Diseases 0.000 claims description 13
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 13
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 12
- 208000026139 Memory disease Diseases 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 11
- 230000006984 memory degeneration Effects 0.000 claims description 11
- 208000023060 memory loss Diseases 0.000 claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 11
- 239000000556 agonist Substances 0.000 claims description 10
- 229910052786 argon Inorganic materials 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims description 9
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 125000005110 aryl thio group Chemical group 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 230000027455 binding Effects 0.000 claims description 7
- 125000002837 carbocyclic group Chemical group 0.000 claims description 7
- 230000001713 cholinergic effect Effects 0.000 claims description 7
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 230000015654 memory Effects 0.000 claims description 7
- 229960002715 nicotine Drugs 0.000 claims description 7
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 210000002569 neuron Anatomy 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- LLSRLLPHUVVLQJ-UHFFFAOYSA-N 1-cycloheptyldiazepane Chemical group C1CCCCCC1N1NCCCCC1 LLSRLLPHUVVLQJ-UHFFFAOYSA-N 0.000 claims description 5
- DNAZCSLXJXKFSN-VJIKYCBLSA-N 5-hydroxy-n-[(3s)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl]-1,2-benzothiazole-3-carboxamide;iodide Chemical compound [I-].C1=C(O)C=C2C(C(=O)N[C@H]3C4CC[N+](CC4)(C3)C)=NSC2=C1 DNAZCSLXJXKFSN-VJIKYCBLSA-N 0.000 claims description 5
- JLIHVNUIYBYZPX-LLVKDONJSA-N N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-4-hydroxy-1H-indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NNC2=C1C(O)=CC=C2 JLIHVNUIYBYZPX-LLVKDONJSA-N 0.000 claims description 5
- ACFJWUDIYCFUQS-SNVBAGLBSA-N N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-5,7-dibromo-4-hydroxy-2H-indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NNC2=C1C(O)=C(Br)C=C2Br ACFJWUDIYCFUQS-SNVBAGLBSA-N 0.000 claims description 5
- VVFPTCPKNDXWBF-LLVKDONJSA-N N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-5-bromo-4-hydroxy-1H-indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NNC2=C1C(O)=C(Br)C=C2 VVFPTCPKNDXWBF-LLVKDONJSA-N 0.000 claims description 5
- GLTWIURZTPMBTA-GFCCVEGCSA-N N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-hydroxy-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NSC2=CC(O)=CC=C21 GLTWIURZTPMBTA-GFCCVEGCSA-N 0.000 claims description 5
- 201000004810 Vascular dementia Diseases 0.000 claims description 5
- 230000007000 age related cognitive decline Effects 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 5
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 5
- LJEXBQWZLZFSSN-HNNXBMFYSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-ethyl-6-methoxyindazole-3-carboxamide Chemical compound C12=CC=C(OC)C=C2N(CC)N=C1C(=O)N[C@@H]1C(CC2)CCN2C1 LJEXBQWZLZFSSN-HNNXBMFYSA-N 0.000 claims description 5
- NBLLSKMFNOYWGA-AWEZNQCLSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-(difluoromethoxy)-n-methyl-1h-indazole-3-carboxamide Chemical compound C1=C(OC(F)F)C=C2C(C(=O)N([C@@H]3C4CCN(CC4)C3)C)=NNC2=C1 NBLLSKMFNOYWGA-AWEZNQCLSA-N 0.000 claims description 5
- CDIIRPQKBBSHHC-HNNXBMFYSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-methoxy-n-methyl-1h-indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1N(C)C(=O)C1=NNC2=CC=C(OC)C=C21 CDIIRPQKBBSHHC-HNNXBMFYSA-N 0.000 claims description 5
- MKPGOIZSZGGKGK-AWEZNQCLSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(difluoromethoxy)-n-methyl-1h-indazole-3-carboxamide Chemical compound FC(F)OC1=CC=C2C(C(=O)N([C@@H]3C4CCN(CC4)C3)C)=NNC2=C1 MKPGOIZSZGGKGK-AWEZNQCLSA-N 0.000 claims description 5
- NCJUWMDMIHBGSN-AWEZNQCLSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-methoxy-n-methyl-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1N(C)C(=O)C1=NSC2=CC(OC)=CC=C21 NCJUWMDMIHBGSN-AWEZNQCLSA-N 0.000 claims description 5
- GETRXZCCCNYYIV-HNNXBMFYSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-methoxy-n-methyl-1h-indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1N(C)C(=O)C1=NNC2=CC(OC)=CC=C21 GETRXZCCCNYYIV-HNNXBMFYSA-N 0.000 claims description 5
- RDSODELYJDFMBF-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-n-methyl-5-(oxan-4-yl)-1h-indazole-3-carboxamide Chemical compound CN([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=C2)=NNC1=CC=C2C1CCOCC1 RDSODELYJDFMBF-IBGZPJMESA-N 0.000 claims description 5
- YMWLIMACGUHANC-INIZCTEOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-n-methyl-6-(1,3-thiazol-2-yl)-1h-indazole-3-carboxamide Chemical compound CN([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NNC1=CC=2C1=NC=CS1 YMWLIMACGUHANC-INIZCTEOSA-N 0.000 claims description 5
- WQLZMRXMTRRRQR-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-n-methyl-6-(oxan-4-yl)-1h-indazole-3-carboxamide Chemical compound CN([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NNC1=CC=2C1CCOCC1 WQLZMRXMTRRRQR-IBGZPJMESA-N 0.000 claims description 5
- KPKFCXSWRVNEBQ-GOSISDBHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-(cyclopropylmethyl)-6-(1,3-oxazol-2-yl)indazole-3-carboxamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=C(C=C11)C=2OC=CN=2)=NN1CC1CC1 KPKFCXSWRVNEBQ-GOSISDBHSA-N 0.000 claims description 5
- YLWNWPRABKNCGA-CQSZACIVSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-(difluoromethyl)-6-(1,3-thiazol-2-yl)indazole-3-carboxamide Chemical compound C1=C2N(C(F)F)N=C(C(=O)N[C@H]3C4CCN(CC4)C3)C2=CC=C1C1=NC=CS1 YLWNWPRABKNCGA-CQSZACIVSA-N 0.000 claims description 5
- PGEHQXWFCPTXLO-OAHLLOKOSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-(difluoromethyl)-6-(propylcarbamoylamino)indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NN(C(F)F)C2=CC(NC(=O)NCCC)=CC=C21 PGEHQXWFCPTXLO-OAHLLOKOSA-N 0.000 claims description 5
- VQDFGMVDXFKJGX-CYBMUJFWSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-(difluoromethyl)-6-methoxyindazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NN(C(F)F)C2=CC(OC)=CC=C21 VQDFGMVDXFKJGX-CYBMUJFWSA-N 0.000 claims description 5
- SMJVOFILIBVERT-GOSISDBHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-cyclopropyl-6-(propylcarbamoylamino)indazole-3-carboxamide Chemical compound C12=CC(NC(=O)NCCC)=CC=C2C(C(=O)N[C@H]2C3CCN(CC3)C2)=NN1C1CC1 SMJVOFILIBVERT-GOSISDBHSA-N 0.000 claims description 5
- DLARADLKNHHUJE-MRXNPFEDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-ethyl-6-(1,3-oxazol-2-yl)indazole-3-carboxamide Chemical compound C1=C2N(CC)N=C(C(=O)N[C@H]3C4CCN(CC4)C3)C2=CC=C1C1=NC=CO1 DLARADLKNHHUJE-MRXNPFEDSA-N 0.000 claims description 5
- MMPSJJWTNKNLSB-QGZVFWFLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-ethyl-6-(2-oxopyrrolidin-1-yl)indazole-3-carboxamide Chemical compound C1=C2N(CC)N=C(C(=O)N[C@H]3C4CCN(CC4)C3)C2=CC=C1N1CCCC1=O MMPSJJWTNKNLSB-QGZVFWFLSA-N 0.000 claims description 5
- LJEXBQWZLZFSSN-OAHLLOKOSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-ethyl-6-methoxyindazole-3-carboxamide Chemical compound C12=CC=C(OC)C=C2N(CC)N=C1C(=O)N[C@H]1C(CC2)CCN2C1 LJEXBQWZLZFSSN-OAHLLOKOSA-N 0.000 claims description 5
- AOPGWWFRFLXWRH-GOSISDBHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-ethyl-n-methyl-6-(1,3-oxazol-2-yl)indazole-3-carboxamide Chemical compound C1=C2N(CC)N=C(C(=O)N(C)[C@H]3C4CCN(CC4)C3)C2=CC=C1C1=NC=CO1 AOPGWWFRFLXWRH-GOSISDBHSA-N 0.000 claims description 5
- AVAQAIXJHLFBQM-MRXNPFEDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-methyl-6-(propylcarbamoylamino)indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NN(C)C2=CC(NC(=O)NCCC)=CC=C21 AVAQAIXJHLFBQM-MRXNPFEDSA-N 0.000 claims description 5
- IKXVBFQRYVFHDF-QGZVFWFLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-propan-2-yl-6-(1,3-thiazol-2-yl)indazole-3-carboxamide Chemical compound C1=C2N(C(C)C)N=C(C(=O)N[C@H]3C4CCN(CC4)C3)C2=CC=C1C1=NC=CS1 IKXVBFQRYVFHDF-QGZVFWFLSA-N 0.000 claims description 5
- XHLPSFUPKCQDKE-QGZVFWFLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-propyl-6-(1,3-thiazol-2-yl)indazole-3-carboxamide Chemical compound C1=C2N(CCC)N=C(C(=O)N[C@H]3C4CCN(CC4)C3)C2=CC=C1C1=NC=CS1 XHLPSFUPKCQDKE-QGZVFWFLSA-N 0.000 claims description 5
- KALULFQIHKKFCX-CYBMUJFWSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-5,6-dimethoxy-1h-indazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NNC2=C1C=C(OC)C(OC)=C2 KALULFQIHKKFCX-CYBMUJFWSA-N 0.000 claims description 5
- NBLLSKMFNOYWGA-CQSZACIVSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-5-(difluoromethoxy)-n-methyl-1h-indazole-3-carboxamide Chemical compound C1=C(OC(F)F)C=C2C(C(=O)N([C@H]3C4CCN(CC4)C3)C)=NNC2=C1 NBLLSKMFNOYWGA-CQSZACIVSA-N 0.000 claims description 5
- JXJCOTSOYYIMTK-GFCCVEGCSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-5-hydroxy-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NSC2=CC=C(O)C=C21 JXJCOTSOYYIMTK-GFCCVEGCSA-N 0.000 claims description 5
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- DOUKNGQHWNTBGW-BJLQDIEVSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(1s,4s)-5-cyclopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C([C@]1(N(C=2C=C3SN=C(C3=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)C[C@@]2(C1)[H])[H])N2C1CC1 DOUKNGQHWNTBGW-BJLQDIEVSA-N 0.000 claims description 3
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- KRVDZCIJALCFCD-DAFXYXGESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[3-[methyl(2,2,2-trifluoroethyl)amino]pyrrolidin-1-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1C(N(CC(F)(F)F)C)CCN1C1=CC=C(C(=NS2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 KRVDZCIJALCFCD-DAFXYXGESA-N 0.000 claims description 3
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- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
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- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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- 238000000746 purification Methods 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical group C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
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- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 1
- FJYZXKYGRCRNNP-UHFFFAOYSA-N tert-butyl 5-bromo-1,2-benzothiazole-3-carboxylate Chemical compound C1=C(Br)C=C2C(C(=O)OC(C)(C)C)=NSC2=C1 FJYZXKYGRCRNNP-UHFFFAOYSA-N 0.000 description 1
- ULLIEAKUNMXLAM-UHFFFAOYSA-N tert-butyl 6-bromo-1,2-benzothiazole-3-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OC(C)(C)C)=NSC2=C1 ULLIEAKUNMXLAM-UHFFFAOYSA-N 0.000 description 1
- OJSDQXGKXGPFPP-UHFFFAOYSA-N tert-butyl 6-formyl-1h-indazole-3-carboxylate Chemical compound O=CC1=CC=C2C(C(=O)OC(C)(C)C)=NNC2=C1 OJSDQXGKXGPFPP-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
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- 239000003053 toxin Substances 0.000 description 1
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- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
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- LYTCVQQGCSNFJU-LKGYBJPKSA-N α-bungarotoxin Chemical compound C(/[C@H]1O[C@H]2C[C@H]3O[C@@H](CC(=C)C=O)C[C@H](O)[C@]3(C)O[C@@H]2C[C@@H]1O[C@@H]1C2)=C/C[C@]1(C)O[C@H]1[C@@]2(C)O[C@]2(C)CC[C@@H]3O[C@@H]4C[C@]5(C)O[C@@H]6C(C)=CC(=O)O[C@H]6C[C@H]5O[C@H]4C[C@@H](C)[C@H]3O[C@H]2C1 LYTCVQQGCSNFJU-LKGYBJPKSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61P25/16—Anti-Parkinson drugs
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Hematology (AREA)
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- Anesthesiology (AREA)
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- Oncology (AREA)
- Child & Adolescent Psychology (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71955205P | 2005-09-23 | 2005-09-23 | |
| US60/719,552 | 2005-09-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080048550A true KR20080048550A (ko) | 2008-06-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087009574A Ceased KR20080048550A (ko) | 2005-09-23 | 2006-09-22 | 인다졸, 벤조티아졸, 벤조이소티아졸, 벤즈이속사졸,피라졸로피리딘, 이소티아졸로피리딘, 및 이들의 제법 및용도 |
Country Status (12)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101532211B1 (ko) * | 2014-04-30 | 2015-06-30 | 세종대학교산학협력단 | Ampk 억제기능에 기반한 뇌졸중 치료용 약학적 조성물 및 방법 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| US8394842B2 (en) | 2006-03-28 | 2013-03-12 | High Point Pharmaceuticals, Llc | Benzothiazoles having histamine H3 receptor activity |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| AU2008322426C1 (en) * | 2007-11-16 | 2014-10-23 | Rigel Pharmaceuticals, Inc. | Carboxamide, sulfonamide and amine compounds for metabolic disorders |
| CN101952278A (zh) * | 2008-02-15 | 2011-01-19 | 弗·哈夫曼-拉罗切有限公司 | 3-烷基-哌嗪衍生物及其用途 |
| SI2346833T1 (sl) * | 2008-10-13 | 2013-06-28 | F. Hoffmann-La Roche Ag | Postopek brez diazonija za pripravo indazolnega intermediata v sintezi bicikliäśnih amidov 5-(trifluorometoksi)-1h-3-indazolkarboksilne kisline |
| WO2010059844A1 (en) | 2008-11-19 | 2010-05-27 | Envivo Pharmaceuticals, Inc. | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| TWI558398B (zh) | 2009-09-22 | 2016-11-21 | 諾華公司 | 菸鹼乙醯膽鹼受體α７活化劑之用途 |
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2006
- 2006-09-22 BR BRPI0617534-1A patent/BRPI0617534A2/pt not_active IP Right Cessation
- 2006-09-22 CA CA002622677A patent/CA2622677A1/en not_active Abandoned
- 2006-09-22 SG SG201006955-7A patent/SG165417A1/en unknown
- 2006-09-22 CN CNA2006800439794A patent/CN101312968A/zh active Pending
- 2006-09-22 KR KR1020087009574A patent/KR20080048550A/ko not_active Ceased
- 2006-09-22 JP JP2008532459A patent/JP2009509964A/ja active Pending
- 2006-09-22 RU RU2008115268/04A patent/RU2450003C2/ru not_active IP Right Cessation
- 2006-09-22 WO PCT/US2006/037142 patent/WO2007038367A1/en active Application Filing
- 2006-09-22 EP EP06815264A patent/EP1940833A1/en not_active Withdrawn
- 2006-09-22 AU AU2006295397A patent/AU2006295397A1/en not_active Abandoned
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2008
- 2008-03-12 ZA ZA200802342A patent/ZA200802342B/xx unknown
- 2008-03-20 IL IL190358A patent/IL190358A0/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101532211B1 (ko) * | 2014-04-30 | 2015-06-30 | 세종대학교산학협력단 | Ampk 억제기능에 기반한 뇌졸중 치료용 약학적 조성물 및 방법 |
| WO2015167246A1 (ko) * | 2014-04-30 | 2015-11-05 | 세종대학교 산학협력단 | Ａｍｐｋ 억제기능에 기반한 뇌졸중 치료용 약학적 조성물 및 방법 |
Also Published As
| Publication number | Publication date |
|---|---|
| SG165417A1 (en) | 2010-10-28 |
| RU2008115268A (ru) | 2009-10-27 |
| AU2006295397A1 (en) | 2007-04-05 |
| CA2622677A1 (en) | 2007-04-05 |
| IL190358A0 (en) | 2009-09-22 |
| EP1940833A1 (en) | 2008-07-09 |
| ZA200802342B (en) | 2009-03-25 |
| BRPI0617534A2 (pt) | 2011-07-26 |
| RU2450003C2 (ru) | 2012-05-10 |
| CN101312968A (zh) | 2008-11-26 |
| WO2007038367A1 (en) | 2007-04-05 |
| JP2009509964A (ja) | 2009-03-12 |
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