CA2622677A1 - Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof - Google Patents

Info

Publication number

CA2622677A1

CA2622677A1 CA002622677A CA2622677A CA2622677A1 CA 2622677 A1 CA2622677 A1 CA 2622677A1 CA 002622677 A CA002622677 A CA 002622677A CA 2622677 A CA2622677 A CA 2622677A CA 2622677 A1 CA2622677 A1 CA 2622677A1

Authority

CA

Canada

Prior art keywords

carbon atoms

alkyl

oct

azabicyclo

carboxamide

Prior art date

2005-09-23

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 title abstract description 10
• 150000002473 indoazoles Chemical class 0.000 title abstract 2
• 238000002360 preparation method Methods 0.000 title description 12
• CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical class C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 title description 6
• 150000005229 pyrazolopyridines Chemical class 0.000 title description 2
• YJMPFOXUBAJFFA-UHFFFAOYSA-N [1,2]thiazolo[4,3-b]pyridine Chemical class C1=CC=NC2=CSN=C21 YJMPFOXUBAJFFA-UHFFFAOYSA-N 0.000 title 1
• 150000008316 benzisoxazoles Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 337
• 238000000034 method Methods 0.000 claims abstract description 152
• 239000000203 mixture Substances 0.000 claims abstract description 58
• 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims abstract description 36
• 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims abstract description 36
• 238000011282 treatment Methods 0.000 claims abstract description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
• 201000010099 disease Diseases 0.000 claims abstract description 20
• 230000004913 activation Effects 0.000 claims abstract description 9
• 230000002950 deficient Effects 0.000 claims abstract description 5
• 125000004432 carbon atom Chemical group C* 0.000 claims description 1706
• 125000000217 alkyl group Chemical group 0.000 claims description 610
• -1 NR6R7 Chemical group 0.000 claims description 320
• 125000003545 alkoxy group Chemical group 0.000 claims description 188
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 140
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 136
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 113
• 125000003342 alkenyl group Chemical group 0.000 claims description 108
• 125000000304 alkynyl group Chemical group 0.000 claims description 108
• 150000003839 salts Chemical class 0.000 claims description 104
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 102
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 101
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 97
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 66
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 66
• 125000004414 alkyl thio group Chemical group 0.000 claims description 60
• 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
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 53
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 51
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 51
• 229910052736 halogen Inorganic materials 0.000 claims description 47
• 150000002367 halogens Chemical class 0.000 claims description 46
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 44
• 229920006395 saturated elastomer Polymers 0.000 claims description 44
• 125000001424 substituent group Chemical group 0.000 claims description 44
• 229910052801 chlorine Inorganic materials 0.000 claims description 41
• 229910052731 fluorine Inorganic materials 0.000 claims description 41
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
• 102000005962 receptors Human genes 0.000 claims description 39
• 108020003175 receptors Proteins 0.000 claims description 39
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 38
• 125000006413 ring segment Chemical group 0.000 claims description 38
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 37
• 125000003118 aryl group Chemical group 0.000 claims description 37
• 229910052794 bromium Inorganic materials 0.000 claims description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims description 37
• 229910052760 oxygen Inorganic materials 0.000 claims description 37
• 150000001204 N-oxides Chemical class 0.000 claims description 35
• 229910052740 iodine Inorganic materials 0.000 claims description 35
• 125000000623 heterocyclic group Chemical group 0.000 claims description 30
• 125000004423 acyloxy group Chemical group 0.000 claims description 26
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 26
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 23
• 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
• 125000003282 alkyl amino group Chemical group 0.000 claims description 20
• 125000002252 acyl group Chemical group 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
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 18
• 206010012289 Dementia Diseases 0.000 claims description 18
• 208000010877 cognitive disease Diseases 0.000 claims description 18
• 125000004043 oxo group Chemical group O=* 0.000 claims description 17
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
• 238000011321 prophylaxis Methods 0.000 claims description 15
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 14
• 206010027175 memory impairment Diseases 0.000 claims description 14
• 208000000044 Amnesia Diseases 0.000 claims description 13
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 13
• 229910052757 nitrogen Inorganic materials 0.000 claims description 13
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 11
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 11
• 208000026139 Memory disease Diseases 0.000 claims description 10
• 241001465754 Metazoa Species 0.000 claims description 10
• 239000000556 agonist Substances 0.000 claims description 10
• 208000024827 Alzheimer disease Diseases 0.000 claims description 9
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 9
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 9
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
• 201000004810 Vascular dementia Diseases 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 230000006984 memory degeneration Effects 0.000 claims description 8
• 208000023060 memory loss Diseases 0.000 claims description 8
• 230000004770 neurodegeneration Effects 0.000 claims description 8
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
• 208000028698 Cognitive impairment Diseases 0.000 claims description 7
• 208000023105 Huntington disease Diseases 0.000 claims description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
• 208000018737 Parkinson disease Diseases 0.000 claims description 7
• 208000028017 Psychotic 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
• 229910052786 argon Inorganic materials 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
• 230000007278 cognition impairment 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
• 230000000694 effects Effects 0.000 claims description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims description 7
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
• LLSRLLPHUVVLQJ-UHFFFAOYSA-N 1-cycloheptyldiazepane Chemical group C1CCCCCC1N1NCCCCC1 LLSRLLPHUVVLQJ-UHFFFAOYSA-N 0.000 claims description 6
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 6
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 6
• 230000006735 deficit Effects 0.000 claims description 6
• 230000004064 dysfunction Effects 0.000 claims description 6
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 6
• 208000027866 inflammatory disease Diseases 0.000 claims description 6
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 6
• 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 6
• 201000000980 schizophrenia Diseases 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• GGTBELZDHKHESR-UHFFFAOYSA-N 2-cycloheptyloxazepane Chemical group C1CCCCCC1N1OCCCCC1 GGTBELZDHKHESR-UHFFFAOYSA-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
• 208000006011 Stroke Diseases 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• 230000005540 biological transmission Effects 0.000 claims description 5
• 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 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
• 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
• 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
• 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
• CDIIRPQKBBSHHC-OAHLLOKOSA-N n-[(3s)-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-OAHLLOKOSA-N 0.000 claims description 5
• MRWSLRJLSYNXEP-QGZVFWFLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(1,3-oxazol-2-yl)-1-propylindazole-3-carboxamide Chemical compound C1=C2N(CCC)N=C(C(=O)N[C@H]3C4CCN(CC4)C3)C2=CC=C1C1=NC=CO1 MRWSLRJLSYNXEP-QGZVFWFLSA-N 0.000 claims description 5
• HCHKVJNYNKHIGB-GOSISDBHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(1,3-thiazol-2-yl)-1-thiophen-3-ylindazole-3-carboxamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=C(C=C11)C=2SC=CN=2)=NN1C=1C=CSC=1 HCHKVJNYNKHIGB-GOSISDBHSA-N 0.000 claims description 5
• INXSFZUBPUKBAA-PKESZJFOSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-methoxypyrrolidin-1-yl)-1,2-benzothiazole-3-carboxamide;hydrochloride Chemical compound Cl.C1C(OC)CCN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 INXSFZUBPUKBAA-PKESZJFOSA-N 0.000 claims description 5
• MKPGOIZSZGGKGK-CQSZACIVSA-N n-[(3s)-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-CQSZACIVSA-N 0.000 claims description 5
• LJRMDUSLDCDSLB-QGZVFWFLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(furan-3-ylmethoxy)-1,2-benzothiazole-3-carboxamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NSC1=CC=2OCC=1C=COC=1 LJRMDUSLDCDSLB-QGZVFWFLSA-N 0.000 claims description 5
• RTYNUJYXOCMKNQ-FBMWCMRBSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(oxolan-3-yloxy)-1h-indazole-3-carboxamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NNC1=CC=2OC1CCOC1 RTYNUJYXOCMKNQ-FBMWCMRBSA-N 0.000 claims description 5
• VHMKMIXTXOLLSO-MRXNPFEDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-n-methyl-6-(1,3-oxazol-2-yl)-1h-indazole-3-carboxamide Chemical compound CN([C@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NNC1=CC=2C1=NC=CO1 VHMKMIXTXOLLSO-MRXNPFEDSA-N 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• 208000011580 syndromic disease Diseases 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 4
• JPJAHTRBVGIFET-KGLQGEEPSA-N 6-(cyclopropylmethoxy)-n-[(3s)-1-(cyclopropylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-1,2-benzothiazole-3-carboxamide;bromide Chemical compound [Br-].C([C@H](C(CC1)CC2)NC(=O)C=3C4=CC=C(OCC5CC5)C=C4SN=3)[N+]21CC1CC1 JPJAHTRBVGIFET-KGLQGEEPSA-N 0.000 claims description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
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• 206010044221 Toxic encephalopathy Diseases 0.000 claims description 4
• 230000003213 activating effect Effects 0.000 claims description 4
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• 150000001450 anions Chemical class 0.000 claims description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 230000001939 inductive effect Effects 0.000 claims description 4
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• 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 4
• 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 4
• 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 4
• 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 4
• 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 4
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• 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 3
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• 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 3
• 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 3
• KJGZTJYVDPCJFK-KPMSDPLLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(1-methylpyrrolidin-3-yl)oxy-1h-indazole-3-carboxamide Chemical compound C1N(C)CCC1OC1=CC=C(C(=NN2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 KJGZTJYVDPCJFK-KPMSDPLLSA-N 0.000 claims 3
• QANNTZCRFNSNGO-OMOCHNIRSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-methoxypyrrolidin-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound C1C(OC)CCN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 QANNTZCRFNSNGO-OMOCHNIRSA-N 0.000 claims 3
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• DLARADLKNHHUJE-INIZCTEOSA-N n-[(3r)-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-INIZCTEOSA-N 0.000 claims 2
• AHPNHYFJXZOJDZ-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-1,2-benzothiazole-3-carboxamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NSC1=CC=2N1CCN2CCC1CC2 AHPNHYFJXZOJDZ-IBGZPJMESA-N 0.000 claims 2
• OPCOSSJANZPAQC-OYKVQYDMSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(1-azabicyclo[2.2.2]octan-3-yloxy)-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2C1OC1=CC=C2C(C(N[C@@H]3C4CCN(CC4)C3)=O)=NSC2=C1 OPCOSSJANZPAQC-OYKVQYDMSA-N 0.000 claims 2
• SERHSHYNJAZWGI-RUINGEJQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(2-methylpiperazin-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound CC1CNCCN1C1=CC=C(C(=NS2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 SERHSHYNJAZWGI-RUINGEJQSA-N 0.000 claims 2
• QWUQHEDELPXYKR-RUINGEJQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-methylpiperazin-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound C1CNC(C)CN1C1=CC=C(C(=NS2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 QWUQHEDELPXYKR-RUINGEJQSA-N 0.000 claims 2
• ILUNTYBAPOBZGE-HNNXBMFYSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4,5-dihydro-1h-imidazol-2-yl)-1h-indazole-3-carboxamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NNC1=CC=2C1=NCCN1 ILUNTYBAPOBZGE-HNNXBMFYSA-N 0.000 claims 2
• AIEYPFNAZAQGDT-SFHVURJKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4-methyl-1,4-diazepan-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound C1CN(C)CCCN1C1=CC=C(C(=NS2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 AIEYPFNAZAQGDT-SFHVURJKSA-N 0.000 claims 2
• YIPLPZONCABMSW-QRTARXTBSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(1s,4s)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=NSC2=CC(N3C[C@]4(NC[C@]3([H])C4)[H])=CC=C21 YIPLPZONCABMSW-QRTARXTBSA-N 0.000 claims 2
• 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 2
• SALPMAXLHRQAPQ-QUENFVSXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[1-(cyclopropanecarbonyl)-3,4,4a,5,7,7a-hexahydro-2h-pyrrolo[3,4-b]pyridin-6-yl]-1,2-benzothiazole-3-carboxamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NSC1=CC=2N(CC12)CC1CCCN2C(=O)C1CC1 SALPMAXLHRQAPQ-QUENFVSXSA-N 0.000 claims 2
• SEZMMIPOBTXTEA-WMCAAGNKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[3-(dimethylamino)pyrrolidin-1-yl]-2h-pyrazolo[3,4-b]pyridine-3-carboxamide Chemical compound C1C(N(C)C)CCN1C1=CC=C(C(=NN2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=N1 SEZMMIPOBTXTEA-WMCAAGNKSA-N 0.000 claims 2
• OFFFQICGZLVGEA-JRZJBTRGSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[3-(methylamino)pyrrolidin-1-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1C(NC)CCN1C1=CC=C(C(=NS2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 OFFFQICGZLVGEA-JRZJBTRGSA-N 0.000 claims 2
• VXPJCAZSXDAAAL-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-methoxy-1,2-benzoxazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=NOC2=CC(OC)=CC=C21 VXPJCAZSXDAAAL-ZDUSSCGKSA-N 0.000 claims 2
• OZIYFRRXGPXXDW-INIZCTEOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-piperazin-1-yl-1,2-benzothiazole-3-carboxamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NSC1=CC=2N1CCNCC1 OZIYFRRXGPXXDW-INIZCTEOSA-N 0.000 claims 2
• PIDKUZOOEPTSPI-RDJZCZTQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=CC2=C1SN=C2C(=O)N[C@@H]1C(CC2)CCN2C1 PIDKUZOOEPTSPI-RDJZCZTQSA-N 0.000 claims 2
• XDPQUPREVRZXNO-NSHDSACASA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-fluoro-6-methoxy-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=NSC2=C(F)C(OC)=CC=C21 XDPQUPREVRZXNO-NSHDSACASA-N 0.000 claims 2
• ZGGYIVUEFFUZRX-GFCCVEGCSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1h-pyrazolo[3,4-c]pyridine-3-carboxamide Chemical compound N1=CC=C2C(C(N[C@H]3C4CCN(CC4)C3)=O)=NNC2=C1 ZGGYIVUEFFUZRX-GFCCVEGCSA-N 0.000 claims 2
• OPCOSSJANZPAQC-MRTLOADZSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(1-azabicyclo[2.2.2]octan-3-yloxy)-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2C1OC1=CC=C2C(C(N[C@H]3C4CCN(CC4)C3)=O)=NSC2=C1 OPCOSSJANZPAQC-MRTLOADZSA-N 0.000 claims 2
• UFVCXVYNCMTGHK-MRXNPFEDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(1-methyl-4,5-dihydroimidazol-2-yl)-1h-indazole-3-carboxamide Chemical compound CN1CCN=C1C1=CC=C(C(=NN2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 UFVCXVYNCMTGHK-MRXNPFEDSA-N 0.000 claims 2
• WGFXFRVKAYTEOV-MRXNPFEDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-ethyl-2-oxoimidazolidin-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound O=C1N(CC)CCN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 WGFXFRVKAYTEOV-MRXNPFEDSA-N 0.000 claims 2
• JCBHEXJAZCRMNJ-MRXNPFEDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-methylpyrazol-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound N1=C(C)C=CN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 JCBHEXJAZCRMNJ-MRXNPFEDSA-N 0.000 claims 2
• AIEYPFNAZAQGDT-GOSISDBHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4-methyl-1,4-diazepan-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound C1CN(C)CCCN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 AIEYPFNAZAQGDT-GOSISDBHSA-N 0.000 claims 2
• GPWNPAULGBLLEA-FAFZWHIHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(5-methyl-2,5-diazabicyclo[2.2.2]octan-2-yl)-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NSC2=CC(N3CC4CCC3CN4C)=CC=C21 GPWNPAULGBLLEA-FAFZWHIHSA-N 0.000 claims 2
• ZYXWSPGDIGRWLF-MRXNPFEDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(5-methylpyrazol-1-yl)-1,2-benzothiazole-3-carboxamide Chemical compound CC1=CC=NN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 ZYXWSPGDIGRWLF-MRXNPFEDSA-N 0.000 claims 2
• IVYWDRAWLTUMFE-FAFZWHIHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NSC2=CC(N3CC4CCC(C3)N4C)=CC=C21 IVYWDRAWLTUMFE-FAFZWHIHSA-N 0.000 claims 2
• YIPLPZONCABMSW-JLJPHGGASA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(1s,4s)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NSC2=CC(N3C[C@]4(NC[C@]3([H])C4)[H])=CC=C21 YIPLPZONCABMSW-JLJPHGGASA-N 0.000 claims 2
• QWSOZFFRWVKTNH-YQQAZPJKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NSC2=CC(N3C[C@]4(OC[C@]3([H])C4)[H])=CC=C21 QWSOZFFRWVKTNH-YQQAZPJKSA-N 0.000 claims 2
• DQWZCYLIBXHEIN-XYJFISCASA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=NSC2=CC(N3C[C@]4(N(C[C@]3([H])C4)C)[H])=CC=C21 DQWZCYLIBXHEIN-XYJFISCASA-N 0.000 claims 2
• MQHHLXJJSOOTSK-GDBMZVCRSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1[C@H](O)CCN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 MQHHLXJJSOOTSK-GDBMZVCRSA-N 0.000 claims 2
• CHHKUKIZVHLZHF-FUHWJXTLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 CHHKUKIZVHLZHF-FUHWJXTLSA-N 0.000 claims 2
• MQHHLXJJSOOTSK-GOEBONIOSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(3s)-3-hydroxypyrrolidin-1-yl]-1,2-benzothiazole-3-carboxamide Chemical compound C1[C@@H](O)CCN1C1=CC=C(C(=NS2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 MQHHLXJJSOOTSK-GOEBONIOSA-N 0.000 claims 2
• VJGNOXVGSIIBKG-DOTOQJQBSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(3s)-3-methoxypyrrolidin-1-yl]-1,2-benzoxazole-3-carboxamide Chemical compound C1[C@@H](OC)CCN1C1=CC=C(C(=NO2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=C1 VJGNOXVGSIIBKG-DOTOQJQBSA-N 0.000 claims 2
• SALPMAXLHRQAPQ-NFOQDIRWSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[1-(cyclopropanecarbonyl)-3,4,4a,5,7,7a-hexahydro-2h-pyrrolo[3,4-b]pyridin-6-yl]-1,2-benzothiazole-3-carboxamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(C1=CC=2)=NSC1=CC=2N(CC12)CC1CCCN2C(=O)C1CC1 SALPMAXLHRQAPQ-NFOQDIRWSA-N 0.000 claims 2
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• SEZMMIPOBTXTEA-BZSJEYESSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-6-[3-(dimethylamino)pyrrolidin-1-yl]-2h-pyrazolo[3,4-b]pyridine-3-carboxamide Chemical compound C1C(N(C)C)CCN1C1=CC=C(C(=NN2)C(=O)N[C@H]3C4CCN(CC4)C3)C2=N1 SEZMMIPOBTXTEA-BZSJEYESSA-N 0.000 claims 2
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