AU2020277027A1 - Compounds for treating huntington's disease - Google Patents
Compounds for treating huntington's disease Download PDFInfo
- Publication number
- AU2020277027A1 AU2020277027A1 AU2020277027A AU2020277027A AU2020277027A1 AU 2020277027 A1 AU2020277027 A1 AU 2020277027A1 AU 2020277027 A AU2020277027 A AU 2020277027A AU 2020277027 A AU2020277027 A AU 2020277027A AU 2020277027 A1 AU2020277027 A1 AU 2020277027A1
- Authority
- AU
- Australia
- Prior art keywords
- pyridin
- pyridazin
- fluoro
- oxy
- methyl
- 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.)
- Abandoned
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 507
- 208000023105 Huntington disease Diseases 0.000 title claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- -1 piperidin-1-olate-yl Chemical group 0.000 claims description 5044
- 125000001424 substituent group Chemical group 0.000 claims description 280
- 125000000623 heterocyclic group Chemical group 0.000 claims description 265
- 125000001072 heteroaryl group Chemical group 0.000 claims description 183
- 125000004076 pyridyl group Chemical group 0.000 claims description 104
- 229910052760 oxygen Inorganic materials 0.000 claims description 88
- 125000005842 heteroatom Chemical group 0.000 claims description 86
- 125000002950 monocyclic group Chemical group 0.000 claims description 86
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 80
- 125000004193 piperazinyl group Chemical group 0.000 claims description 80
- 125000003386 piperidinyl group Chemical group 0.000 claims description 77
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 74
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 64
- 125000002619 bicyclic group Chemical group 0.000 claims description 48
- 229920006395 saturated elastomer Polymers 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 41
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 36
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 31
- 125000005955 1H-indazolyl group Chemical group 0.000 claims description 31
- 125000002883 imidazolyl group Chemical group 0.000 claims description 31
- 125000002971 oxazolyl group Chemical group 0.000 claims description 31
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 29
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 19
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 3
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- UDZAEWMURDKNIY-REDHCSJFSA-N 2-[6-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound C(C)(C)(C)N[C@H]1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] UDZAEWMURDKNIY-REDHCSJFSA-N 0.000 claims 2
- LMFOXRKPQPWMBX-CYQFQFRFSA-N 2-[6-[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol trihydrochloride Chemical compound CC1=NN2C=C(C=CC2=N1)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@H]5CC(NC([C@H]5F)(C)C)(C)C)O.Cl.Cl.Cl LMFOXRKPQPWMBX-CYQFQFRFSA-N 0.000 claims 2
- MZHUYPDLNAQKKT-CPEHYTGNSA-N 2-[6-[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-(2-methylimidazo[1,2-a]pyridin-6-yl)pyridin-3-ol trihydrochloride Chemical compound CC1=CN2C=C(C=CC2=N1)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@H]5CC(NC([C@H]5F)(C)C)(C)C)O.Cl.Cl.Cl MZHUYPDLNAQKKT-CPEHYTGNSA-N 0.000 claims 2
- OASWFGLMIQVGCL-CESJSFPBSA-N 2-[6-[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-(2-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-3-ol trihydrochloride Chemical compound CC1=CN2C=C(C=NC2=N1)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@H]5CC(NC([C@H]5F)(C)C)(C)C)O.Cl.Cl.Cl OASWFGLMIQVGCL-CESJSFPBSA-N 0.000 claims 2
- SBBKJFMLZNJVNX-JXFKEZNVSA-N 2-[6-[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-([1,2,4]triazolo[1,5-a]pyrazin-2-yl)pyridin-3-ol Chemical compound F[C@@H]1C(NC(C[C@@H]1OC1=CC=C(N=N1)C1=NC=C(C=C1O)C1=NN2C(C=NC=C2)=N1)(C)C)(C)C SBBKJFMLZNJVNX-JXFKEZNVSA-N 0.000 claims 2
- POTPNCWOKPZJCM-UQASCPDOSA-N 2-[6-[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-[2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl]pyridin-3-ol trihydrochloride Chemical compound CC1=CN2C=C(C=C(C2=N1)C(F)(F)F)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@H]5CC(NC([C@H]5F)(C)C)(C)C)O.Cl.Cl.Cl POTPNCWOKPZJCM-UQASCPDOSA-N 0.000 claims 2
- LMFOXRKPQPWMBX-LZYRFSMASA-N 2-[6-[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol trihydrochloride Chemical compound CC1=NN2C=C(C=CC2=N1)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@@H]5CC(NC([C@@H]5F)(C)C)(C)C)O.Cl.Cl.Cl LMFOXRKPQPWMBX-LZYRFSMASA-N 0.000 claims 2
- MZHUYPDLNAQKKT-YQWSPDFPSA-N 2-[6-[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-(2-methylimidazo[1,2-a]pyridin-6-yl)pyridin-3-ol trihydrochloride Chemical compound CC1=CN2C=C(C=CC2=N1)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@@H]5CC(NC([C@@H]5F)(C)C)(C)C)O.Cl.Cl.Cl MZHUYPDLNAQKKT-YQWSPDFPSA-N 0.000 claims 2
- OASWFGLMIQVGCL-VGNPVSFESA-N 2-[6-[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-(2-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-3-ol trihydrochloride Chemical compound CC1=CN2C=C(C=NC2=N1)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@@H]5CC(NC([C@@H]5F)(C)C)(C)C)O.Cl.Cl.Cl OASWFGLMIQVGCL-VGNPVSFESA-N 0.000 claims 2
- POTPNCWOKPZJCM-QNPMOXIUSA-N 2-[6-[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]-5-[2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl]pyridin-3-ol trihydrochloride Chemical compound CC1=CN2C=C(C=C(C2=N1)C(F)(F)F)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@@H]5CC(NC([C@@H]5F)(C)C)(C)C)O.Cl.Cl.Cl POTPNCWOKPZJCM-QNPMOXIUSA-N 0.000 claims 2
- PYVBNWBYLGFDBQ-JSXJMZBESA-N 2-[6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl]-5-[(6-methylpyridin-3-yl)amino]pyridin-3-ol dihydrochloride Chemical compound C[C@@H]1CN(C[C@@H](N1)C)C2=NN=C(C=C2)C3=C(C=C(C=N3)NC4=CN=C(C=C4)C)O.Cl.Cl PYVBNWBYLGFDBQ-JSXJMZBESA-N 0.000 claims 2
- PIMZNXQDCRTYFK-HPRDVNIFSA-N 2-[6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)oxy]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound CC1(NC2(CC2)CC(C1)OC1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H])C PIMZNXQDCRTYFK-HPRDVNIFSA-N 0.000 claims 2
- DVONPMSAMCXLJH-UHFFFAOYSA-N 2-[6-[(6,6-dimethyl-2-oxa-5-azaspiro[3.5]nonan-8-yl)oxy]pyridazin-3-yl]-5-(1H-pyrazol-4-yl)pyridin-3-ol Chemical compound CC1(NC2(COC2)CC(C1)OC1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NNC=1)C DVONPMSAMCXLJH-UHFFFAOYSA-N 0.000 claims 2
- UDZAEWMURDKNIY-GKOSEXJESA-N 2-[6-[3-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound C(C)(C)(C)NC1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] UDZAEWMURDKNIY-GKOSEXJESA-N 0.000 claims 2
- XNPOOULYYABWIZ-NHPNDNCXSA-N 2-[6-[[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound F[C@H]1C(NC(C[C@H]1NC1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H])(C)C)(C)C XNPOOULYYABWIZ-NHPNDNCXSA-N 0.000 claims 2
- OCXJONGFKVSVJJ-RGEXYPLXSA-N 2-[6-[[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino]pyridazin-3-yl]-5-[6-(trideuteriomethoxy)pyrimidin-4-yl]pyridin-3-ol Chemical compound F[C@H]1C(NC(C[C@H]1NC1=CC=C(N=N1)C1=NC=C(C=C1O)C1=NC=NC(=C1)OC([2H])([2H])[2H])(C)C)(C)C OCXJONGFKVSVJJ-RGEXYPLXSA-N 0.000 claims 2
- DHCOZZMTMPLPJX-FRYRKQBNSA-N 2-[6-[[(5R,7R)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound C[C@H]1NC2(CC2)C[C@@H](C1)OC1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] DHCOZZMTMPLPJX-FRYRKQBNSA-N 0.000 claims 2
- DHCOZZMTMPLPJX-JJHWETPOSA-N 2-[6-[[(5R,7S)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound C[C@H]1NC2(CC2)C[C@H](C1)OC1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] DHCOZZMTMPLPJX-JJHWETPOSA-N 0.000 claims 2
- DHCOZZMTMPLPJX-QEHOZGPLSA-N 2-[6-[[(5S,7R)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound C[C@@H]1NC2(CC2)C[C@@H](C1)OC1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] DHCOZZMTMPLPJX-QEHOZGPLSA-N 0.000 claims 2
- DHCOZZMTMPLPJX-VBYHJNFMSA-N 2-[6-[[(5S,7S)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy]pyridazin-3-yl]-5-[1-(trideuteriomethyl)pyrazol-4-yl]pyridin-3-ol Chemical compound C[C@@H]1NC2(CC2)C[C@H](C1)OC1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] DHCOZZMTMPLPJX-VBYHJNFMSA-N 0.000 claims 2
- BZUUIAQPHOYZGJ-DCXNZVDVSA-N 5-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-[6-[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]pyridin-3-ol trihydrochloride Chemical compound CC1=CC(=CN2C1=NC(=C2)C)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@H]5CC(NC([C@H]5F)(C)C)(C)C)O.Cl.Cl.Cl BZUUIAQPHOYZGJ-DCXNZVDVSA-N 0.000 claims 2
- BZUUIAQPHOYZGJ-OKBDLKLZSA-N 5-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-[6-[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]pyridin-3-ol trihydrochloride Chemical compound CC1=CC(=CN2C1=NC(=C2)C)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@@H]5CC(NC([C@@H]5F)(C)C)(C)C)O.Cl.Cl.Cl BZUUIAQPHOYZGJ-OKBDLKLZSA-N 0.000 claims 2
- BQFHASXMOBLLJY-MMFWGRTPSA-N 5-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-2-[6-[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]pyridin-3-ol trihydrochloride Chemical compound CCC1=CC(=CN2C1=NC(=C2)C)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@H]5CC(NC([C@H]5F)(C)C)(C)C)O.Cl.Cl.Cl BQFHASXMOBLLJY-MMFWGRTPSA-N 0.000 claims 2
- BQFHASXMOBLLJY-PTVVCQEBSA-N 5-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-2-[6-[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxypyridazin-3-yl]pyridin-3-ol trihydrochloride Chemical compound CCC1=CC(=CN2C1=NC(=C2)C)C3=CC(=C(N=C3)C4=NN=C(C=C4)O[C@@H]5CC(NC([C@@H]5F)(C)C)(C)C)O.Cl.Cl.Cl BQFHASXMOBLLJY-PTVVCQEBSA-N 0.000 claims 2
- JDUDPYOJDOETHD-UHFFFAOYSA-N 5-(8-methoxy-2-methylimidazo[1,2-b]pyridazin-6-yl)-2-[6-(2,2,6,6-tetramethylpiperidin-4-yl)oxypyridazin-3-yl]pyridin-3-ol dihydrochloride Chemical compound CC1=CN2C(=N1)C(=CC(=N2)C3=CC(=C(N=C3)C4=NN=C(C=C4)OC5CC(NC(C5)(C)C)(C)C)O)OC.Cl.Cl JDUDPYOJDOETHD-UHFFFAOYSA-N 0.000 claims 2
- WZJUHLHFBOTCGA-FEUJSUOTSA-N C(=O)OC=1C(=NC=C(C=1)C=1C=NN(C=1)C([2H])([2H])[2H])C=1N=NC(=CC=1)N[C@@H]1[C@@H](C(NC(C1)(C)C)(C)C)F Chemical compound C(=O)OC=1C(=NC=C(C=1)C=1C=NN(C=1)C([2H])([2H])[2H])C=1N=NC(=CC=1)N[C@@H]1[C@@H](C(NC(C1)(C)C)(C)C)F WZJUHLHFBOTCGA-FEUJSUOTSA-N 0.000 claims 2
- WZJUHLHFBOTCGA-IGWYIDSESA-N C(=O)OC=1C(=NC=C(C=1)C=1C=NN(C=1)C([2H])([2H])[2H])C=1N=NC(=CC=1)N[C@H]1[C@H](C(NC(C1)(C)C)(C)C)F Chemical compound C(=O)OC=1C(=NC=C(C=1)C=1C=NN(C=1)C([2H])([2H])[2H])C=1N=NC(=CC=1)N[C@H]1[C@H](C(NC(C1)(C)C)(C)C)F WZJUHLHFBOTCGA-IGWYIDSESA-N 0.000 claims 2
- FZDNNTNXYXFACG-OAHLLOKOSA-N C(C)(C)(C)N[C@H]1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CN=C(O1)C Chemical compound C(C)(C)(C)N[C@H]1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CN=C(O1)C FZDNNTNXYXFACG-OAHLLOKOSA-N 0.000 claims 2
- NCNDGFXSDFDQKK-OAHLLOKOSA-N C(C)(C)(C)N[C@H]1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=NC=NC(=C1)OC Chemical compound C(C)(C)(C)N[C@H]1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=NC=NC(=C1)OC NCNDGFXSDFDQKK-OAHLLOKOSA-N 0.000 claims 2
- LNZOITSVCMYZCO-CYBMUJFWSA-N C(C)(C)(C)N[C@H]1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)N1N=CC=N1 Chemical compound C(C)(C)(C)N[C@H]1CN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)N1N=CC=N1 LNZOITSVCMYZCO-CYBMUJFWSA-N 0.000 claims 2
- WHQRPEHDKAJBHE-UHFFFAOYSA-N C(C)C1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CC2=CN(N=C2C(=C1)F)C Chemical compound C(C)C1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CC2=CN(N=C2C(=C1)F)C WHQRPEHDKAJBHE-UHFFFAOYSA-N 0.000 claims 2
- MXXLQCOUCLLFSU-UHFFFAOYSA-N C(C)C1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NNC=1 Chemical compound C(C)C1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NNC=1 MXXLQCOUCLLFSU-UHFFFAOYSA-N 0.000 claims 2
- KPMQLXZPWZONJH-DHLKQENFSA-N C(C)C=1C=2N(C=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@@H]1[C@@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C Chemical compound C(C)C=1C=2N(C=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@@H]1[C@@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C KPMQLXZPWZONJH-DHLKQENFSA-N 0.000 claims 2
- KPMQLXZPWZONJH-RCZVLFRGSA-N C(C)C=1C=2N(C=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@H]1[C@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C Chemical compound C(C)C=1C=2N(C=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@H]1[C@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C KPMQLXZPWZONJH-RCZVLFRGSA-N 0.000 claims 2
- PHMMRFLYHRITGY-URXFXBBRSA-N C(C)C=1C=2N(N=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@@H]1[C@@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C Chemical compound C(C)C=1C=2N(N=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@@H]1[C@@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C PHMMRFLYHRITGY-URXFXBBRSA-N 0.000 claims 2
- PHMMRFLYHRITGY-ZJSXRUAMSA-N C(C)C=1C=2N(N=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@H]1[C@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C Chemical compound C(C)C=1C=2N(N=C(C=1)C=1C=C(C(=NC=1)C=1N=NC(=CC=1)O[C@H]1[C@H](C(NC(C1)(C)C)(C)C)F)O)C=C(N=2)C PHMMRFLYHRITGY-ZJSXRUAMSA-N 0.000 claims 2
- MXXLQCOUCLLFSU-AWEZNQCLSA-N C(C)[C@H]1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NNC=1 Chemical compound C(C)[C@H]1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NNC=1 MXXLQCOUCLLFSU-AWEZNQCLSA-N 0.000 claims 2
- BJZBYKGXGRAMDN-UHFFFAOYSA-N C1(CC1)C1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NNC=1 Chemical compound C1(CC1)C1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NNC=1 BJZBYKGXGRAMDN-UHFFFAOYSA-N 0.000 claims 2
- HFMLSCOYVZXECN-UHFFFAOYSA-N C1(CC1)N1CCN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CC2=CN(N=C2C(=C1)F)C Chemical compound C1(CC1)N1CCN(CC1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CC2=CN(N=C2C(=C1)F)C HFMLSCOYVZXECN-UHFFFAOYSA-N 0.000 claims 2
- LFOAPBSNNALFGK-JCNGFBMWSA-N C1(CC1)[C@H]1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] Chemical compound C1(CC1)[C@H]1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)C=1C=NN(C=1)C([2H])([2H])[2H] LFOAPBSNNALFGK-JCNGFBMWSA-N 0.000 claims 2
- ACDOAQVTWJVTBW-OAHLLOKOSA-N C1(CC1)[C@H]1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)N1N=CC=N1 Chemical compound C1(CC1)[C@H]1CN(CCN1)C1=CC=C(N=N1)C1=NC=C(C=C1O)N1N=CC=N1 ACDOAQVTWJVTBW-OAHLLOKOSA-N 0.000 claims 2
- APANAEVLXSWKNS-UHFFFAOYSA-N C12N(CC(NC1)C2)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CC2=CN(N=C2C(=C1)F)C Chemical compound C12N(CC(NC1)C2)C1=CC=C(N=N1)C1=NC=C(C=C1O)C1=CC2=CN(N=C2C(=C1)F)C APANAEVLXSWKNS-UHFFFAOYSA-N 0.000 claims 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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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
- A61K31/495—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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
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- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| PCT/US2020/032446 WO2020231977A1 (en) | 2019-05-13 | 2020-05-12 | Compounds for treating huntington's disease |
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| EP3634953B1 (en) | 2017-06-05 | 2024-01-03 | PTC Therapeutics, Inc. | Compounds for treating huntington's disease |
| MX2019015580A (es) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics Inc | Metodos para tratar la enfermedad de huntington. |
| CN111182898B (zh) | 2017-06-28 | 2024-04-16 | Ptc医疗公司 | 用于治疗亨廷顿氏病的方法 |
| EP3728228A1 (en) | 2017-12-22 | 2020-10-28 | Ravenna Pharmaceuticals, Inc. | Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors |
| EA202092001A1 (ru) | 2018-03-27 | 2021-01-29 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения болезни гентингтона |
| HRP20240935T1 (hr) | 2018-06-27 | 2024-11-22 | Ptc Therapeutics, Inc. | Heterociklični i heteroaril spojevi za liječenje huntingtonove bolesti |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| JP7649257B2 (ja) | 2019-05-13 | 2025-03-19 | ピーティーシー セラピューティクス, インコーポレイテッド | ハンチントン病を処置するための化合物 |
| TW202112767A (zh) | 2019-06-17 | 2021-04-01 | 美商佩特拉製藥公司 | 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物 |
| CN115768762A (zh) * | 2020-04-09 | 2023-03-07 | Ptc医疗公司 | 用于治疗亨廷顿氏病的化合物 |
| CA3182912A1 (en) | 2020-05-13 | 2021-11-18 | Chdi Foundation, Inc. | Htt modulators for treating huntington's disease |
| IL310992A (en) | 2021-08-25 | 2024-04-01 | Ptc Therapeutics Inc | NLRP3 inhibitors |
| US20240368163A1 (en) * | 2021-08-30 | 2024-11-07 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| US20250333397A1 (en) * | 2021-08-30 | 2025-10-30 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| MX2024005933A (es) | 2021-11-17 | 2024-08-06 | Chdi Foundation Inc | Moduladores de htt pata tratar la enfermedad de huntington. |
| IL314025A (en) * | 2022-01-07 | 2024-08-01 | Transthera Sciences Nanjing Inc | Nlrp3 inflammasome inhibitor and uses thereof |
| CN119059962A (zh) * | 2024-09-09 | 2024-12-03 | 郑州药领医药科技有限公司 | 一种n保护的2,2-二甲基哌啶-4-酮的制备方法 |
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- 2020-05-12 JP JP2021568200A patent/JP7649257B2/ja active Active
- 2020-05-12 EP EP23162466.9A patent/EP4219466A1/en active Pending
- 2020-05-12 CA CA3139821A patent/CA3139821A1/en active Pending
- 2020-05-12 EP EP20729481.0A patent/EP3969446B1/en active Active
- 2020-05-12 US US17/610,617 patent/US12577226B2/en active Active
- 2020-05-12 AU AU2020277027A patent/AU2020277027A1/en not_active Abandoned
- 2020-05-12 BR BR112021022624A patent/BR112021022624A2/pt not_active Application Discontinuation
- 2020-05-12 KR KR1020217036718A patent/KR20220022114A/ko active Pending
- 2020-05-12 MX MX2021013854A patent/MX2021013854A/es unknown
- 2020-05-12 IL IL287945A patent/IL287945B2/en unknown
- 2020-05-12 CN CN202080050837.0A patent/CN114245794B/zh active Active
- 2020-05-12 WO PCT/US2020/032446 patent/WO2020231977A1/en not_active Ceased
- 2020-05-12 SG SG11202112504YA patent/SG11202112504YA/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA3139821A1 (en) | 2020-11-19 |
| SG11202112504YA (en) | 2021-12-30 |
| JP7649257B2 (ja) | 2025-03-19 |
| EP3969446B1 (en) | 2023-09-27 |
| CN114245794B (zh) | 2024-09-13 |
| MX2021013854A (es) | 2022-03-22 |
| US12577226B2 (en) | 2026-03-17 |
| WO2020231977A1 (en) | 2020-11-19 |
| US20220204478A1 (en) | 2022-06-30 |
| EP4219466A1 (en) | 2023-08-02 |
| IL287945A (en) | 2022-01-01 |
| CN114245794A (zh) | 2022-03-25 |
| KR20220022114A (ko) | 2022-02-24 |
| JP2022533120A (ja) | 2022-07-21 |
| EP3969446A1 (en) | 2022-03-23 |
| BR112021022624A2 (pt) | 2022-01-04 |
| IL287945B1 (en) | 2025-11-01 |
| IL287945B2 (en) | 2026-03-01 |
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