JP7352294B2 - ムスカリン性アセチルコリン受容体ｍ４のアンタゴニスト - Google Patents
ムスカリン性アセチルコリン受容体ｍ４のアンタゴニスト Download PDFInfo
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- JP7352294B2 JP7352294B2 JP2020541908A JP2020541908A JP7352294B2 JP 7352294 B2 JP7352294 B2 JP 7352294B2 JP 2020541908 A JP2020541908 A JP 2020541908A JP 2020541908 A JP2020541908 A JP 2020541908A JP 7352294 B2 JP7352294 B2 JP 7352294B2
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- JP
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- Prior art keywords
- azabicyclo
- pyridazin
- amine
- hexane
- phenyl
- 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.)
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- 239000005557 antagonist Substances 0.000 title description 20
- 102000000413 Muscarinic acetylcholine receptor M4 Human genes 0.000 title 1
- 108050008897 Muscarinic acetylcholine receptor M4 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 318
- -1 -NHCOR e Chemical group 0.000 claims description 170
- 150000003839 salts Chemical class 0.000 claims description 120
- 239000000203 mixture Substances 0.000 claims description 98
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 90
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 70
- 125000001424 substituent group Chemical group 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 53
- 125000005843 halogen group Chemical group 0.000 claims description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
- 239000008194 pharmaceutical composition Substances 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 125000005842 heteroatom Chemical group 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 35
- 208000035475 disorder Diseases 0.000 claims description 35
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 29
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 24
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 23
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 230000008485 antagonism Effects 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 208000018737 Parkinson disease Diseases 0.000 claims description 15
- 230000008901 benefit Effects 0.000 claims description 15
- 208000016285 Movement disease Diseases 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 201000000980 schizophrenia Diseases 0.000 claims description 11
- 208000014094 Dystonic disease Diseases 0.000 claims description 10
- 208000010118 dystonia Diseases 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 208000012661 Dyskinesia Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 claims description 6
- 206010041349 Somnolence Diseases 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 206010008748 Chorea Diseases 0.000 claims description 5
- 208000028698 Cognitive impairment Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 206010034010 Parkinsonism Diseases 0.000 claims description 5
- 208000012601 choreatic disease Diseases 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 5
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 4
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 4
- 208000016620 Tourette disease Diseases 0.000 claims description 4
- 206010008129 cerebral palsy Diseases 0.000 claims description 4
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 4
- HDUZTFUKPGWCKE-NWMVZANLSA-N (1R,5S)-3-(1,3-benzodioxol-5-ylmethyl)-N-[6-(2,5-difluorophenyl)pyridazin-3-yl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound O1COC2=C1C=CC(=C2)CN1C[C@H]2C([C@H]2C1)NC=1N=NC(=CC=1)C1=C(C=CC(=C1)F)F HDUZTFUKPGWCKE-NWMVZANLSA-N 0.000 claims description 3
- ZEAFXVDVXUZGBJ-NWMVZANLSA-N (1R,5S)-3-(1,3-benzodioxol-5-ylmethyl)-N-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound O1COC2=C1C=CC(=C2)CN1C[C@H]2C([C@H]2C1)NC=1N=NC(=CC=1)C1=C(C=CC(=C1)F)Cl ZEAFXVDVXUZGBJ-NWMVZANLSA-N 0.000 claims description 3
- RHKVBINBSIFKNN-LIMIJEPZSA-N (1R,5S)-3-[(1,5-dimethylpyrazol-3-yl)methyl]-N-[6-(2-methylindazol-5-yl)pyridazin-3-yl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound CN1N=C(C=C1C)CN1C[C@H]2C([C@H]2C1)NC=1N=NC(=CC=1)C1=CC2=CN(N=C2C=C1)C RHKVBINBSIFKNN-LIMIJEPZSA-N 0.000 claims description 3
- MLDIEIATPLTZJH-GWTOYCKXSA-N (1R,5S)-N-[6-(2,3-difluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=C(C=CC=C1F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 MLDIEIATPLTZJH-GWTOYCKXSA-N 0.000 claims description 3
- WBMGPWTWWLOIFE-QRTHJKPMSA-N (1R,5S)-N-[6-(2,4-difluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=C(C=CC(=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 WBMGPWTWWLOIFE-QRTHJKPMSA-N 0.000 claims description 3
- DTINNFOQJBRXFN-NYTJIUQPSA-N (1R,5S)-N-[6-(2,5-difluorophenyl)pyridazin-3-yl]-3-(3,3-dimethylbutyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CCC(C)(C)C DTINNFOQJBRXFN-NYTJIUQPSA-N 0.000 claims description 3
- IHZKBWZLOQMOHS-QRTHJKPMSA-N (1R,5S)-N-[6-(2,5-difluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 IHZKBWZLOQMOHS-QRTHJKPMSA-N 0.000 claims description 3
- RRPNIBSPICTVRF-QRTHJKPMSA-N (1R,5S)-N-[6-(2,5-difluorophenyl)pyridazin-3-yl]-3-(pyridin-2-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1=NC=CC=C1 RRPNIBSPICTVRF-QRTHJKPMSA-N 0.000 claims description 3
- QHLLFYIIMGGIRK-GWTOYCKXSA-N (1R,5S)-N-[6-(2-chloro-3-fluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=CC=C1F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 QHLLFYIIMGGIRK-GWTOYCKXSA-N 0.000 claims description 3
- TVPKPMAHUNWJLM-QRTHJKPMSA-N (1R,5S)-N-[6-(2-chloro-4-fluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=CC(=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 TVPKPMAHUNWJLM-QRTHJKPMSA-N 0.000 claims description 3
- QLJASFVHRLHMMQ-NYTJIUQPSA-N (1R,5S)-N-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]-3-(3,3-dimethylbutyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CCC(C)(C)C QLJASFVHRLHMMQ-NYTJIUQPSA-N 0.000 claims description 3
- QFJLETHKVQVNRO-QRTHJKPMSA-N (1R,5S)-N-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 QFJLETHKVQVNRO-QRTHJKPMSA-N 0.000 claims description 3
- GCQNQOGCOQTOKH-QRTHJKPMSA-N (1R,5S)-N-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]-3-(pyridin-2-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1=NC=CC=C1 GCQNQOGCOQTOKH-QRTHJKPMSA-N 0.000 claims description 3
- ORRPMTCADOGUCX-QRTHJKPMSA-N (1R,5S)-N-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]-3-[(1,5-dimethylpyrazol-3-yl)methyl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1=NN(C(=C1)C)C ORRPMTCADOGUCX-QRTHJKPMSA-N 0.000 claims description 3
- MEXPLCYCBSJXPT-LIMIJEPZSA-N (1R,5S)-N-[6-(2-methylindazol-5-yl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound CN1N=C2C=CC(=CC2=C1)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 MEXPLCYCBSJXPT-LIMIJEPZSA-N 0.000 claims description 3
- WBBAZRCDYWDMIF-VSOVRNOCSA-N (1S,5R)-3-(3,3-dimethylbutyl)-N-[6-(2-methylindazol-5-yl)pyridazin-3-yl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound CC(CCN1C[C@H]2C([C@H]2C1)NC=1N=NC(=CC=1)C1=CC2=CN(N=C2C=C1)C)(C)C WBBAZRCDYWDMIF-VSOVRNOCSA-N 0.000 claims description 3
- CVNGSARVBMYURR-HTZLVSCSSA-N (1S,5R)-3-(oxan-4-ylmethyl)-N-(6-phenylpyridazin-3-yl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound C1(=CC=CC=C1)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 CVNGSARVBMYURR-HTZLVSCSSA-N 0.000 claims description 3
- NFTHWVKKGOXHPM-VXMMSVGHSA-N (1S,5R)-3-(oxan-4-ylmethyl)-N-(6-quinolin-6-ylpyridazin-3-yl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound N1=CC=CC2=CC(=CC=C12)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 NFTHWVKKGOXHPM-VXMMSVGHSA-N 0.000 claims description 3
- RAFCHKUKILSMFD-OFFJZUQKSA-N (1S,5R)-N-(6-naphthalen-2-ylpyridazin-3-yl)-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound C1=C(C=CC2=CC=CC=C12)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 RAFCHKUKILSMFD-OFFJZUQKSA-N 0.000 claims description 3
- FVSIYBGHGAFTCB-AQKKSAQBSA-N (1S,5R)-N-[6-(1,3-benzodioxol-5-yl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound O1COC2=C1C=CC(=C2)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 FVSIYBGHGAFTCB-AQKKSAQBSA-N 0.000 claims description 3
- PBTGSRQWGOVBRR-AQKKSAQBSA-N (1S,5R)-N-[6-(2,5-difluorophenyl)pyridazin-3-yl]-3-[(2-fluorophenyl)methyl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1=C(C=CC=C1)F PBTGSRQWGOVBRR-AQKKSAQBSA-N 0.000 claims description 3
- NOUYSUSABILXEW-VSOVRNOCSA-N (1S,5R)-N-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]-3-[(3-fluorophenyl)methyl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1=CC(=CC=C1)F NOUYSUSABILXEW-VSOVRNOCSA-N 0.000 claims description 3
- IRDOIEZXWRDSSU-VSOVRNOCSA-N (1S,5R)-N-[6-(2-chloro-5-fluorophenyl)pyridazin-3-yl]-3-[(4-fluorophenyl)methyl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=C(C=C1)F)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1=CC=C(C=C1)F IRDOIEZXWRDSSU-VSOVRNOCSA-N 0.000 claims description 3
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- OKIQYVNYTGZEJI-QRTHJKPMSA-N (1S,5R)-N-[6-(2-chlorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound ClC1=C(C=CC=C1)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 OKIQYVNYTGZEJI-QRTHJKPMSA-N 0.000 claims description 3
- LZVNBHRQXHEFFT-QRTHJKPMSA-N (1S,5R)-N-[6-(2-fluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=C(C=CC=C1)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 LZVNBHRQXHEFFT-QRTHJKPMSA-N 0.000 claims description 3
- GWTWGACGOBOYFR-HTZLVSCSSA-N (1S,5R)-N-[6-(3-fluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC=1C=C(C=CC=1)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 GWTWGACGOBOYFR-HTZLVSCSSA-N 0.000 claims description 3
- XOCJQSABCJSYCX-HTZLVSCSSA-N (1S,5R)-N-[6-(4-fluorophenyl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound FC1=CC=C(C=C1)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 XOCJQSABCJSYCX-HTZLVSCSSA-N 0.000 claims description 3
- PGLJXJZMYGUVNL-LIMIJEPZSA-N (1S,5R)-N-[6-(6-cyclopropylpyridin-3-yl)pyridazin-3-yl]-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound C1(CC1)C1=CC=C(C=N1)C1=CC=C(N=N1)NC1[C@H]2CN(C[C@@H]12)CC1CCOCC1 PGLJXJZMYGUVNL-LIMIJEPZSA-N 0.000 claims description 3
- MPRZIGYQAMQNFH-DETIRCLXSA-N N-[4-[6-[[(1R,5S)-3-(oxan-4-ylmethyl)-3-azabicyclo[3.1.0]hexan-6-yl]amino]pyridazin-3-yl]phenyl]acetamide Chemical compound O1CCC(CC1)CN1C[C@H]2C([C@H]2C1)NC1=CC=C(N=N1)C1=CC=C(C=C1)NC(C)=O MPRZIGYQAMQNFH-DETIRCLXSA-N 0.000 claims description 3
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 119
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 119
- 238000000034 method Methods 0.000 description 101
- 125000003118 aryl group Chemical group 0.000 description 51
- 239000003814 drug Substances 0.000 description 41
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 34
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
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- 125000004432 carbon atom Chemical group C* 0.000 description 17
- 238000009472 formulation Methods 0.000 description 16
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
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- 125000003342 alkenyl group Chemical group 0.000 description 11
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- 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
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- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
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- 230000002588 toxic effect Effects 0.000 description 1
- PHTUQLWOUWZIMZ-GZTJUZNOSA-N trans-dothiepin Chemical compound C1SC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 PHTUQLWOUWZIMZ-GZTJUZNOSA-N 0.000 description 1
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- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
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Classifications
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/495—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US62/625,656 | 2018-02-02 | ||
| PCT/US2019/016300 WO2019152809A1 (en) | 2018-02-02 | 2019-02-01 | Antagonists of the muscarinic acetylcholine receptor m4 |
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| JP2021513519A JP2021513519A (ja) | 2021-05-27 |
| JP2021513519A5 JP2021513519A5 (https=) | 2022-02-16 |
| JPWO2019152809A5 JPWO2019152809A5 (https=) | 2022-02-16 |
| JP7352294B2 true JP7352294B2 (ja) | 2023-09-28 |
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| EP (1) | EP3746421B1 (https=) |
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| AU (1) | AU2019216492A1 (https=) |
| CA (1) | CA3090130A1 (https=) |
| IL (1) | IL276411B2 (https=) |
| WO (1) | WO2019152809A1 (https=) |
| ZA (1) | ZA202004638B (https=) |
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| US12600726B2 (en) | 2017-07-12 | 2026-04-14 | Vanderbilt University | Antagonists of the muscarinic acetylcholine receptor M4 |
| IL310346A (en) | 2017-10-20 | 2024-03-01 | Univ Vanderbilt | Muscarinic acetylcholine M4 receptor antagonists |
| EP3728228A1 (en) | 2017-12-22 | 2020-10-28 | Ravenna Pharmaceuticals, Inc. | Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors |
| WO2020243423A1 (en) | 2019-05-31 | 2020-12-03 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
| KR20220030222A (ko) | 2019-05-31 | 2022-03-10 | 이케나 온콜로지, 인코포레이티드 | Tead 억제제 및 이의 용도 |
| 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 |
| AU2020358000A1 (en) * | 2019-10-04 | 2022-04-07 | Vanderbilt University | Antagonists of the muscarinic acetylcholine receptor M4 |
| WO2021174176A1 (en) * | 2020-02-28 | 2021-09-02 | Remix Therapeutics Inc. | Pyridazine dervatives for modulating nucleic acid splicing |
| IL303128A (en) | 2020-11-26 | 2023-07-01 | Rezubio Pharmaceuticals Co Ltd | Anticholinergic agents |
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| DE102004039789A1 (de) | 2004-08-16 | 2006-03-02 | Sanofi-Aventis Deutschland Gmbh | Arylsubstituierte polycyclische Amine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
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-
2019
- 2019-02-01 CN CN201980012827.5A patent/CN111788182B/zh not_active Expired - Fee Related
- 2019-02-01 JP JP2020541908A patent/JP7352294B2/ja active Active
- 2019-02-01 WO PCT/US2019/016300 patent/WO2019152809A1/en not_active Ceased
- 2019-02-01 KR KR1020207023725A patent/KR20200116945A/ko not_active Ceased
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- 2019-02-01 AU AU2019216492A patent/AU2019216492A1/en not_active Abandoned
- 2019-02-01 CA CA3090130A patent/CA3090130A1/en active Pending
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2020
- 2020-07-27 ZA ZA2020/04638A patent/ZA202004638B/en unknown
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| WO2004089898A1 (en) | 2003-04-09 | 2004-10-21 | Ranbaxy Laboratories Limited | Substituted azabicyclo hexane derivatives as muscarinic receptor antagonists |
| WO2006035282A2 (en) | 2004-09-27 | 2006-04-06 | Ranbaxy Laboratories Limited | Muscarinic receptor antagonists |
| WO2006035280A1 (en) | 2004-09-27 | 2006-04-06 | Ranbaxy Laboratories Limited | 3,4-dihydroisoquinoline compounds as muscrinic receptor antagonists for the treatment of respiratory, urinary and gastrointestinal diseases |
| WO2007007281A2 (en) | 2005-07-11 | 2007-01-18 | Ranbaxy Laboratories Limited | Muscarinic receptor antagonists |
| JP2009515820A (ja) | 2005-10-21 | 2009-04-16 | ノバルティス アクチエンゲゼルシャフト | 新規１−アザ−ビシクロアルキル誘導体 |
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| CA3090130A1 (en) | 2019-08-08 |
| EP3746421B1 (en) | 2023-11-29 |
| IL276411B1 (en) | 2023-12-01 |
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| US11414406B2 (en) | 2022-08-16 |
| CN111788182A (zh) | 2020-10-16 |
| CN111788182B (zh) | 2023-09-26 |
| EP3746421A1 (en) | 2020-12-09 |
| ZA202004638B (en) | 2023-02-22 |
| EP3746421A4 (en) | 2021-10-27 |
| IL276411B2 (en) | 2024-04-01 |
| US20200369650A1 (en) | 2020-11-26 |
| AU2019216492A1 (en) | 2020-08-20 |
| IL276411A (en) | 2020-09-30 |
| JP2021513519A (ja) | 2021-05-27 |
| KR20200116945A (ko) | 2020-10-13 |
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