JP2019503362A5 - - Google Patents
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- JP2019503362A5 JP2019503362A5 JP2018532784A JP2018532784A JP2019503362A5 JP 2019503362 A5 JP2019503362 A5 JP 2019503362A5 JP 2018532784 A JP2018532784 A JP 2018532784A JP 2018532784 A JP2018532784 A JP 2018532784A JP 2019503362 A5 JP2019503362 A5 JP 2019503362A5
- Authority
- JP
- Japan
- Prior art keywords
- cyano
- carboxamide
- compound
- pyrrolidine
- fluoro
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims 30
- 150000003839 salts Chemical class 0.000 claims 8
- 125000003118 aryl group Chemical group 0.000 claims 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 5
- 230000007812 deficiency Effects 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 208000006136 Leigh Disease Diseases 0.000 claims 3
- 208000017507 Leigh syndrome Diseases 0.000 claims 3
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 claims 3
- 208000008955 Mucolipidoses Diseases 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims 3
- 208000011580 syndromic disease Diseases 0.000 claims 3
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 2
- 206010058892 Carnitine deficiency Diseases 0.000 claims 2
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 2
- -1 cyano, hydroxyl Chemical group 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 208000006443 lactic acidosis Diseases 0.000 claims 2
- 230000004770 neurodegeneration Effects 0.000 claims 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- IKUKFPCTXAIFDT-OAHLLOKOSA-N (3R)-1-cyano-3-fluoro-N-(1-phenylpyrazol-4-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1C[C@](CC1)(C(=O)NC=1C=NN(C=1)C1=CC=CC=C1)F IKUKFPCTXAIFDT-OAHLLOKOSA-N 0.000 claims 1
- GHVXROVZZIREJP-OAHLLOKOSA-N (3R)-1-cyano-3-fluoro-N-(3-phenyl-1,2-oxazol-5-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1C[C@](CC1)(C(=O)NC1=CC(=NO1)C1=CC=CC=C1)F GHVXROVZZIREJP-OAHLLOKOSA-N 0.000 claims 1
- FWOJFVNNHZFPJX-OAHLLOKOSA-N (3R)-1-cyano-3-fluoro-N-(5-phenyl-1,3-thiazol-2-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1C[C@](CC1)(C(=O)NC=1SC(=CN=1)C1=CC=CC=C1)F FWOJFVNNHZFPJX-OAHLLOKOSA-N 0.000 claims 1
- SQTCXMUZGNMDBH-GOSISDBHSA-N (3R)-1-cyano-3-fluoro-N-[3-(3-imidazol-1-ylphenyl)-1,2-oxazol-5-yl]pyrrolidine-3-carboxamide Chemical compound N1(C=NC=C1)C=1C=C(C=CC=1)C1=NOC(=C1)NC(=O)[C@@]1(CN(CC1)C#N)F SQTCXMUZGNMDBH-GOSISDBHSA-N 0.000 claims 1
- QEJZVECSPGZTPG-MRXNPFEDSA-N (3R)-1-cyano-3-fluoro-N-[5-(1H-indazol-7-yl)-1,3-thiazol-2-yl]pyrrolidine-3-carboxamide Chemical compound N1N=CC2=CC=CC(=C12)C1=CN=C(S1)NC(=O)[C@@]1(CN(CC1)C#N)F QEJZVECSPGZTPG-MRXNPFEDSA-N 0.000 claims 1
- BOUYJCIWJJKRGE-QGZVFWFLSA-N (3R)-1-cyano-3-fluoro-N-[5-[3-(methylcarbamoyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-3-carboxamide Chemical compound C(#N)N1C[C@](CC1)(C(=O)NC=1SC(=CN=1)C1=CC(=CC=C1)C(NC)=O)F BOUYJCIWJJKRGE-QGZVFWFLSA-N 0.000 claims 1
- CEJYMAHZEOGZSL-MRXNPFEDSA-N (3R)-1-cyano-N-[1-(4-cyanophenyl)imidazol-4-yl]-3-fluoropyrrolidine-3-carboxamide Chemical compound C(#N)N1C[C@](CC1)(C(=O)NC=1N=CN(C=1)C1=CC=C(C=C1)C#N)F CEJYMAHZEOGZSL-MRXNPFEDSA-N 0.000 claims 1
- YJRSRHUISLZSEN-MRXNPFEDSA-N (3R)-N-(1-benzylpyrazol-4-yl)-1-cyano-3-fluoropyrrolidine-3-carboxamide Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)NC(=O)[C@@]1(CN(CC1)C#N)F YJRSRHUISLZSEN-MRXNPFEDSA-N 0.000 claims 1
- IKUKFPCTXAIFDT-HNNXBMFYSA-N (3S)-1-cyano-3-fluoro-N-(1-phenylpyrazol-4-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1C[C@@](CC1)(C(=O)NC=1C=NN(C=1)C1=CC=CC=C1)F IKUKFPCTXAIFDT-HNNXBMFYSA-N 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- JUAJCIQKLKEZGN-UHFFFAOYSA-N 1-cyano-3-fluoro-N-(1-phenylimidazol-4-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC=1N=CN(C=1)C1=CC=CC=C1)F JUAJCIQKLKEZGN-UHFFFAOYSA-N 0.000 claims 1
- KNBLJWUSPMIRPH-UHFFFAOYSA-N 1-cyano-3-fluoro-N-(3-phenoxyphenyl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC1=CC(=CC=C1)OC1=CC=CC=C1)F KNBLJWUSPMIRPH-UHFFFAOYSA-N 0.000 claims 1
- GHVXROVZZIREJP-UHFFFAOYSA-N 1-cyano-3-fluoro-N-(3-phenyl-1,2-oxazol-5-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC1=CC(=NO1)C1=CC=CC=C1)F GHVXROVZZIREJP-UHFFFAOYSA-N 0.000 claims 1
- XWJPDZIVYGNBAR-UHFFFAOYSA-N 1-cyano-3-fluoro-N-(4-phenyl-1,3-thiazol-2-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC=1SC=C(N=1)C1=CC=CC=C1)F XWJPDZIVYGNBAR-UHFFFAOYSA-N 0.000 claims 1
- KASDLCBIWMCJCT-UHFFFAOYSA-N 1-cyano-3-fluoro-N-(5-phenyl-1,2-oxazol-3-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC1=NOC(=C1)C1=CC=CC=C1)F KASDLCBIWMCJCT-UHFFFAOYSA-N 0.000 claims 1
- OXGAVOSEYAPCCX-UHFFFAOYSA-N 1-cyano-3-fluoro-N-(6-phenyl-1,3-benzothiazol-2-yl)pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC=1SC2=C(N=1)C=CC(=C2)C1=CC=CC=C1)F OXGAVOSEYAPCCX-UHFFFAOYSA-N 0.000 claims 1
- SQTCXMUZGNMDBH-UHFFFAOYSA-N 1-cyano-3-fluoro-N-[3-(3-imidazol-1-ylphenyl)-1,2-oxazol-5-yl]pyrrolidine-3-carboxamide Chemical compound FC1(CCN(C1)C#N)C(=O)NC1=CC(=NO1)C1=CC(=CC=C1)N1C=CN=C1 SQTCXMUZGNMDBH-UHFFFAOYSA-N 0.000 claims 1
- RSIDXKVLNXPHNH-UHFFFAOYSA-N 1-cyano-3-fluoro-N-[5-(1H-indazol-4-yl)-1,3-thiazol-2-yl]pyrrolidine-3-carboxamide Chemical compound N1N=CC2=C(C=CC=C12)C1=CN=C(S1)NC(=O)C1(CN(CC1)C#N)F RSIDXKVLNXPHNH-UHFFFAOYSA-N 0.000 claims 1
- ILRVDZSSHLNGSH-UHFFFAOYSA-N 1-cyano-3-fluoro-N-[5-(3-imidazol-1-ylphenyl)-1,3-thiazol-2-yl]pyrrolidine-3-carboxamide Chemical compound FC1(CCN(C1)C#N)C(=O)NC1=NC=C(S1)C1=CC(=CC=C1)N1C=CN=C1 ILRVDZSSHLNGSH-UHFFFAOYSA-N 0.000 claims 1
- BOUYJCIWJJKRGE-UHFFFAOYSA-N 1-cyano-3-fluoro-N-[5-[3-(methylcarbamoyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC=1SC(=CN=1)C1=CC(=CC=C1)C(NC)=O)F BOUYJCIWJJKRGE-UHFFFAOYSA-N 0.000 claims 1
- GTUAUIQQGQEKJX-UHFFFAOYSA-N 1-cyano-3-fluoro-N-[6-(1H-pyrazol-4-yl)-1,3-benzothiazol-2-yl]pyrrolidine-3-carboxamide Chemical compound N1N=CC(=C1)C1=CC2=C(N=C(S2)NC(=O)C2(CN(CC2)C#N)F)C=C1 GTUAUIQQGQEKJX-UHFFFAOYSA-N 0.000 claims 1
- XIKOQFUSZMNXFX-UHFFFAOYSA-N 1-cyano-3-fluoro-N-[6-(1H-pyrazol-5-yl)imidazo[1,2-a]pyridin-2-yl]pyrrolidine-3-carboxamide Chemical compound N1N=CC=C1C=1C=CC=2N(C=1)C=C(N=2)NC(=O)C1(CN(CC1)C#N)F XIKOQFUSZMNXFX-UHFFFAOYSA-N 0.000 claims 1
- CFZKYYXJMZSXLK-UHFFFAOYSA-N 1-cyano-3-fluoro-N-[6-[3-(methylcarbamoyl)phenyl]-1,3-benzothiazol-2-yl]pyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC=1SC2=C(N=1)C=CC(=C2)C1=CC(=CC=C1)C(NC)=O)F CFZKYYXJMZSXLK-UHFFFAOYSA-N 0.000 claims 1
- DPWJFZSUUNMKOT-UHFFFAOYSA-N 1-cyano-3-fluoro-N-quinolin-3-ylpyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC=1C=NC2=CC=CC=C2C=1)F DPWJFZSUUNMKOT-UHFFFAOYSA-N 0.000 claims 1
- NPANYYNLECHSPH-UHFFFAOYSA-N 1-cyano-3-fluoro-N-quinolin-6-ylpyrrolidine-3-carboxamide Chemical compound C(#N)N1CC(CC1)(C(=O)NC=1C=C2C=CC=NC2=CC=1)F NPANYYNLECHSPH-UHFFFAOYSA-N 0.000 claims 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims 1
- 208000009270 3-hydroxyacyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 201000005943 Barth syndrome Diseases 0.000 claims 1
- 208000014644 Brain disease Diseases 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- KMMCJHZDMNJFQJ-UHFFFAOYSA-N CC1=NC(=CS1)C1=CC=CC(NC(=O)C2(F)CCN(C2)C#N)=C1 Chemical compound CC1=NC(=CS1)C1=CC=CC(NC(=O)C2(F)CCN(C2)C#N)=C1 KMMCJHZDMNJFQJ-UHFFFAOYSA-N 0.000 claims 1
- 208000031229 Cardiomyopathies Diseases 0.000 claims 1
- 108700005857 Carnitine palmitoyl transferase 1A deficiency Proteins 0.000 claims 1
- 208000005359 Carnitine palmitoyl transferase 1A deficiency Diseases 0.000 claims 1
- 108700005858 Carnitine palmitoyl transferase 2 deficiency Proteins 0.000 claims 1
- 201000002929 Carnitine palmitoyltransferase II deficiency Diseases 0.000 claims 1
- 206010008025 Cerebellar ataxia Diseases 0.000 claims 1
- 201000000915 Chronic Progressive External Ophthalmoplegia Diseases 0.000 claims 1
- 208000010354 Coenzyme Q10 deficiency Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 208000021075 Creatine deficiency syndrome Diseases 0.000 claims 1
- 208000011518 Danon disease Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims 1
- 102000015782 Electron Transport Complex III Human genes 0.000 claims 1
- 108010024882 Electron Transport Complex III Proteins 0.000 claims 1
- 208000032274 Encephalopathy Diseases 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 1
- 208000009796 Gangliosidoses Diseases 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 208000001500 Glycogen Storage Disease Type IIb Diseases 0.000 claims 1
- 208000035148 Glycogen storage disease due to LAMP-2 deficiency Diseases 0.000 claims 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 101000804964 Homo sapiens DNA polymerase subunit gamma-1 Proteins 0.000 claims 1
- 101000595929 Homo sapiens POLG alternative reading frame Proteins 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 102100030358 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Human genes 0.000 claims 1
- 101710150008 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Proteins 0.000 claims 1
- 206010048804 Kearns-Sayre syndrome Diseases 0.000 claims 1
- 208000009829 Lewy Body Disease Diseases 0.000 claims 1
- 201000002832 Lewy body dementia Diseases 0.000 claims 1
- 108700006159 Long-chain acyl-CoA dehydrogenase deficiency Proteins 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 108700000232 Medium chain acyl CoA dehydrogenase deficiency Proteins 0.000 claims 1
- 201000002169 Mitochondrial myopathy Diseases 0.000 claims 1
- 206010072928 Mucolipidosis type II Diseases 0.000 claims 1
- 208000001769 Multiple Acyl Coenzyme A Dehydrogenase Deficiency Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims 1
- WCODAHHDYHWBAC-UHFFFAOYSA-N N-[4-chloro-3-(trifluoromethyl)phenyl]-1-cyano-3-fluoropyrrolidine-3-carboxamide Chemical compound ClC1=C(C=C(C=C1)NC(=O)C1(CN(CC1)C#N)F)C(F)(F)F WCODAHHDYHWBAC-UHFFFAOYSA-N 0.000 claims 1
- AJUDKYLOGJPRAE-UHFFFAOYSA-N N-[5-(3-carbamoylphenyl)-1,3-thiazol-2-yl]-1-cyano-3-fluoropyrrolidine-3-carboxamide Chemical compound C(N)(=O)C=1C=C(C=CC=1)C1=CN=C(S1)NC(=O)C1(CN(CC1)C#N)F AJUDKYLOGJPRAE-UHFFFAOYSA-N 0.000 claims 1
- 206010062940 Neuropathy, ataxia, retinitis pigmentosa syndrome Diseases 0.000 claims 1
- 102100035196 POLG alternative reading frame Human genes 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- 208000013234 Pearson syndrome Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 208000002009 Pyruvate Dehydrogenase Complex Deficiency Disease Diseases 0.000 claims 1
- 208000021886 Pyruvate carboxylase deficiency Diseases 0.000 claims 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims 1
- FEWAQVWHYPOHFV-UHFFFAOYSA-N S1C=NC2=C1C=C(C=C2)NC(=O)C1(CN(CC1)C#N)F Chemical compound S1C=NC2=C1C=C(C=C2)NC(=O)C1(CN(CC1)C#N)F FEWAQVWHYPOHFV-UHFFFAOYSA-N 0.000 claims 1
- 125000004450 alkenylene group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims 1
- 210000000601 blood cell Anatomy 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
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- 201000004010 carnitine palmitoyltransferase I deficiency Diseases 0.000 claims 1
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- 239000003814 drug Substances 0.000 claims 1
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- 125000001153 fluoro group Chemical group F* 0.000 claims 1
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
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- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 210000003470 mitochondria Anatomy 0.000 claims 1
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- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 claims 1
- 230000004065 mitochondrial dysfunction Effects 0.000 claims 1
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- 208000020460 mucolipidosis II alpha/beta Diseases 0.000 claims 1
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
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- 201000010866 very long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- 0 CC(*)(C1(*=*1)N(C1(*)*2=CC2)C#N)C1(C(NC1=CC=CC=CC=CC=C1)=O)F Chemical compound CC(*)(C1(*=*1)N(C1(*)*2=CC2)C#N)C1(C(NC1=CC=CC=CC=CC=C1)=O)F 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1522768.9A GB201522768D0 (en) | 2015-12-23 | 2015-12-23 | Novel compounds |
| GB1522768.9 | 2015-12-23 | ||
| PCT/GB2016/054022 WO2017109488A1 (en) | 2015-12-23 | 2016-12-21 | Cyanopyrrolidine dervivatives as inhibitors for dubs |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019503362A JP2019503362A (ja) | 2019-02-07 |
| JP2019503362A5 true JP2019503362A5 (https=) | 2020-02-06 |
| JP6810148B2 JP6810148B2 (ja) | 2021-01-06 |
Family
ID=55311537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018532784A Active JP6810148B2 (ja) | 2015-12-23 | 2016-12-21 | Ｄｕｂの阻害剤としてのシアノピロリジン誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US10590075B2 (https=) |
| EP (1) | EP3394049B1 (https=) |
| JP (1) | JP6810148B2 (https=) |
| CN (1) | CN108290872B (https=) |
| GB (1) | GB201522768D0 (https=) |
| WO (1) | WO2017109488A1 (https=) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX373656B (es) | 2015-03-30 | 2020-04-02 | Mission Therapeutics Ltd | Compuestos de 1-ciano-pirrolidina como inhibidores de las enzimas desubiquitinantes, como la hidrolasa 30 de la c-terminal de la ubiquitina (usp30), y el uso de los mismos en el tratamiento de condiciones de disfunción mitocondrial y tratamiento de cancér. |
| US10669234B2 (en) | 2015-07-14 | 2020-06-02 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| GB201522267D0 (en) | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201522768D0 (en) | 2015-12-23 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201602854D0 (en) | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
| GB201603779D0 (en) | 2016-03-04 | 2016-04-20 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| JP6959252B2 (ja) | 2016-03-24 | 2021-11-02 | ミッション セラピューティクス リミティド | Ｄｕｂ阻害剤としての１−シアノピロリジン誘導体 |
| ES2850349T3 (es) | 2016-09-27 | 2021-08-27 | Mission Therapeutics Ltd | Derivados de cianopirrolidina con actividad como inhibidores de USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| GB201708652D0 (en) | 2017-05-31 | 2017-07-12 | Mission Therapeutics Ltd | Novel compounds and uses |
| JP7208931B2 (ja) | 2017-06-20 | 2023-01-19 | ミッション セラピューティクス リミティド | Ｄｕｂ阻害剤としての活性をもつ置換シアノピロリジン類 |
| BR112020003725A2 (pt) | 2017-10-06 | 2020-11-03 | Forma Therapeutics, Inc. | inibição da peptidase 30 específica de ubiquitina |
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス，インコーポレイテッド | ユビキチン特異的ペプチダーゼ３０（ｕｓｐ３０）阻害剤として有用な縮合二環化合物 |
| JP7434285B2 (ja) | 2018-08-14 | 2024-02-20 | アムジエン・インコーポレーテツド | Ｎ－シアノ－７－アザノルボルナン誘導体及びその使用 |
| LT3860989T (lt) | 2018-10-05 | 2023-06-12 | Forma Therapeutics, Inc. | Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai |
| GB201905371D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201905375D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201912674D0 (en) | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| WO2021204856A1 (en) * | 2020-04-08 | 2021-10-14 | Mission Therapeutics Limited | N-cyanopyrrolidines with activity as usp30 inhibitors |
| IL298526A (en) | 2020-05-28 | 2023-01-01 | Mission Therapeutics Ltd | N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction |
| BR112022019722A2 (pt) | 2020-06-04 | 2022-12-20 | Mission Therapeutics Ltd | N-cianopirrolidinas com atividade como inibidores de usp30 |
| DK4161929T3 (da) | 2020-06-08 | 2025-08-18 | Mission Therapeutics Ltd | 1-(5-(2-cyanopyridin-4-yl)oxazol-2-carbonyl)-4-methylhexahydropyrrolo[3,4-b]pyrrol-5(1h)-carbonitril som usp30-hæmmer til anvendelse i behandling af mitokondriedysfunktion, cancer og fibrose |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| US20250034122A1 (en) | 2021-12-01 | 2025-01-30 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
| WO2024151847A1 (en) * | 2023-01-13 | 2024-07-18 | The University Of North Carolina At Chapel Hill | Identification of otud7b inhibitor 7bi and its application in reducing growth of nsclc and leukemia cells |
| EP4727939A1 (en) * | 2023-06-14 | 2026-04-22 | Prothena Biosciences Limited | 5-(cinnolin-6-yl)thiazole compounds for treating neurological disorders |
| AU2024301960A1 (en) * | 2023-06-14 | 2026-01-22 | Prothena Biosciences Limited | Bicyclic heteroaromatic compounds for treating neurological disorders |
| GB202408928D0 (en) | 2024-06-21 | 2024-08-07 | Mission Therapeutics Ltd | Novel compounds |
| GB202411060D0 (en) | 2024-07-29 | 2024-09-11 | Mission Therapeutics Ltd | Novel compounds |
Family Cites Families (21)
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| WO2001077073A1 (en) | 2000-04-06 | 2001-10-18 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
| EP2619184B1 (en) * | 2010-09-24 | 2018-05-23 | The Regents of the University of Michigan | Deubiquitinase inhibitors and methods for use of the same |
| PT2780326T (pt) * | 2011-10-19 | 2019-03-04 | Vivolux Ab | Método para inibição da atividade da desubiquitinação |
| CA2861066C (en) * | 2012-01-12 | 2024-01-02 | Yale University | Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase |
| US9868736B2 (en) * | 2013-10-10 | 2018-01-16 | The Regents Of The University Of Michigan | Deubiquitinase inhibitors and methods for use of the same |
| US9963444B2 (en) | 2014-05-19 | 2018-05-08 | Northeastern University | N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof |
| GB201416754D0 (en) * | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| MX373656B (es) | 2015-03-30 | 2020-04-02 | Mission Therapeutics Ltd | Compuestos de 1-ciano-pirrolidina como inhibidores de las enzimas desubiquitinantes, como la hidrolasa 30 de la c-terminal de la ubiquitina (usp30), y el uso de los mismos en el tratamiento de condiciones de disfunción mitocondrial y tratamiento de cancér. |
| US10669234B2 (en) | 2015-07-14 | 2020-06-02 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| GB201522267D0 (en) | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201522768D0 (en) | 2015-12-23 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201602854D0 (en) * | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
| GB201603779D0 (en) | 2016-03-04 | 2016-04-20 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| JP6959252B2 (ja) | 2016-03-24 | 2021-11-02 | ミッション セラピューティクス リミティド | Ｄｕｂ阻害剤としての１−シアノピロリジン誘導体 |
| ES2850349T3 (es) | 2016-09-27 | 2021-08-27 | Mission Therapeutics Ltd | Derivados de cianopirrolidina con actividad como inhibidores de USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
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- 2016-12-21 WO PCT/GB2016/054022 patent/WO2017109488A1/en not_active Ceased
- 2016-12-21 US US16/060,299 patent/US10590075B2/en active Active
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