JP2018524367A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018524367A5 JP2018524367A5 JP2018501285A JP2018501285A JP2018524367A5 JP 2018524367 A5 JP2018524367 A5 JP 2018524367A5 JP 2018501285 A JP2018501285 A JP 2018501285A JP 2018501285 A JP2018501285 A JP 2018501285A JP 2018524367 A5 JP2018524367 A5 JP 2018524367A5
- Authority
- JP
- Japan
- Prior art keywords
- cyano
- pyrrolidine
- carbonitrile
- carbonyl
- carboxamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims 22
- -1 methoxyethoxy Chemical group 0.000 claims 17
- 125000003118 aryl group Chemical group 0.000 claims 12
- 125000000623 heterocyclic group Chemical group 0.000 claims 10
- 125000000217 alkyl group Chemical group 0.000 claims 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
- 206010028980 Neoplasm Diseases 0.000 claims 6
- 201000011510 cancer Diseases 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 6
- 125000003545 alkoxy group Chemical group 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 230000007812 deficiency Effects 0.000 claims 5
- 125000005843 halogen group Chemical group 0.000 claims 5
- 125000001072 heteroaryl group Chemical group 0.000 claims 5
- 125000002950 monocyclic group Chemical group 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 125000002947 alkylene group Chemical group 0.000 claims 4
- 125000005529 alkyleneoxy group Chemical group 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 208000011580 syndromic disease Diseases 0.000 claims 4
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 3
- 208000008955 Mucolipidoses Diseases 0.000 claims 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 2
- 208000014644 Brain disease Diseases 0.000 claims 2
- 206010058892 Carnitine deficiency Diseases 0.000 claims 2
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 claims 2
- 208000032274 Encephalopathy Diseases 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 claims 2
- 201000002169 Mitochondrial myopathy Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- 208000036142 Viral infection Diseases 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims 2
- 208000006443 lactic acidosis Diseases 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 230000004065 mitochondrial dysfunction Effects 0.000 claims 2
- 230000002438 mitochondrial effect Effects 0.000 claims 2
- 230000035772 mutation Effects 0.000 claims 2
- 230000004770 neurodegeneration Effects 0.000 claims 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 102000045222 parkin Human genes 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- 150000003573 thiols Chemical class 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 230000009385 viral infection Effects 0.000 claims 2
- COKNKHWUKNJCMB-ZDUSSCGKSA-N (2S)-1-cyano-N-(5-cyano-4-phenyl-1,3-thiazol-2-yl)-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC(=C(N=1)C1=CC=CC=C1)C#N COKNKHWUKNJCMB-ZDUSSCGKSA-N 0.000 claims 1
- KCPHOFOOLGXKGK-HNNXBMFYSA-N (2S)-1-cyano-N-[3-(3-methoxyphenyl)-1,2-oxazol-5-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C1=CC(=NO1)C1=CC(=CC=C1)OC KCPHOFOOLGXKGK-HNNXBMFYSA-N 0.000 claims 1
- DCBBFYWGMDFIRP-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(2-cyanopyridin-4-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=CC(=NC=C1)C#N DCBBFYWGMDFIRP-AWEZNQCLSA-N 0.000 claims 1
- IJXKVEAWLXTUTE-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(2-methoxyphenyl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=C(C=CC=C1)OC IJXKVEAWLXTUTE-AWEZNQCLSA-N 0.000 claims 1
- LJALYPZMAKFPSM-HNNXBMFYSA-N (2S)-1-cyano-N-[4-(3-cyanophenyl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=CC(=CC=C1)C#N LJALYPZMAKFPSM-HNNXBMFYSA-N 0.000 claims 1
- RPKFCLFVAACYOG-ZDUSSCGKSA-N (2S)-1-cyano-N-[4-(3-cyanophenyl)-5-fluoro-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC(=C(N=1)C1=CC(=CC=C1)C#N)F RPKFCLFVAACYOG-ZDUSSCGKSA-N 0.000 claims 1
- VJDMCZGYBLAWAZ-INIZCTEOSA-N (2S)-1-cyano-N-[4-(3-ethylphenyl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=CC(=CC=C1)CC VJDMCZGYBLAWAZ-INIZCTEOSA-N 0.000 claims 1
- HAGHQCDRXRUHJX-HNNXBMFYSA-N (2S)-1-cyano-N-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=CC(=CC=C1)OC HAGHQCDRXRUHJX-HNNXBMFYSA-N 0.000 claims 1
- YVXVYNHRYPBFFU-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(5-cyanopyridin-3-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C=1C=NC=C(C=1)C#N YVXVYNHRYPBFFU-AWEZNQCLSA-N 0.000 claims 1
- KFVZUBKAWMNHOI-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(6-cyano-3-ethoxypyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1OCC)C#N KFVZUBKAWMNHOI-AWEZNQCLSA-N 0.000 claims 1
- AAKVUGNGGLMSKC-ZDUSSCGKSA-N (2S)-1-cyano-N-[4-(6-cyano-3-methoxypyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1OC)C#N AAKVUGNGGLMSKC-ZDUSSCGKSA-N 0.000 claims 1
- ZUBBSKORVRCGAW-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(6-cyano-3-methylpyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1C)C#N ZUBBSKORVRCGAW-AWEZNQCLSA-N 0.000 claims 1
- SDXFIPRXASXHKJ-HNNXBMFYSA-N (2S)-1-cyano-N-[4-(6-cyano-5-ethoxypyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=C(C=C1)OCC)C#N SDXFIPRXASXHKJ-HNNXBMFYSA-N 0.000 claims 1
- APFKLZAHDDDAOH-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(6-cyano-5-methoxypyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=C(C=C1)OC)C#N APFKLZAHDDDAOH-AWEZNQCLSA-N 0.000 claims 1
- AFWVFDKSXQAVKQ-HNNXBMFYSA-N (2S)-1-cyano-N-[4-(6-cyano-5-methylpyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=C(C=C1)C)C#N AFWVFDKSXQAVKQ-HNNXBMFYSA-N 0.000 claims 1
- RWUYLRLELHSDQH-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(6-cyanopyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1)C#N RWUYLRLELHSDQH-AWEZNQCLSA-N 0.000 claims 1
- WDNHBRPZDSJTGI-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(6-cyanopyridin-2-yl)-5-ethyl-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC(=C(N=1)C1=NC(=CC=C1)C#N)CC WDNHBRPZDSJTGI-AWEZNQCLSA-N 0.000 claims 1
- HHRMQBUASZODPH-AWEZNQCLSA-N (2S)-1-cyano-N-[4-(6-cyanopyridin-2-yl)-5-methyl-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC(=C(N=1)C1=NC(=CC=C1)C#N)C HHRMQBUASZODPH-AWEZNQCLSA-N 0.000 claims 1
- JELYJKAQAGOBRO-INIZCTEOSA-N (2S)-1-cyano-N-[4-(6-cyclopropylpyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1)C1CC1 JELYJKAQAGOBRO-INIZCTEOSA-N 0.000 claims 1
- FJGGYYJGDVVUII-ZDUSSCGKSA-N (2S)-1-cyano-N-[4-(6-methoxypyridin-2-yl)-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1)OC FJGGYYJGDVVUII-ZDUSSCGKSA-N 0.000 claims 1
- ITEZYZUQTSNQSW-INIZCTEOSA-N (2S)-1-cyano-N-[4-[3-(methoxymethyl)phenyl]-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=CC(=CC=C1)COC ITEZYZUQTSNQSW-INIZCTEOSA-N 0.000 claims 1
- BBZPOMQJPPJJMO-HNNXBMFYSA-N (2S)-1-cyano-N-[4-[6-cyano-3-(2-methoxyethoxy)pyridin-2-yl]-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1OCCOC)C#N BBZPOMQJPPJJMO-HNNXBMFYSA-N 0.000 claims 1
- FFNWQIMPGVAHBV-INIZCTEOSA-N (2S)-1-cyano-N-[4-[6-cyano-5-(dimethylamino)pyridin-2-yl]-1,3-thiazol-2-yl]-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=C(C=C1)N(C)C)C#N FFNWQIMPGVAHBV-INIZCTEOSA-N 0.000 claims 1
- JAIBYYLRJLKSSA-HNNXBMFYSA-N (2S)-1-cyano-N-ethyl-N-(4-phenyl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=CC=CC=C1)CC JAIBYYLRJLKSSA-HNNXBMFYSA-N 0.000 claims 1
- NWIHLTTYGVLQQC-AWEZNQCLSA-N (2S)-1-cyano-N-methyl-N-(1-phenylpyrazol-3-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C1=NN(C=C1)C1=CC=CC=C1)C NWIHLTTYGVLQQC-AWEZNQCLSA-N 0.000 claims 1
- LRPSPLJSJDKUIB-AWEZNQCLSA-N (2S)-1-cyano-N-methyl-N-(3-phenyl-1,2-oxazol-5-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C1=CC(=NO1)C1=CC=CC=C1)C LRPSPLJSJDKUIB-AWEZNQCLSA-N 0.000 claims 1
- XYJWIHFCSQUHLU-AWEZNQCLSA-N (2S)-1-cyano-N-methyl-N-(4-phenyl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=CC=CC=C1)C XYJWIHFCSQUHLU-AWEZNQCLSA-N 0.000 claims 1
- QNESVFTZDYIHNM-NSHDSACASA-N (2S)-1-cyano-N-methyl-N-(4-propan-2-yl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C(C)C QNESVFTZDYIHNM-NSHDSACASA-N 0.000 claims 1
- FAJFRTTWIMGORN-ZDUSSCGKSA-N (2S)-1-cyano-N-methyl-N-(4-pyridin-2-yl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=NC=CC=C1)C FAJFRTTWIMGORN-ZDUSSCGKSA-N 0.000 claims 1
- UVROMVXOLVZJBN-ZDUSSCGKSA-N (2S)-1-cyano-N-methyl-N-(4-pyridin-3-yl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C=1C=NC=CC=1)C UVROMVXOLVZJBN-ZDUSSCGKSA-N 0.000 claims 1
- NJZNESGNKPSFFK-ZDUSSCGKSA-N (2S)-1-cyano-N-methyl-N-(4-pyridin-4-yl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=CC=NC=C1)C NJZNESGNKPSFFK-ZDUSSCGKSA-N 0.000 claims 1
- KNCJNJOLZXCRRY-ZDUSSCGKSA-N (2S)-1-cyano-N-methyl-N-(5-phenyl-1,2-oxazol-3-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C1=NOC(=C1)C1=CC=CC=C1)C KNCJNJOLZXCRRY-ZDUSSCGKSA-N 0.000 claims 1
- XIDYNFKSCDNYHH-ZDUSSCGKSA-N (2S)-1-cyano-N-methyl-N-(5-phenyl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC(=CN=1)C1=CC=CC=C1)C XIDYNFKSCDNYHH-ZDUSSCGKSA-N 0.000 claims 1
- XQZCEIALIBSWOY-HNNXBMFYSA-N (2S)-1-cyano-N-methyl-N-[4-(6-propan-2-yloxypyridin-2-yl)-1,3-thiazol-2-yl]pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C)C=1SC=C(N=1)C1=NC(=CC=C1)OC(C)C XQZCEIALIBSWOY-HNNXBMFYSA-N 0.000 claims 1
- OZUQOMQSCJENAA-KFJBMODSSA-N (2S)-1-cyano-N-methyl-N-[4-(oxolan-3-yl)-1,3-thiazol-2-yl]pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1COCC1)C OZUQOMQSCJENAA-KFJBMODSSA-N 0.000 claims 1
- JQYNODAUGQIMPL-AWEZNQCLSA-N (2S)-1-cyano-N-methyl-N-[4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=CC(=CC=C1)C(F)(F)F)C JQYNODAUGQIMPL-AWEZNQCLSA-N 0.000 claims 1
- TXCMDMSYSGEVDO-INIZCTEOSA-N (2S)-1-cyano-N-methyl-N-[4-[3-[methyl(methylsulfonyl)amino]phenyl]-1,3-thiazol-2-yl]pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=CC(=CC=C1)N(S(=O)(=O)C)C)C TXCMDMSYSGEVDO-INIZCTEOSA-N 0.000 claims 1
- XCEQUYZBRPULKA-HNNXBMFYSA-N (2S)-2-(1-phenyl-5,6-dihydropyrrolo[3,2-c]pyrazole-4-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C1(=CC=CC=C1)N1N=CC2=C1CCN2C(=O)[C@H]1N(CCC1)C#N XCEQUYZBRPULKA-HNNXBMFYSA-N 0.000 claims 1
- RPNXKHUIZNCHOE-AWEZNQCLSA-N (2S)-2-(4-ethoxy-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C(C)OC1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N RPNXKHUIZNCHOE-AWEZNQCLSA-N 0.000 claims 1
- GHESLAQUATUPKG-IBGZPJMESA-N (2S)-2-(4-phenyl-1,3-dihydroisoindole-2-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C1(=CC=CC=C1)C1=C2CN(CC2=CC=C1)C(=O)[C@H]1N(CCC1)C#N GHESLAQUATUPKG-IBGZPJMESA-N 0.000 claims 1
- GDWRBPHQNJJHCB-IBGZPJMESA-N (2S)-2-(4-phenyl-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C1(=CC=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N GDWRBPHQNJJHCB-IBGZPJMESA-N 0.000 claims 1
- UEOUYNRYGPLQPF-WMCAAGNKSA-N (2S)-2-(4-pyrazolidin-3-yl-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C1C[C@H](N(C1)C#N)C(=O)N2CCC3=C(C=CC=C32)C4CCNN4 UEOUYNRYGPLQPF-WMCAAGNKSA-N 0.000 claims 1
- HIUWPHSAUQMWQZ-SFHVURJKSA-N (2S)-2-(4-pyridin-2-yl-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound N1=C(C=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N HIUWPHSAUQMWQZ-SFHVURJKSA-N 0.000 claims 1
- WGHVSQRRRUPDBP-SFHVURJKSA-N (2S)-2-(4-pyridin-4-yl-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound N1=CC=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N WGHVSQRRRUPDBP-SFHVURJKSA-N 0.000 claims 1
- HBUQOCHFSXXTAY-FQEVSTJZSA-N (2S)-2-(5-phenyl-3,4-dihydro-2H-quinoline-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C1(=CC=CC=C1)C1=C2CCCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N HBUQOCHFSXXTAY-FQEVSTJZSA-N 0.000 claims 1
- BIFZPYLOFPBBCD-WMCAAGNKSA-N (2S)-2-(5-pyrazolidin-3-yl-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C1C[C@H](N(C1)C#N)C(=O)N2CCC3=C2C=CC(=C3)C4CCNN4 BIFZPYLOFPBBCD-WMCAAGNKSA-N 0.000 claims 1
- BNKOCYHYDZKWKP-SFHVURJKSA-N (2S)-2-(6-phenyl-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound C1(=CC=CC=C1)C1=CC=C2CCN(C2=C1)C(=O)[C@H]1N(CCC1)C#N BNKOCYHYDZKWKP-SFHVURJKSA-N 0.000 claims 1
- XOZAOVYOVHMOBC-SFHVURJKSA-N (2S)-2-(8-phenyl-2,3-dihydro-1,4-benzoxazine-4-carbonyl)pyrrolidine-1-carbonitrile Chemical compound O=C([C@@H]1CCCN1C#N)N1CCOC2=C1C=CC=C2C1=CC=CC=C1 XOZAOVYOVHMOBC-SFHVURJKSA-N 0.000 claims 1
- AZVYCCRALWFRRD-INIZCTEOSA-N (2S)-2-[4-(1H-pyrazol-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound N1N=CC(=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N AZVYCCRALWFRRD-INIZCTEOSA-N 0.000 claims 1
- PJYJFXAKGZEDNG-IBGZPJMESA-N (2S)-2-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound N1C=C(C=2C1=NC=CC=2)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N PJYJFXAKGZEDNG-IBGZPJMESA-N 0.000 claims 1
- CRINRUDDKSBHIM-IBGZPJMESA-N (2S)-2-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound N1C=CC=2C1=NC=CC=2C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N CRINRUDDKSBHIM-IBGZPJMESA-N 0.000 claims 1
- ITVHSCOFHWBGHL-KRWDZBQOSA-N (2S)-2-[4-(2H-pyrazolo[3,4-b]pyridin-3-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound N1N=C(C=2C1=NC=CC=2)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N ITVHSCOFHWBGHL-KRWDZBQOSA-N 0.000 claims 1
- MRVYZKBROYHVDF-KRWDZBQOSA-N (2S)-2-[4-(3,5-dimethyl-1,2-oxazol-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CC1=NOC(=C1C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N)C MRVYZKBROYHVDF-KRWDZBQOSA-N 0.000 claims 1
- PCXSBVQMMUHDPY-RXFZURLPSA-N (2S)-2-[4-(3,5-dimethylpyrazolidin-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CC1C(C(NN1)C)C2=C3CCN(C3=CC=C2)C(=O)[C@@H]4CCCN4C#N PCXSBVQMMUHDPY-RXFZURLPSA-N 0.000 claims 1
- ACQWIAVWDCJLJK-NRFANRHFSA-N (2S)-2-[4-(3-cyanophenyl)-6-(5-methyl-1H-1,2,4-triazol-3-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C(#N)C=1C=C(C=CC=1)C1=C2CCN(C2=CC(=C1)C1=NN=C(N1)C)C(=O)[C@H]1N(CCC1)C#N ACQWIAVWDCJLJK-NRFANRHFSA-N 0.000 claims 1
- TVHPJDRLSFVKMM-AVAKVYKDSA-N (2S)-2-[4-(3-cyclopropylpyrazolidin-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C1C[C@H](N(C1)C#N)C(=O)N2CCC3=C(C=CC=C32)C4CNNC4C5CC5 TVHPJDRLSFVKMM-AVAKVYKDSA-N 0.000 claims 1
- VGXSHTSUKOOVIG-FQEVSTJZSA-N (2S)-2-[4-(3-methoxyphenyl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound COC=1C=C(C=CC=1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N VGXSHTSUKOOVIG-FQEVSTJZSA-N 0.000 claims 1
- SLJKHYWZWJNXQN-NRFANRHFSA-N (2S)-2-[4-(4-cyanophenyl)-6-(5-methyl-1H-1,2,4-triazol-3-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C(#N)C1=CC=C(C=C1)C1=C2CCN(C2=CC(=C1)C1=NN=C(N1)C)C(=O)[C@H]1N(CCC1)C#N SLJKHYWZWJNXQN-NRFANRHFSA-N 0.000 claims 1
- FVZXOSYEKUHRSU-KRWDZBQOSA-N (2S)-2-[4-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CC1=C(C=NN1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N FVZXOSYEKUHRSU-KRWDZBQOSA-N 0.000 claims 1
- AIDJSSPSMPDBMV-HNNXBMFYSA-N (2S)-2-[4-[5-(trifluoromethyl)-1H-pyrazol-4-yl]-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound FC(C1=C(C=NN1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N)(F)F AIDJSSPSMPDBMV-HNNXBMFYSA-N 0.000 claims 1
- ZTFYENXJVUNCMA-ZDUSSCGKSA-N (2S)-2-[4-[5-(trifluoromethyl)-1H-pyrazol-4-yl]-2,3-dihydropyrrolo[3,2-c]pyridine-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound FC(C1=C(C=NN1)C1=NC=CC2=C1CCN2C(=O)[C@H]1N(CCC1)C#N)(F)F ZTFYENXJVUNCMA-ZDUSSCGKSA-N 0.000 claims 1
- UMJRIWVVIRJDFL-NRFANRHFSA-N (2S)-2-[5-(1-methylindazol-5-yl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CN1N=CC2=CC(=CC=C12)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N UMJRIWVVIRJDFL-NRFANRHFSA-N 0.000 claims 1
- YOPQXVMPFMTKLY-FQEVSTJZSA-N (2S)-2-[5-(2-cyanophenyl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C(#N)C1=C(C=CC=C1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N YOPQXVMPFMTKLY-FQEVSTJZSA-N 0.000 claims 1
- HKTUPWJHHQLKKU-KRWDZBQOSA-N (2S)-2-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CC1=NOC(=C1C=1C=C2CCN(C2=CC=1)C(=O)[C@H]1N(CCC1)C#N)C HKTUPWJHHQLKKU-KRWDZBQOSA-N 0.000 claims 1
- NAJHZPGWDIYZGC-IBGZPJMESA-N (2S)-2-[5-(3-cyano-2-fluorophenyl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C(#N)C=1C(=C(C=CC=1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N)F NAJHZPGWDIYZGC-IBGZPJMESA-N 0.000 claims 1
- WRFQTTNBJCSRCN-FQEVSTJZSA-N (2S)-2-[5-(3-cyanophenyl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C(#N)C=1C=C(C=CC=1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N WRFQTTNBJCSRCN-FQEVSTJZSA-N 0.000 claims 1
- QFEQKVJBDNLCAH-UHTQNSLKSA-N (2S)-2-[5-(3-methyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CC1C2CCC(CC2NN1)C3=CC4=C(CN(C4)C(=O)[C@@H]5CCCN5C#N)C=C3 QFEQKVJBDNLCAH-UHTQNSLKSA-N 0.000 claims 1
- GFCNPYUHBGCNDP-IBGZPJMESA-N (2S)-2-[5-(3-nitrophenyl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound [N+](=O)([O-])C=1C=C(C=CC=1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N GFCNPYUHBGCNDP-IBGZPJMESA-N 0.000 claims 1
- HMBGZKFBFMGLBA-FQEVSTJZSA-N (2S)-2-[5-(4-cyanophenyl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C(#N)C1=CC=C(C=C1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N HMBGZKFBFMGLBA-FQEVSTJZSA-N 0.000 claims 1
- XJORGKDALFSCCA-FQEVSTJZSA-N (2S)-2-[5-(4-methylsulfonylphenyl)-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CS(=O)(=O)C1=CC=C(C=C1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N XJORGKDALFSCCA-FQEVSTJZSA-N 0.000 claims 1
- NMCNSAXVHYTCSP-IBGZPJMESA-N (2S)-2-[5-[3-(trifluoromethoxy)phenyl]-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound FC(OC=1C=C(C=CC=1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N)(F)F NMCNSAXVHYTCSP-IBGZPJMESA-N 0.000 claims 1
- NJKYHSIJIMVBPR-PCKAHOCUSA-N (2S)-2-[5-[3-(trifluoromethyl)pyrazolidin-4-yl]-1,3-dihydroisoindole-2-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C1C[C@H](N(C1)C#N)C(=O)N2CC3=C(C2)C=C(C=C3)C4CNNC4C(F)(F)F NJKYHSIJIMVBPR-PCKAHOCUSA-N 0.000 claims 1
- UWIAIQJNMUKTFT-SIWZUTFBSA-N (2S)-2-[5-[3-(trifluoromethyl)pyrazolidin-4-yl]-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound C1C[C@H](N(C1)C#N)C(=O)N2CCC3=C2C=CC(=C3)C4CNNC4C(F)(F)F UWIAIQJNMUKTFT-SIWZUTFBSA-N 0.000 claims 1
- COCVMGPHJWIQML-FQEVSTJZSA-N (2S)-2-[6-(5-methyl-1H-1,2,4-triazol-3-yl)-4-phenyl-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound CC=1NC(=NN=1)C1=CC(=C2CCN(C2=C1)C(=O)[C@H]1N(CCC1)C#N)C1=CC=CC=C1 COCVMGPHJWIQML-FQEVSTJZSA-N 0.000 claims 1
- XOANBZMRYZSVBZ-INIZCTEOSA-N (2S)-4,4-difluoro-2-[4-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound FC1(C[C@H](N(C1)C#N)C(=O)N1CCC2=C(C=CC=C12)C=1C=NNC=1C)F XOANBZMRYZSVBZ-INIZCTEOSA-N 0.000 claims 1
- BHILSXATFZMXGG-AWEZNQCLSA-N (2S)-4,4-difluoro-2-[4-[5-(trifluoromethyl)-1H-pyrazol-4-yl]-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound FC1(C[C@H](N(C1)C#N)C(=O)N1CCC2=C(C=CC=C12)C=1C=NNC=1C(F)(F)F)F BHILSXATFZMXGG-AWEZNQCLSA-N 0.000 claims 1
- SAMGWGZMVFDEQB-JTQLQIEISA-N (2S)-N-(4-tert-butyl-1,3-thiazol-2-yl)-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound C(C)(C)(C)C=1N=C(SC=1)N(C(=O)[C@H]1N(CCC1)C#N)C SAMGWGZMVFDEQB-JTQLQIEISA-N 0.000 claims 1
- OZQSHOAYDYFPRI-HNNXBMFYSA-N (2S)-N-(5-benzyl-1,3-thiazol-2-yl)-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound C(C1=CC=CC=C1)C1=CN=C(S1)N(C(=O)[C@H]1N(CCC1)C#N)C OZQSHOAYDYFPRI-HNNXBMFYSA-N 0.000 claims 1
- RLYNKSMCPXKHJQ-AWEZNQCLSA-N (2S)-N-[3-(2-chlorophenyl)-1,2-oxazol-5-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound ClC1=C(C=CC=C1)C1=NOC(=C1)N(C(=O)[C@H]1N(CCC1)C#N)C RLYNKSMCPXKHJQ-AWEZNQCLSA-N 0.000 claims 1
- ITPZQAOZSCHWGH-AWEZNQCLSA-N (2S)-N-[3-(3-chlorophenyl)-1,2-oxazol-5-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound ClC=1C=C(C=CC=1)C1=NOC(=C1)N(C(=O)[C@H]1N(CCC1)C#N)C ITPZQAOZSCHWGH-AWEZNQCLSA-N 0.000 claims 1
- UGRRMXPVIFJDNJ-AWEZNQCLSA-N (2S)-N-[3-(4-chlorophenyl)-1,2-oxazol-5-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=C(C=C1)C1=NOC(=C1)N(C(=O)[C@H]1N(CCC1)C#N)C UGRRMXPVIFJDNJ-AWEZNQCLSA-N 0.000 claims 1
- KTBZQJVLCMGVDY-AWEZNQCLSA-N (2S)-N-[4-(2-chlorophenyl)-1,3-thiazol-2-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound ClC1=C(C=CC=C1)C=1N=C(SC=1)N(C(=O)[C@H]1N(CCC1)C#N)C KTBZQJVLCMGVDY-AWEZNQCLSA-N 0.000 claims 1
- SQNJTBNFEHPSFE-INIZCTEOSA-N (2S)-N-[4-(3-acetamidophenyl)-1,3-thiazol-2-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound C(C)(=O)NC=1C=C(C=CC=1)C=1N=C(SC=1)N(C(=O)[C@H]1N(CCC1)C#N)C SQNJTBNFEHPSFE-INIZCTEOSA-N 0.000 claims 1
- HLYWOXLKZGUNLZ-AWEZNQCLSA-N (2S)-N-[4-(3-chloro-4-fluorophenyl)-1,3-thiazol-2-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound ClC=1C=C(C=CC=1F)C=1N=C(SC=1)N(C(=O)[C@H]1N(CCC1)C#N)C HLYWOXLKZGUNLZ-AWEZNQCLSA-N 0.000 claims 1
- MPFJAXKSYDXRGF-AWEZNQCLSA-N (2S)-N-[4-(3-chlorophenyl)-1,3-thiazol-2-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound ClC=1C=C(C=CC=1)C=1N=C(SC=1)N(C(=O)[C@H]1N(CCC1)C#N)C MPFJAXKSYDXRGF-AWEZNQCLSA-N 0.000 claims 1
- NYHSLNVRVJOYFH-AWEZNQCLSA-N (2S)-N-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=C(C=C1)C=1N=C(SC=1)N(C(=O)[C@H]1N(CCC1)C#N)C NYHSLNVRVJOYFH-AWEZNQCLSA-N 0.000 claims 1
- NJKJVEDERGWOOB-KRWDZBQOSA-N (2S)-N-[4-[3-[acetyl(methyl)amino]phenyl]-1,3-thiazol-2-yl]-1-cyano-N-methylpyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=CC(=CC=C1)N(C(C)=O)C)C NJKJVEDERGWOOB-KRWDZBQOSA-N 0.000 claims 1
- RQELPKFGBFTZSL-QUCCMNQESA-N (2S,4S)-1-cyano-N-methyl-4-phenyl-N-(4-phenyl-1,3-thiazol-2-yl)pyrrolidine-2-carboxamide Chemical compound C(#N)N1[C@@H](C[C@H](C1)C1=CC=CC=C1)C(=O)N(C=1SC=C(N=1)C1=CC=CC=C1)C RQELPKFGBFTZSL-QUCCMNQESA-N 0.000 claims 1
- BIKCGHPVEKXRAG-SJCJKPOMSA-N (2S,4S)-4-fluoro-2-[4-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound F[C@H]1C[C@H](N(C1)C#N)C(=O)N1CCC2=C(C=CC=C12)C=1C=NNC=1C BIKCGHPVEKXRAG-SJCJKPOMSA-N 0.000 claims 1
- AHCBJXSHVXHGHF-BONVTDFDSA-N (2S,4S)-4-fluoro-2-[4-[5-(trifluoromethyl)-1H-pyrazol-4-yl]-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carbonitrile Chemical compound F[C@H]1C[C@H](N(C1)C#N)C(=O)N1CCC2=C(C=CC=C12)C=1C=NNC=1C(F)(F)F AHCBJXSHVXHGHF-BONVTDFDSA-N 0.000 claims 1
- DJQHWGVEXLMBAZ-JXFKEZNVSA-N (2S,4S)-4-methoxy-2-(4-phenyl-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carbonitrile Chemical compound CO[C@H]1C[C@H](N(C1)C#N)C(=O)N1CCC2=C(C=CC=C12)C1=CC=CC=C1 DJQHWGVEXLMBAZ-JXFKEZNVSA-N 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- HMDPLQQUMZHZRG-IBGZPJMESA-N 1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-4-(3,4-dichlorophenyl)-N-methyl-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)c1cc2N(CCc2c(c1)-c1ccc(Cl)c(Cl)c1)C(=O)[C@@H]1CCCN1C#N HMDPLQQUMZHZRG-IBGZPJMESA-N 0.000 claims 1
- YBGZJESLGRCDEE-NRFANRHFSA-N 1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-4-(3-ethylphenyl)-N-methyl-2,3-dihydroindole-6-carboxamide Chemical compound CCC1=CC=CC(=C1)C1=CC(=CC2=C1CCN2C(=O)[C@@H]1CCCN1C#N)C(=O)NC YBGZJESLGRCDEE-NRFANRHFSA-N 0.000 claims 1
- WFXCOIDBGACSFK-FQEVSTJZSA-N 1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-ethyl-4-phenyl-2,3-dihydroindole-6-carboxamide Chemical compound CCNC(=O)C1=CC2=C(CCN2C(=O)[C@@H]2CCCN2C#N)C(=C1)C1=CC=CC=C1 WFXCOIDBGACSFK-FQEVSTJZSA-N 0.000 claims 1
- KEWYUVLIPGUNSG-IBGZPJMESA-N 1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)C1=CC2=C(CCN2C(=O)[C@@H]2CCCN2C#N)C(=C1)C1=CNC2=C1C=CC=N2 KEWYUVLIPGUNSG-IBGZPJMESA-N 0.000 claims 1
- LHZGPCBUTBOMOE-IBGZPJMESA-N 1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-4-[4-(trifluoromethyl)phenyl]-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)C1=CC(=C2CCN(C(=O)[C@@H]3CCCN3C#N)C2=C1)C1=CC=C(C=C1)C(F)(F)F LHZGPCBUTBOMOE-IBGZPJMESA-N 0.000 claims 1
- FDMMUQYTSILOPR-QFIPXVFZSA-N 1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-4-quinolin-6-yl-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)C1=CC2=C(CCN2C(=O)[C@@H]2CCCN2C#N)C(=C1)C1=CC2=C(C=C1)N=CC=C2 FDMMUQYTSILOPR-QFIPXVFZSA-N 0.000 claims 1
- 208000009270 3-hydroxyacyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- FTDLODJAIMNALU-SFHVURJKSA-N 4-(1,3-benzodioxol-5-yl)-1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)c1cc2N(CCc2c(c1)-c1ccc2OCOc2c1)C(=O)[C@@H]1CCCN1C#N FTDLODJAIMNALU-SFHVURJKSA-N 0.000 claims 1
- WHFKIEYBBULDCZ-IBGZPJMESA-N 4-(2-chlorophenyl)-1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)c1cc2N(CCc2c(c1)-c1ccccc1Cl)C(=O)[C@@H]1CCCN1C#N WHFKIEYBBULDCZ-IBGZPJMESA-N 0.000 claims 1
- CUARZSQLWSSUBD-FQEVSTJZSA-N 4-(3-cyanophenyl)-1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)c1cc2N(CCc2c(c1)-c1cccc(c1)C#N)C(=O)[C@@H]1CCCN1C#N CUARZSQLWSSUBD-FQEVSTJZSA-N 0.000 claims 1
- OMYYPBQIHHRCPF-IBGZPJMESA-N 4-(4-chlorophenyl)-1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)c1cc2N(CCc2c(c1)-c1ccc(Cl)cc1)C(=O)[C@@H]1CCCN1C#N OMYYPBQIHHRCPF-IBGZPJMESA-N 0.000 claims 1
- SQEIQQQQYKFXCH-FQEVSTJZSA-N 4-(4-cyanophenyl)-1-[(2S)-1-cyanopyrrolidine-2-carbonyl]-N-methyl-2,3-dihydroindole-6-carboxamide Chemical compound CNC(=O)c1cc2N(CCc2c(c1)-c1ccc(cc1)C#N)C(=O)[C@@H]1CCCN1C#N SQEIQQQQYKFXCH-FQEVSTJZSA-N 0.000 claims 1
- 102100026882 Alpha-synuclein Human genes 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 206010003591 Ataxia Diseases 0.000 claims 1
- 201000005943 Barth syndrome Diseases 0.000 claims 1
- WLUCIYYGHLKLSV-FQEVSTJZSA-N C(#N)C1=C(C=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound C(#N)C1=C(C=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N WLUCIYYGHLKLSV-FQEVSTJZSA-N 0.000 claims 1
- LURHVDXFRRUNIS-FQEVSTJZSA-N C(#N)C1=CC=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound C(#N)C1=CC=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N LURHVDXFRRUNIS-FQEVSTJZSA-N 0.000 claims 1
- WNYLPSCEQVXVEU-FQEVSTJZSA-N C(#N)C=1C=C(C=CC=1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound C(#N)C=1C=C(C=CC=1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N WNYLPSCEQVXVEU-FQEVSTJZSA-N 0.000 claims 1
- IORAJTZSNAZPSA-LBPRGKRZSA-N C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=NC(=CC=C1)C(F)(F)F)C Chemical compound C(#N)N1[C@@H](CCC1)C(=O)N(C=1SC=C(N=1)C1=NC(=CC=C1)C(F)(F)F)C IORAJTZSNAZPSA-LBPRGKRZSA-N 0.000 claims 1
- RGFNLDIHPNPDQW-HNNXBMFYSA-N C(C)(C)OC1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound C(C)(C)OC1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N RGFNLDIHPNPDQW-HNNXBMFYSA-N 0.000 claims 1
- PTEPIQYGZOAPCJ-IBGZPJMESA-N C1(=CC=CC=C1)C=1C=C2CCN(C2=CC=1)C(=O)[C@H]1N(CCC1)C#N Chemical compound C1(=CC=CC=C1)C=1C=C2CCN(C2=CC=1)C(=O)[C@H]1N(CCC1)C#N PTEPIQYGZOAPCJ-IBGZPJMESA-N 0.000 claims 1
- AEWPXKRBWMHBRQ-IBGZPJMESA-N C1(=CC=CC=C1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N Chemical compound C1(=CC=CC=C1)C=1C=C2CN(CC2=CC=1)C(=O)[C@H]1N(CCC1)C#N AEWPXKRBWMHBRQ-IBGZPJMESA-N 0.000 claims 1
- AHXHFWKYIYXQMV-INIZCTEOSA-N C1(CC1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound C1(CC1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N AHXHFWKYIYXQMV-INIZCTEOSA-N 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- GPNAJIZRASNSIG-FQEVSTJZSA-N CC1=C(C(=CC=C1)C)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound CC1=C(C(=CC=C1)C)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N GPNAJIZRASNSIG-FQEVSTJZSA-N 0.000 claims 1
- DTPPEGSKBHKTOF-KRWDZBQOSA-N CC1=C(C=NO1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound CC1=C(C=NO1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N DTPPEGSKBHKTOF-KRWDZBQOSA-N 0.000 claims 1
- VQXZQBLOCQIOOC-KRWDZBQOSA-N CC1=C(C=NO1)C=1C=C2CCN(C2=CC=1)C(=O)[C@H]1N(CCC1)C#N Chemical compound CC1=C(C=NO1)C=1C=C2CCN(C2=CC=1)C(=O)[C@H]1N(CCC1)C#N VQXZQBLOCQIOOC-KRWDZBQOSA-N 0.000 claims 1
- QXXVNRVLJDODMU-KRWDZBQOSA-N CNC1=NC=CC(=N1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound CNC1=NC=CC(=N1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N QXXVNRVLJDODMU-KRWDZBQOSA-N 0.000 claims 1
- LMVCADKTOPZYBN-IBGZPJMESA-N COC1=C(C=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound COC1=C(C=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N LMVCADKTOPZYBN-IBGZPJMESA-N 0.000 claims 1
- NXYQNEYXTVQPQF-FQEVSTJZSA-N COC1=CC=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound COC1=CC=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N NXYQNEYXTVQPQF-FQEVSTJZSA-N 0.000 claims 1
- DJQHWGVEXLMBAZ-UZLBHIALSA-N CO[C@@H]1C[C@H](N(C1)C#N)C(=O)N1CCC2=C(C=CC=C12)C1=CC=CC=C1 Chemical compound CO[C@@H]1C[C@H](N(C1)C#N)C(=O)N1CCC2=C(C=CC=C12)C1=CC=CC=C1 DJQHWGVEXLMBAZ-UZLBHIALSA-N 0.000 claims 1
- XTBVWWRXYVWTQH-FQEVSTJZSA-N C[Si](C)(C)C#CC1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C(=O)OC(C)(C)C Chemical compound C[Si](C)(C)C#CC1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C(=O)OC(C)(C)C XTBVWWRXYVWTQH-FQEVSTJZSA-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
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- VMYMUPNFTDKDMR-IBGZPJMESA-N ClC=1C=C(C=CC=1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound ClC=1C=C(C=CC=1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N VMYMUPNFTDKDMR-IBGZPJMESA-N 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
- 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
- 201000011240 Frontotemporal dementia 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
- 101000605835 Homo sapiens Serine/threonine-protein kinase PINK1, mitochondrial 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
- 206010061218 Inflammation 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
- 208000019693 Lung disease Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 108700000232 Medium chain acyl CoA dehydrogenase deficiency Proteins 0.000 claims 1
- 208000025370 Middle East respiratory syndrome 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
- 208000000149 Multiple Sulfatase Deficiency Disease Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 208000035032 Multiple sulfatase deficiency Diseases 0.000 claims 1
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims 1
- HFYHHCUUAZHVOR-KRWDZBQOSA-N N1=C2C(=NC=C1)NC=C2C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound N1=C2C(=NC=C1)NC=C2C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N HFYHHCUUAZHVOR-KRWDZBQOSA-N 0.000 claims 1
- KHDWCTFCLZXTEQ-SFHVURJKSA-N N1=CC(=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound N1=CC(=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N KHDWCTFCLZXTEQ-SFHVURJKSA-N 0.000 claims 1
- SOGGLSWYHHABAC-KRWDZBQOSA-N N1=CN=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound N1=CN=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N SOGGLSWYHHABAC-KRWDZBQOSA-N 0.000 claims 1
- FJHVMDWNTLUVSA-KRWDZBQOSA-N N1=NC=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound N1=NC=C(C=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N FJHVMDWNTLUVSA-KRWDZBQOSA-N 0.000 claims 1
- YOGAXMPPMMXAEY-INIZCTEOSA-N NC1=CN=CC(=N1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound NC1=CN=CC(=N1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N YOGAXMPPMMXAEY-INIZCTEOSA-N 0.000 claims 1
- PGWVBDMLLJFVDO-INIZCTEOSA-N NC1=NC=C(C=N1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound NC1=NC=C(C=N1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N PGWVBDMLLJFVDO-INIZCTEOSA-N 0.000 claims 1
- IREHCLMOMHIEHD-SFHVURJKSA-N O(C1=CC=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N Chemical compound O(C1=CC=CC=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C#N IREHCLMOMHIEHD-SFHVURJKSA-N 0.000 claims 1
- CXGNWVHMUQBCPU-IBGZPJMESA-N O(C1=CC=CC=C1)C=1C=C2CCN(C2=CC=1)C(=O)[C@H]1N(CCC1)C#N Chemical compound O(C1=CC=CC=C1)C=1C=C2CCN(C2=CC=1)C(=O)[C@H]1N(CCC1)C#N CXGNWVHMUQBCPU-IBGZPJMESA-N 0.000 claims 1
- 102100035196 POLG alternative reading frame Human genes 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 208000027089 Parkinsonian 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
- 102100038376 Serine/threonine-protein kinase PINK1, mitochondrial Human genes 0.000 claims 1
- 108090000185 alpha-Synuclein Proteins 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims 1
- 125000002618 bicyclic heterocycle group Chemical group 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
- 210000000481 breast Anatomy 0.000 claims 1
- 201000004010 carnitine palmitoyltransferase I deficiency Diseases 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 201000008609 cerebral creatine deficiency syndrome Diseases 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims 1
- 125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 201000009028 early myoclonic encephalopathy Diseases 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- 210000003128 head Anatomy 0.000 claims 1
- 208000014188 hereditary optic neuropathy Diseases 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims 1
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 231100000518 lethal Toxicity 0.000 claims 1
- 230000001665 lethal effect Effects 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 208000004687 long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 208000003531 maternally-inherited Leigh syndrome Diseases 0.000 claims 1
- 208000005548 medium chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- APNYYKPFLAHMIB-HNNXBMFYSA-N methyl 4-bromo-1-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]-2,3-dihydroindole-6-carboxylate Chemical compound COC(=O)C1=CC(Br)=C2CCN(C(=O)[C@@H]3CCCN3C(=O)OC(C)(C)C)C2=C1 APNYYKPFLAHMIB-HNNXBMFYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 201000002697 mitochondrial DNA depletion syndrome Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 208000020460 mucolipidosis II alpha/beta Diseases 0.000 claims 1
- 208000020468 mucolipidosis III alpha/beta Diseases 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 210000003205 muscle Anatomy 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 210000003739 neck Anatomy 0.000 claims 1
- 230000001537 neural effect Effects 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 230000000414 obstructive effect Effects 0.000 claims 1
- 108010007425 oligomycin sensitivity conferring protein Proteins 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 208000021090 palsy Diseases 0.000 claims 1
- 210000000496 pancreas Anatomy 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 208000020016 psychiatric disease Diseases 0.000 claims 1
- QJRYYOWARFCJQZ-UHFFFAOYSA-N pyrrolidine-1-carbonitrile Chemical compound N#CN1CCCC1 QJRYYOWARFCJQZ-UHFFFAOYSA-N 0.000 claims 1
- 201000006473 pyruvate decarboxylase deficiency Diseases 0.000 claims 1
- 208000015445 pyruvate dehydrogenase deficiency Diseases 0.000 claims 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
- 201000000980 schizophrenia Diseases 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- MBSCHPZZVVPDMW-HNNXBMFYSA-N tert-butyl (2S)-2-(4-bromo-2,3-dihydroindole-1-carbonyl)pyrrolidine-1-carboxylate Chemical compound BrC1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C(=O)OC(C)(C)C MBSCHPZZVVPDMW-HNNXBMFYSA-N 0.000 claims 1
- GFWQTQCAFKEBJY-QFIPXVFZSA-N tert-butyl (2S)-2-(5-phenyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N1CCC2=C(C1)C=CC=C2C1=CC=CC=C1 GFWQTQCAFKEBJY-QFIPXVFZSA-N 0.000 claims 1
- FVXNFTFVFLVUAU-IBGZPJMESA-N tert-butyl (2S)-2-[4-(2-aminopyridin-4-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carboxylate Chemical compound NC1=NC=CC(=C1)C1=C2CCN(C2=CC=C1)C(=O)[C@H]1N(CCC1)C(=O)OC(C)(C)C FVXNFTFVFLVUAU-IBGZPJMESA-N 0.000 claims 1
- WJDNWLZOVHJGIK-NRFANRHFSA-N tert-butyl (2S)-2-[4-phenyl-6-(1H-1,2,4-triazol-5-yl)-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N1CCC2=C(C=C(C=C12)C1=NN=CN1)C1=CC=CC=C1 WJDNWLZOVHJGIK-NRFANRHFSA-N 0.000 claims 1
- ZBKMMWZJRWVUKF-QFIPXVFZSA-N tert-butyl (2S)-2-[6-(1H-imidazol-2-yl)-4-phenyl-2,3-dihydroindole-1-carbonyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N1CCC2=C(C=C(C=C12)C1=NC=CN1)C1=CC=CC=C1 ZBKMMWZJRWVUKF-QFIPXVFZSA-N 0.000 claims 1
- IDGCQIKYYGMWLZ-KRWDZBQOSA-N tert-butyl (2S)-2-[[4-(3-chlorophenyl)-1,3-thiazol-2-yl]-ethylcarbamoyl]pyrrolidine-1-carboxylate Chemical compound CCN(C(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C)C1=NC(=CS1)C1=CC(Cl)=CC=C1 IDGCQIKYYGMWLZ-KRWDZBQOSA-N 0.000 claims 1
- SFITVTVUGOFBQN-SFHVURJKSA-N tert-butyl (2S)-2-[[4-(4-acetamidophenyl)-1,3-thiazol-2-yl]-methylcarbamoyl]pyrrolidine-1-carboxylate Chemical compound CN(C(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C)C1=NC(=CS1)C1=CC=C(NC(C)=O)C=C1 SFITVTVUGOFBQN-SFHVURJKSA-N 0.000 claims 1
- AMSVWAAHYCTIPV-AWEZNQCLSA-N tert-butyl (2S)-2-[[5-(3-bromophenyl)-1,2-oxazol-3-yl]carbamoyl]pyrrolidine-1-carboxylate Chemical compound BrC=1C=C(C=CC=1)C1=CC(=NO1)NC(=O)[C@H]1N(CCC1)C(=O)OC(C)(C)C AMSVWAAHYCTIPV-AWEZNQCLSA-N 0.000 claims 1
- FPDGCJCXKOPYMM-HNNXBMFYSA-N tert-butyl (2S)-2-[[5-(3-chlorophenyl)-1,2-oxazol-3-yl]-methylcarbamoyl]pyrrolidine-1-carboxylate Chemical compound CN(C(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C)C1=NOC(=C1)C1=CC(Cl)=CC=C1 FPDGCJCXKOPYMM-HNNXBMFYSA-N 0.000 claims 1
- CRFZMUGEOKSLSK-INIZCTEOSA-N tert-butyl (2S)-2-[[5-(3-methoxyphenyl)-1,2-oxazol-3-yl]-methylcarbamoyl]pyrrolidine-1-carboxylate Chemical compound COC=1C=C(C=CC=1)C1=CC(=NO1)N(C(=O)[C@H]1N(CCC1)C(=O)OC(C)(C)C)C CRFZMUGEOKSLSK-INIZCTEOSA-N 0.000 claims 1
- KNMIHEMZRYEGMW-RDJZCZTQSA-N tert-butyl (2S,4S)-4-methoxy-2-[methyl-(4-phenyl-1,3-thiazol-2-yl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound CO[C@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C(N(C=1SC=C(N=1)C1=CC=CC=C1)C)=O KNMIHEMZRYEGMW-RDJZCZTQSA-N 0.000 claims 1
- 210000001550 testis Anatomy 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- 201000010866 very long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1512270.8 | 2015-07-14 | ||
| GBGB1512270.8A GB201512270D0 (en) | 2015-07-14 | 2015-07-14 | Novel Compounds |
| GBGB1604642.7A GB201604642D0 (en) | 2016-03-18 | 2016-03-18 | Novel compounds |
| GB1604642.7 | 2016-03-18 | ||
| PCT/GB2016/052130 WO2017009650A1 (en) | 2015-07-14 | 2016-07-14 | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018524367A JP2018524367A (ja) | 2018-08-30 |
| JP2018524367A5 true JP2018524367A5 (enExample) | 2019-08-22 |
| JP6802251B2 JP6802251B2 (ja) | 2020-12-16 |
Family
ID=56618186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018501285A Active JP6802251B2 (ja) | 2015-07-14 | 2016-07-14 | 癌の処置のためのｄｕｂ阻害剤としてのシアノピロリジン |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US10669234B2 (enExample) |
| EP (2) | EP3322702B1 (enExample) |
| JP (1) | JP6802251B2 (enExample) |
| CN (1) | CN107849013B (enExample) |
| ES (1) | ES2773046T3 (enExample) |
| WO (1) | WO2017009650A1 (enExample) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201416754D0 (en) | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| MD3277677T2 (ro) * | 2015-03-30 | 2021-07-31 | Mission Therapeutics Ltd | Compuși de 1-ciano-pirolidină utilizați ca inhibitori de USP30 |
| WO2017009650A1 (en) | 2015-07-14 | 2017-01-19 | 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 |
| CN108884068B (zh) | 2016-03-24 | 2021-02-26 | 特殊治疗有限公司 | 作为dub抑制剂的1-氰基-吡咯烷衍生物 |
| JP6959332B2 (ja) | 2016-09-27 | 2021-11-02 | ミッション セラピューティクス リミティド | Ｕｓｐ３０の阻害剤としての活性を有するシアノピロリジン誘導体 |
| 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 |
| WO2018213150A1 (en) * | 2017-05-15 | 2018-11-22 | Mitobridge, Inc. | Usp30 inhibitors |
| GB201708652D0 (en) * | 2017-05-31 | 2017-07-12 | Mission Therapeutics Ltd | Novel compounds and uses |
| CN110831936B (zh) | 2017-06-20 | 2023-03-28 | 特殊治疗有限公司 | 具有dub抑制剂活性的取代氰基吡咯烷 |
| ES2950757T3 (es) | 2017-10-06 | 2023-10-13 | Forma Therapeutics Inc | Inhibición de la peptidasa específica de la ubiquitina 30 |
| IL315310A (en) | 2017-12-26 | 2024-10-01 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
| EP3737675A4 (en) | 2018-01-12 | 2022-01-05 | Kymera Therapeutics, Inc. | Crbn ligands and uses thereof |
| CA3135740A1 (en) * | 2018-05-04 | 2019-11-07 | Remedy Plan, Inc. | Cancer treatments targeting cancer stem cells |
| BR112020021921A2 (pt) | 2018-05-17 | 2021-01-26 | Forma Therapeutics, Inc. | compostos bicíclicos fundidos úteis como inibidores de peptidase 30 específica de ubiquitina |
| WO2020010227A1 (en) | 2018-07-06 | 2020-01-09 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
| US11292792B2 (en) | 2018-07-06 | 2022-04-05 | Kymera Therapeutics, Inc. | Tricyclic CRBN ligands and uses thereof |
| WO2020011243A1 (en) * | 2018-07-12 | 2020-01-16 | Betta Pharmaceuticals Co., Ltd | Immunomodulators, compositions and methods thereof |
| US11572374B2 (en) | 2018-08-14 | 2023-02-07 | Amgen Inc. | N-cyano-7-azanorbornane derivatives and uses thereof |
| LT3860989T (lt) | 2018-10-05 | 2023-06-12 | Forma Therapeutics, Inc. | Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai |
| US11352350B2 (en) | 2018-11-30 | 2022-06-07 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| CN120698985A (zh) | 2018-12-20 | 2025-09-26 | C4医药公司 | 靶向蛋白降解 |
| JP7473565B2 (ja) | 2019-01-28 | 2024-04-23 | ミトコンドリア エモーション， インク． | マイトフュージン活性化物質及びその使用方法 |
| JP7734917B2 (ja) | 2019-01-28 | 2025-09-08 | ミトコンドリア エモーション， インク． | トランス－４－ヒドロキシシクロヘキシルフェニルアミドマイトフュージン活性化物質及びその使用方法 |
| CN109776377B (zh) * | 2019-02-01 | 2021-08-24 | 沈阳药科大学 | 吲哚啉类化合物及其制备方法和应用 |
| SG11202110829YA (en) | 2019-04-05 | 2021-10-28 | Kymera Therapeutics Inc | Stat degraders and uses thereof |
| GB201905375D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| GB201905371D0 (en) | 2019-04-16 | 2019-05-29 | Mission Therapeutics Ltd | Novel compounds |
| WO2021011631A1 (en) * | 2019-07-15 | 2021-01-21 | Kymera Therapeutics, Inc. | Fused-glutarimide crbn ligands and uses thereof |
| US20230093080A1 (en) * | 2019-07-15 | 2023-03-23 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
| GB201912674D0 (en) | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| EP4076520A4 (en) | 2019-12-17 | 2024-03-27 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| BR112022012410A2 (pt) | 2019-12-23 | 2022-08-30 | Kymera Therapeutics Inc | Degradadores smarca e usos dos mesmos |
| PH12022552458A1 (en) | 2020-03-19 | 2024-01-22 | Kymera Therapeutics Inc | Mdm2 degraders and uses thereof |
| KR20230006487A (ko) | 2020-04-08 | 2023-01-10 | 미션 테라퓨틱스 엘티디 | Usp30 억제제로서의 활성을 갖는 n-시아노피롤리딘 |
| MX2022014429A (es) | 2020-05-28 | 2022-12-07 | Mission Therapeutics Ltd | N-cianopirrolidinas con actividad como inhibidores de usp30. |
| TW202210483A (zh) | 2020-06-03 | 2022-03-16 | 美商凱麥拉醫療公司 | Irak降解劑之結晶型 |
| US20230303547A1 (en) | 2020-06-04 | 2023-09-28 | Mission Therapeutics Limited | N-cyanopyrrolidines with activity as usp30 inhibitors |
| HUE072598T2 (hu) | 2020-06-08 | 2025-11-28 | Mission Therapeutics Ltd | 1-(5-(2-cianopiridin-4-il)oxazol-2-karbonil)-4-metilhexahidropirrolo[3,4-B]pirrol-5(1H)-karbonitril felhasználásra, mint USP30 inhibitor, mitokondriális diszfunkció, rák és fibrózisok kezelésében |
| US20230212131A1 (en) * | 2020-06-09 | 2023-07-06 | Anima Biotech Inc. | Collagen 1 translation inhibitors and methods of use thereof |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| TW202241891A (zh) | 2020-12-30 | 2022-11-01 | 美商凱麥拉醫療公司 | Irak降解劑及其用途 |
| JP2024506656A (ja) | 2021-02-15 | 2024-02-14 | カイメラ セラピューティクス， インコーポレイテッド | Ｉｒａｋ４分解剤およびその使用 |
| US12097261B2 (en) | 2021-05-07 | 2024-09-24 | Kymera Therapeutics, Inc. | CDK2 degraders and uses thereof |
| AU2022317661A1 (en) * | 2021-07-26 | 2024-01-18 | Dana-Farber Cancer Institute, Inc. | Small molecule inhibition of deubiquitinating enzyme josephin domain containing 1 (josd1) as a targeted therapy for leukemias with mutant janus kinase 2 (jak2) |
| WO2023076556A1 (en) | 2021-10-29 | 2023-05-04 | Kymera Therapeutics, Inc. | Irak4 degraders and synthesis thereof |
| EP4441044A1 (en) | 2021-12-01 | 2024-10-09 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
| CN114478577A (zh) * | 2021-12-08 | 2022-05-13 | 河北合佳创新医药科技有限公司 | 一种n-甲酰基头孢噻肟的制备方法 |
| JP2025504059A (ja) | 2022-01-31 | 2025-02-06 | カイメラ セラピューティクス， インコーポレイテッド | Ｉｒａｋデグレーダー及びその使用 |
| CN119528901A (zh) * | 2024-11-05 | 2025-02-28 | 上海市同济医院 | 噻唑类化合物、去sumo和/或去泛素化酶抑制剂及其制备方法和应用 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1272467A4 (en) * | 2000-04-06 | 2003-05-07 | Merck Frosst Canada Inc | Cathepsin cysteine protease inhibitors |
| AR071480A1 (es) | 2008-04-18 | 2010-06-23 | Glaxo Group Ltd | Compuesto de 1- ciano -3- pirrolidinil -bencenosulfonamida composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para tratar la enfermedad pulmonar obstructiva cronica (copd ) |
| CN103261169A (zh) * | 2010-09-24 | 2013-08-21 | 密歇根大学董事会 | 脱泛素酶抑制剂及其应用方法 |
| KR102438072B1 (ko) * | 2012-01-12 | 2022-08-31 | 예일 유니버시티 | E3 유비퀴틴 리가아제에 의한 표적 단백질 및 다른 폴리펩티드의 증진된 분해를 위한 화합물 및 방법 |
| GB201416754D0 (en) | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| WO2017009650A1 (en) | 2015-07-14 | 2017-01-19 | 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 |
| CN108884068B (zh) | 2016-03-24 | 2021-02-26 | 特殊治疗有限公司 | 作为dub抑制剂的1-氰基-吡咯烷衍生物 |
-
2016
- 2016-07-14 WO PCT/GB2016/052130 patent/WO2017009650A1/en not_active Ceased
- 2016-07-14 ES ES16750199T patent/ES2773046T3/es active Active
- 2016-07-14 CN CN201680040161.0A patent/CN107849013B/zh active Active
- 2016-07-14 EP EP16750199.8A patent/EP3322702B1/en active Active
- 2016-07-14 US US15/738,900 patent/US10669234B2/en active Active
- 2016-07-14 EP EP19209239.3A patent/EP3800186B1/en active Active
- 2016-07-14 JP JP2018501285A patent/JP6802251B2/ja active Active
-
2020
- 2020-04-08 US US16/843,339 patent/US11319287B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2018524367A5 (enExample) | ||
| JP2019501142A5 (enExample) | ||
| JP2019504009A5 (enExample) | ||
| US20220251041A1 (en) | 1-cyano-pyrrolidine compounds as usp30 inhibitors | |
| JP2019533659A5 (enExample) | ||
| JP2018510183A5 (enExample) | ||
| JP2019513135A5 (enExample) | ||
| JP5055136B2 (ja) | Ｖｅｇｆ−ｒ２阻害剤としてのイミダゾ（１，２−ａ）ピリジン化合物 | |
| US9926307B2 (en) | Compounds | |
| JP2020521730A5 (enExample) | ||
| JP2019509274A5 (enExample) | ||
| JP2019532945A5 (enExample) | ||
| WO2018065768A1 (en) | Cyano-substituted heterocycles with activity as inhibitors of usp30 | |
| JP2016514124A (ja) | 変異ｉｄｈの阻害薬としての３−ピリミジン−４−イル−オキサゾリジン−２−オン | |
| JP2016522246A5 (enExample) | ||
| CA2422923A1 (en) | Pyridine derivatives with ikb-kinase (ikk-.beta.) inhibiting activity | |
| JP2016523911A5 (enExample) | ||
| JP2017528515A5 (enExample) | ||
| JP2019537581A5 (enExample) | ||
| JP2015528435A5 (enExample) |