JP2018510183A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018510183A5 JP2018510183A5 JP2017551189A JP2017551189A JP2018510183A5 JP 2018510183 A5 JP2018510183 A5 JP 2018510183A5 JP 2017551189 A JP2017551189 A JP 2017551189A JP 2017551189 A JP2017551189 A JP 2017551189A JP 2018510183 A5 JP2018510183 A5 JP 2018510183A5
- Authority
- JP
- Japan
- Prior art keywords
- cyanopyrrolidin
- carboxamide
- alkylene
- methyl
- pyrazol
- 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
- -1 cyano, hydroxyl Chemical group 0.000 claims 70
- 150000001875 compounds Chemical class 0.000 claims 51
- 125000000217 alkyl group Chemical group 0.000 claims 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 37
- 125000000623 heterocyclic group Chemical group 0.000 claims 28
- 125000003545 alkoxy group Chemical group 0.000 claims 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims 20
- 125000003118 aryl group Chemical group 0.000 claims 17
- 229910052731 fluorine Inorganic materials 0.000 claims 15
- 150000003839 salts Chemical class 0.000 claims 15
- 125000001072 heteroaryl group Chemical group 0.000 claims 14
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 13
- 125000001153 fluoro group Chemical group F* 0.000 claims 11
- 125000001424 substituent group Chemical group 0.000 claims 11
- 208000011580 syndromic disease Diseases 0.000 claims 11
- 125000004043 oxo group Chemical group O=* 0.000 claims 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims 10
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 9
- 206010028980 Neoplasm Diseases 0.000 claims 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims 9
- 230000007812 deficiency Effects 0.000 claims 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 9
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 8
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 8
- 125000004450 alkenylene group Chemical group 0.000 claims 8
- 125000002947 alkylene group Chemical group 0.000 claims 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 8
- 229910052736 halogen Inorganic materials 0.000 claims 8
- 150000002367 halogens Chemical class 0.000 claims 8
- 201000011510 cancer Diseases 0.000 claims 7
- 125000002950 monocyclic group Chemical group 0.000 claims 7
- 208000008955 Mucolipidoses Diseases 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 125000002619 bicyclic group Chemical group 0.000 claims 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 4
- 208000014644 Brain disease Diseases 0.000 claims 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 4
- 206010058892 Carnitine deficiency Diseases 0.000 claims 4
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 claims 4
- 208000032274 Encephalopathy Diseases 0.000 claims 4
- 201000002169 Mitochondrial myopathy Diseases 0.000 claims 4
- 235000010290 biphenyl Nutrition 0.000 claims 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 4
- 208000006443 lactic acidosis Diseases 0.000 claims 4
- 230000004065 mitochondrial dysfunction Effects 0.000 claims 4
- 230000002438 mitochondrial effect Effects 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 4
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 claims 4
- 150000003573 thiols Chemical class 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 208000006011 Stroke Diseases 0.000 claims 3
- UCOHKZKRNWNULS-UHFFFAOYSA-N aminocyanamide Chemical compound NNC#N UCOHKZKRNWNULS-UHFFFAOYSA-N 0.000 claims 3
- 125000002393 azetidinyl group Chemical group 0.000 claims 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 3
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims 3
- 125000002757 morpholinyl group Chemical group 0.000 claims 3
- 210000003205 muscle Anatomy 0.000 claims 3
- 230000035772 mutation Effects 0.000 claims 3
- 230000004770 neurodegeneration Effects 0.000 claims 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims 3
- 125000004193 piperazinyl group Chemical group 0.000 claims 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 3
- 208000009270 3-hydroxyacyl-CoA dehydrogenase deficiency Diseases 0.000 claims 2
- 208000019932 Aciduria Diseases 0.000 claims 2
- 206010003591 Ataxia Diseases 0.000 claims 2
- 201000005943 Barth syndrome Diseases 0.000 claims 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims 2
- 108700005857 Carnitine palmitoyl transferase 1A deficiency Proteins 0.000 claims 2
- 208000005359 Carnitine palmitoyl transferase 1A deficiency Diseases 0.000 claims 2
- 108700005858 Carnitine palmitoyl transferase 2 deficiency Proteins 0.000 claims 2
- 201000002929 Carnitine palmitoyltransferase II deficiency Diseases 0.000 claims 2
- 206010008025 Cerebellar ataxia Diseases 0.000 claims 2
- 208000010354 Coenzyme Q10 deficiency Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 206010010904 Convulsion Diseases 0.000 claims 2
- 208000021075 Creatine deficiency syndrome Diseases 0.000 claims 2
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims 2
- 102000015782 Electron Transport Complex III Human genes 0.000 claims 2
- 108010024882 Electron Transport Complex III Proteins 0.000 claims 2
- 206010016654 Fibrosis Diseases 0.000 claims 2
- 201000008892 GM1 Gangliosidosis Diseases 0.000 claims 2
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims 2
- 101000804964 Homo sapiens DNA polymerase subunit gamma-1 Proteins 0.000 claims 2
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 claims 2
- 101000595929 Homo sapiens POLG alternative reading frame Proteins 0.000 claims 2
- 102100030358 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Human genes 0.000 claims 2
- 101710150008 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Proteins 0.000 claims 2
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 claims 2
- 108700006159 Long-chain acyl-CoA dehydrogenase deficiency Proteins 0.000 claims 2
- 108700000232 Medium chain acyl CoA dehydrogenase deficiency Proteins 0.000 claims 2
- 206010072928 Mucolipidosis type II Diseases 0.000 claims 2
- 208000001769 Multiple Acyl Coenzyme A Dehydrogenase Deficiency Diseases 0.000 claims 2
- 208000000149 Multiple Sulfatase Deficiency Disease Diseases 0.000 claims 2
- 208000035032 Multiple sulfatase deficiency Diseases 0.000 claims 2
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims 2
- 102100035196 POLG alternative reading frame Human genes 0.000 claims 2
- 206010033799 Paralysis Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 208000013234 Pearson syndrome Diseases 0.000 claims 2
- 208000002009 Pyruvate Dehydrogenase Complex Deficiency Disease Diseases 0.000 claims 2
- 208000021886 Pyruvate carboxylase deficiency Diseases 0.000 claims 2
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 2
- 206010057644 Testis cancer Diseases 0.000 claims 2
- 201000004010 carnitine palmitoyltransferase I deficiency Diseases 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 201000008609 cerebral creatine deficiency syndrome Diseases 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 230000007547 defect Effects 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 201000009028 early myoclonic encephalopathy Diseases 0.000 claims 2
- 230000004761 fibrosis Effects 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims 2
- 208000004687 long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 2
- 208000005548 medium chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 201000002697 mitochondrial DNA depletion syndrome Diseases 0.000 claims 2
- 208000020460 mucolipidosis II alpha/beta Diseases 0.000 claims 2
- 208000020468 mucolipidosis III alpha/beta Diseases 0.000 claims 2
- 208000010125 myocardial infarction Diseases 0.000 claims 2
- 208000031225 myocardial ischemia Diseases 0.000 claims 2
- 230000001537 neural effect Effects 0.000 claims 2
- 201000001119 neuropathy Diseases 0.000 claims 2
- 230000007823 neuropathy Effects 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 108010007425 oligomycin sensitivity conferring protein Proteins 0.000 claims 2
- 238000007254 oxidation reaction Methods 0.000 claims 2
- 102000045222 parkin Human genes 0.000 claims 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 230000000750 progressive effect Effects 0.000 claims 2
- 208000020016 psychiatric disease Diseases 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 201000006473 pyruvate decarboxylase deficiency Diseases 0.000 claims 2
- 208000015445 pyruvate dehydrogenase deficiency Diseases 0.000 claims 2
- 201000000980 schizophrenia Diseases 0.000 claims 2
- 201000003120 testicular cancer Diseases 0.000 claims 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims 2
- NUXIWBUQKROULG-CJNGLKHVSA-N (3aR,6aR)-1-(1-phenylimidazole-4-carbonyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound C1(=CC=CC=C1)N1C=NC(=C1)C(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N NUXIWBUQKROULG-CJNGLKHVSA-N 0.000 claims 1
- DYMWDTUJPDRKIQ-HIFRSBDPSA-N (3aR,6aR)-1-(2,3-dihydroindole-1-carbonyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound N1(CCC2=CC=CC=C12)C(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N DYMWDTUJPDRKIQ-HIFRSBDPSA-N 0.000 claims 1
- CSQVJQNXYCHHTK-QQPKSGGNSA-N (3aR,6aR)-1-(3-phenoxyazetidine-1-carbonyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile N-(1-cyanopiperidin-3-yl)-3-phenylbenzamide Chemical compound O=C(NC1CCCN(C1)C#N)c1cccc(c1)-c1ccccc1.O=C(N1CC(C1)Oc1ccccc1)N1CC[C@@H]2CN(C[C@H]12)C#N CSQVJQNXYCHHTK-QQPKSGGNSA-N 0.000 claims 1
- CMMRNABFYAATQI-HIFRSBDPSA-N (3aR,6aR)-1-(3-phenyl-1,2-oxazole-5-carbonyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound C1(=CC=CC=C1)C1=NOC(=C1)C(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N CMMRNABFYAATQI-HIFRSBDPSA-N 0.000 claims 1
- JHHSTONZRLHGMH-CJNGLKHVSA-N (3aR,6aR)-1-(3-phenyl-1H-pyrazole-5-carbonyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound C1(=CC=CC=C1)C1=NNC(=C1)C(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N JHHSTONZRLHGMH-CJNGLKHVSA-N 0.000 claims 1
- OUGVBBDEQQIAEA-QAPCUYQASA-N (3aR,6aR)-1-(4-fluoro-3-pyridin-4-ylbenzoyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound FC1=C(C=C(C(=O)N2[C@@H]3[C@H](CC2)CN(C3)C#N)C=C1)C1=CC=NC=C1 OUGVBBDEQQIAEA-QAPCUYQASA-N 0.000 claims 1
- LVLDVEIEEYCFQX-CJNGLKHVSA-N (3aR,6aR)-1-[3-(4-methoxyphenyl)-1,2-oxazole-5-carbonyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound COC1=CC=C(C=C1)C1=NOC(=C1)C(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N LVLDVEIEEYCFQX-CJNGLKHVSA-N 0.000 claims 1
- IHVYISFJPUVGPN-DYVFJYSZSA-N (3aR,6aR)-1-[3-(4-methoxyphenyl)-1H-pyrazole-5-carbonyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound COC1=CC=C(C=C1)C1=NNC(=C1)C(=O)N1[C@@H]2[C@H](CC1)CN(C2)C#N IHVYISFJPUVGPN-DYVFJYSZSA-N 0.000 claims 1
- QKSAQXTVNSAFHP-PBHICJAKSA-N (3aR,6aR)-1-[3-methoxy-4-(1-methylpyrazol-4-yl)benzoyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound COC=1C=C(C(=O)N2[C@@H]3[C@H](CC2)CN(C3)C#N)C=CC=1C=1C=NN(C=1)C QKSAQXTVNSAFHP-PBHICJAKSA-N 0.000 claims 1
- XISMVCGRSIDEMH-KDOFPFPSSA-N (3aR,6aR)-1-[4-(3-chloropyridin-4-yl)-3-methoxybenzoyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound ClC=1C=NC=CC=1C1=C(C=C(C(=O)N2[C@@H]3[C@H](CC2)CN(C3)C#N)C=C1)OC XISMVCGRSIDEMH-KDOFPFPSSA-N 0.000 claims 1
- KWDLHMCDAUEXPE-DYVFJYSZSA-N (3aR,6aR)-1-[4-fluoro-3-(1-methylpyrazol-4-yl)benzoyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carbonitrile Chemical compound FC1=C(C=C(C(=O)N2[C@@H]3[C@H](CC2)CN(C3)C#N)C=C1)C=1C=NN(C=1)C KWDLHMCDAUEXPE-DYVFJYSZSA-N 0.000 claims 1
- QLSFKZAGQZHUKY-RISCZKNCSA-N (3aR,6aR)-5-cyano-N-(4-cyano-2-fluorophenyl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound FC1=C(NC(=O)N2CC[C@@H]3CN(C[C@H]23)C#N)C=CC(=C1)C#N QLSFKZAGQZHUKY-RISCZKNCSA-N 0.000 claims 1
- YPTROWCJXWUAJD-NEPJUHHUSA-N (3aR,6aR)-5-cyano-N-(5-methylpyridin-2-yl)-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound CC1=CN=C(C=C1)NC(=O)N2CC[C@H]3[C@@H]2CN(C3)C#N YPTROWCJXWUAJD-NEPJUHHUSA-N 0.000 claims 1
- ORRROJOQVQBSPY-APWZRJJASA-N (3aR,6aR)-5-cyano-N-[2-fluoro-4-(2-methylpyridin-4-yl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound C(#N)N1C[C@@H]2N(CC[C@@H]2C1)C(=O)NC1=C(C=C(C=C1)C1=CC(=NC=C1)C)F ORRROJOQVQBSPY-APWZRJJASA-N 0.000 claims 1
- DDFGJQDAKCUHFI-RNCFNFMXSA-N (3aR,6aR)-5-cyano-N-[2-fluoro-4-(trifluoromethoxy)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound FC1=C(NC(=O)N2CC[C@@H]3CN(C[C@H]23)C#N)C=CC(OC(F)(F)F)=C1 DDFGJQDAKCUHFI-RNCFNFMXSA-N 0.000 claims 1
- NKSQYNVJOYRSIC-RNCFNFMXSA-N (3aR,6aR)-5-cyano-N-[2-fluoro-4-(trifluoromethyl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound FC1=C(NC(=O)N2CC[C@@H]3CN(C[C@H]23)C#N)C=CC(=C1)C(F)(F)F NKSQYNVJOYRSIC-RNCFNFMXSA-N 0.000 claims 1
- RNGVIKCHXWALJA-RNCFNFMXSA-N (3aR,6aR)-5-cyano-N-[2-fluoro-5-(trifluoromethyl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound FC1=C(NC(=O)N2CC[C@@H]3CN(C[C@H]23)C#N)C=C(C=C1)C(F)(F)F RNGVIKCHXWALJA-RNCFNFMXSA-N 0.000 claims 1
- HYNKWSOOZFQERY-MJGOQNOKSA-N (3aR,6aR)-5-cyano-N-[3-(2-methylpyridin-4-yl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound CC1=NC=CC(=C1)C1=CC=CC(NC(=O)N2CC[C@@H]3CN(C[C@H]23)C#N)=C1 HYNKWSOOZFQERY-MJGOQNOKSA-N 0.000 claims 1
- SVUMILBXHLHUDA-MJGOQNOKSA-N (3aR,6aR)-5-cyano-N-[4-(2-methylpyridin-4-yl)phenyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-1-carboxamide Chemical compound CC1=NC=CC(=C1)C1=CC=C(NC(=O)N2CC[C@@H]3CN(C[C@H]23)C#N)C=C1 SVUMILBXHLHUDA-MJGOQNOKSA-N 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- IEVPIDPBYIXIQS-UHFFFAOYSA-N 1-(1-cyanopyrrolidin-3-yl)-1-(2-methoxyethyl)-3-[4-(trifluoromethyl)phenyl]urea Chemical compound C(#N)N1CC(CC1)N(C(=O)NC1=CC=C(C=C1)C(F)(F)F)CCOC IEVPIDPBYIXIQS-UHFFFAOYSA-N 0.000 claims 1
- IKBBDBCYLOYWSA-UHFFFAOYSA-N 1-(1-cyanopyrrolidin-3-yl)-1-methyl-3-(3-phenoxyphenyl)urea 1-(1-cyanopyrrolidin-3-yl)-1-methyl-3-(4-phenylphenyl)urea Chemical compound CN(C1CCN(C1)C#N)C(=O)Nc1ccc(cc1)-c1ccccc1.CN(C1CCN(C1)C#N)C(=O)Nc1cccc(Oc2ccccc2)c1 IKBBDBCYLOYWSA-UHFFFAOYSA-N 0.000 claims 1
- HWGCIUXHGRINBV-HLIUPHQXSA-N 1-[(3R)-1-cyanopyrrolidin-3-yl]-1-methyl-3-[4-(1-methylpyrazol-4-yl)phenyl]urea 1-[(3R)-1-cyanopyrrolidin-3-yl]-1-methyl-3-[4-(trifluoromethyl)phenyl]urea Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)NC1=CC=C(C=C1)C(F)(F)F)C.C(#N)N1C[C@@H](CC1)N(C(=O)NC1=CC=C(C=C1)C=1C=NN(C1)C)C HWGCIUXHGRINBV-HLIUPHQXSA-N 0.000 claims 1
- LSJPCGONGCTFFW-SNVBAGLBSA-N 2-(2-chlorophenyl)-N-[(3R)-1-cyanopyrrolidin-3-yl]-1,3-thiazole-5-carboxamide Chemical compound ClC1=C(C=CC=C1)C=1SC(=CN=1)C(=O)N[C@H]1CN(CC1)C#N LSJPCGONGCTFFW-SNVBAGLBSA-N 0.000 claims 1
- ZUYGZLCUQVYYHF-UHFFFAOYSA-N 2-(4-acetyl-1,4-diazepan-1-yl)-N-(1-cyanopyrrolidin-3-yl)pyridine-4-carboxamide Chemical compound C(C)(=O)N1CCN(CCC1)C=1C=C(C(=O)NC2CN(CC2)C#N)C=CN=1 ZUYGZLCUQVYYHF-UHFFFAOYSA-N 0.000 claims 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- GLFISEMLNCKZKB-GFCCVEGCSA-N 3-(1H-benzimidazol-2-yl)-N-[(3R)-1-cyanopyrrolidin-3-yl]azetidine-1-carboxamide Chemical compound N1C(=NC2=C1C=CC=C2)C1CN(C1)C(=O)N[C@H]1CN(CC1)C#N GLFISEMLNCKZKB-GFCCVEGCSA-N 0.000 claims 1
- PRSXVLVCZRHGOR-UHFFFAOYSA-N 3-(3-benzylphenyl)-1-(1-cyanopyrrolidin-3-yl)-1-methylurea 3-(3-chlorophenyl)-1-(1-cyanopyrrolidin-3-yl)-1-methylurea 1-(1-cyanopyrrolidin-3-yl)-3-(3-phenoxyphenyl)urea Chemical compound CN(C1CCN(C1)C#N)C(=O)Nc1cccc(Cl)c1.O=C(NC1CCN(C1)C#N)Nc1cccc(Oc2ccccc2)c1.CN(C1CCN(C1)C#N)C(=O)Nc1cccc(Cc2ccccc2)c1 PRSXVLVCZRHGOR-UHFFFAOYSA-N 0.000 claims 1
- ZCLHBFLSTMSYFI-UHFFFAOYSA-N 3-(3-chlorophenyl)-N-(1-cyanopyrrolidin-3-yl)-1,2-oxazole-5-carboxamide Chemical compound ClC=1C=C(C=CC=1)C1=NOC(=C1)C(=O)NC1CN(CC1)C#N ZCLHBFLSTMSYFI-UHFFFAOYSA-N 0.000 claims 1
- RUPJYXSXSNJTQC-CQSZACIVSA-N 3-(3-chlorophenyl)-N-[(3R)-1-cyanopyrrolidin-3-yl]azetidine-1-carboxamide Chemical compound ClC=1C=C(C=CC=1)C1CN(C1)C(=O)N[C@H]1CN(CC1)C#N RUPJYXSXSNJTQC-CQSZACIVSA-N 0.000 claims 1
- ZSPMQFBHTJEIDE-CQSZACIVSA-N 3-(4-chlorophenyl)-N-[(3R)-1-cyanopyrrolidin-3-yl]azetidine-1-carboxamide Chemical compound ClC1=CC=C(C=C1)C1CN(C1)C(=O)N[C@H]1CN(CC1)C#N ZSPMQFBHTJEIDE-CQSZACIVSA-N 0.000 claims 1
- OPAARFSKBDJNTB-MRXNPFEDSA-N 3-[2-(4-chlorophenyl)pyrimidin-4-yl]-N-[(3R)-1-cyanopyrrolidin-3-yl]azetidine-1-carboxamide Chemical compound ClC1=CC=C(C=C1)C1=NC=CC(=N1)C1CN(C1)C(=O)N[C@H]1CN(CC1)C#N OPAARFSKBDJNTB-MRXNPFEDSA-N 0.000 claims 1
- YDZRHEBFSNARLZ-CQSZACIVSA-N 3-chloro-N-[(3R)-1-cyanopyrrolidin-3-yl]-5-(4-fluorophenyl)pyridine-2-carboxamide Chemical compound ClC=1C(=NC=C(C=1)C1=CC=C(C=C1)F)C(=O)N[C@H]1CN(CC1)C#N YDZRHEBFSNARLZ-CQSZACIVSA-N 0.000 claims 1
- VSCJNJXZOVCPQP-CQSZACIVSA-N 4-[benzenesulfonyl(methyl)amino]-N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluorobenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)N(S(=O)(=O)C1=CC=CC=C1)C)F)=O VSCJNJXZOVCPQP-CQSZACIVSA-N 0.000 claims 1
- PWLHPLDJIMPECZ-UHFFFAOYSA-N 6-(4-carbamoylpiperidin-1-yl)-N-(1-cyanopyrrolidin-3-yl)pyridine-3-carboxamide Chemical compound C(N)(=O)C1CCN(CC1)C1=NC=C(C(=O)NC2CN(CC2)C#N)C=C1 PWLHPLDJIMPECZ-UHFFFAOYSA-N 0.000 claims 1
- UFMYCTWRHBZPRU-OAHLLOKOSA-N 6-(4-chlorophenyl)-N-[(3R)-1-cyanopyrrolidin-3-yl]pyridine-3-carboxamide Chemical compound ClC1=CC=C(C=C1)C1=NC=C(C(=O)N[C@H]2CN(CC2)C#N)C=C1 UFMYCTWRHBZPRU-OAHLLOKOSA-N 0.000 claims 1
- OHKHAFDJNKIGKA-JOCHJYFZSA-N 6-[7-(3-cyanophenyl)imidazo[1,2-a]pyridin-2-yl]-N-[(3R)-1-cyanopyrrolidin-3-yl]pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1CN(C[C@@H]1NC(=O)C2=C3C=CC(=CN3N=C2)C4=CN5C=CC(=CC5=N4)C6=CC=CC(=C6)C#N)C#N OHKHAFDJNKIGKA-JOCHJYFZSA-N 0.000 claims 1
- MURCJUZFRZIJMS-UHFFFAOYSA-N 6-[benzyl(methyl)amino]-N-(1-cyanopyrrolidin-3-yl)pyridine-2-carboxamide Chemical compound C(C1=CC=CC=C1)N(C1=CC=CC(=N1)C(=O)NC1CN(CC1)C#N)C MURCJUZFRZIJMS-UHFFFAOYSA-N 0.000 claims 1
- IRVIHSNOWWEOQC-QGZVFWFLSA-N 7-(3-cyanophenyl)-N-[(3R)-1-cyanopyrrolidin-3-yl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound O=C(N[C@@H]1CCN(C1)C#N)C1=CN=C2C=C(C=CN12)C1=CC(=CC=C1)C#N IRVIHSNOWWEOQC-QGZVFWFLSA-N 0.000 claims 1
- 102100026882 Alpha-synuclein Human genes 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 102000051485 Bcl-2 family Human genes 0.000 claims 1
- 108700038897 Bcl-2 family Proteins 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- CSWILQJSVBNEOI-WYGBLSGGSA-N C(#N)N1C[C@@H](CC1)N(C(=O)N1CC(OCC1)C1=CC=CC=C1)C.C(#N)N1C[C@@H](CC1)N(C(=O)C1=CC=2C(=CN=C(C2)C=2C=NN(C2)C)N1)C Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)N1CC(OCC1)C1=CC=CC=C1)C.C(#N)N1C[C@@H](CC1)N(C(=O)C1=CC=2C(=CN=C(C2)C=2C=NN(C2)C)N1)C CSWILQJSVBNEOI-WYGBLSGGSA-N 0.000 claims 1
- CBYKNLVZHJZKNF-XRXIBTDESA-N C(#N)N1C[C@@H](CC1)N(C(=O)NC1=CC(=NC=C1)N1CC2=CC=CC=C2C1)C.C(#N)N1C[C@@H](CC1)NC(=O)C=1N(C2=CC=C(C=C2C1)C=1C=NN(C1)C)C Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)NC1=CC(=NC=C1)N1CC2=CC=CC=C2C1)C.C(#N)N1C[C@@H](CC1)NC(=O)C=1N(C2=CC=C(C=C2C1)C=1C=NN(C1)C)C CBYKNLVZHJZKNF-XRXIBTDESA-N 0.000 claims 1
- SQWCOVDGZOKMLC-RFSBDEKTSA-N C(#N)N1C[C@@H](CC1)N(C(=O)NC=1C=NC(=CC1)C(F)(F)F)C.C(#N)N1C[C@@H](CC1)N(C(=O)N1CCC2=CC=CC=C12)C Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)NC=1C=NC(=CC1)C(F)(F)F)C.C(#N)N1C[C@@H](CC1)N(C(=O)N1CCC2=CC=CC=C12)C SQWCOVDGZOKMLC-RFSBDEKTSA-N 0.000 claims 1
- CYFLIFVGWNWURO-OYVFXSTNSA-N C(#N)N1C[C@@H](CC1)NC(=O)C1=NNC(=C1)C1=C(C=CC=C1)OC.C(#N)N1C[C@@H](CC1)NC(=O)C1=NNC(=C1)C1=NC=CC=C1 Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=NNC(=C1)C1=C(C=CC=C1)OC.C(#N)N1C[C@@H](CC1)NC(=O)C1=NNC(=C1)C1=NC=CC=C1 CYFLIFVGWNWURO-OYVFXSTNSA-N 0.000 claims 1
- SRYZUHKASIOWOR-VVBZJRPGSA-N C(#N)N1C[C@@H](CC1)NC(C1=C(C(=C(C=C1)NC1=NC=CC(=N1)C1CC1)F)F)=O.C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)NC1=NC=CC(=N1)C1CC1)F)=O Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C(=C(C=C1)NC1=NC=CC(=N1)C1CC1)F)F)=O.C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)NC1=NC=CC(=N1)C1CC1)F)=O SRYZUHKASIOWOR-VVBZJRPGSA-N 0.000 claims 1
- VCNYURMMXKODRV-MBYPRKQLSA-N C(#N)N1C[C@@H](CC1)NC(C1=CN=C(C=C1)N1CCOCC1)=O.C(#N)N1C[C@@H](CC1)NC(=O)C1=NNC(=C1)C1=C(C=CC=C1)F Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CN=C(C=C1)N1CCOCC1)=O.C(#N)N1C[C@@H](CC1)NC(=O)C1=NNC(=C1)C1=C(C=CC=C1)F VCNYURMMXKODRV-MBYPRKQLSA-N 0.000 claims 1
- QBSHNJXJDUUMQL-QKYOFRMZSA-N C(#N)N1C[C@@H]([C@H](C1)C)NC(=O)C1=CN=C(S1)C1=CC=CC=C1.C(#N)N1C[C@H]([C@@H](C1)C)NC(=O)C1=CN=C(S1)C1=CC=CC=C1 Chemical compound C(#N)N1C[C@@H]([C@H](C1)C)NC(=O)C1=CN=C(S1)C1=CC=CC=C1.C(#N)N1C[C@H]([C@@H](C1)C)NC(=O)C1=CN=C(S1)C1=CC=CC=C1 QBSHNJXJDUUMQL-QKYOFRMZSA-N 0.000 claims 1
- WYBBABIVUJIICZ-QKYOFRMZSA-N C(#N)N1C[C@@H]([C@H](C1)C)NC(=O)C=1SC(=CN1)C1=CC=CC=C1.C(#N)N1C[C@H]([C@@H](C1)C)NC(=O)C=1SC(=CN1)C1=CC=CC=C1 Chemical compound C(#N)N1C[C@@H]([C@H](C1)C)NC(=O)C=1SC(=CN1)C1=CC=CC=C1.C(#N)N1C[C@H]([C@@H](C1)C)NC(=O)C=1SC(=CN1)C1=CC=CC=C1 WYBBABIVUJIICZ-QKYOFRMZSA-N 0.000 claims 1
- GUQZBSQUTHAMNZ-VXLLPVPCSA-N C1CN([C@@H]2[C@H]1CN(C2)C#N)C(=O)C3CCC(NC3=O)C4=CC=CC=C4 Chemical compound C1CN([C@@H]2[C@H]1CN(C2)C#N)C(=O)C3CCC(NC3=O)C4=CC=CC=C4 GUQZBSQUTHAMNZ-VXLLPVPCSA-N 0.000 claims 1
- IJRYNFCKESIJJY-DYVFJYSZSA-N CN1C=CC(=N1)C2=CC(=C(C=C2)NC(=O)N3CC[C@H]4[C@@H]3CN(C4)C#N)F Chemical compound CN1C=CC(=N1)C2=CC(=C(C=C2)NC(=O)N3CC[C@H]4[C@@H]3CN(C4)C#N)F IJRYNFCKESIJJY-DYVFJYSZSA-N 0.000 claims 1
- UJYJJGYUXHHRIZ-CRFPUYPASA-N ClC=1C=C(C(=O)N2[C@@H]3[C@H](CC2)CN(C3)C#N)C=CC1N1CCOCC1.ClC=1C=CC(=NC1)NC(N(C)[C@H]1CN(CC1)C#N)=O Chemical compound ClC=1C=C(C(=O)N2[C@@H]3[C@H](CC2)CN(C3)C#N)C=CC1N1CCOCC1.ClC=1C=CC(=NC1)NC(N(C)[C@H]1CN(CC1)C#N)=O UJYJJGYUXHHRIZ-CRFPUYPASA-N 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 201000011240 Frontotemporal dementia Diseases 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010021137 Hypovolaemia Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 208000006136 Leigh Disease Diseases 0.000 claims 1
- 208000017507 Leigh syndrome Diseases 0.000 claims 1
- 208000009829 Lewy Body Disease Diseases 0.000 claims 1
- 201000002832 Lewy body dementia Diseases 0.000 claims 1
- 108010027062 Long-Chain Acyl-CoA Dehydrogenase Proteins 0.000 claims 1
- 102000018653 Long-Chain Acyl-CoA Dehydrogenase Human genes 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- GIDDGZBVWUQVDY-UHFFFAOYSA-N N-(1-cyano-3-methylpyrrolidin-3-yl)-2-fluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1CC(CC1)(C)NC(C1=C(C=C(C=C1)C=1C=NN(C=1)C)F)=O GIDDGZBVWUQVDY-UHFFFAOYSA-N 0.000 claims 1
- GPFFVTDRKDVTRS-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-2-(3,4-dihydro-1H-isoquinolin-2-yl)pyridine-4-carboxamide Chemical compound C(#N)N1CC(CC1)NC(C1=CC(=NC=C1)N1CC2=CC=CC=C2CC1)=O GPFFVTDRKDVTRS-UHFFFAOYSA-N 0.000 claims 1
- XIZQSEMKOBOYED-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-4-(3,5-dimethyl-1,2-oxazol-4-yl)benzamide Chemical compound C(#N)N1CC(CC1)NC(C1=CC=C(C=C1)C=1C(=NOC=1C)C)=O XIZQSEMKOBOYED-UHFFFAOYSA-N 0.000 claims 1
- NEOICUABAWDZJA-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-4-phenoxybenzamide Chemical compound C(#N)N1CC(CC1)NC(C1=CC=C(C=C1)OC1=CC=CC=C1)=O NEOICUABAWDZJA-UHFFFAOYSA-N 0.000 claims 1
- IKWTYCKYUFAZEW-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-4-phenyl-1,3-thiazole-2-carboxamide Chemical compound C(#N)N1CC(CC1)NC(=O)C=1SC=C(N=1)C1=CC=CC=C1 IKWTYCKYUFAZEW-UHFFFAOYSA-N 0.000 claims 1
- MTJXHXNNDCGFDT-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-6-(2-pyridin-3-ylpyrrolidin-1-yl)pyridine-3-carboxamide Chemical compound C(#N)N1CC(CC1)NC(C1=CN=C(C=C1)N1C(CCC1)C=1C=NC=CC=1)=O MTJXHXNNDCGFDT-UHFFFAOYSA-N 0.000 claims 1
- PQLWLVGEAZJHNL-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-6-(3,4-dihydro-1H-isoquinolin-2-yl)pyridine-2-carboxamide Chemical compound C(#N)N1CC(CC1)NC(C1=NC(=CC=C1)N1CC2=CC=CC=C2CC1)=O PQLWLVGEAZJHNL-UHFFFAOYSA-N 0.000 claims 1
- QOVKDRQPMRQLQR-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-6-(4-phenoxypiperidin-1-yl)pyridine-2-carboxamide Chemical compound C(#N)N1CC(CC1)NC(C1=NC(=CC=C1)N1CCC(CC1)OC1=CC=CC=C1)=O QOVKDRQPMRQLQR-UHFFFAOYSA-N 0.000 claims 1
- QDOUYTYLACIKAP-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-6-(4-phenoxypiperidin-1-yl)pyridine-3-carboxamide Chemical compound C(#N)N1CC(CC1)NC(C1=CN=C(C=C1)N1CCC(CC1)OC1=CC=CC=C1)=O QDOUYTYLACIKAP-UHFFFAOYSA-N 0.000 claims 1
- DUFRQWNYGNGNMH-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-6-(4-pyridin-4-ylpiperidin-1-yl)pyridine-3-carboxamide Chemical compound C(#N)N1CC(CC1)NC(C1=CN=C(C=C1)N1CCC(CC1)C1=CC=NC=C1)=O DUFRQWNYGNGNMH-UHFFFAOYSA-N 0.000 claims 1
- WZLHPLOWRQEEIW-UHFFFAOYSA-N N-(1-cyanopyrrolidin-3-yl)-6-[4-(2,4-difluorophenyl)piperazin-1-yl]pyridine-3-carboxamide Chemical compound C(#N)N1CC(CC1)NC(C1=CN=C(C=C1)N1CCN(CC1)C1=C(C=C(C=C1)F)F)=O WZLHPLOWRQEEIW-UHFFFAOYSA-N 0.000 claims 1
- UUUIGNXIXREHHC-QGZVFWFLSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-1-(4-cyclopropylpyrimidin-2-yl)-2,3-dihydroindole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C=1C=C2CCN(C2=CC=1)C1=NC=CC(=N1)C1CC1 UUUIGNXIXREHHC-QGZVFWFLSA-N 0.000 claims 1
- CGYUQCMKKVYZJQ-QGZVFWFLSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-1-(cyclopropylmethyl)-6-(3,5-dimethyl-1,2-oxazol-4-yl)indazole-3-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=NN(C2=CC(=CC=C12)C=1C(=NOC=1C)C)CC1CC1 CGYUQCMKKVYZJQ-QGZVFWFLSA-N 0.000 claims 1
- BOMGDTJZOJZGEN-ARLHGKGLSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-1-phenylpyrrolidine-3-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1CN(CC1)C1=CC=CC=C1 BOMGDTJZOJZGEN-ARLHGKGLSA-N 0.000 claims 1
- CJHSXABYSBRNRW-LLVKDONJSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2,3-difluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C(=C(C=C1)C=1C=NN(C=1)C)F)F)=O CJHSXABYSBRNRW-LLVKDONJSA-N 0.000 claims 1
- BBLAMPVZCJAERV-LLVKDONJSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2,5-difluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C(=C1)F)C=1C=NN(C=1)C)F)=O BBLAMPVZCJAERV-LLVKDONJSA-N 0.000 claims 1
- ANHVHDBICIVOLR-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2,5-difluoro-4-piperidin-1-ylbenzamide Chemical compound C1CCN(CC1)C2=C(C=C(C(=C2)F)C(=O)N[C@@H]3CCN(C3)C#N)F ANHVHDBICIVOLR-GFCCVEGCSA-N 0.000 claims 1
- VWGLSOAHTWBVEV-LLVKDONJSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2,5-difluoro-4-pyrrolidin-1-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C(=C1)F)N1CCCC1)F)=O VWGLSOAHTWBVEV-LLVKDONJSA-N 0.000 claims 1
- XGIWRPWCYIUSKL-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2,6-difluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1F)C=1C=NN(C=1)C)F)=O XGIWRPWCYIUSKL-GFCCVEGCSA-N 0.000 claims 1
- GPFFVTDRKDVTRS-GOSISDBHSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-(3,4-dihydro-1H-isoquinolin-2-yl)pyridine-4-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=NC=C1)N1CC2=CC=CC=C2CC1)=O GPFFVTDRKDVTRS-GOSISDBHSA-N 0.000 claims 1
- MQAYVICWIVHQHM-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-3-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C(=CC=C1)C=1C=NN(C=1)C)F)=O MQAYVICWIVHQHM-GFCCVEGCSA-N 0.000 claims 1
- WVBYVBJYEZVBGY-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-3-methoxy-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C(=C(C=C1)C=1C=NN(C=1)C)OC)F)=O WVBYVBJYEZVBGY-GFCCVEGCSA-N 0.000 claims 1
- CEBODDRYMRREQK-MRXNPFEDSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-(1-methylindazol-5-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C=1C=C2C=NN(C2=CC=1)C)F)=O CEBODDRYMRREQK-MRXNPFEDSA-N 0.000 claims 1
- UMCQIHGZCKELTJ-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C=1C=NN(C=1)C)F)=O UMCQIHGZCKELTJ-CYBMUJFWSA-N 0.000 claims 1
- OFRZTFKFRAQWLW-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-(2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=C2C(N=C(N1)C)=NC=C2)F)=O OFRZTFKFRAQWLW-CYBMUJFWSA-N 0.000 claims 1
- QMXNMZVWAITDFL-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-(2-methylpyrimidin-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=NC(=NC=C1)C)F)=O QMXNMZVWAITDFL-CYBMUJFWSA-N 0.000 claims 1
- XVQONQLZKJGPGZ-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-(4-methylimidazol-1-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)N1C=NC(=C1)C)F)=O XVQONQLZKJGPGZ-GFCCVEGCSA-N 0.000 claims 1
- XYKCKEKCKGZVMC-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-(5-fluoro-2-methylpyrimidin-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=NC(=NC=C1F)C)F)=O XYKCKEKCKGZVMC-GFCCVEGCSA-N 0.000 claims 1
- KHVOHWHZSMDUNA-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-[1-(2-methoxyethyl)pyrazol-4-yl]benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C=1C=NN(C=1)CCOC)F)=O KHVOHWHZSMDUNA-OAHLLOKOSA-N 0.000 claims 1
- ALISHZYUMKMKSX-LLVKDONJSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-[2-(trifluoromethyl)pyrimidin-4-yl]benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=NC(=NC=C1)C(F)(F)F)F)=O ALISHZYUMKMKSX-LLVKDONJSA-N 0.000 claims 1
- IPXOEJLZCIZKQP-SNVBAGLBSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-[5-(trifluoromethyl)-1H-pyrazol-4-yl]benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C=1C=NNC=1C(F)(F)F)F)=O IPXOEJLZCIZKQP-SNVBAGLBSA-N 0.000 claims 1
- HCOIOBMSMDOIFA-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-imidazo[1,2-a]pyrazin-3-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=CN=C2N1C=CN=C2)F)=O HCOIOBMSMDOIFA-CYBMUJFWSA-N 0.000 claims 1
- RPBBEGTXSLMRET-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-imidazo[1,2-a]pyrimidin-6-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C=1C=NC=2N(C=1)C=CN=2)F)=O RPBBEGTXSLMRET-CQSZACIVSA-N 0.000 claims 1
- CTCNTIVYWMNJFU-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-pyrazolo[1,5-a]pyrimidin-5-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=NC=2N(C=C1)N=CC=2)F)=O CTCNTIVYWMNJFU-CYBMUJFWSA-N 0.000 claims 1
- ZGOOADAFZDDZME-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-pyridazin-4-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=CN=NC=C1)F)=O ZGOOADAFZDDZME-CYBMUJFWSA-N 0.000 claims 1
- DPENKAMUFPTBEJ-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-pyrimidin-4-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C1=NC=NC=C1)F)=O DPENKAMUFPTBEJ-GFCCVEGCSA-N 0.000 claims 1
- WALBHSXBGAUZKG-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-4-pyrrolidin-1-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)N1CCCC1)F)=O WALBHSXBGAUZKG-GFCCVEGCSA-N 0.000 claims 1
- AAUJAYLNXWDMDN-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-fluoro-5-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=CC(=C1)C=1C=NN(C=1)C)F)=O AAUJAYLNXWDMDN-CYBMUJFWSA-N 0.000 claims 1
- ZJFNEBISFHZYQT-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-2-methoxy-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=C(C=C(C=C1)C=1C=NN(C=1)C)OC)=O ZJFNEBISFHZYQT-CQSZACIVSA-N 0.000 claims 1
- ZTXZOAKQKYPPBN-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3,5-difluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C(=C1)F)C=1C=NN(C=1)C)F)=O ZTXZOAKQKYPPBN-GFCCVEGCSA-N 0.000 claims 1
- XANCKNDJDGAWCS-GLGOKHISSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(1-methylpyrazol-4-yl)pyrrolidine-1-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)N1CC(CC1)C=1C=NN(C=1)C XANCKNDJDGAWCS-GLGOKHISSA-N 0.000 claims 1
- KTSLAFXDDRUFSA-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(1-phenylpyrazol-3-yl)azetidine-1-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)N1CC(C1)C1=NN(C=C1)C1=CC=CC=C1 KTSLAFXDDRUFSA-OAHLLOKOSA-N 0.000 claims 1
- NCQUDMJRPXRBPA-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(1-pyrazin-2-ylpyrazol-3-yl)azetidine-1-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)N1CC(C1)C1=NN(C=C1)C1=NC=CN=C1 NCQUDMJRPXRBPA-CYBMUJFWSA-N 0.000 claims 1
- VPLQNBYFNUEOOI-SNVBAGLBSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(2,4-difluorophenyl)-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C1=C(C=C(C=C1)F)F VPLQNBYFNUEOOI-SNVBAGLBSA-N 0.000 claims 1
- GLXWRJDUQUUWQA-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(3,4-dimethoxyphenyl)-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C1=CC(=C(C=C1)OC)OC GLXWRJDUQUUWQA-GFCCVEGCSA-N 0.000 claims 1
- ZIVSOTIVNKAORH-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(3-methoxyphenyl)-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C1=CC(=CC=C1)OC ZIVSOTIVNKAORH-GFCCVEGCSA-N 0.000 claims 1
- DNVLSGQWQVJZKR-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(4-methoxyphenyl)-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C1=CC=C(C=C1)OC DNVLSGQWQVJZKR-GFCCVEGCSA-N 0.000 claims 1
- HRRKEFUZNGSJAZ-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-(4-methoxyphenyl)azetidine-1-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)N1CC(C1)C1=CC=C(C=C1)OC HRRKEFUZNGSJAZ-CQSZACIVSA-N 0.000 claims 1
- VBQNSOUPOJHGMR-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-[4-(trifluoromethyl)phenyl]-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C1=CC=C(C=C1)C(F)(F)F VBQNSOUPOJHGMR-GFCCVEGCSA-N 0.000 claims 1
- KIRYUEKURHFSGX-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-[methyl(2-methylpropanoyl)amino]benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=CC=C1)N(C(C(C)C)=O)C)=O KIRYUEKURHFSGX-CQSZACIVSA-N 0.000 claims 1
- ABOUVMQCYPNIBT-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-1-methyl-5-(1-methylpyrazol-4-yl)indole-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C=1N(C2=CC=C(C=C2C=1F)C=1C=NN(C=1)C)C ABOUVMQCYPNIBT-CQSZACIVSA-N 0.000 claims 1
- FNOMVXJLTJMMGJ-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)C=1C=NN(C=1)C)F)=O FNOMVXJLTJMMGJ-CYBMUJFWSA-N 0.000 claims 1
- BTMRGYAJJAVGSJ-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-4-(4-methylimidazol-1-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)N1C=NC(=C1)C)F)=O BTMRGYAJJAVGSJ-CYBMUJFWSA-N 0.000 claims 1
- MGBGNRGIGOLJIE-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-4-(pyrimidin-2-ylamino)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)NC1=NC=CC=N1)F)=O MGBGNRGIGOLJIE-GFCCVEGCSA-N 0.000 claims 1
- KAZVRNMRUXHFSH-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-5-(1-methylindazol-5-yl)pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1F)C=1C=C2C=NN(C2=CC=1)C)=O KAZVRNMRUXHFSH-OAHLLOKOSA-N 0.000 claims 1
- SCWRPIOZZNFBHK-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-5-(1-methylpyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1F)C=1C=C2C(=NC=1)N(C=C2)C)=O SCWRPIOZZNFBHK-OAHLLOKOSA-N 0.000 claims 1
- MHWJCAWDDYVIMN-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-5-imidazo[1,2-a]pyridin-6-ylpyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1F)C=1C=CC=2N(C=1)C=CN=2)=O MHWJCAWDDYVIMN-CQSZACIVSA-N 0.000 claims 1
- LORIXYUTELMIGV-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-5-pyrazolo[1,5-a]pyrimidin-5-ylpyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1F)C1=NC=2N(C=C1)N=CC=2)=O LORIXYUTELMIGV-GFCCVEGCSA-N 0.000 claims 1
- FFBLJPPQYUNUEM-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-fluoro-N-methyl-4-(4-methylimidazol-1-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)N(C(C1=CC(=C(C=C1)N1C=NC(=C1)C)F)=O)C FFBLJPPQYUNUEM-CQSZACIVSA-N 0.000 claims 1
- MZJRTLUPQNJAJJ-MRXNPFEDSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-methoxy-4-(2-methylpyridin-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)C1=CC(=NC=C1)C)OC)=O MZJRTLUPQNJAJJ-MRXNPFEDSA-N 0.000 claims 1
- PVTURUFYCWXEGM-GOSISDBHSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-methoxy-4-(2-morpholin-4-ylpyridin-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)C1=CC(=NC=C1)N1CCOCC1)OC)=O PVTURUFYCWXEGM-GOSISDBHSA-N 0.000 claims 1
- SFLXXHOKGMCFIS-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-methoxy-4-(pyrimidin-2-ylamino)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)NC1=NC=CC=N1)OC)=O SFLXXHOKGMCFIS-CYBMUJFWSA-N 0.000 claims 1
- RYOCHUAOFZQMLP-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-methoxy-4-[(4-methylpyrimidin-2-yl)amino]benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)NC1=NC=CC(=N1)C)OC)=O RYOCHUAOFZQMLP-CQSZACIVSA-N 0.000 claims 1
- SDSHASIAJMQRNK-SNVBAGLBSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-pyridin-2-yl-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C1=NC=CC=C1 SDSHASIAJMQRNK-SNVBAGLBSA-N 0.000 claims 1
- OZVKDRROSKNCJC-ZGTCLIOFSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-pyridin-2-ylpyrrolidine-1-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)N1CC(CC1)C1=NC=CC=C1 OZVKDRROSKNCJC-ZGTCLIOFSA-N 0.000 claims 1
- YZDDSFXRMVHPRG-LLVKDONJSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-pyridin-3-yl-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C=1C=NC=CC=1 YZDDSFXRMVHPRG-LLVKDONJSA-N 0.000 claims 1
- HCGZNXDPBZKYNW-LLVKDONJSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-pyridin-3-yl-1H-pyrazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=NNC(=C1)C=1C=NC=CC=1 HCGZNXDPBZKYNW-LLVKDONJSA-N 0.000 claims 1
- VSOICVQVGNRJGO-LLVKDONJSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-3-pyridin-4-yl-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CC(=NO1)C1=CC=NC=C1 VSOICVQVGNRJGO-LLVKDONJSA-N 0.000 claims 1
- MZHLSXSHPGQFES-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC=C(C=C1)C=1C=NN(C=1)C)=O MZHLSXSHPGQFES-OAHLLOKOSA-N 0.000 claims 1
- LVATWXODBSHCTF-MRXNPFEDSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-4-(4-cyclopropylpyrimidin-2-yl)-2,3-dihydro-1,4-benzoxazine-7-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C=1C=CC2=C(OCCN2C2=NC=CC(=N2)C2CC2)C=1 LVATWXODBSHCTF-MRXNPFEDSA-N 0.000 claims 1
- MMXHCXOZTITRAO-UONOGXRCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-4-[(3S)-3-ethylpyrrolidin-1-yl]-2-fluorobenzamide Chemical compound CC[C@H]1CCN(C1)C2=CC(=C(C=C2)C(=O)N[C@@H]3CCN(C3)C#N)F MMXHCXOZTITRAO-UONOGXRCSA-N 0.000 claims 1
- VRHSERRLMSCTNY-GFCCVEGCSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-4-[methyl(2-methylpropanoyl)amino]pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=CC(=C1)N(C(C(C)C)=O)C)=O VRHSERRLMSCTNY-GFCCVEGCSA-N 0.000 claims 1
- JIQQUTLHGNCQEO-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-4-fluoro-3-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)F)C=1C=NN(C=1)C)=O JIQQUTLHGNCQEO-CYBMUJFWSA-N 0.000 claims 1
- QDVVFAZLEFMOHY-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-4-fluoro-3-pyridin-4-ylbenzamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CC(=C(C=C1)F)C1=CC=NC=C1)=O QDVVFAZLEFMOHY-CQSZACIVSA-N 0.000 claims 1
- LFGKFGRTXYUMGM-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-5-(1,3-dimethylpyrazol-4-yl)pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1)C=1C(=NN(C=1)C)C)=O LFGKFGRTXYUMGM-CYBMUJFWSA-N 0.000 claims 1
- UKXYUWAVQXPACQ-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-5-(1-methylpyrazol-4-yl)pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1)C=1C=NN(C=1)C)=O UKXYUWAVQXPACQ-CYBMUJFWSA-N 0.000 claims 1
- GUPSFTJGPXXICE-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-5-(4-fluorophenyl)pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1)C1=CC=C(C=C1)F)=O GUPSFTJGPXXICE-OAHLLOKOSA-N 0.000 claims 1
- PHNYTORUZVDISA-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-5-phenylpyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=NC=C(C=C1)C1=CC=CC=C1)=O PHNYTORUZVDISA-OAHLLOKOSA-N 0.000 claims 1
- HTVXMORNGLJXTB-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(1,3-dimethylpyrazol-4-yl)-3-fluoroimidazo[1,2-a]pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C=1N=C2N(C=C(C=C2)C=2C(=NN(C=2)C)C)C=1F HTVXMORNGLJXTB-CYBMUJFWSA-N 0.000 claims 1
- IYBSDASRAHMSFO-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(1,3-dimethylpyrazol-4-yl)imidazo[1,2-a]pyridine-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C=1N=C2N(C=C(C=C2)C=2C(=NN(C=2)C)C)C=1 IYBSDASRAHMSFO-CQSZACIVSA-N 0.000 claims 1
- JQSPDRKSPNCYJM-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C=1C=NN2C=1C=CC(=C2)C=1C=NN(C=1)C JQSPDRKSPNCYJM-CQSZACIVSA-N 0.000 claims 1
- QLKZFMMKSCFPSU-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(1-methylpyrazol-4-yl)pyridine-3-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(C1=CN=C(C=C1)C=1C=NN(C=1)C)=O QLKZFMMKSCFPSU-CYBMUJFWSA-N 0.000 claims 1
- GPFMOHHORSUPPX-QGZVFWFLSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(2-methylpropyl)indazole-3-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=NN(C2=CC(=CC=C12)C=1C(=NOC=1C)C)CC(C)C GPFMOHHORSUPPX-QGZVFWFLSA-N 0.000 claims 1
- OWJRHEASECNJSY-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-3-fluoroimidazo[1,2-a]pyridine-2-carboxamide Chemical compound CC1=C(C(C)=NO1)C1=CN2C(F)=C(N=C2C=C1)C(=O)N[C@@H]1CCN(C1)C#N OWJRHEASECNJSY-CYBMUJFWSA-N 0.000 claims 1
- IJTONWPTRNPZBZ-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-N-methyl-1H-benzimidazole-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)C1=NC2=C(N1)C=C(C=C2)C=1C(=NOC=1C)C)C IJTONWPTRNPZBZ-CQSZACIVSA-N 0.000 claims 1
- ZVTXOPLNDAQZDV-MRXNPFEDSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-N-methyl-1H-indole-2-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)C=1NC2=CC(=CC=C2C=1)C=1C(=NOC=1C)C)C ZVTXOPLNDAQZDV-MRXNPFEDSA-N 0.000 claims 1
- SKZLISRSNCWYST-MRXNPFEDSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(3-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1CN(C[C@@H]1NC(=O)C2=C3C=CC(=CN3N=C2)C4=CC(=CC=C4)F)C#N SKZLISRSNCWYST-MRXNPFEDSA-N 0.000 claims 1
- NLSHYRNTFISOAL-GOSISDBHSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-(4-ethynylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C#CC1=CC=C(C=C1)C2=CN3C(=C(C=N3)C(=O)N[C@@H]4CCN(C4)C#N)C=C2 NLSHYRNTFISOAL-GOSISDBHSA-N 0.000 claims 1
- CKJFBUMTFMRSCS-HSZRJFAPSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-6-[2-fluoro-4-(2-piperidin-1-ylpyridin-4-yl)phenyl]pyrazolo[1,5-a]pyridine-3-carboxamide Chemical compound C1CCN(CC1)C2=NC=CC(=C2)C3=CC(=C(C=C3)C4=CN5C(=C(C=N5)C(=O)N[C@@H]6CCN(C6)C#N)C=C4)F CKJFBUMTFMRSCS-HSZRJFAPSA-N 0.000 claims 1
- RNBOEKKJFQPIES-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=CN=C2N1C=CC(=C2)C=1C=NN(C=1)C RNBOEKKJFQPIES-CQSZACIVSA-N 0.000 claims 1
- RGOQYMPJSKAKLW-CQSZACIVSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-7-(1-methylpyrazol-4-yl)imidazo[1,5-a]pyridine-3-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)NC(=O)C1=NC=C2N1C=CC(=C2)C=1C=NN(C=1)C RGOQYMPJSKAKLW-CQSZACIVSA-N 0.000 claims 1
- QYCBTWHXIZGQLE-GOSISDBHSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-7-(2,6-dimethylpyridin-4-yl)-N-methylimidazo[1,2-a]pyridine-3-carboxamide Chemical compound CN([C@@H]1CCN(C1)C#N)C(=O)C1=CN=C2C=C(C=CN12)C1=CC(C)=NC(C)=C1 QYCBTWHXIZGQLE-GOSISDBHSA-N 0.000 claims 1
- XUWVCVFMBVJMKQ-MRXNPFEDSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-7-(2-methylpyridin-4-yl)imidazo[1,2-a]pyridine-3-carboxamide Chemical compound Cc1cc(ccn1)-c1ccn2c(cnc2c1)C(=O)N[C@@H]1CCN(C1)C#N XUWVCVFMBVJMKQ-MRXNPFEDSA-N 0.000 claims 1
- OGQFBZBTRWAMFW-OAHLLOKOSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-N-ethyl-3-fluoro-4-(1-methylpyrazol-4-yl)benzamide Chemical compound C(#N)N1C[C@@H](CC1)N(C(C1=CC(=C(C=C1)C=1C=NN(C=1)C)F)=O)CC OGQFBZBTRWAMFW-OAHLLOKOSA-N 0.000 claims 1
- RFIXOTYXVXONHP-GOSISDBHSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-N-ethyl-7-(2-methylpyridin-4-yl)imidazo[1,2-a]pyridine-3-carboxamide Chemical compound CCN([C@@H]1CCN(C1)C#N)C(=O)C1=CN=C2C=C(C=CN12)C1=CC(C)=NC=C1 RFIXOTYXVXONHP-GOSISDBHSA-N 0.000 claims 1
- GABWQTLYSDVEKK-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-N-methyl-3-(2-methylpyridin-4-yl)-1,2-oxazole-5-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)C1=CC(=NO1)C1=CC(=NC=C1)C)C GABWQTLYSDVEKK-CYBMUJFWSA-N 0.000 claims 1
- PFTMLHQTEZRXGH-CYBMUJFWSA-N N-[(3R)-1-cyanopyrrolidin-3-yl]-N-methyl-3-phenoxyazetidine-1-carboxamide Chemical compound C(#N)N1C[C@@H](CC1)N(C(=O)N1CC(C1)OC1=CC=CC=C1)C PFTMLHQTEZRXGH-CYBMUJFWSA-N 0.000 claims 1
- JCQSDWYGPKZKOA-INIZCTEOSA-N N-[(3S)-1-cyanopyrrolidin-3-yl]-4-pyridin-4-ylbenzamide Chemical compound C(#N)N1C[C@H](CC1)NC(C1=CC=C(C=C1)C1=CC=NC=C1)=O JCQSDWYGPKZKOA-INIZCTEOSA-N 0.000 claims 1
- BHSLDHWOJGUMIM-DNYRVLSESA-N O=C1N(CCCN1C=1SC=C(N1)C1=CC=CC=C1)[C@H]1CN(CC1)C#N.O=C1N(CCN1C=1SC=C(N1)C1=CC=CC=C1)[C@H]1CN(CC1)C#N Chemical compound O=C1N(CCCN1C=1SC=C(N1)C1=CC=CC=C1)[C@H]1CN(CC1)C#N.O=C1N(CCN1C=1SC=C(N1)C1=CC=CC=C1)[C@H]1CN(CC1)C#N BHSLDHWOJGUMIM-DNYRVLSESA-N 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 208000027089 Parkinsonian disease Diseases 0.000 claims 1
- 241001377010 Pila Species 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 102100038376 Serine/threonine-protein kinase PINK1, mitochondrial Human genes 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims 1
- VEKIYFGCEAJDDT-UHFFFAOYSA-N alpha,beta-Dipyridyl Natural products N1=CC=CC=C1C1=CC=CN=C1 VEKIYFGCEAJDDT-UHFFFAOYSA-N 0.000 claims 1
- 108090000185 alpha-Synuclein Proteins 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 230000005775 apoptotic pathway Effects 0.000 claims 1
- PVXOUGHWLCBJOW-UHFFFAOYSA-N azetidine-1-carboxamide Chemical compound NC(=O)N1CCC1 PVXOUGHWLCBJOW-UHFFFAOYSA-N 0.000 claims 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
- 210000000601 blood cell Anatomy 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000005959 diazepanyl group Chemical group 0.000 claims 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- BWELICHMKYRHJC-UHFFFAOYSA-N ethyl 4-[5-[(1-cyanopyrrolidin-3-yl)carbamoyl]pyridin-2-yl]piperazine-1-carboxylate Chemical compound C(#N)N1CC(CC1)NC(=O)C=1C=CC(=NC=1)N1CCN(CC1)C(=O)OCC BWELICHMKYRHJC-UHFFFAOYSA-N 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- BEHYAANJUKYBTH-UHFFFAOYSA-N imidazo[1,2-a]pyridine-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CN21 BEHYAANJUKYBTH-UHFFFAOYSA-N 0.000 claims 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 230000004130 lipolysis Effects 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000035935 pregnancy Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- FCHKJPINELGUMC-ABAIWWIYSA-N tert-butyl (3aR,6aR)-1-[(4-chloro-2-fluorophenyl)carbamoyl]-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrole-5-carboxylate Chemical compound ClC1=CC(=C(C=C1)NC(=O)N1[C@@H]2[C@H](CC1)CN(C2)C(=O)OC(C)(C)C)F FCHKJPINELGUMC-ABAIWWIYSA-N 0.000 claims 1
- GGNIKGLUPSHSBV-UHFFFAOYSA-N thiazole-5-carboxamide Chemical compound NC(=O)C1=CN=CS1 GGNIKGLUPSHSBV-UHFFFAOYSA-N 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 201000010866 very long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- 0 C*(**C(*)(C(*)(C1(*)*)N(*)C(**)=O)O*)C(*)(*)N1C#N Chemical compound C*(**C(*)(C(*)(C1(*)*)N(*)C(**)=O)O*)C(*)(*)N1C#N 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1505429.9 | 2015-03-30 | ||
| GBGB1505429.9A GB201505429D0 (en) | 2015-03-30 | 2015-03-30 | Novel compounds |
| GBGB1512829.1A GB201512829D0 (en) | 2015-07-21 | 2015-07-21 | Novel compounds |
| GB1512829.1 | 2015-07-21 | ||
| PCT/GB2016/050851 WO2016156816A1 (en) | 2015-03-30 | 2016-03-24 | 1-cyano-pyrrolidine compounds as usp30 inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020088995A Division JP7216682B2 (ja) | 2015-03-30 | 2020-05-21 | Ｕｓｐ３０阻害剤としての１－シアノ－ピロリジン化合物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018510183A JP2018510183A (ja) | 2018-04-12 |
| JP2018510183A5 true JP2018510183A5 (OSRAM) | 2019-05-09 |
| JP6708661B2 JP6708661B2 (ja) | 2020-06-10 |
Family
ID=55646790
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017551189A Active JP6708661B2 (ja) | 2015-03-30 | 2016-03-24 | Ｕｓｐ３０阻害剤としての１−シアノ−ピロリジン化合物 |
| JP2020088995A Active JP7216682B2 (ja) | 2015-03-30 | 2020-05-21 | Ｕｓｐ３０阻害剤としての１－シアノ－ピロリジン化合物 |
| JP2022099677A Active JP7389856B2 (ja) | 2015-03-30 | 2022-06-21 | Ｕｓｐ３０阻害剤としての１－シアノ－ピロリジン化合物 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020088995A Active JP7216682B2 (ja) | 2015-03-30 | 2020-05-21 | Ｕｓｐ３０阻害剤としての１－シアノ－ピロリジン化合物 |
| JP2022099677A Active JP7389856B2 (ja) | 2015-03-30 | 2022-06-21 | Ｕｓｐ３０阻害剤としての１－シアノ－ピロリジン化合物 |
Country Status (29)
| Country | Link |
|---|---|
| US (6) | US10343992B2 (OSRAM) |
| EP (3) | EP3277677B9 (OSRAM) |
| JP (3) | JP6708661B2 (OSRAM) |
| KR (1) | KR102578325B1 (OSRAM) |
| CN (2) | CN112707893B (OSRAM) |
| AU (1) | AU2016240033B2 (OSRAM) |
| BR (1) | BR112017020900B1 (OSRAM) |
| CA (1) | CA2976741C (OSRAM) |
| CO (1) | CO2017011172A2 (OSRAM) |
| CY (1) | CY1124170T1 (OSRAM) |
| DK (1) | DK3277677T3 (OSRAM) |
| ES (1) | ES2864950T3 (OSRAM) |
| HR (1) | HRP20210791T2 (OSRAM) |
| HU (1) | HUE054474T2 (OSRAM) |
| IL (1) | IL254721B (OSRAM) |
| LT (1) | LT3277677T (OSRAM) |
| MD (1) | MD3277677T2 (OSRAM) |
| MX (1) | MX373656B (OSRAM) |
| MY (1) | MY188957A (OSRAM) |
| NZ (1) | NZ736450A (OSRAM) |
| PL (1) | PL3277677T3 (OSRAM) |
| PT (1) | PT3277677T (OSRAM) |
| RS (1) | RS61759B9 (OSRAM) |
| RU (1) | RU2717238C2 (OSRAM) |
| SG (1) | SG11201706542TA (OSRAM) |
| SI (1) | SI3277677T1 (OSRAM) |
| SM (1) | SMT202100287T1 (OSRAM) |
| WO (1) | WO2016156816A1 (OSRAM) |
| ZA (1) | ZA201705717B (OSRAM) |
Families Citing this family (41)
| 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 |
| 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 |
| JOP20190072A1 (ar) * | 2016-10-13 | 2019-04-07 | Glaxosmithkline Ip Dev Ltd | مشتقات 1، 3 سيكلوبوتان ثنائي الاستبدال أو آزيتيدين كمثبطات للإنزيم المخلق للبروستاجلاندين d المكون للدم |
| 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 |
| BR112020021921A2 (pt) | 2018-05-17 | 2021-01-26 | Forma Therapeutics, Inc. | compostos bicíclicos fundidos úteis como inibidores de peptidase 30 específica de ubiquitina |
| 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 |
| CN120698985A (zh) | 2018-12-20 | 2025-09-26 | C4医药公司 | 靶向蛋白降解 |
| 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 |
| GB201912674D0 (en) * | 2019-09-04 | 2019-10-16 | Mission Therapeutics Ltd | Novel compounds |
| EP4126853A1 (en) * | 2020-03-30 | 2023-02-08 | The Scripps Research Institute | Small molecule inhibitors of influenza hemagglutinin |
| CN111303128B (zh) * | 2020-04-07 | 2020-10-27 | 苏州信诺维医药科技有限公司 | 一种多环类化合物、其制备方法及应用 |
| 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. |
| 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 |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| US20240059673A1 (en) * | 2020-12-22 | 2024-02-22 | Gilead Sciences, Inc. | Substituted indole compounds |
| US11661431B2 (en) | 2021-04-16 | 2023-05-30 | Gilead Sciences, Inc. | Thienopyrrole compounds |
| CN117957234A (zh) | 2021-09-10 | 2024-04-30 | 吉利德科学公司 | 噻吩并吡咯化合物 |
| AU2022362107A1 (en) | 2021-10-11 | 2024-05-02 | Anebulo Pharmaceuticals, Inc. | Crystalline forms of a cannabinoid receptor type 1 (cb1) modulator and methods of use and preparation thereof |
| EP4441044A1 (en) | 2021-12-01 | 2024-10-09 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
| WO2024086708A2 (en) * | 2022-10-19 | 2024-04-25 | Ohio State Innovation Foundation | Compositions and methods for preventing cardiomyopathy |
| TW202446368A (zh) * | 2023-02-28 | 2024-12-01 | 美商賽堤爾醫療公司 | 經取代之吡咯啶及吡咯啶酮化合物 |
| 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 (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5665754A (en) | 1993-09-20 | 1997-09-09 | Glaxo Wellcome Inc. | Substituted pyrrolidines |
| US6187797B1 (en) | 1996-12-23 | 2001-02-13 | Dupont Pharmaceuticals Company | Phenyl-isoxazoles as factor XA Inhibitors |
| EP1272467A4 (en) | 2000-04-06 | 2003-05-07 | Merck Frosst Canada Inc | Cathepsin cysteine protease inhibitors |
| WO2004022536A1 (en) | 2002-09-04 | 2004-03-18 | Glenmark Pharmaceuticals Limited | New heterocyclic amide compounds useful for the treatment of inflammatory and allergic disorders: process for their preparation and pharmaceutical compositions containing them |
| KR100944301B1 (ko) * | 2005-02-22 | 2010-02-24 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Ｍｄｍ２의 소분자 억제제 및 이의 용도 |
| 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 ) |
| HUE060249T2 (hu) | 2008-06-16 | 2023-02-28 | Univ Tennessee Res Found | Vegyületek rák kezelésére |
| US8354444B2 (en) * | 2008-09-18 | 2013-01-15 | Hoffmann-La Roche Inc. | Substituted pyrrolidine-2-carboxamides |
| CA2741666C (en) | 2008-10-31 | 2017-04-11 | Merck Sharp & Dohme Corp. | P2x3, receptor antagonists for treatment of pain |
| EP2410858B1 (en) | 2009-03-23 | 2016-09-07 | Merck Sharp & Dohme Corp. | P2x3 receptor antagonists for treatment of pain |
| 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 |
| KR102022575B1 (ko) * | 2011-10-19 | 2019-09-18 | 비보룩스 아베 | 탈유비퀴틴화 활성의 저해 방법 |
| 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 |
| AU2014239542A1 (en) | 2013-03-15 | 2015-10-01 | Araxes Pharma Llc | Covalent inhibitors of KRas G12C |
| WO2016019237A2 (en) | 2014-07-31 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| US10160727B2 (en) | 2014-08-06 | 2018-12-25 | Shionogi & Co., Ltd. | Heterocycle and carbocycle derivatives having TrkA inhibitory activity |
| 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 |
-
2016
- 2016-03-24 MD MDE20180120T patent/MD3277677T2/ro unknown
- 2016-03-24 WO PCT/GB2016/050851 patent/WO2016156816A1/en not_active Ceased
- 2016-03-24 JP JP2017551189A patent/JP6708661B2/ja active Active
- 2016-03-24 CN CN202110132842.2A patent/CN112707893B/zh active Active
- 2016-03-24 EP EP16713043.4A patent/EP3277677B9/en active Active
- 2016-03-24 ES ES16713043T patent/ES2864950T3/es active Active
- 2016-03-24 DK DK16713043.4T patent/DK3277677T3/da active
- 2016-03-24 HR HRP20210791TT patent/HRP20210791T2/hr unknown
- 2016-03-24 US US15/558,632 patent/US10343992B2/en active Active
- 2016-03-24 CA CA2976741A patent/CA2976741C/en active Active
- 2016-03-24 EP EP21190809.0A patent/EP3943490A1/en active Pending
- 2016-03-24 SM SM20210287T patent/SMT202100287T1/it unknown
- 2016-03-24 LT LTEP16713043.4T patent/LT3277677T/lt unknown
- 2016-03-24 RU RU2017134901A patent/RU2717238C2/ru active
- 2016-03-24 AU AU2016240033A patent/AU2016240033B2/en active Active
- 2016-03-24 CN CN201680019213.6A patent/CN107484415B/zh active Active
- 2016-03-24 KR KR1020177031166A patent/KR102578325B1/ko active Active
- 2016-03-24 HU HUE16713043A patent/HUE054474T2/hu unknown
- 2016-03-24 RS RS20210502A patent/RS61759B9/sr unknown
- 2016-03-24 MY MYPI2017001206A patent/MY188957A/en unknown
- 2016-03-24 SG SG11201706542TA patent/SG11201706542TA/en unknown
- 2016-03-24 BR BR112017020900-4A patent/BR112017020900B1/pt active IP Right Grant
- 2016-03-24 SI SI201631157T patent/SI3277677T1/sl unknown
- 2016-03-24 PL PL16713043T patent/PL3277677T3/pl unknown
- 2016-03-24 PT PT167130434T patent/PT3277677T/pt unknown
- 2016-03-24 NZ NZ736450A patent/NZ736450A/en unknown
- 2016-03-24 EP EP21156385.3A patent/EP3842427A1/en active Pending
- 2016-03-24 MX MX2017012566A patent/MX373656B/es active IP Right Grant
-
2017
- 2017-08-22 ZA ZA2017/05717A patent/ZA201705717B/en unknown
- 2017-09-26 IL IL254721A patent/IL254721B/en active IP Right Grant
- 2017-10-30 CO CONC2017/0011172A patent/CO2017011172A2/es unknown
-
2019
- 2019-03-11 US US16/297,937 patent/US11053198B2/en active Active
- 2019-05-22 US US16/419,558 patent/US10689345B2/en active Active
- 2019-05-22 US US16/419,747 patent/US11066365B2/en active Active
-
2020
- 2020-02-12 US US16/788,446 patent/US11390584B2/en active Active
- 2020-05-21 JP JP2020088995A patent/JP7216682B2/ja active Active
-
2021
- 2021-05-20 CY CY20211100441T patent/CY1124170T1/el unknown
-
2022
- 2022-03-31 US US17/709,556 patent/US20220251041A1/en active Pending
- 2022-06-21 JP JP2022099677A patent/JP7389856B2/ja active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2018510183A5 (OSRAM) | ||
| HRP20210791T1 (hr) | 1-cijano-pirolidin spojevi kao usp30 inhibitori | |
| JP2019504009A5 (OSRAM) | ||
| JP2019533659A5 (OSRAM) | ||
| JP2018524367A5 (OSRAM) | ||
| RU2017105296A (ru) | Новые соединения | |
| JP2019513135A5 (OSRAM) | ||
| JP2017530960A5 (OSRAM) | ||
| JP2019535689A5 (OSRAM) | ||
| JP2007510689A5 (OSRAM) | ||
| JP2018500376A5 (OSRAM) | ||
| JP2019501142A5 (OSRAM) | ||
| JP2016522246A5 (OSRAM) | ||
| CA2494091A1 (en) | Substituted furo [2,3-b| pyridine derivatives | |
| JPWO2019198692A5 (OSRAM) | ||
| Sharma | Pyridazine (1, 2-diazine): a versatile pharmacophore known for its utility in biological systems | |
| RU2025122871A (ru) | Новые гетероциклические соединения | |
| CN120603827A (zh) | 新型杂环化合物 | |
| HK1245266B (zh) | 作为usp30抑制剂的1-氰基吡咯烷化合物 |