JP2019508462A5 - - Google Patents
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- Publication number
- JP2019508462A5 JP2019508462A5 JP2018548677A JP2018548677A JP2019508462A5 JP 2019508462 A5 JP2019508462 A5 JP 2019508462A5 JP 2018548677 A JP2018548677 A JP 2018548677A JP 2018548677 A JP2018548677 A JP 2018548677A JP 2019508462 A5 JP2019508462 A5 JP 2019508462A5
- Authority
- JP
- Japan
- Prior art keywords
- dihydropyrrolo
- pyrazole
- carbonitrile
- phenyl
- cyano
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- -1 substituted Chemical class 0.000 claims 16
- 150000001875 compounds Chemical class 0.000 claims 14
- 239000001257 hydrogen Substances 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 10
- 125000002947 alkylene group Chemical group 0.000 claims 8
- 208000008955 Mucolipidoses Diseases 0.000 claims 6
- 230000007812 deficiency Effects 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 208000011580 syndromic disease Diseases 0.000 claims 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 125000004450 alkenylene group Chemical group 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000003118 aryl group Chemical group 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- GGGOFAQLGFPVOQ-UHFFFAOYSA-N 3-phenyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C1(=CC=CC=C1)C=1C2=C(NN=1)CN(C2)C#N GGGOFAQLGFPVOQ-UHFFFAOYSA-N 0.000 claims 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 2
- 208000014644 Brain disease Diseases 0.000 claims 2
- 206010058892 Carnitine deficiency Diseases 0.000 claims 2
- 201000000915 Chronic Progressive External Ophthalmoplegia Diseases 0.000 claims 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 2
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 claims 2
- 208000032274 Encephalopathy Diseases 0.000 claims 2
- 102100030358 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Human genes 0.000 claims 2
- 208000006136 Leigh Disease Diseases 0.000 claims 2
- 208000017507 Leigh syndrome Diseases 0.000 claims 2
- 108700006159 Long-chain acyl-CoA dehydrogenase deficiency Proteins 0.000 claims 2
- 201000002169 Mitochondrial myopathy Diseases 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
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 2
- 208000006443 lactic acidosis Diseases 0.000 claims 2
- 208000004687 long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 230000002438 mitochondrial effect Effects 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- 208000020460 mucolipidosis II alpha/beta Diseases 0.000 claims 2
- 208000020468 mucolipidosis III alpha/beta Diseases 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 claims 2
- 238000002560 therapeutic procedure Methods 0.000 claims 2
- 150000003573 thiols Chemical class 0.000 claims 2
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims 1
- JUVGEDHVBWLQLU-UHFFFAOYSA-N 1-(1-methylindazol-5-yl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound CN1N=CC2=C1C=CC(=C2)N1N=CC2=C1CN(C2)C#N JUVGEDHVBWLQLU-UHFFFAOYSA-N 0.000 claims 1
- RGJYHIIRCTVIHI-UHFFFAOYSA-N 1-(1-phenylimidazol-4-yl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1CC2=C(C1)N(N=C2)C1=CN(C=N1)C1=CC=CC=C1 RGJYHIIRCTVIHI-UHFFFAOYSA-N 0.000 claims 1
- BOYDSQYMTOVMAP-UHFFFAOYSA-N 1-(1-phenylpyrazol-4-yl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1CC2=C(C1)N(N=C2)C1=CN(N=C1)C1=CC=CC=C1 BOYDSQYMTOVMAP-UHFFFAOYSA-N 0.000 claims 1
- XXGXMUVQOXAODU-UHFFFAOYSA-N 1-(1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1CC2=C(C1)N(N=C2)C1=NNC2=C1C=CC=C2 XXGXMUVQOXAODU-UHFFFAOYSA-N 0.000 claims 1
- CMSCJJHUMGPEJA-UHFFFAOYSA-N 1-(2-fluorophenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=C(C=CC=C1)N1N=CC2=C1CN(C2)C#N CMSCJJHUMGPEJA-UHFFFAOYSA-N 0.000 claims 1
- XEGYLEDSQXPUSI-UHFFFAOYSA-N 1-(3-methoxyphenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound COC1=CC=CC(=C1)N1N=CC2=C1CN(C2)C#N XEGYLEDSQXPUSI-UHFFFAOYSA-N 0.000 claims 1
- JQACROPZTZISGG-UHFFFAOYSA-N 1-(4-fluorophenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=CC=C(C=C1)N1N=CC2=C1CN(C2)C#N JQACROPZTZISGG-UHFFFAOYSA-N 0.000 claims 1
- AHLCLDWMUIRZPK-UHFFFAOYSA-N 1-(4-methoxyphenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound COC1=CC=C(C=C1)N1N=CC2=C1CN(C2)C#N AHLCLDWMUIRZPK-UHFFFAOYSA-N 0.000 claims 1
- SCCOCFXSISOVJP-UHFFFAOYSA-N 1-(5-phenyl-1H-pyrazol-3-yl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1CC2=C(C1)N(N=C2)C1=CC(=NN1)C1=CC=CC=C1 SCCOCFXSISOVJP-UHFFFAOYSA-N 0.000 claims 1
- YTUDTZUXRVSLDN-UHFFFAOYSA-N 1-benzyl-3-(2-methoxy-5-propan-2-ylphenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound COC1=C(C=C(C=C1)C(C)C)C1=NN(CC2=CC=CC=C2)C2=C1CN(C2)C#N YTUDTZUXRVSLDN-UHFFFAOYSA-N 0.000 claims 1
- HGPLLHMZCCSMKO-UHFFFAOYSA-N 1-benzyl-3-(isoquinolin-3-ylamino)-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1CC2=C(C1)C(NC1=CC3=CC=CC=C3C=N1)=NN2CC1=CC=CC=C1 HGPLLHMZCCSMKO-UHFFFAOYSA-N 0.000 claims 1
- LLVIBOLZPFHAQS-UHFFFAOYSA-N 1-methyl-3-phenyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound CN1N=C(C2=C1CN(C2)C#N)C1=CC=CC=C1 LLVIBOLZPFHAQS-UHFFFAOYSA-N 0.000 claims 1
- AINYECDWHLOUAS-UHFFFAOYSA-N 1-phenyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1CC2=C(C1)N(N=C2)C1=CC=CC=C1 AINYECDWHLOUAS-UHFFFAOYSA-N 0.000 claims 1
- PIZVMZGJPRKAKX-UHFFFAOYSA-N 1-quinolin-3-yl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1CC2=C(C1)N(N=C2)C1=CC2=CC=CC=C2N=C1 PIZVMZGJPRKAKX-UHFFFAOYSA-N 0.000 claims 1
- YMJLEPMVGQBLHL-UHFFFAOYSA-N 1h-pyrazole-5-carbonitrile Chemical compound N#CC1=CC=NN1 YMJLEPMVGQBLHL-UHFFFAOYSA-N 0.000 claims 1
- PUWHDEMPPGOJPL-UHFFFAOYSA-N 2-methyl-3-phenyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound CN1N=C2C(=C1C1=CC=CC=C1)CN(C2)C#N PUWHDEMPPGOJPL-UHFFFAOYSA-N 0.000 claims 1
- SGYAYXGQLGJTSA-UHFFFAOYSA-N 3-(1-methylindazol-5-yl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound CN1N=CC2=CC(=CC=C12)C=1C2=C(NN=1)CN(C2)C#N SGYAYXGQLGJTSA-UHFFFAOYSA-N 0.000 claims 1
- LBMJENCEMCJDAU-UHFFFAOYSA-N 3-(2-benzylpyrazol-3-yl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(C1=CC=CC=C1)N1N=CC=C1C=1C2=C(NN=1)CN(C2)C#N LBMJENCEMCJDAU-UHFFFAOYSA-N 0.000 claims 1
- PLGQXDOVJSLWPX-UHFFFAOYSA-N 3-(2-fluoro-5-methylphenyl)-1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=C(C=C(C=C1)C)C=1C2=C(N(N=1)C)CN(C2)C#N PLGQXDOVJSLWPX-UHFFFAOYSA-N 0.000 claims 1
- SLLXJWBWPDBAFU-UHFFFAOYSA-N 3-(2-fluoro-5-methylphenyl)-2-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=C(C=C(C=C1)C)C1=C2C(=NN1C)CN(C2)C#N SLLXJWBWPDBAFU-UHFFFAOYSA-N 0.000 claims 1
- DVPNNNCKOSAVAJ-UHFFFAOYSA-N 3-(2-fluoro-5-methylphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=C(C=C(C=C1)C)C=1C2=C(NN=1)CN(C2)C#N DVPNNNCKOSAVAJ-UHFFFAOYSA-N 0.000 claims 1
- YCDUBVATLLSRND-UHFFFAOYSA-N 3-(2-fluorophenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=C(C=CC=C1)C=1C2=C(NN=1)CN(C2)C#N YCDUBVATLLSRND-UHFFFAOYSA-N 0.000 claims 1
- CJNQBOBXYKJLOA-UHFFFAOYSA-N 3-(2-methoxy-4-pyrazol-1-ylphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound COC1=C(C=CC(=C1)N1C=CC=N1)C1=C2CN(CC2=NN1)C#N CJNQBOBXYKJLOA-UHFFFAOYSA-N 0.000 claims 1
- PXHVHDOFIBAUCW-UHFFFAOYSA-N 3-(2-methoxy-5-propan-2-ylphenyl)-1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(C)(C)C=1C=CC(=C(C=1)C=1C2=C(N(N=1)C)CN(C2)C#N)OC PXHVHDOFIBAUCW-UHFFFAOYSA-N 0.000 claims 1
- LNKWZICQKHVTSE-UHFFFAOYSA-N 3-(2-methoxy-5-propan-2-ylphenyl)-2-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(C)(C)C=1C=CC(=C(C=1)C1=C2C(=NN1C)CN(C2)C#N)OC LNKWZICQKHVTSE-UHFFFAOYSA-N 0.000 claims 1
- DDTMXFGNQVGMKO-UHFFFAOYSA-N 3-(2-methoxy-5-propan-2-ylphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound COc1ccc(cc1-c1n[nH]c2CN(Cc12)C#N)C(C)C DDTMXFGNQVGMKO-UHFFFAOYSA-N 0.000 claims 1
- DLZBJZCDFSKSPS-UHFFFAOYSA-N 3-(2-methylpyrazol-3-yl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound CN1N=CC=C1C=1C2=C(NN=1)CN(C2)C#N DLZBJZCDFSKSPS-UHFFFAOYSA-N 0.000 claims 1
- RHBUUHGQLBTRGB-UHFFFAOYSA-N 3-(3-cyanophenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(#N)C=1C=C(C=CC=1)C=1C2=C(NN=1)CN(C2)C#N RHBUUHGQLBTRGB-UHFFFAOYSA-N 0.000 claims 1
- IGDANYVMEOAYSL-UHFFFAOYSA-N 3-(3-fluorophenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC=1C=C(C=CC=1)C=1C2=C(NN=1)CN(C2)C#N IGDANYVMEOAYSL-UHFFFAOYSA-N 0.000 claims 1
- CHKVVIWIDQHQIH-UHFFFAOYSA-N 3-(4-chloro-2-methoxyphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound COC1=C(C=CC(Cl)=C1)C1=C2CN(CC2=NN1)C#N CHKVVIWIDQHQIH-UHFFFAOYSA-N 0.000 claims 1
- ZMNKPCXOTOHCIV-UHFFFAOYSA-N 3-(4-cyanophenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(#N)C1=CC=C(C=C1)C=1C2=C(NN=1)CN(C2)C#N ZMNKPCXOTOHCIV-UHFFFAOYSA-N 0.000 claims 1
- XHEARYBLESEJLK-UHFFFAOYSA-N 3-(4-fluorophenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=CC=C(C=C1)C=1C2=C(NN=1)CN(C2)C#N XHEARYBLESEJLK-UHFFFAOYSA-N 0.000 claims 1
- RHLXYLPJJBCJEJ-UHFFFAOYSA-N 3-(4-morpholin-4-ylphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound N#CN1Cc2[nH]nc(c2C1)-c1ccc(cc1)N1CCOCC1 RHLXYLPJJBCJEJ-UHFFFAOYSA-N 0.000 claims 1
- CRXAEZHYQKBIIL-UHFFFAOYSA-N 3-(4-phenoxyphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)C=1C2=C(NN=1)CN(C2)C#N CRXAEZHYQKBIIL-UHFFFAOYSA-N 0.000 claims 1
- JBGQYSLZJROGNG-UHFFFAOYSA-N 3-(4-phenylmethoxyphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)C=1C2=C(NN=1)CN(C2)C#N JBGQYSLZJROGNG-UHFFFAOYSA-N 0.000 claims 1
- LEDICMICIXAOKQ-UHFFFAOYSA-N 3-(5-cyano-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl)-N,N-dimethylbenzenesulfonamide Chemical compound C(#N)N1CC=2NN=C(C=2C1)C=1C=C(C=CC=1)S(=O)(=O)N(C)C LEDICMICIXAOKQ-UHFFFAOYSA-N 0.000 claims 1
- LGHFYVPSZYNVEJ-UHFFFAOYSA-N 3-(5-cyano-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl)-N-cyclopropylbenzenesulfonamide Chemical compound C(#N)N1CC=2NN=C(C=2C1)C=1C=C(C=CC=1)S(=O)(=O)NC1CC1 LGHFYVPSZYNVEJ-UHFFFAOYSA-N 0.000 claims 1
- IVKKFIRXHPBEID-UHFFFAOYSA-N 3-(5-cyano-4,6-dihydropyrrolo[3,4-c]pyrazol-1-yl)-1H-pyrazole-5-carboxamide Chemical compound NC(=O)C1=NNC(=C1)N1N=CC2=C1CN(C2)C#N IVKKFIRXHPBEID-UHFFFAOYSA-N 0.000 claims 1
- XPXCVEUZLNMGDZ-UHFFFAOYSA-N 3-(5-cyano-4,6-dihydropyrrolo[3,4-c]pyrazol-1-yl)-N-(1-phenylethyl)benzamide Chemical compound CC(NC(=O)C1=CC(=CC=C1)N1N=CC2=C1CN(C2)C#N)C1=CC=CC=C1 XPXCVEUZLNMGDZ-UHFFFAOYSA-N 0.000 claims 1
- RUKUSKRNNYQAND-UHFFFAOYSA-N 3-(5-ethyl-2-methoxyphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(C)C=1C=CC(=C(C=1)C=1C2=C(NN=1)CN(C2)C#N)OC RUKUSKRNNYQAND-UHFFFAOYSA-N 0.000 claims 1
- LYAPAMVUYLIWDO-UHFFFAOYSA-N 3-(5-fluoro-2-propan-2-yloxyphenyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC=1C=CC(=C(C=1)C=1C2=C(NN=1)CN(C2)C#N)OC(C)C LYAPAMVUYLIWDO-UHFFFAOYSA-N 0.000 claims 1
- JXFOYPPXSPQHIS-UHFFFAOYSA-N 3-(5-methyl-1H-indazol-4-yl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound CC=1C(=C2C=NNC2=CC=1)C=1C2=C(NN=1)CN(C2)C#N JXFOYPPXSPQHIS-UHFFFAOYSA-N 0.000 claims 1
- WPYLYVHOWSRIDL-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound COC1=CC=C(C=N1)C=1C2=C(NN=1)CN(C2)C#N WPYLYVHOWSRIDL-UHFFFAOYSA-N 0.000 claims 1
- JJBMCXMUWLYSNP-UHFFFAOYSA-N 3-(6-propan-2-yloxypyridin-3-yl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C(C)(C)OC1=CC=C(C=N1)C=1C2=C(NN=1)CN(C2)C#N JJBMCXMUWLYSNP-UHFFFAOYSA-N 0.000 claims 1
- VGCBGAOUNUBEBS-UHFFFAOYSA-N 3-(isoquinolin-3-ylamino)-2-methyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C1=NC(=CC2=CC=CC=C12)NC1=C2C(=NN1C)CN(C2)C#N VGCBGAOUNUBEBS-UHFFFAOYSA-N 0.000 claims 1
- NGJBVKTXLFSMAK-UHFFFAOYSA-N 3-(isoquinolin-3-ylamino)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound C1=NC(=CC2=CC=CC=C12)NC=1C2=C(NN=1)CN(C2)C#N NGJBVKTXLFSMAK-UHFFFAOYSA-N 0.000 claims 1
- AZRBHYPOFXPIKN-UHFFFAOYSA-N 3-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound CN1CCC(CC1)N1N=CC(=C1)C=1C2=C(NN=1)CN(C2)C#N AZRBHYPOFXPIKN-UHFFFAOYSA-N 0.000 claims 1
- BUWVGYAPNOMAPP-UHFFFAOYSA-N 3-[2-chloro-5-(trifluoromethoxy)phenyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound ClC1=C(C=C(C=C1)OC(F)(F)F)C=1C2=C(NN=1)CN(C2)C#N BUWVGYAPNOMAPP-UHFFFAOYSA-N 0.000 claims 1
- OTMHRZKJSLANPT-UHFFFAOYSA-N 3-[2-fluoro-4-(4-methylpiperazin-1-yl)phenyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=C(C=CC(=C1)N1CCN(CC1)C)C=1C2=C(NN=1)CN(C2)C#N OTMHRZKJSLANPT-UHFFFAOYSA-N 0.000 claims 1
- XVQNZZBWUWQBDF-UHFFFAOYSA-N 3-[2-fluoro-4-(trifluoromethyl)phenyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)C=1C2=C(NN=1)CN(C2)C#N XVQNZZBWUWQBDF-UHFFFAOYSA-N 0.000 claims 1
- UABKLFAPPJJCBC-UHFFFAOYSA-N 3-[3-(2-oxo-1,3-oxazolidin-3-yl)phenyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound O=C1OCCN1C=1C=C(C=CC=1)C=1C2=C(NN=1)CN(C2)C#N UABKLFAPPJJCBC-UHFFFAOYSA-N 0.000 claims 1
- BPJOBJXQTDRWAI-UHFFFAOYSA-N 3-[3-(2-oxopyrrolidin-1-yl)phenyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carbonitrile Chemical compound O=C1N(CCC1)C=1C=C(C=CC=1)C=1C2=C(NN=1)CN(C2)C#N BPJOBJXQTDRWAI-UHFFFAOYSA-N 0.000 claims 1
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| AU2001256981A1 (en) | 2000-04-06 | 2001-10-23 | Axys Pharmaceuticals, Inc. | Cathepsin cysteine protease inhibitors |
| US20130156731A1 (en) | 2009-12-22 | 2013-06-20 | Kevin X. Chen | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseas |
| JP5852658B2 (ja) * | 2010-09-24 | 2016-02-03 | ザ リージェンツ オブ ザ ユニバーシティー オブ ミシガン | デユビキチナーゼ阻害剤およびその使用方法 |
| US9315518B2 (en) | 2011-06-16 | 2016-04-19 | Merck Sharp & Dohme Corp. | Imidazopyridin-2-one derivatives |
| EP2565186A1 (en) | 2011-09-02 | 2013-03-06 | Hybrigenics S.A. | Selective and reversible inhibitors of ubiquitin specific protease 7 |
| HK1199249A1 (en) * | 2011-09-30 | 2015-06-26 | 山东轩竹医药科技有限公司 | Oxazolidinone antibiotics containing fused ring |
| EP2938610A2 (en) * | 2012-12-28 | 2015-11-04 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Inhibitors of the usp1/uaf1 deubiquitinase complex and uses thereof |
| CA2944669A1 (en) | 2014-04-04 | 2015-10-08 | Syros Pharmaceuticals, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
| CN106794364B (zh) * | 2014-04-30 | 2019-12-24 | 哥伦比亚大学董事会 | 取代的4-苯基哌啶及其制备和用途 |
| GB201416754D0 (en) | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| CN107484415B (zh) | 2015-03-30 | 2021-01-29 | 特殊治疗有限公司 | 作为usp30抑制剂的1-氰基吡咯烷化合物 |
| EP3322702B1 (en) | 2015-07-14 | 2019-11-20 | 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 |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| WO2017163078A1 (en) | 2016-03-24 | 2017-09-28 | Mission Therapeutics Limited | 1-cyano-pyrrolidine derivatives as dbu inhibitors |
| CN109790112B (zh) | 2016-09-27 | 2022-08-26 | 特殊治疗有限公司 | 具有作为usp30抑制剂活性的氰基吡咯烷衍生物 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
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