JP2016519156A5 - - Google Patents
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- Publication number
- JP2016519156A5 JP2016519156A5 JP2016514486A JP2016514486A JP2016519156A5 JP 2016519156 A5 JP2016519156 A5 JP 2016519156A5 JP 2016514486 A JP2016514486 A JP 2016514486A JP 2016514486 A JP2016514486 A JP 2016514486A JP 2016519156 A5 JP2016519156 A5 JP 2016519156A5
- Authority
- JP
- Japan
- Prior art keywords
- ylmethyl
- amino
- amide
- carboxylic acid
- pyrazole
- 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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- 125000000217 alkyl group Chemical group 0.000 claims 34
- 125000003545 alkoxy group Chemical group 0.000 claims 25
- 150000001875 compounds Chemical class 0.000 claims 24
- 125000001424 substituent group Chemical group 0.000 claims 16
- 125000001072 heteroaryl group Chemical group 0.000 claims 15
- 125000003118 aryl group Chemical group 0.000 claims 12
- 102000003827 Plasma Kallikrein Human genes 0.000 claims 10
- 108090000113 Plasma Kallikrein Proteins 0.000 claims 10
- 201000010099 disease Diseases 0.000 claims 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 10
- 230000000694 effects Effects 0.000 claims 10
- 125000005843 halogen group Chemical group 0.000 claims 10
- -1 methylenedioxy, ethylenedioxy Chemical group 0.000 claims 8
- 229910052760 oxygen Inorganic materials 0.000 claims 7
- 229910052717 sulfur Inorganic materials 0.000 claims 7
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims 6
- 150000001408 amides Chemical class 0.000 claims 6
- 201000011190 diabetic macular edema Diseases 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 5
- 125000002757 morpholinyl group Chemical group 0.000 claims 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 125000003386 piperidinyl group Chemical group 0.000 claims 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 4
- 206010019860 Hereditary angioedema Diseases 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 3
- 150000001491 aromatic compounds Chemical class 0.000 claims 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 229920006395 saturated elastomer Polymers 0.000 claims 3
- 239000012453 solvate Substances 0.000 claims 3
- 238000001356 surgical procedure Methods 0.000 claims 3
- 150000005258 1H-pyrrolo(2,3-b)pyridines Chemical class 0.000 claims 2
- QTARJTQMMMFRRC-UHFFFAOYSA-N 5-amino-n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-(pyrazol-1-ylmethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound NC1=C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)C=NN1CC(C=C1)=CC=C1CN1C=CC=N1 QTARJTQMMMFRRC-UHFFFAOYSA-N 0.000 claims 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims 2
- 208000001953 Hypotension Diseases 0.000 claims 2
- 206010061218 Inflammation Diseases 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 206010033645 Pancreatitis Diseases 0.000 claims 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 2
- 206010040070 Septic Shock Diseases 0.000 claims 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 2
- 206010003246 arthritis Diseases 0.000 claims 2
- MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims 2
- 235000010290 biphenyl Nutrition 0.000 claims 2
- 239000004305 biphenyl Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 230000002612 cardiopulmonary effect Effects 0.000 claims 2
- 230000006735 deficit Effects 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 229930195733 hydrocarbon Natural products 0.000 claims 2
- 150000002430 hydrocarbons Chemical class 0.000 claims 2
- 230000036543 hypotension Effects 0.000 claims 2
- 230000004054 inflammatory process Effects 0.000 claims 2
- 208000017169 kidney disease Diseases 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 201000001119 neuropathy Diseases 0.000 claims 2
- 230000007823 neuropathy Effects 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims 2
- 230000002207 retinal effect Effects 0.000 claims 2
- 229930195734 saturated hydrocarbon Natural products 0.000 claims 2
- 230000036303 septic shock Effects 0.000 claims 2
- 230000008728 vascular permeability Effects 0.000 claims 2
- OWQPOVKKUWUEKE-UHFFFAOYSA-N 1,2,3-benzotriazine Chemical class N1=NN=CC2=CC=CC=C21 OWQPOVKKUWUEKE-UHFFFAOYSA-N 0.000 claims 1
- GDAXJBDYNVDMDF-UHFFFAOYSA-N 1,2,4-benzotriazine Chemical compound N1=NC=NC2=CC=CC=C21 GDAXJBDYNVDMDF-UHFFFAOYSA-N 0.000 claims 1
- 150000005057 1,7-naphthyridines Chemical class 0.000 claims 1
- 150000005058 1,8-naphthyridines Chemical class 0.000 claims 1
- VPLIKMCHOHMYFL-UHFFFAOYSA-N 1-[[2-[(4-methylpyrazol-1-yl)methyl]-1,3-thiazol-4-yl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound Cc1cnn(Cc2nc(Cn3cc(C(O)=O)c(n3)C(F)(F)F)cs2)c1 VPLIKMCHOHMYFL-UHFFFAOYSA-N 0.000 claims 1
- UVUGVZJMKMGPPT-UHFFFAOYSA-N 1-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound OC(=O)c1cn(Cc2ccc(Cn3ccccc3=O)cc2)nc1C(F)(F)F UVUGVZJMKMGPPT-UHFFFAOYSA-N 0.000 claims 1
- ZNSUFNBJZUAHMQ-UHFFFAOYSA-N 1-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]-N-(1H-pyrrolo[2,3-b]pyridin-5-ylmethyl)-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound N1C=CC=2C1=NC=C(C=2)CNC(=O)C=1C(=NN(C=1)CC1=CC=C(C=C1)CN1C(C=CC=C1)=O)C(F)(F)F ZNSUFNBJZUAHMQ-UHFFFAOYSA-N 0.000 claims 1
- CLZJGBDROZBBHL-UHFFFAOYSA-N 1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]-N-(1H-pyrrolo[2,3-b]pyridin-5-ylmethyl)-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound N1C=CC=2C1=NC=C(C=2)CNC(=O)C=1C(=NN(C=1)CC1=CC=C(C=C1)CN1N=CC(=C1)C)C(F)(F)F CLZJGBDROZBBHL-UHFFFAOYSA-N 0.000 claims 1
- UXSWNBHODCRZQX-UHFFFAOYSA-N 1-[[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound OC(=O)c1cn(Cc2ccc(nc2)N2CCC(F)(F)C2)nc1C(F)(F)F UXSWNBHODCRZQX-UHFFFAOYSA-N 0.000 claims 1
- KYEOVWIJJFNXPL-UHFFFAOYSA-N 1-[[6-[3-(hydroxymethyl)pyrrolidin-1-yl]pyridin-3-yl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound OCC1CCN(C1)c1ccc(Cn2cc(C(O)=O)c(n2)C(F)(F)F)cn1 KYEOVWIJJFNXPL-UHFFFAOYSA-N 0.000 claims 1
- HDIHRESJULZUPH-UHFFFAOYSA-N 1-ethyl-4-methyl-5-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]pyrrole-2-carboxylic acid Chemical compound CCn1c(Cc2ccc(Cn3ccccc3=O)cc2)c(C)cc1C(O)=O HDIHRESJULZUPH-UHFFFAOYSA-N 0.000 claims 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims 1
- PWINZESYUZCYRY-UHFFFAOYSA-N 3-amino-n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(6-ethoxypyridin-3-yl)methyl]pyrazole-4-carboxamide Chemical compound C1=NC(OCC)=CC=C1CN1N=C(N)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 PWINZESYUZCYRY-UHFFFAOYSA-N 0.000 claims 1
- HIYGQPZTBFIDNY-UHFFFAOYSA-N 3-amino-n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(6-pyrrolidin-1-ylpyridin-3-yl)methyl]pyrazole-4-carboxamide Chemical compound C1=C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)C(N)=NN1CC(C=N1)=CC=C1N1CCCC1 HIYGQPZTBFIDNY-UHFFFAOYSA-N 0.000 claims 1
- GJNUIQWJKPAZQA-UHFFFAOYSA-N 3-amino-n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]pyrazole-4-carboxamide Chemical compound C1=C(C)C=NN1CC(C=C1)=CC=C1CN1N=C(N)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 GJNUIQWJKPAZQA-UHFFFAOYSA-N 0.000 claims 1
- KRYGFFGIEKPPMW-UHFFFAOYSA-N 3-cyclopropyl-1-[[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl]pyrazole-4-carboxylic acid Chemical compound OC(=O)c1cn(Cc2ccc(nc2)N2CCC(F)(F)C2)nc1C1CC1 KRYGFFGIEKPPMW-UHFFFAOYSA-N 0.000 claims 1
- CDDROBVTAJIFPI-UHFFFAOYSA-N 3-cyclopropyl-1-[[6-[2-methoxyethyl(methyl)amino]pyridin-3-yl]methyl]pyrazole-4-carboxylic acid Chemical compound COCCN(C)c1ccc(Cn2cc(C(O)=O)c(n2)C2CC2)cn1 CDDROBVTAJIFPI-UHFFFAOYSA-N 0.000 claims 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
- 208000032843 Hemorrhage Diseases 0.000 claims 1
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 1
- GOKGDYJODZLJNF-UHFFFAOYSA-N N-(1H-indol-5-ylmethyl)-1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound N1C=CC2=CC(=CC=C12)CNC(=O)C=1C(=NN(C=1)CC1=CC=C(C=C1)CN1N=CC(=C1)C)C(F)(F)F GOKGDYJODZLJNF-UHFFFAOYSA-N 0.000 claims 1
- NVEZCZPWINYFRQ-UHFFFAOYSA-N N-(2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-4-ylmethyl)-3-amino-1-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]pyrazole-4-carboxamide Chemical compound Nc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCC1CCCC2NNCC12 NVEZCZPWINYFRQ-UHFFFAOYSA-N 0.000 claims 1
- ZXPGXTZEIVIBIC-UHFFFAOYSA-N N-[(4,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methyl]-1-[[4-[(2-oxopyridin-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound CC1=C2C(=NC(=C1CNC(=O)C=1C(=NN(C=1)CC1=CC=C(C=C1)CN1C(C=CC=C1)=O)C(F)(F)F)C)NC=C2 ZXPGXTZEIVIBIC-UHFFFAOYSA-N 0.000 claims 1
- PYSGSTYUQNZDJG-UHFFFAOYSA-N N-[(4,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methyl]-1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound CC1=C2C(=NC(=C1CNC(=O)C=1C(=NN(C=1)CC1=CC=C(C=C1)CN1N=CC(=C1)C)C(F)(F)F)C)NC=C2 PYSGSTYUQNZDJG-UHFFFAOYSA-N 0.000 claims 1
- 206010051077 Post procedural haemorrhage Diseases 0.000 claims 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 208000034158 bleeding Diseases 0.000 claims 1
- 230000000740 bleeding effect Effects 0.000 claims 1
- 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 150000002473 indoazoles Chemical class 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- 150000002475 indoles Chemical class 0.000 claims 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 1
- 150000002537 isoquinolines Chemical class 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- DAOSBZHACYXGLP-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(2-pyrrolidin-1-ylpyridin-4-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(C=1)=CC=NC=1N1CCCC1 DAOSBZHACYXGLP-UHFFFAOYSA-N 0.000 claims 1
- BGFWCDCOIGUICN-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(2-pyrrolidin-1-ylpyrimidin-5-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(C=N1)=CN=C1N1CCCC1 BGFWCDCOIGUICN-UHFFFAOYSA-N 0.000 claims 1
- KXNHEPBASBKDTB-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(5-chloro-6-ethoxypyridin-3-yl)methyl]-3-cyclopropylpyrazole-4-carboxamide Chemical compound C1=C(Cl)C(OCC)=NC=C1CN1N=C(C2CC2)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 KXNHEPBASBKDTB-UHFFFAOYSA-N 0.000 claims 1
- AKRGGXIRZBHZIN-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(5-chloro-6-pyrrolidin-1-ylpyridin-3-yl)methyl]-3-cyclopropylpyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C2CC2)=CN1CC(C=C1Cl)=CN=C1N1CCCC1 AKRGGXIRZBHZIN-UHFFFAOYSA-N 0.000 claims 1
- XCDBZZWRWFCHFE-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(5-fluoro-6-pyrrolidin-1-ylpyridin-3-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(C=C1F)=CN=C1N1CCCC1 XCDBZZWRWFCHFE-UHFFFAOYSA-N 0.000 claims 1
- GTQYYNKRYLNCBH-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(5-pyrrolidin-1-ylpyrazin-2-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(N=C1)=CN=C1N1CCCC1 GTQYYNKRYLNCBH-UHFFFAOYSA-N 0.000 claims 1
- GGVYRGRBULRJBJ-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(6-ethoxy-5-fluoropyridin-3-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=C(F)C(OCC)=NC=C1CN1N=C(C(F)(F)F)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 GGVYRGRBULRJBJ-UHFFFAOYSA-N 0.000 claims 1
- GKPBRBZRCXWGEQ-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(6-ethoxypyridin-3-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=NC(OCC)=CC=C1CN1N=C(C(F)(F)F)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 GKPBRBZRCXWGEQ-UHFFFAOYSA-N 0.000 claims 1
- DWFRBDIXHQEHJF-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(6-propoxypyridin-3-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=NC(OCCC)=CC=C1CN1N=C(C(F)(F)F)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 DWFRBDIXHQEHJF-UHFFFAOYSA-N 0.000 claims 1
- SLRCFYCDNOSNHM-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[(6-pyrrolidin-1-ylpyridin-3-yl)methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(C=N1)=CC=C1N1CCCC1 SLRCFYCDNOSNHM-UHFFFAOYSA-N 0.000 claims 1
- NTKGSHJOYRJNMU-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[2-(pyrazol-1-ylmethyl)-1,3-thiazol-4-yl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(N=1)=CSC=1CN1C=CC=N1 NTKGSHJOYRJNMU-UHFFFAOYSA-N 0.000 claims 1
- SCXKYBZCYMWSLK-INIZCTEOSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[2-[(3s)-3-methylpyrrolidin-1-yl]pyridin-4-yl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1[C@@H](C)CCN1C1=CC(CN2N=C(C(C(=O)NCC=3C=C4C=CN=C(N)C4=CC=3)=C2)C(F)(F)F)=CC=N1 SCXKYBZCYMWSLK-INIZCTEOSA-N 0.000 claims 1
- VRYHLJFFMXJWLQ-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-(pyrazol-1-ylmethyl)phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(C=C1)=CC=C1CN1C=CC=N1 VRYHLJFFMXJWLQ-UHFFFAOYSA-N 0.000 claims 1
- NWLUWTWQKQUQDZ-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-[(4-carbamoylpyrazol-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=C(C(=O)N)C=NN1CC(C=C1)=CC=C1CN1N=C(C(F)(F)F)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 NWLUWTWQKQUQDZ-UHFFFAOYSA-N 0.000 claims 1
- ZSWFNMZXDBXLIE-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-[(4-cyanopyrazol-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C=1C=C2C(N)=NC=CC2=CC=1CNC(=O)C(C(=N1)C(F)(F)F)=CN1CC(C=C1)=CC=C1CN1C=C(C#N)C=N1 ZSWFNMZXDBXLIE-UHFFFAOYSA-N 0.000 claims 1
- HXLUIKPALDGUQR-UHFFFAOYSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[4-[(4-methylpyrazol-1-yl)methyl]phenyl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=C(C)C=NN1CC(C=C1)=CC=C1CN1N=C(C(F)(F)F)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 HXLUIKPALDGUQR-UHFFFAOYSA-N 0.000 claims 1
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- DSSWHEZOLVGIOD-MRXNPFEDSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[6-[(2r)-2-methylpyrrolidin-1-yl]pyridin-3-yl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C[C@@H]1CCCN1C(N=C1)=CC=C1CN1N=C(C(F)(F)F)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 DSSWHEZOLVGIOD-MRXNPFEDSA-N 0.000 claims 1
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- WETAMWXIAPCHJG-INIZCTEOSA-N n-[(1-aminoisoquinolin-6-yl)methyl]-1-[[6-[(3s)-3-methylpyrrolidin-1-yl]pyridin-3-yl]methyl]-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1[C@@H](C)CCN1C(N=C1)=CC=C1CN1N=C(C(F)(F)F)C(C(=O)NCC=2C=C3C=CN=C(N)C3=CC=2)=C1 WETAMWXIAPCHJG-INIZCTEOSA-N 0.000 claims 1
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| JP6855477B2 (ja) * | 2015-10-27 | 2021-04-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 血漿カリクレイン阻害薬としてのヘテロアリールカルボキサミド誘導体 |
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| CN110022875A (zh) | 2016-07-11 | 2019-07-16 | 莱福斯希医药公司 | 治疗性抑制化合物 |
| JP7175914B2 (ja) * | 2017-04-21 | 2022-11-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 血漿カリクレイン阻害剤としてのヘテロアリールカルボキサミド誘導体 |
| HUE057912T2 (hu) | 2017-11-29 | 2022-06-28 | Kalvista Pharmaceuticals Ltd | Plazma kallikrein inhibitort tartalmazó dózisformák |
| GB201719881D0 (en) | 2017-11-29 | 2018-01-10 | Kalvista Pharmaceuticals Ltd | Solid forms of plasma kallikrein inhibitor and salts thereof |
| US10695334B2 (en) | 2018-08-16 | 2020-06-30 | Boehringer Ingelheim International Gmbh | Heteroaromatic carboxamide derivatives as plasma kallikrein inhibitors |
| CN112839711A (zh) | 2018-10-10 | 2021-05-25 | 勃林格殷格翰国际有限公司 | 作为血浆激肽释放酶抑制剂的苯基四唑衍生物 |
| WO2020113094A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
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| GB201910125D0 (en) | 2019-07-15 | 2019-08-28 | Kalvista Pharmaceuticals Ltd | Treatments of angioedema |
| WO2021028645A1 (en) | 2019-08-09 | 2021-02-18 | Kalvista Pharmaceuticals Limited | Plasma kallikrein inhibitors |
| WO2021032935A1 (en) | 2019-08-21 | 2021-02-25 | Kalvista Pharmaceuticals Limited | Enzyme inhibitors |
| GB201918994D0 (en) | 2019-12-20 | 2020-02-05 | Kalvista Pharmaceuticals Ltd | Treatments of diabetic macular edema and impaired visual acuity |
| TWI873290B (zh) | 2020-02-13 | 2025-02-21 | 德商百靈佳殷格翰國際股份有限公司 | 作為血漿激肽釋放酶抑制劑之雜芳族甲醯胺衍生物 |
| TW202144331A (zh) | 2020-02-13 | 2021-12-01 | 德商百靈佳殷格翰國際股份有限公司 | 作為血漿激肽釋放酶抑制劑之雜芳族甲醯胺衍生物 |
| JP7245397B2 (ja) * | 2020-03-04 | 2023-03-23 | メッドシャイン ディスカバリー インコーポレイテッド | 複素環化合物 |
| KR20230038526A (ko) | 2020-07-10 | 2023-03-20 | 머크 샤프 앤드 돔 엘엘씨 | 혈장 칼리크레인 억제제 |
| TW202228686A (zh) | 2020-10-15 | 2022-08-01 | 英商卡爾維斯塔製藥有限公司 | 血管性水腫之治療 |
| US20230381162A1 (en) | 2020-10-23 | 2023-11-30 | Kalvista Pharmaceuticals Limited | Treatments of angioedema |
| JP2024505596A (ja) | 2021-02-09 | 2024-02-06 | カルビスタ・ファーマシューティカルズ・リミテッド | 遺伝性血管性浮腫の治療 |
| WO2023002219A1 (en) | 2021-07-23 | 2023-01-26 | Kalvista Pharmaceuticals Limited | Treatments of hereditary angioedema |
| WO2023185634A1 (zh) * | 2022-03-30 | 2023-10-05 | 南京明德新药研发有限公司 | 作为血浆激肽释放酶抑制剂的杂环类化合物 |
| US20250281397A1 (en) | 2022-04-27 | 2025-09-11 | Kalvista Pharmaceuticals Limited | Formulations of a plasma kallikrein inhibitor |
| WO2024180100A1 (en) | 2023-02-27 | 2024-09-06 | Kalvista Pharmaceuticals Limited | New solid form of a plasma kallikrein inhibitor |
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| WO2025172692A1 (en) | 2024-02-13 | 2025-08-21 | Kalvista Pharmaceuticals Limited | Oral sebetralstat for the treatment of an attack of hereditary angioedema |
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- 2014-05-23 KR KR1020157036257A patent/KR102276700B1/ko not_active Expired - Fee Related
- 2014-05-23 AU AU2014270152A patent/AU2014270152B9/en not_active Ceased
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- 2014-05-23 BR BR112015028879-0A patent/BR112015028879B1/pt not_active IP Right Cessation
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