CA3021335A1 - Substituted bicyclic heterocyclic compounds - Google Patents
Substituted bicyclic heterocyclic compounds Download PDFInfo
- Publication number
- CA3021335A1 CA3021335A1 CA3021335A CA3021335A CA3021335A1 CA 3021335 A1 CA3021335 A1 CA 3021335A1 CA 3021335 A CA3021335 A CA 3021335A CA 3021335 A CA3021335 A CA 3021335A CA 3021335 A1 CA3021335 A1 CA 3021335A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- pyridinyl
- oxo
- dihydroisobenzofuran
- pyrimidin
- 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.)
- Abandoned
Links
- 125000002618 bicyclic heterocycle group Chemical group 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 251
- 150000003839 salts Chemical class 0.000 claims abstract description 64
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 18
- -1 -OH Chemical group 0.000 claims description 382
- 125000001072 heteroaryl group Chemical group 0.000 claims description 100
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 78
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
- 229910052757 nitrogen Inorganic materials 0.000 claims description 60
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 54
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 229910052799 carbon Chemical group 0.000 claims description 29
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 25
- 125000001041 indolyl group Chemical group 0.000 claims description 25
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 24
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 206010019280 Heart failures Diseases 0.000 claims description 20
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 20
- 125000004076 pyridyl group Chemical group 0.000 claims description 20
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
- 208000004880 Polyuria Diseases 0.000 claims description 18
- 230000035619 diuresis Effects 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 230000012495 positive regulation of renal sodium excretion Effects 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 125000005466 alkylenyl group Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 206010020772 Hypertension Diseases 0.000 claims description 11
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- LYUXFKKRHRUXQP-UHFFFAOYSA-N 2-fluoro-5-[[6-[(1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound FC1=C(C=C(NC2=NC=C3CN(CC4=CC=C5C(=O)OCC5=C4)CCC3=N2)C=C1)C#N LYUXFKKRHRUXQP-UHFFFAOYSA-N 0.000 claims description 7
- 206010030113 Oedema Diseases 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- AGLNCQJYRXKZQZ-UHFFFAOYSA-N 2-fluoro-4-[[2-[(1-oxo-3H-2-benzofuran-5-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]benzonitrile Chemical compound Fc1cc(Nc2ccc3CN(Cc4ccc5C(=O)OCc5c4)CCc3c2)ccc1C#N AGLNCQJYRXKZQZ-UHFFFAOYSA-N 0.000 claims description 6
- 206010007556 Cardiac failure acute Diseases 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 5
- 208000003037 Diastolic Heart Failure Diseases 0.000 claims description 5
- 206010016803 Fluid overload Diseases 0.000 claims description 5
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 5
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 5
- 208000008253 Systolic Heart Failure Diseases 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 230000002980 postoperative effect Effects 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 4
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 claims description 4
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 4
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims description 4
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 4
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 4
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 4
- UWIVBVVTOQJPJS-UHFFFAOYSA-N 2-fluoro-4-[[2-[2-(1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)NC=1C=C2CCN(CC2=CC=1)CCC=1C=C2COC(C2=CC=1)=O UWIVBVVTOQJPJS-UHFFFAOYSA-N 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 125000005873 benzo[d]thiazolyl group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 208000029078 coronary artery disease Diseases 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- JVQZNHUFSUXMIY-UHFFFAOYSA-N 2-[[2-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]pyrimidine-5-carbonitrile Chemical compound Cc1c2COC(=O)c2ccc1CN1CCc2cc(Nc3ncc(cn3)C#N)ccc2C1 JVQZNHUFSUXMIY-UHFFFAOYSA-N 0.000 claims description 3
- NVTHCTSQOSPGOP-UHFFFAOYSA-N 2-fluoro-4-[[2-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)NC=1C=C2CCN(CC2=CC=1)CC=1C(=C2COC(C2=CC=1)=O)C NVTHCTSQOSPGOP-UHFFFAOYSA-N 0.000 claims description 3
- NVQZFYZVDYXYJR-UHFFFAOYSA-N 2-fluoro-4-[[2-[2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]benzonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(O)CN1CCC2=C(C1)C=CC(NC1=CC(F)=C(C=C1)C#N)=C2 NVQZFYZVDYXYJR-UHFFFAOYSA-N 0.000 claims description 3
- BNTBWSVJRWLHIB-UHFFFAOYSA-N 2-fluoro-4-[[6-[2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)NC=1N=CC2=C(N=1)CCN(C2)CCC=1C(=C2COC(C2=CC=1)=O)C BNTBWSVJRWLHIB-UHFFFAOYSA-N 0.000 claims description 3
- SUQJLBWAYFXPDM-UHFFFAOYSA-N 2-fluoro-6-[[2-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]benzonitrile Chemical compound FC1=C(C#N)C(=CC=C1)NC=1C=C2CCN(CC2=CC=1)CC=1C(=C2COC(C2=CC=1)=O)C SUQJLBWAYFXPDM-UHFFFAOYSA-N 0.000 claims description 3
- IDENZEKIPQZNHF-UHFFFAOYSA-N 2-fluoro-4-[[6-[2-(1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-1,6-naphthyridin-2-yl]amino]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)NC1=NC=2CCN(CC=2C=C1)CCC=1C=C2COC(C2=CC=1)=O IDENZEKIPQZNHF-UHFFFAOYSA-N 0.000 claims description 2
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 4
- HHXYDAHWEBSDSW-UHFFFAOYSA-N 1-[6-[2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]-2,3-dihydroindole-4-carbonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(O)CN1CCC2=NC(=NC=C2C1)N1CCC2=C(C=CC=C12)C#N HHXYDAHWEBSDSW-UHFFFAOYSA-N 0.000 claims 2
- FVLKLTUAMHIPMA-UHFFFAOYSA-N 2-fluoro-4-[[6-[2-hydroxy-1-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(CO)N1CCC2=NC(NC3=CC(F)=C(C=C3)C#N)=NC=C2C1 FVLKLTUAMHIPMA-UHFFFAOYSA-N 0.000 claims 2
- GVJUMYIQSNFBQS-UHFFFAOYSA-N 2-fluoro-4-[[7-(hydroxymethyl)-6-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1CN1CC2=CN=C(NC3=CC(F)=C(C=C3)C#N)N=C2CC1CO GVJUMYIQSNFBQS-UHFFFAOYSA-N 0.000 claims 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- PDKKASJXYCTVJV-UHFFFAOYSA-N 1-[6-[(1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]indazole-5-carbonitrile Chemical compound O=C1OCC2=CC(CN3CCC4=NC(=NC=C4C3)N3N=CC4=C3C=CC(=C4)C#N)=CC=C12 PDKKASJXYCTVJV-UHFFFAOYSA-N 0.000 claims 1
- AMRKKIOKNDHAAI-UHFFFAOYSA-N 1-[6-[(1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]pyrrolo[2,3-b]pyridine-5-carbonitrile Chemical compound O=C1OCC2=CC(CN3CCC4=NC(=NC=C4C3)N3C=CC4=C3N=CC(=C4)C#N)=CC=C12 AMRKKIOKNDHAAI-UHFFFAOYSA-N 0.000 claims 1
- KGJJTPJVUUWODD-UHFFFAOYSA-N 1-[6-[2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]indazole-3-carbonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(O)CN1CCC2=NC(=NC=C2C1)N1N=C(C#N)C2=C1C=CC=C2 KGJJTPJVUUWODD-UHFFFAOYSA-N 0.000 claims 1
- LUDUGDBSNJKSHW-UHFFFAOYSA-N 1-[6-[2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]pyrazole-4-carbonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(O)CN1CCC2=NC(=NC=C2C1)N1C=C(C=N1)C#N LUDUGDBSNJKSHW-UHFFFAOYSA-N 0.000 claims 1
- MKUSRPDNOVWCRF-UHFFFAOYSA-N 1-[6-[2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]pyrrolo[3,2-b]pyridine-3-carbonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(O)CN1CCC2=NC(=NC=C2C1)N1C=C(C#N)C2=C1C=CC=N2 MKUSRPDNOVWCRF-UHFFFAOYSA-N 0.000 claims 1
- KCTGOULTUMTUQH-UHFFFAOYSA-N 2-fluoro-4-[[2-[(3-methyl-2-oxo-1,3-benzoxazol-5-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]benzonitrile Chemical compound Cn1c2cc(CN3CCc4cc(Nc5ccc(C#N)c(F)c5)ccc4C3)ccc2oc1=O KCTGOULTUMTUQH-UHFFFAOYSA-N 0.000 claims 1
- JQZYMXJBCDAKNM-UHFFFAOYSA-N 2-fluoro-4-[[2-[2-hydroxy-1-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]benzonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(CO)N1CCC2=C(C1)C=CC(NC1=CC(F)=C(C=C1)C#N)=C2 JQZYMXJBCDAKNM-UHFFFAOYSA-N 0.000 claims 1
- GKBAFSROZUWOIP-UHFFFAOYSA-N 2-fluoro-4-[[6-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)NC=1N=CC2=C(N=1)CCN(C2)CC=1C(=C2COC(C2=CC=1)=O)C GKBAFSROZUWOIP-UHFFFAOYSA-N 0.000 claims 1
- DGYWALNFLHLHFD-UHFFFAOYSA-N 2-fluoro-4-[[6-[2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=C2COC(=O)C2=CC=C1C(O)CN1CCC2=NC(NC3=CC(F)=C(C=C3)C#N)=NC=C2C1 DGYWALNFLHLHFD-UHFFFAOYSA-N 0.000 claims 1
- JYXCBDUVPKJTOB-UHFFFAOYSA-N 2-fluoro-4-[[[2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)-3,4-dihydro-1H-isoquinolin-6-yl]amino]methyl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)CNC=1C=C2CCN(CC2=CC=1)C=1C(=C2COC(C2=CC=1)=O)C JYXCBDUVPKJTOB-UHFFFAOYSA-N 0.000 claims 1
- GVIKCFCQVPGVLF-UHFFFAOYSA-N 2-fluoro-4-[methyl-[6-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]benzonitrile Chemical compound CN(C1=CC(F)=C(C=C1)C#N)C1=NC=C2CN(CC3=CC=C4C(=O)OCC4=C3C)CCC2=N1 GVIKCFCQVPGVLF-UHFFFAOYSA-N 0.000 claims 1
- RXYGZBKQLWIWTM-UHFFFAOYSA-N 3-methyl-5-[[2-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]-1,3-benzoxazol-2-one Chemical compound Cc1c2COC(=O)c2ccc1CN1CCc2cc(Nc3ccc4oc(=O)n(C)c4c3)ccc2C1 RXYGZBKQLWIWTM-UHFFFAOYSA-N 0.000 claims 1
- CRRGLEQDTJJSEY-UHFFFAOYSA-N 3-methyl-5-[[6-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]-1,3-benzoxazol-2-one Chemical compound Cc1c2COC(=O)c2ccc1CN1CCc2nc(Nc3ccc4oc(=O)n(C)c4c3)ncc2C1 CRRGLEQDTJJSEY-UHFFFAOYSA-N 0.000 claims 1
- WIZXASUWJRPUHL-UHFFFAOYSA-N 4-methyl-5-[[2-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)amino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methyl]-3H-2-benzofuran-1-one Chemical compound CC1=C2COC(=O)C2=CC=C1CN1CCC2=NC(NC3=CC=C4C(=O)OCC4=C3C)=NC=C2C1 WIZXASUWJRPUHL-UHFFFAOYSA-N 0.000 claims 1
- WKGOYBKPASWBQA-UHFFFAOYSA-N 4-methyl-5-[[6-(pyrazolo[1,5-a]pyrimidin-5-ylamino)-3,4-dihydro-1H-isoquinolin-2-yl]methyl]-3H-2-benzofuran-1-one Chemical compound CC1=C2COC(=O)C2=CC=C1CN1CCC2=C(C1)C=CC(NC1=NC3=CC=NN3C=C1)=C2 WKGOYBKPASWBQA-UHFFFAOYSA-N 0.000 claims 1
- RMQYEUXSUAUCRB-UHFFFAOYSA-N 4-methyl-6-[[2-[(1-oxo-3H-2-benzofuran-5-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]amino]pyridine-3-carbonitrile Chemical compound Cc1cc(Nc2ccc3CN(Cc4ccc5C(=O)OCc5c4)CCc3c2)ncc1C#N RMQYEUXSUAUCRB-UHFFFAOYSA-N 0.000 claims 1
- KTYXUDCNLGSFSP-UHFFFAOYSA-N 4-methyl-6-[[6-[(4-methyl-1-oxo-3H-2-benzofuran-5-yl)methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]amino]pyridine-3-carbonitrile Chemical compound CC1=CC(=NC=C1C#N)NC=1N=CC2=C(N=1)CCN(C2)CC=1C(=C2COC(C2=CC=1)=O)C KTYXUDCNLGSFSP-UHFFFAOYSA-N 0.000 claims 1
- FTPBTOYQLJQZNK-UHFFFAOYSA-N 5-[1-hydroxy-2-(2-imidazo[4,5-b]pyridin-1-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)ethyl]-4-methyl-3H-2-benzofuran-1-one Chemical compound Cc1c2COC(=O)c2ccc1C(O)CN1CCc2nc(ncc2C1)-n1cnc2ncccc12 FTPBTOYQLJQZNK-UHFFFAOYSA-N 0.000 claims 1
- SBEUHKXMICFRQH-UHFFFAOYSA-N 5-[1-hydroxy-2-(2-imidazo[4,5-b]pyridin-3-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)ethyl]-4-methyl-3H-2-benzofuran-1-one Chemical compound N1=CN(C2=NC=CC=C21)C=1N=CC2=C(N=1)CCN(C2)CC(O)C=1C(=C2COC(C2=CC=1)=O)C SBEUHKXMICFRQH-UHFFFAOYSA-N 0.000 claims 1
- BCRHBHIDTOBOGG-UHFFFAOYSA-N 5-[1-hydroxy-2-(2-pyrazolo[4,3-b]pyridin-1-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)ethyl]-4-methyl-3H-2-benzofuran-1-one Chemical compound CC1=C2COC(=O)C2=CC=C1C(O)CN1CCC2=NC(=NC=C2C1)N1N=CC2=C1C=CC=N2 BCRHBHIDTOBOGG-UHFFFAOYSA-N 0.000 claims 1
- ICZHCGFXYXPNLM-UHFFFAOYSA-N 5-[1-hydroxy-2-(2-pyrrolo[3,2-b]pyridin-1-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)ethyl]-4-methyl-3H-2-benzofuran-1-one Chemical compound N1(C=CC2=NC=CC=C21)C=1N=CC2=C(N=1)CCN(C2)CC(O)C=1C(=C2COC(C2=CC=1)=O)C ICZHCGFXYXPNLM-UHFFFAOYSA-N 0.000 claims 1
- XNYUWUJJVKPIEY-UHFFFAOYSA-N 5-[1-hydroxy-2-[2-(2-methylimidazol-1-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]ethyl]-4-methyl-3H-2-benzofuran-1-one Chemical compound Cc1nccn1-c1ncc2CN(CC(O)c3ccc4C(=O)OCc4c3C)CCc2n1 XNYUWUJJVKPIEY-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/04—1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US201662325255P | 2016-04-20 | 2016-04-20 | |
| US62/325,255 | 2016-04-20 | ||
| PCT/US2017/028231 WO2017184662A1 (en) | 2016-04-20 | 2017-04-19 | Substituted bicyclic heterocyclic compounds |
Publications (1)
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| CA3021335A1 true CA3021335A1 (en) | 2017-10-26 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3021335A Abandoned CA3021335A1 (en) | 2016-04-20 | 2017-04-19 | Substituted bicyclic heterocyclic compounds |
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| US (1) | US10851108B2 (https=) |
| EP (1) | EP3445762B1 (https=) |
| JP (1) | JP6905993B2 (https=) |
| KR (1) | KR102417686B1 (https=) |
| CN (1) | CN109311874B (https=) |
| AU (1) | AU2017252546B2 (https=) |
| BR (1) | BR112018071548A2 (https=) |
| CA (1) | CA3021335A1 (https=) |
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| IL (1) | IL262448B (https=) |
| MX (1) | MX381425B (https=) |
| SG (1) | SG11201809173TA (https=) |
| WO (1) | WO2017184662A1 (https=) |
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| EP3535258B1 (en) * | 2016-11-03 | 2021-11-24 | Bristol-Myers Squibb Company | Substituted bicycle heterocyclic derivatives useful as romk channel inhibitors |
| HUE056142T2 (hu) | 2017-06-01 | 2022-01-28 | Bristol Myers Squibb Co | Szubsztituált nitrogéntartalmú vegyületek |
| US12084453B2 (en) | 2021-12-10 | 2024-09-10 | Incyte Corporation | Bicyclic amines as CDK12 inhibitors |
| TW202527931A (zh) * | 2023-11-08 | 2025-07-16 | 美商奧科坦特公司 | 視紫質的藥理校正劑及其用途 |
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| GB8824291D0 (en) | 1988-10-17 | 1988-11-23 | Zambeletti Spa L | Novel use |
| DE102004020908A1 (de) | 2004-04-28 | 2005-11-17 | Grünenthal GmbH | Substituierte 5,6,7,8,-Tetrahydro-pyrido[4,3-d]pyrimidin-2-yl- und 5,6,7,8,-Tetrahydro-chinazolin-2-yl-Verbindungen |
| US8247556B2 (en) | 2005-10-21 | 2012-08-21 | Amgen Inc. | Method for preparing 6-substituted-7-aza-indoles |
| CA2624625A1 (en) | 2005-11-04 | 2007-05-10 | Pfizer Limited | Tetrahydronaphthyridine derivative |
| EA200900779A1 (ru) | 2006-12-14 | 2010-02-26 | Байер Шеринг Фарма Акциенгезельшафт | Производные дигидропиридина, полезные как ингибиторы протеинкиназы |
| US8673920B2 (en) | 2009-05-06 | 2014-03-18 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| US8455522B2 (en) | 2009-05-15 | 2013-06-04 | Novartis Ag | Benzoxazolone derivatives as aldosterone synthase inhibitors |
| DE102009022896A1 (de) | 2009-05-27 | 2010-12-02 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Piperidine |
| EP2632465B1 (en) | 2010-10-27 | 2015-12-30 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2632464B1 (en) | 2010-10-29 | 2015-04-29 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| MX2014001946A (es) | 2011-08-19 | 2014-03-27 | Merck Sharp & Dohme | Inhibidores del canal de potasio medularmente externo renal. |
| WO2013026914A1 (en) | 2011-08-25 | 2013-02-28 | F. Hoffmann-La Roche Ag | Serine/threonine pak1 inhibitors |
| WO2013039802A1 (en) * | 2011-09-16 | 2013-03-21 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2013062892A1 (en) | 2011-10-25 | 2013-05-02 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2013062900A1 (en) | 2011-10-25 | 2013-05-02 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2013066714A1 (en) | 2011-10-31 | 2013-05-10 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2773351B1 (en) | 2011-10-31 | 2017-08-23 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2773206B1 (en) | 2011-10-31 | 2018-02-21 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP2790511B1 (en) | 2011-12-16 | 2016-09-14 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| CN104011050A (zh) | 2011-12-22 | 2014-08-27 | 霍夫曼-拉罗奇有限公司 | 作为丝氨酸/苏氨酸激酶抑制剂的2,4-二氨基-嘧啶衍生物 |
| WO2014015495A1 (en) | 2012-07-26 | 2014-01-30 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| AR092031A1 (es) | 2012-07-26 | 2015-03-18 | Merck Sharp & Dohme | Inhibidores del canal de potasio medular externo renal |
| JP6215338B2 (ja) | 2012-11-08 | 2017-10-18 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | キナーゼモジュレーターとして有用な二環式ヘテロ環置換ピリジル化合物 |
| TWI692469B (zh) | 2012-11-09 | 2020-05-01 | 南韓商Ｌｇ化學股份有限公司 | Ｇｐｒ４０受體促效劑，製造該促效劑的方法以及含有該促效劑作爲活性劑的醫藥組成物 |
| EP2925322B1 (en) | 2012-11-29 | 2018-10-24 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2014089324A1 (en) | 2012-12-07 | 2014-06-12 | Calitor Sciences, Llc | Substituted cyclic compounds and methods of use |
| US9573961B2 (en) | 2012-12-19 | 2017-02-21 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| US9604998B2 (en) | 2013-02-18 | 2017-03-28 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2014150132A1 (en) | 2013-03-15 | 2014-09-25 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| JP6103527B2 (ja) | 2013-04-17 | 2017-03-29 | 矢崎総業株式会社 | 余長吸収装置及びコイルユニット |
| FR3008977A1 (fr) | 2013-07-23 | 2015-01-30 | Servier Lab | Nouveaux derives d'isoindoline ou d'isoquinoline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| WO2015017305A1 (en) | 2013-07-31 | 2015-02-05 | Merck Sharp & Dohme Corp | Inhibitors of the renal outer medullary potassium channel |
| EP3063142B1 (en) | 2013-10-31 | 2019-01-30 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2015095097A2 (en) * | 2013-12-18 | 2015-06-25 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2015096035A1 (en) * | 2013-12-24 | 2015-07-02 | Merck Sharp & Dohme Corp. | Inhibitors of renal outer medullary potassium channel |
| WO2015103756A1 (en) | 2014-01-09 | 2015-07-16 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| BR112016029065A2 (pt) | 2014-07-14 | 2017-08-22 | Merck Sharp & Dohme | ?composto, composição farmacêutica, e, uso de um composto? |
| WO2016008064A1 (en) * | 2014-07-14 | 2016-01-21 | Merck Sharp & Dohme Corp. | Inhibitors of renal outer medullary potassium channel |
| EP3207030A4 (en) | 2014-10-14 | 2018-06-06 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2016065582A1 (en) | 2014-10-30 | 2016-05-06 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2016065602A1 (en) | 2014-10-31 | 2016-05-06 | Merck Sharp & Dohme Corp. | Inhibitors of renal outer medullary potassium channel |
| WO2016065603A1 (en) | 2014-10-31 | 2016-05-06 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| EP3212617A1 (en) | 2014-10-31 | 2017-09-06 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| CN105980379B (zh) | 2014-12-08 | 2018-09-07 | 江苏恒瑞医药股份有限公司 | 吡啶甲酰胺类衍生物、其制备方法及其在医药上的应用 |
| CN105693706B (zh) | 2014-12-10 | 2019-11-22 | 江苏恒瑞医药股份有限公司 | 异苯并呋喃酮类衍生物、其制备方法及其在医药上的应用 |
| EP3250204B1 (en) | 2015-01-29 | 2019-10-30 | Merck Sharp & Dohme Corp. | Inhibitors of the renal outer medullary potassium channel |
| WO2016127358A1 (en) | 2015-02-12 | 2016-08-18 | Merck Sharp & Dohme Corp. | Inhibitors of renal outer medullary potassium channel |
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2017
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- 2017-04-19 MX MX2018012840A patent/MX381425B/es unknown
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2018
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| IL262448B (en) | 2020-08-31 |
| JP2019515911A (ja) | 2019-06-13 |
| EP3445762B1 (en) | 2023-09-13 |
| EA201892382A1 (ru) | 2019-03-29 |
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| AU2017252546A1 (en) | 2018-12-06 |
| US10851108B2 (en) | 2020-12-01 |
| CN109311874A (zh) | 2019-02-05 |
| WO2017184662A1 (en) | 2017-10-26 |
| MX381425B (es) | 2025-03-12 |
| BR112018071548A2 (pt) | 2019-04-16 |
| EP3445762A1 (en) | 2019-02-27 |
| ES2962315T3 (es) | 2024-03-18 |
| SG11201809173TA (en) | 2018-11-29 |
| CN109311874B (zh) | 2021-07-30 |
| US20190127380A1 (en) | 2019-05-02 |
| KR20180134999A (ko) | 2018-12-19 |
| EA037300B1 (ru) | 2021-03-05 |
| AU2017252546B2 (en) | 2021-07-29 |
| JP6905993B2 (ja) | 2021-07-21 |
| KR102417686B1 (ko) | 2022-07-07 |
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