JP2008507539A - 置換アリール−アミン誘導体および使用方法 - Google Patents
置換アリール−アミン誘導体および使用方法 Download PDFInfo
- Publication number
- JP2008507539A JP2008507539A JP2007522715A JP2007522715A JP2008507539A JP 2008507539 A JP2008507539 A JP 2008507539A JP 2007522715 A JP2007522715 A JP 2007522715A JP 2007522715 A JP2007522715 A JP 2007522715A JP 2008507539 A JP2008507539 A JP 2008507539A
- Authority
- JP
- Japan
- Prior art keywords
- pyridinecarboxamide
- phenyl
- methyl
- isoquinolinylamino
- dihydro
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims description 142
- 150000004982 aromatic amines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 250
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 46
- 201000010099 disease Diseases 0.000 claims abstract description 44
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 43
- 230000033115 angiogenesis Effects 0.000 claims abstract description 24
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- -1 7-isoquinolinyl Chemical group 0.000 claims description 754
- 238000006243 chemical reaction Methods 0.000 claims description 82
- 150000003839 salts Chemical group 0.000 claims description 49
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 35
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 239000002246 antineoplastic agent Substances 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 239000011570 nicotinamide Substances 0.000 claims description 28
- 229960003966 nicotinamide Drugs 0.000 claims description 28
- 229940079593 drug Drugs 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000005843 halogen group Chemical group 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 15
- 229940041181 antineoplastic drug Drugs 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
- 108091008605 VEGF receptors Proteins 0.000 claims description 10
- 229940124597 therapeutic agent Drugs 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 9
- 229910019142 PO4 Inorganic materials 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 9
- 239000012830 cancer therapeutic Substances 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 8
- 239000010452 phosphate Substances 0.000 claims description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 8
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 229940127089 cytotoxic agent Drugs 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000005433 dihydrobenzodioxinyl group Chemical group O1C(COC2=C1C=CC=C2)* 0.000 claims description 6
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 6
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 6
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 6
- 230000035755 proliferation Effects 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000005493 quinolyl group Chemical group 0.000 claims description 6
- DJMAGYPYQQKCTM-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-(2-methyl-1,3-benzothiazol-5-yl)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3C=C4N=C(SC4=CC=3)C)=CC=C21 DJMAGYPYQQKCTM-UHFFFAOYSA-N 0.000 claims description 5
- PESBGORKGLRGHQ-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-(3-oxo-4h-1,4-benzothiazin-6-yl)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(NC=3C=C4NC(=O)CSC4=CC=3)=O)=CC=C21 PESBGORKGLRGHQ-UHFFFAOYSA-N 0.000 claims description 5
- AKSCHOXLLVBOFT-JOCHJYFZSA-N 2-(isoquinolin-7-ylamino)-n-[3-[[(2r)-oxolan-2-yl]methoxy]-5-(trifluoromethyl)phenyl]pyridine-3-carboxamide Chemical compound C=1C(C(F)(F)F)=CC(NC(=O)C=2C(=NC=CC=2)NC=2C=C3C=NC=CC3=CC=2)=CC=1OC[C@H]1CCCO1 AKSCHOXLLVBOFT-JOCHJYFZSA-N 0.000 claims description 5
- GDMJWPCFBRNRKH-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-[3-methoxy-5-(trifluoromethyl)phenyl]pyridine-3-carboxamide Chemical compound FC(F)(F)C1=CC(OC)=CC(NC(=O)C=2C(=NC=CC=2)NC=2C=C3C=NC=CC3=CC=2)=C1 GDMJWPCFBRNRKH-UHFFFAOYSA-N 0.000 claims description 5
- OLPNNMJDBFQZQB-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-[4-(1,1,2,2,2-pentafluoroethyl)phenyl]pyridine-3-carboxamide Chemical compound C1=CC(C(F)(F)C(F)(F)F)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 OLPNNMJDBFQZQB-UHFFFAOYSA-N 0.000 claims description 5
- ZCQJVITWBZAQDX-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-[4-(2-methylbutan-2-yl)phenyl]pyridine-3-carboxamide Chemical compound C1=CC(C(C)(C)CC)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 ZCQJVITWBZAQDX-UHFFFAOYSA-N 0.000 claims description 5
- HTOPDFCQOYISPA-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 HTOPDFCQOYISPA-UHFFFAOYSA-N 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- ZCWMAKVIEHLWLT-UHFFFAOYSA-N 5-fluoro-2-(isoquinolin-7-ylamino)-n-(3-methyl-4-propan-2-ylphenyl)pyridine-3-carboxamide Chemical compound C1=C(C)C(C(C)C)=CC=C1NC(=O)C1=CC(F)=CN=C1NC1=CC=C(C=CN=C2)C2=C1 ZCWMAKVIEHLWLT-UHFFFAOYSA-N 0.000 claims description 5
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 5
- 229910002651 NO3 Inorganic materials 0.000 claims description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 5
- 229940088597 hormone Drugs 0.000 claims description 5
- 239000005556 hormone Substances 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 229940043355 kinase inhibitor Drugs 0.000 claims description 5
- MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical compound OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 claims description 5
- UFDGPOXUTKMJHQ-UHFFFAOYSA-N n-(1-acetyl-3,3-dimethyl-2h-indol-6-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC3=CC=C4C(C)(C)CN(C4=C3)C(=O)C)=CC=C21 UFDGPOXUTKMJHQ-UHFFFAOYSA-N 0.000 claims description 5
- FVRUYZXEAVYBNU-UHFFFAOYSA-N n-(2-acetyl-4,4-dimethyl-1,3-dihydroisoquinolin-7-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3C=C4CN(CC(C)(C)C4=CC=3)C(=O)C)=CC=C21 FVRUYZXEAVYBNU-UHFFFAOYSA-N 0.000 claims description 5
- QXEDXOPALNBGJA-UHFFFAOYSA-N n-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3C=C4NCC(C4=CC=3)(C)C)=CC=C21 QXEDXOPALNBGJA-UHFFFAOYSA-N 0.000 claims description 5
- CNSLKRCMYSGRPL-UHFFFAOYSA-N n-(4,4-dimethyl-2,3-dihydro-1h-isoquinolin-7-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3C=C4CNCC(C4=CC=3)(C)C)=CC=C21 CNSLKRCMYSGRPL-UHFFFAOYSA-N 0.000 claims description 5
- NTGGEYBVJKZMAE-UHFFFAOYSA-N n-(4,4-dimethyl-2,3-dihydro-1h-quinolin-7-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3C=C4NCCC(C4=CC=3)(C)C)=CC=C21 NTGGEYBVJKZMAE-UHFFFAOYSA-N 0.000 claims description 5
- QDFHXWVTGSVHGY-UHFFFAOYSA-N n-(4,4-dimethyl-2-oxo-1,3-dihydroquinolin-7-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3C=C4NC(=O)CC(C4=CC=3)(C)C)=CC=C21 QDFHXWVTGSVHGY-UHFFFAOYSA-N 0.000 claims description 5
- IUKOEGQRFWJYRS-UHFFFAOYSA-N n-(4-tert-butylphenyl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 IUKOEGQRFWJYRS-UHFFFAOYSA-N 0.000 claims description 5
- BGUVJBTYKVDAKN-UHFFFAOYSA-N n-(5,5-dimethyl-7-oxo-6,8-dihydro-1,8-naphthyridin-2-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3N=C4NC(=O)CC(C4=CC=3)(C)C)=CC=C21 BGUVJBTYKVDAKN-UHFFFAOYSA-N 0.000 claims description 5
- QBYGIMVDFAZWSF-UHFFFAOYSA-N n-(5-tert-butyl-1,2-oxazol-3-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound O1C(C(C)(C)C)=CC(NC(=O)C=2C(=NC=CC=2)NC=2C=C3C=NC=CC3=CC=2)=N1 QBYGIMVDFAZWSF-UHFFFAOYSA-N 0.000 claims description 5
- NMNURIBYRTZCEB-UHFFFAOYSA-N n-(6-tert-butylpyridin-3-yl)-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=NC(C(C)(C)C)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 NMNURIBYRTZCEB-UHFFFAOYSA-N 0.000 claims description 5
- JQDMUABLBWELTJ-UHFFFAOYSA-N n-[2-(2-aminoacetyl)-4,4-dimethyl-1,3-dihydroisoquinolin-7-yl]-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CN=CC2=CC(NC3=NC=CC=C3C(=O)NC=3C=C4CN(CC(C4=CC=3)(C)C)C(=O)CN)=CC=C21 JQDMUABLBWELTJ-UHFFFAOYSA-N 0.000 claims description 5
- RHQHOQJDKYBTBE-SANMLTNESA-N n-[3,3-dimethyl-1-[(2s)-oxolane-2-carbonyl]-2h-indol-6-yl]-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C12=CC(NC(=O)C=3C(=NC=CC=3)NC=3C=C4C=NC=CC4=CC=3)=CC=C2C(C)(C)CN1C(=O)[C@@H]1CCCO1 RHQHOQJDKYBTBE-SANMLTNESA-N 0.000 claims description 5
- WIMMDLMOPAFLOM-UHFFFAOYSA-N n-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CC(C(O)(C(F)(F)F)C(F)(F)F)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 WIMMDLMOPAFLOM-UHFFFAOYSA-N 0.000 claims description 5
- PTMIQGWFSGOMNB-UHFFFAOYSA-N n-[5-(azetidin-1-yl)pyridin-2-yl]-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C=1C=CN=C(NC=2C=C3C=NC=CC3=CC=2)C=1C(=O)NC(N=C1)=CC=C1N1CCC1 PTMIQGWFSGOMNB-UHFFFAOYSA-N 0.000 claims description 5
- CPTCWKFJRMRMPW-UHFFFAOYSA-N n-[6-(azetidin-1-yl)pyridin-3-yl]-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C=1C=CN=C(NC=2C=C3C=NC=CC3=CC=2)C=1C(=O)NC(C=N1)=CC=C1N1CCC1 CPTCWKFJRMRMPW-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- NPWMLGSDABOHTK-HNNXBMFYSA-N (2s)-2-[4-[[2-(isoquinolin-7-ylamino)pyridine-3-carbonyl]amino]phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 NPWMLGSDABOHTK-HNNXBMFYSA-N 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 4
- WUPRNILYHOSCHC-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-[3-methyl-4-(1,1,2,2,2-pentafluoroethyl)phenyl]pyridine-3-carboxamide Chemical compound C1=C(C(F)(F)C(F)(F)F)C(C)=CC(NC(=O)C=2C(=NC=CC=2)NC=2C=C3C=NC=CC3=CC=2)=C1 WUPRNILYHOSCHC-UHFFFAOYSA-N 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 4
- 230000000340 anti-metabolite Effects 0.000 claims description 4
- 229940100197 antimetabolite Drugs 0.000 claims description 4
- 239000002256 antimetabolite Substances 0.000 claims description 4
- 229940077388 benzenesulfonate Drugs 0.000 claims description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 230000017531 blood circulation Effects 0.000 claims description 4
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 claims description 4
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 4
- 229940058213 medronate Drugs 0.000 claims description 4
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- KZCPHXHBHXRAEB-UHFFFAOYSA-N n-[4-(1,1,1,3,3,3-hexafluoro-2-methoxypropan-2-yl)phenyl]-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=CC(C(OC)(C(F)(F)F)C(F)(F)F)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 KZCPHXHBHXRAEB-UHFFFAOYSA-N 0.000 claims description 4
- OVEQFNZUXGSCFP-UHFFFAOYSA-N n-[4-chloro-3-(trifluoromethyl)phenyl]-2-(isoquinolin-7-ylamino)pyridine-3-carboxamide Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(NC(=O)C=2C(=NC=CC=2)NC=2C=C3C=NC=CC3=CC=2)=C1 OVEQFNZUXGSCFP-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 4
- 229960001860 salicylate Drugs 0.000 claims description 4
- NPWMLGSDABOHTK-OAHLLOKOSA-N (2r)-2-[4-[[2-(isoquinolin-7-ylamino)pyridine-3-carbonyl]amino]phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 NPWMLGSDABOHTK-OAHLLOKOSA-N 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- LGUFRZSXVZRZQI-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-(3-methyl-4-propan-2-ylphenyl)pyridine-3-carboxamide Chemical compound C1=C(C)C(C(C)C)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 LGUFRZSXVZRZQI-UHFFFAOYSA-N 0.000 claims description 3
- YIEVALXERPLBDY-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-(3-methyl-4-pyrrolidin-1-ylphenyl)pyridine-3-carboxamide Chemical compound CC1=CC(NC(=O)C=2C(=NC=CC=2)NC=2C=C3C=NC=CC3=CC=2)=CC=C1N1CCCC1 YIEVALXERPLBDY-UHFFFAOYSA-N 0.000 claims description 3
- OYGNEUUTBZHCGO-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-(4-propan-2-ylphenyl)pyridine-3-carboxamide Chemical compound C1=CC(C(C)C)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 OYGNEUUTBZHCGO-UHFFFAOYSA-N 0.000 claims description 3
- UOMTVJCDSUFYIM-UHFFFAOYSA-N 2-(isoquinolin-7-ylamino)-n-[4-(trifluoromethoxy)phenyl]pyridine-3-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)C1=CC=CN=C1NC1=CC=C(C=CN=C2)C2=C1 UOMTVJCDSUFYIM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
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| PCT/US2005/025800 WO2006012374A1 (en) | 2004-07-22 | 2005-07-20 | Substituted aryl-amine derivatives and methods of use |
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| CA (1) | CA2571627C (enExample) |
| DE (1) | DE602005016261D1 (enExample) |
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| JP2016516812A (ja) * | 2013-04-19 | 2016-06-09 | リサーチ コーポレーション ファウンデーション オブ ヨンナム ユニバーシティ | アミドピリジンオール誘導体またはその薬剤学的に許容可能な塩、及びそれを有効成分として含有する薬学組成物 |
| JP2022508277A (ja) * | 2018-11-28 | 2022-01-19 | バイエル、アクチエンゲゼルシャフト | 殺真菌性化合物としてのピリダジン(チオ)アミド |
| JP2022104792A (ja) * | 2020-12-29 | 2022-07-11 | ヒュサイオン カンパニー リミテッド | ピペルロングミン系化合物及びこれを含む免疫調節剤 |
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| US7507748B2 (en) * | 2004-07-22 | 2009-03-24 | Amgen Inc. | Substituted aryl-amine derivatives and methods of use |
| EP1781284B1 (en) * | 2004-08-25 | 2010-10-13 | The University of Chicago | Use of the combination comprising temozolomide and tnf-alpha for treating glioblastoma |
| US8586571B2 (en) | 2007-10-18 | 2013-11-19 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| WO2011161217A2 (en) | 2010-06-23 | 2011-12-29 | Palacký University in Olomouc | Targeting of vegfr2 |
| RU2535671C1 (ru) * | 2010-10-18 | 2014-12-20 | Раквалиа Фарма Инк. | Производные ариламидов в качестве блокаторов ttx-s |
| WO2012111016A1 (en) * | 2011-02-14 | 2012-08-23 | Council Of Scientific & Industrial Research | 2-anilino nicotinyl linked 2-amino benzothiazole conjugates and process for the preparation thereof |
| EP2714941A4 (en) * | 2011-05-24 | 2014-12-03 | Wistar Inst | COMPOSITIONS AND METHODS FOR MODULATING THE EFFECT OF THE EPSTEIN-BARR NUCLEAR ANTIGEN 1 |
| KR101412794B1 (ko) | 2011-07-27 | 2014-07-01 | 보령제약 주식회사 | 혈관생성억제 작용을 갖는 신규한 화합물, 이의 제조방법 및 이를 포함하는 약학적 조성물 |
| UA112897C2 (uk) | 2012-05-09 | 2016-11-10 | Байєр Фарма Акцієнгезелльшафт | Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань |
| WO2014058729A1 (en) * | 2012-10-09 | 2014-04-17 | California Institute Of Technology | In vivo and in vitro carbene insertion and nitrene transfer reactions catalyzed by heme enzymes |
| EP2906518A4 (en) | 2012-10-09 | 2016-07-27 | California Inst Of Techn | CYCLES CATALYZED IN VIVO AND IN VITRO OLEFINCYCLOPROPANATION |
| US9399762B2 (en) | 2014-02-18 | 2016-07-26 | California Institute Of Technology | Methods and systems for sulfimidation or sulfoximidation of organic molecules |
| JP6800872B2 (ja) | 2015-03-06 | 2020-12-16 | ファーマケア,インク. | リシルオキシダーゼ様2阻害剤とその使用 |
| CN107592861B (zh) | 2015-03-06 | 2021-06-08 | 法玛克亚公司 | 氟化赖氨酰氧化酶样2抑制剂及其用途 |
| EP3101012A1 (en) | 2015-06-04 | 2016-12-07 | Bayer Pharma Aktiengesellschaft | New gadolinium chelate compounds for use in magnetic resonance imaging |
| US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
| CN105837452B (zh) * | 2016-04-05 | 2019-01-29 | 田志高 | 2-甲基-5-硝基苯酚生产工艺 |
| MA46204A (fr) | 2016-09-07 | 2021-03-17 | Pharmakea Inc | Formes cristallines d'un inhibiteur de lysyl oxydase de type 2 et leurs procédés de fabrication |
| BR112019004513A2 (pt) | 2016-09-07 | 2019-06-18 | Pharmakea Inc | usos de um inibidor de lisil oxidase-like 2 |
| CN107245075B (zh) * | 2017-08-04 | 2020-03-17 | 西安交通大学 | 2,4,6-三取代吡啶并[3,4-d]嘧啶类化合物及其盐和应用 |
| RS66798B1 (sr) * | 2018-03-09 | 2025-06-30 | Recurium Ip Holdings Llc | Supstituisani 1,2-dihidro-3h-pirazolo[3,4-d]pirimidin-3-oni |
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| EA003528B1 (ru) | 1997-04-04 | 2003-06-26 | Пфайзер Продактс Инк. | Производные никотинамида, их применение, фармацевтическая композиция, способ лечения и способ ингибирования изоферментов фдэ4 d |
| US20020111495A1 (en) | 1997-04-04 | 2002-08-15 | Pfizer Inc. | Nicotinamide acids, amides, and their mimetics active as inhibitors of PDE4 isozymes |
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| IL135536A0 (en) | 1997-12-19 | 2001-05-20 | Schering Ag | Ortho-anthranilamide derivatives and pharmaceutical compositions containing the same |
| CA2374851A1 (en) | 1999-06-07 | 2000-12-14 | Immunex Corporation | Tek antagonists |
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| CA2395191A1 (en) | 1999-12-23 | 2001-06-28 | Tedman Ehlers | Chalcone and its analogs as agents for the inhibition of angiogenesis and related disease states |
| JP2003520854A (ja) | 2000-01-27 | 2003-07-08 | サイトビア インコーポレイテッド | カスパーゼのアクチベーターおよびアポトーシスのインデューサーとしての置換ニコチンアミドおよび類似物およびそれらの使用 |
| GB0001930D0 (en) | 2000-01-27 | 2000-03-22 | Novartis Ag | Organic compounds |
| EP1259595B1 (en) | 2000-02-25 | 2007-04-04 | Immunex Corporation | Integrin antagonists |
| WO2001078648A2 (en) | 2000-04-17 | 2001-10-25 | Dong Wha Pharm. Ind. Co., Ltd. | 6-methylnicotinamide derivatives as antiviral agents |
| DE10023492A1 (de) | 2000-05-09 | 2001-11-22 | Schering Ag | Aza- und Polyazanthranylamide und deren Verwendung als Arzneimittel |
| DE10023484A1 (de) | 2000-05-09 | 2001-11-22 | Schering Ag | Anthranylamide und deren Verwendung als Arzneimittel |
| MX242553B (es) | 2000-10-20 | 2006-12-06 | Eisai Co Ltd | Derivados aromaticos que contienen nitrogeno. |
| US7102009B2 (en) | 2001-01-12 | 2006-09-05 | Amgen Inc. | Substituted amine derivatives and methods of use |
| US7307088B2 (en) | 2002-07-09 | 2007-12-11 | Amgen Inc. | Substituted anthranilic amide derivatives and methods of use |
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| US7129252B2 (en) | 2003-06-16 | 2006-10-31 | Guoqing P Chen | Six membered amino-amide derivatives an angiogenisis inhibitors |
| US7507748B2 (en) * | 2004-07-22 | 2009-03-24 | Amgen Inc. | Substituted aryl-amine derivatives and methods of use |
-
2005
- 2005-07-19 US US11/185,556 patent/US7507748B2/en not_active Expired - Fee Related
- 2005-07-20 AT AT05791799T patent/ATE440834T1/de not_active IP Right Cessation
- 2005-07-20 AU AU2005267161A patent/AU2005267161B2/en not_active Ceased
- 2005-07-20 EP EP05791799A patent/EP1773817B1/en not_active Expired - Lifetime
- 2005-07-20 CA CA2571627A patent/CA2571627C/en not_active Expired - Fee Related
- 2005-07-20 MX MX2007000672A patent/MX2007000672A/es active IP Right Grant
- 2005-07-20 ES ES05791799T patent/ES2331318T3/es not_active Expired - Lifetime
- 2005-07-20 WO PCT/US2005/025800 patent/WO2006012374A1/en not_active Ceased
- 2005-07-20 JP JP2007522715A patent/JP2008507539A/ja not_active Withdrawn
- 2005-07-20 DE DE602005016261T patent/DE602005016261D1/de not_active Expired - Lifetime
-
2009
- 2009-01-29 US US12/322,361 patent/US8247430B2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016516812A (ja) * | 2013-04-19 | 2016-06-09 | リサーチ コーポレーション ファウンデーション オブ ヨンナム ユニバーシティ | アミドピリジンオール誘導体またはその薬剤学的に許容可能な塩、及びそれを有効成分として含有する薬学組成物 |
| JP2022508277A (ja) * | 2018-11-28 | 2022-01-19 | バイエル、アクチエンゲゼルシャフト | 殺真菌性化合物としてのピリダジン(チオ)アミド |
| JP7578593B2 (ja) | 2018-11-28 | 2024-11-06 | バイエル、アクチエンゲゼルシャフト | 殺真菌性化合物としてのピリダジン(チオ)アミド |
| JP2022104792A (ja) * | 2020-12-29 | 2022-07-11 | ヒュサイオン カンパニー リミテッド | ピペルロングミン系化合物及びこれを含む免疫調節剤 |
| US11878971B2 (en) | 2020-12-29 | 2024-01-23 | Huscion Co., Ltd. | Piperlongumine-based compound and immuno regulator comprising the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2571627A1 (en) | 2006-02-02 |
| US7507748B2 (en) | 2009-03-24 |
| AU2005267161B2 (en) | 2009-02-12 |
| WO2006012374A1 (en) | 2006-02-02 |
| AU2005267161A1 (en) | 2006-02-02 |
| ES2331318T3 (es) | 2009-12-29 |
| US20060040966A1 (en) | 2006-02-23 |
| EP1773817B1 (en) | 2009-08-26 |
| US8247430B2 (en) | 2012-08-21 |
| MX2007000672A (es) | 2007-03-08 |
| DE602005016261D1 (de) | 2009-10-08 |
| CA2571627C (en) | 2010-02-16 |
| EP1773817A1 (en) | 2007-04-18 |
| ATE440834T1 (de) | 2009-09-15 |
| US20090143355A1 (en) | 2009-06-04 |
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