JP2005524609A - ピラゾロピリダジン誘導体 - Google Patents

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Publication number

JP2005524609A

JP2005524609A JP2003552768A JP2003552768A JP2005524609A JP 2005524609 A JP2005524609 A JP 2005524609A JP 2003552768 A JP2003552768 A JP 2003552768A JP 2003552768 A JP2003552768 A JP 2003552768A JP 2005524609 A JP2005524609 A JP 2005524609A

Authority

JP

Japan

Prior art keywords

pyridazin

alkyl

pyrazolo

hydrogen

pyrimidinamine

Prior art date

2001-12-17

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.)

Pending

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• NMEPLWZDUIIAAC-UHFFFAOYSA-N 1h-pyrazolo[4,3-c]pyridazine Chemical class C1=NN=C2C=NNC2=C1 NMEPLWZDUIIAAC-UHFFFAOYSA-N 0.000 title 1
• 238000000034 method Methods 0.000 claims abstract description 57
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 201000010099 disease Diseases 0.000 claims abstract description 22
• 150000001875 compounds Chemical class 0.000 claims description 269
• -1 -NR 4 R 5 Chemical group 0.000 claims description 166
• 239000001257 hydrogen Substances 0.000 claims description 97
• 229910052739 hydrogen Inorganic materials 0.000 claims description 97
• 125000003118 aryl group Chemical group 0.000 claims description 92
• 125000000623 heterocyclic group Chemical group 0.000 claims description 83
• 125000001072 heteroaryl group Chemical group 0.000 claims description 78
• 150000002431 hydrogen Chemical class 0.000 claims description 76
• 150000003839 salts Chemical class 0.000 claims description 71
• 229910052736 halogen Inorganic materials 0.000 claims description 66
• 150000002367 halogens Chemical class 0.000 claims description 65
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 63
• 239000012453 solvate Substances 0.000 claims description 59
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 49
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 45
• 230000000694 effects Effects 0.000 claims description 39
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 34
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 34
• 108091007914 CDKs Proteins 0.000 claims description 33
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 32
• 206010028980 Neoplasm Diseases 0.000 claims description 26
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
• 201000011510 cancer Diseases 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
• 239000003795 chemical substances by application Substances 0.000 claims description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• 239000002585 base Substances 0.000 claims description 19
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 claims description 18
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 claims description 18
• 241000124008 Mammalia Species 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 claims description 16
• 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 claims description 16
• 125000002947 alkylene group Chemical group 0.000 claims description 16
• 150000001412 amines Chemical class 0.000 claims description 16
• 125000004450 alkenylene group Chemical group 0.000 claims description 15
• 125000004419 alkynylene group Chemical group 0.000 claims description 15
• 239000002246 antineoplastic agent Substances 0.000 claims description 15
• 125000000732 arylene group Chemical group 0.000 claims description 14
• 125000005724 cycloalkenylene group Chemical group 0.000 claims description 14
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 14
• 125000005549 heteroarylene group Chemical group 0.000 claims description 14
• 102000009465 Growth Factor Receptors Human genes 0.000 claims description 12
• 108010009202 Growth Factor Receptors Proteins 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 10
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 10
• 229940034982 antineoplastic agent Drugs 0.000 claims description 10
• 231100000433 cytotoxic Toxicity 0.000 claims description 10
• 230000001472 cytotoxic effect Effects 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 230000001404 mediated effect Effects 0.000 claims description 10
• KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• XNSUDGUHSLGJCZ-UHFFFAOYSA-N pyrazolo[1,5-b]pyridazin-6-yl trifluoromethanesulfonate Chemical compound N1=CC=C2N1N=C(C=C2)OS(=O)(=O)C(F)(F)F XNSUDGUHSLGJCZ-UHFFFAOYSA-N 0.000 claims description 9
• 238000002560 therapeutic procedure Methods 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
• 229940124597 therapeutic agent Drugs 0.000 claims description 6
• 102000001301 EGF receptor Human genes 0.000 claims description 5
• 108060006698 EGF receptor Proteins 0.000 claims description 5
• 108091008605 VEGF receptors Proteins 0.000 claims description 5
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 5
• 208000037888 epithelial cell injury Diseases 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• XKYJKKJKDAGKNZ-UHFFFAOYSA-N 3-[2-(cyclopropylamino)pyrimidin-4-yl]-7h-pyrazolo[1,5-b]pyridazin-6-one Chemical compound C1=NN2N=C(O)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 XKYJKKJKDAGKNZ-UHFFFAOYSA-N 0.000 claims description 4
• 108091008606 PDGF receptors Proteins 0.000 claims description 4
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• ONTYJGWYVMEOIF-UHFFFAOYSA-N n-(4-chlorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 ONTYJGWYVMEOIF-UHFFFAOYSA-N 0.000 claims description 4
• OJNPXUBDVGTOJJ-UHFFFAOYSA-N n-cyclopropyl-4-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1=NN2N=C(OC)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 OJNPXUBDVGTOJJ-UHFFFAOYSA-N 0.000 claims description 4
• CAGHIASAHLPQMS-UHFFFAOYSA-N n-cyclopropyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 CAGHIASAHLPQMS-UHFFFAOYSA-N 0.000 claims description 4
• LIYXXFOSHNQSRD-UHFFFAOYSA-N n-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1NC1=CC=CC=C1 LIYXXFOSHNQSRD-UHFFFAOYSA-N 0.000 claims description 4
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 3
• GBRORGYPYNNDGL-UHFFFAOYSA-N 1-(dimethylamino)-3-[4-[[4-(6-morpholin-4-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-yl]amino]phenoxy]propan-2-ol Chemical compound C1=CC(OCC(O)CN(C)C)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCOCC2)=N1 GBRORGYPYNNDGL-UHFFFAOYSA-N 0.000 claims description 3
• PSTOACKLPREGGX-UHFFFAOYSA-N 1-[3-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]propyl]pyrrolidin-2-one Chemical compound O=C1CCCN1CCCNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 PSTOACKLPREGGX-UHFFFAOYSA-N 0.000 claims description 3
• CWRTWFWDDAJOMG-UHFFFAOYSA-N 3-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzonitrile Chemical compound N#CC1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 CWRTWFWDDAJOMG-UHFFFAOYSA-N 0.000 claims description 3
• FLUPOKVTJQLXSE-UHFFFAOYSA-N 4-(2-butylpyrazolo[1,5-b]pyridazin-3-yl)-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound CCCCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 FLUPOKVTJQLXSE-UHFFFAOYSA-N 0.000 claims description 3
• DKXUHTCPDJKABE-UHFFFAOYSA-N 4-(2-butylpyrazolo[1,5-b]pyridazin-3-yl)-n-cyclopropylpyrimidin-2-amine Chemical compound CCCCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC1CC1 DKXUHTCPDJKABE-UHFFFAOYSA-N 0.000 claims description 3
• RBIONWHBBUZDRJ-UHFFFAOYSA-N 4-(2-ethylpyrazolo[1,5-b]pyridazin-3-yl)-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound CCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 RBIONWHBBUZDRJ-UHFFFAOYSA-N 0.000 claims description 3
• CEOSCLCDTBXJBH-UHFFFAOYSA-N 4-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound C1=NN2N=C(OC)C=CC2=C1C(N=1)=CC=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 CEOSCLCDTBXJBH-UHFFFAOYSA-N 0.000 claims description 3
• QKNZQSYOXRAXPX-UHFFFAOYSA-N 4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 QKNZQSYOXRAXPX-UHFFFAOYSA-N 0.000 claims description 3
• VSZVMUGJWVQEOS-UHFFFAOYSA-N 4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 VSZVMUGJWVQEOS-UHFFFAOYSA-N 0.000 claims description 3
• YRSCDRTXWYUNBB-UHFFFAOYSA-N 4-[(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)amino]benzonitrile Chemical compound C1=CC(C#N)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 YRSCDRTXWYUNBB-UHFFFAOYSA-N 0.000 claims description 3
• NZEMZNIMMYPXRT-UHFFFAOYSA-N 4-[6-(2-chlorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]-n-cyclopropylpyrimidin-2-amine Chemical compound ClC1=CC=CC=C1C1=NN2N=CC(C=3N=C(NC4CC4)N=CC=3)=C2C=C1 NZEMZNIMMYPXRT-UHFFFAOYSA-N 0.000 claims description 3
• VHNFQSZQXINXSV-UHFFFAOYSA-N 4-[6-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]-n-(4-methoxyphenyl)pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)C=2C=CC(F)=CC=2)=N1 VHNFQSZQXINXSV-UHFFFAOYSA-N 0.000 claims description 3
• JOSDAWJORYYQIX-UHFFFAOYSA-N 4-pyrazolo[1,5-b]pyridazin-3-yl-n-(2,2,2-trifluoroethyl)pyrimidin-2-amine Chemical compound FC(F)(F)CNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 JOSDAWJORYYQIX-UHFFFAOYSA-N 0.000 claims description 3
• BVUVQUIZCFRPJG-UHFFFAOYSA-N 4-pyrazolo[1,5-b]pyridazin-3-yl-n-(3,4,5-trimethoxyphenyl)pyrimidin-2-amine Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 BVUVQUIZCFRPJG-UHFFFAOYSA-N 0.000 claims description 3
• VKVKUKGJNTVGRG-UHFFFAOYSA-N 4-pyrazolo[1,5-b]pyridazin-3-yl-n-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine Chemical compound FC(F)(F)C1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 VKVKUKGJNTVGRG-UHFFFAOYSA-N 0.000 claims description 3
• QGMKFIGNGWVOSE-UHFFFAOYSA-N n-(1,3-benzodioxol-5-yl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC2=CC=C3OCOC3=C2)=NC=C1 QGMKFIGNGWVOSE-UHFFFAOYSA-N 0.000 claims description 3
• WIIIHAKKVLVGJX-UHFFFAOYSA-N n-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC=2C=C3OCCOC3=CC=2)=NC=C1 WIIIHAKKVLVGJX-UHFFFAOYSA-N 0.000 claims description 3
• MYOUKRZQKNFETG-UHFFFAOYSA-N n-(2-chlorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound ClC1=CC=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 MYOUKRZQKNFETG-UHFFFAOYSA-N 0.000 claims description 3
• WKITVSVNTNNVLF-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 WKITVSVNTNNVLF-UHFFFAOYSA-N 0.000 claims description 3
• XQCOGMDQGWFCGL-UHFFFAOYSA-N n-(3-chloro-4-morpholin-4-ylphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound ClC1=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=CC=C1N1CCOCC1 XQCOGMDQGWFCGL-UHFFFAOYSA-N 0.000 claims description 3
• GBNWWXHUOVAUHT-UHFFFAOYSA-N n-(3-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound COC1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 GBNWWXHUOVAUHT-UHFFFAOYSA-N 0.000 claims description 3
• ZRWNCIWVANTRGL-UHFFFAOYSA-N n-(3-morpholin-4-ylpropyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1NCCCN1CCOCC1 ZRWNCIWVANTRGL-UHFFFAOYSA-N 0.000 claims description 3
• DENIPLMYQYHPPA-UHFFFAOYSA-N n-(3-nitrophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound [O-][N+](=O)C1=CC=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 DENIPLMYQYHPPA-UHFFFAOYSA-N 0.000 claims description 3
• SPYYDYXTVMRMEZ-UHFFFAOYSA-N n-(4-fluorophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 SPYYDYXTVMRMEZ-UHFFFAOYSA-N 0.000 claims description 3
• WPYZRTGDEWJZIP-UHFFFAOYSA-N n-(4-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 WPYZRTGDEWJZIP-UHFFFAOYSA-N 0.000 claims description 3
• ZGPQUFZDMCAFGN-UHFFFAOYSA-N n-(4-methylsulfonylphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 ZGPQUFZDMCAFGN-UHFFFAOYSA-N 0.000 claims description 3
• RVBOIHXTZQGXRV-UHFFFAOYSA-N n-(4-nitrophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 RVBOIHXTZQGXRV-UHFFFAOYSA-N 0.000 claims description 3
• PBWVSMSYTVNKEU-UHFFFAOYSA-N n-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)-1,3-benzoxazol-2-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC=2OC3=CC=CC=C3N=2)=NC=C1 PBWVSMSYTVNKEU-UHFFFAOYSA-N 0.000 claims description 3
• IWGZWYKKIFMJCQ-UHFFFAOYSA-N n-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)-3h-benzimidazol-5-amine Chemical compound C1=NN2N=CC=CC2=C1C1=NC(NC=2C=C3NC=NC3=CC=2)=NC=C1 IWGZWYKKIFMJCQ-UHFFFAOYSA-N 0.000 claims description 3
• NEWXQDRWGLAOAY-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(Cl)=CC=C1CNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 NEWXQDRWGLAOAY-UHFFFAOYSA-N 0.000 claims description 3
• SYAYIIIJZNUJPQ-UHFFFAOYSA-N n-[3-(1,3-oxazol-5-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1NC(C=1)=CC=CC=1C1=CN=CO1 SYAYIIIJZNUJPQ-UHFFFAOYSA-N 0.000 claims description 3
• PWQDMUJHLRNRTQ-UHFFFAOYSA-N n-[3-(4-methylpiperazin-1-yl)propyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1CCCNC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 PWQDMUJHLRNRTQ-UHFFFAOYSA-N 0.000 claims description 3
• NKEZMLRTYBINTC-UHFFFAOYSA-N n-[3-chloro-4-(4-methylpiperazin-1-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C(=C1)Cl)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 NKEZMLRTYBINTC-UHFFFAOYSA-N 0.000 claims description 3
• GBYZMXCPDFNNOB-UHFFFAOYSA-N n-[3-methoxy-5-(trifluoromethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound FC(F)(F)C1=CC(OC)=CC(NC=2N=C(C=CN=2)C2=C3C=CC=NN3N=C2)=C1 GBYZMXCPDFNNOB-UHFFFAOYSA-N 0.000 claims description 3
• AJAGHHORROJWRU-UHFFFAOYSA-N n-[3-methyl-4-(4-methylpiperazin-1-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C(=C1)C)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 AJAGHHORROJWRU-UHFFFAOYSA-N 0.000 claims description 3
• ZOTNSCLLJKXGSD-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C(=C1)C(F)(F)F)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 ZOTNSCLLJKXGSD-UHFFFAOYSA-N 0.000 claims description 3
• RRUGSPOGOGBMMW-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-4-(2-methylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2C)=N1 RRUGSPOGOGBMMW-UHFFFAOYSA-N 0.000 claims description 3
• AUAUBVTWWCYNPP-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 AUAUBVTWWCYNPP-UHFFFAOYSA-N 0.000 claims description 3
• DQKZVZRKPRQVEU-UHFFFAOYSA-N n-[4-(diethylaminomethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound C1=CC(CN(CC)CC)=CC=C1NC1=NC=CC(C2=C3C=CC=NN3N=C2)=N1 DQKZVZRKPRQVEU-UHFFFAOYSA-N 0.000 claims description 3
• LTNXNHHGQLANQP-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]pyrazolo[1,5-b]pyridazin-6-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(NC4CCCC4)=NN3N=C2)=N1 LTNXNHHGQLANQP-UHFFFAOYSA-N 0.000 claims description 3
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