ES2262899T3 - Derivados de pirazolopiridazina. - Google Patents

Info

Publication number

ES2262899T3

ES2262899T3 ES02805104T ES02805104T ES2262899T3 ES 2262899 T3 ES2262899 T3 ES 2262899T3 ES 02805104 T ES02805104 T ES 02805104T ES 02805104 T ES02805104 T ES 02805104T ES 2262899 T3 ES2262899 T3 ES 2262899T3

Authority

ES

Spain

Prior art keywords

pyridazin

alkyl

pyrazolo

pyrimidinamine

hydrogen

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.)

Expired - Lifetime

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• 150000001875 compounds Chemical class 0.000 claims abstract description 265
• -1 -NR4R5 Chemical group 0.000 claims abstract description 172
• 125000003118 aryl group Chemical group 0.000 claims abstract description 94
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 91
• 239000001257 hydrogen Substances 0.000 claims abstract description 90
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 81
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 77
• 150000002431 hydrogen Chemical group 0.000 claims abstract description 74
• 150000003839 salts Chemical class 0.000 claims abstract description 67
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 63
• 150000002367 halogens Chemical group 0.000 claims abstract description 63
• 239000012453 solvate Substances 0.000 claims abstract description 55
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 49
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 43
• 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 36
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 26
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 20
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 19
• 125000004450 alkenylene group Chemical group 0.000 claims abstract description 17
• 125000004419 alkynylene group Chemical group 0.000 claims abstract description 17
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
• 125000000732 arylene group Chemical group 0.000 claims abstract description 15
• 125000005724 cycloalkenylene group Chemical group 0.000 claims abstract description 15
• 125000002993 cycloalkylene group Chemical group 0.000 claims abstract description 15
• 125000005549 heteroarylene group Chemical group 0.000 claims abstract description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 11
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 9
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract description 9
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 146
• 125000001188 haloalkyl group Chemical group 0.000 claims description 56
• 238000000034 method Methods 0.000 claims description 41
• 125000003342 alkenyl group Chemical group 0.000 claims description 37
• 125000000304 alkynyl group Chemical group 0.000 claims description 36
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
• 238000011282 treatment Methods 0.000 claims description 35
• 206010028980 Neoplasm Diseases 0.000 claims description 27
• 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 26
• 201000011510 cancer Diseases 0.000 claims description 24
• 239000008194 pharmaceutical composition Substances 0.000 claims description 21
• 239000002253 acid Substances 0.000 claims description 20
• 125000003545 alkoxy group Chemical group 0.000 claims description 20
• 239000002585 base Substances 0.000 claims description 20
• 150000001412 amines Chemical class 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 15
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 14
• KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 239000003981 vehicle Substances 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
• 238000002360 preparation method Methods 0.000 claims description 9
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 9
• 238000002560 therapeutic procedure Methods 0.000 claims description 9
• SRXHNQITQCEZCO-UHFFFAOYSA-N 4-pyridazin-3-ylpyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N=NC=CC=2)=N1 SRXHNQITQCEZCO-UHFFFAOYSA-N 0.000 claims description 8
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
• 229960004592 isopropanol Drugs 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 5
• 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
• 230000009467 reduction Effects 0.000 claims description 4
• 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
• 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
• 230000003013 cytotoxicity Effects 0.000 claims description 3
• 231100000135 cytotoxicity Toxicity 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
• 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
• 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
• 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
• 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
• 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
• RPRZAINAFJBVOV-UHFFFAOYSA-N n-cyclopropyl-4-(2-ethylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound CCC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC1CC1 RPRZAINAFJBVOV-UHFFFAOYSA-N 0.000 claims description 3
• FAGYWTJBSZCMQC-UHFFFAOYSA-N n-cyclopropyl-4-(2-methylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound CC1=NN2N=CC=CC2=C1C(N=1)=CC=NC=1NC1CC1 FAGYWTJBSZCMQC-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• PTXSJBYEFKLJDV-UHFFFAOYSA-N n-cyclopropyl-4-(6-phenylsulfanylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(SC=4C=CC=CC=4)=NN3N=C2)=N1 PTXSJBYEFKLJDV-UHFFFAOYSA-N 0.000 claims description 3
• MFBCYZQBHGCRST-UHFFFAOYSA-N n-cyclopropyl-4-(6-propan-2-yloxypyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1=NN2N=C(OC(C)C)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 MFBCYZQBHGCRST-UHFFFAOYSA-N 0.000 claims description 3
• OAIXSJCARVACKE-UHFFFAOYSA-N n-cyclopropyl-n-methyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(C2=C3C=CC=NN3N=C2)=NC=1N(C)C1CC1 OAIXSJCARVACKE-UHFFFAOYSA-N 0.000 claims description 3
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 2
• 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 2
• 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 2
• 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 2
• AKAGBRZFDUGGEX-UHFFFAOYSA-N 4-[6-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]-n-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)C=2C=CC(F)=CC=2)=N1 AKAGBRZFDUGGEX-UHFFFAOYSA-N 0.000 claims description 2
• QTYPVJBVNHCPHH-UHFFFAOYSA-N 4-n,4-n-dimethyl-1-n-[4-(6-morpholin-4-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-yl]benzene-1,4-diamine Chemical compound C1=CC(N(C)C)=CC=C1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCOCC2)=N1 QTYPVJBVNHCPHH-UHFFFAOYSA-N 0.000 claims description 2
• 239000005711 Benzoic acid Substances 0.000 claims description 2
• ZIPPKLDBONELEH-UHFFFAOYSA-N N',N'-dimethyl-N-(4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-yl)propane-1,3-diamine methanesulfonic acid Chemical compound CS(=O)(=O)O.CN(CCCNC1=NC=CC(=N1)C=1C=NN2N=CC=CC21)C ZIPPKLDBONELEH-UHFFFAOYSA-N 0.000 claims description 2
• 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
• 235000010233 benzoic acid Nutrition 0.000 claims description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• 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 2
• 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 2
• 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 2
• RNTPQNNOOQMIBD-UHFFFAOYSA-N n-cyclopropyl-4-(6-ethenylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1=NN2N=C(C=C)C=CC2=C1C(N=1)=CC=NC=1NC1CC1 RNTPQNNOOQMIBD-UHFFFAOYSA-N 0.000 claims description 2
• RLKIXFRFDGFKOP-UHFFFAOYSA-N n-cyclopropyl-4-(6-morpholin-4-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCOCC2)=N1 RLKIXFRFDGFKOP-UHFFFAOYSA-N 0.000 claims description 2
• DVNFZJOHZGRBGM-UHFFFAOYSA-N n-cyclopropyl-4-(6-pyrrolidin-1-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)N2CCCC2)=N1 DVNFZJOHZGRBGM-UHFFFAOYSA-N 0.000 claims description 2
• ULKTXVYWINYRCP-UHFFFAOYSA-N n-cyclopropyl-4-(6-thiophen-2-ylpyrazolo[1,5-b]pyridazin-3-yl)pyrimidin-2-amine Chemical compound C1CC1NC1=NC=CC(C2=C3C=CC(=NN3N=C2)C=2SC=CC=2)=N1 ULKTXVYWINYRCP-UHFFFAOYSA-N 0.000 claims description 2
• URAYKDQWSJUBED-UHFFFAOYSA-N n-cyclopropyl-4-[6-(2-fluoropyridin-4-yl)pyrazolo[1,5-b]pyridazin-3-yl]pyrimidin-2-amine Chemical compound C1=NC(F)=CC(C2=NN3N=CC(=C3C=C2)C=2N=C(NC3CC3)N=CC=2)=C1 URAYKDQWSJUBED-UHFFFAOYSA-N 0.000 claims description 2
• RVSCHTJBVVTPSV-UHFFFAOYSA-N n-cyclopropyl-4-[6-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-3-yl]pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN2N=CC(C=3N=C(NC4CC4)N=CC=3)=C2C=C1 RVSCHTJBVVTPSV-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
• 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 7
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract description 7
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 2
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 1
• 239000007787 solid Substances 0.000 description 110
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 76
• 239000000203 mixture Substances 0.000 description 63
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
• 235000002639 sodium chloride Nutrition 0.000 description 58
• 238000006243 chemical reaction Methods 0.000 description 53
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
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