JP2008519790A - キナーゼ阻害剤としての１，４−置換ピラゾロピリミジン - Google Patents
キナーゼ阻害剤としての１，４−置換ピラゾロピリミジン Download PDFInfo
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- JP2008519790A JP2008519790A JP2007540577A JP2007540577A JP2008519790A JP 2008519790 A JP2008519790 A JP 2008519790A JP 2007540577 A JP2007540577 A JP 2007540577A JP 2007540577 A JP2007540577 A JP 2007540577A JP 2008519790 A JP2008519790 A JP 2008519790A
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- Prior art keywords
- phenyl
- pyrazolo
- amine
- methyl
- pyrimidin
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- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 315
- 238000000034 method Methods 0.000 claims abstract description 115
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 107
- 230000000694 effects Effects 0.000 claims abstract description 94
- 201000010099 disease Diseases 0.000 claims abstract description 71
- 102000001253 Protein Kinase Human genes 0.000 claims abstract description 47
- 108060006633 protein kinase Proteins 0.000 claims abstract description 47
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 claims abstract description 18
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 6
- -1 especially c-Abl Proteins 0.000 claims description 177
- 125000000217 alkyl group Chemical group 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 150000003839 salts Chemical class 0.000 claims description 75
- 239000001257 hydrogen Substances 0.000 claims description 72
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 49
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 49
- 125000005843 halogen group Chemical group 0.000 claims description 45
- 238000006243 chemical reaction Methods 0.000 claims description 39
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 208000035475 disorder Diseases 0.000 claims description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 125000003107 substituted aryl group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
- 241001465754 Metazoa Species 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- 230000001225 therapeutic effect Effects 0.000 claims description 20
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims description 19
- 108060006706 SRC Proteins 0.000 claims description 19
- 102000001332 SRC Human genes 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 102000050554 Eph Family Receptors Human genes 0.000 claims description 16
- 108091008815 Eph receptors Proteins 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000004434 sulfur atom Chemical group 0.000 claims description 14
- 108700020796 Oncogene Proteins 0.000 claims description 13
- 102000052575 Proto-Oncogene Human genes 0.000 claims description 13
- 108700020978 Proto-Oncogene Proteins 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 108010058765 Oncogene Protein pp60(v-src) Proteins 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 125000004193 piperazinyl group Chemical group 0.000 claims description 11
- 230000002062 proliferating effect Effects 0.000 claims description 11
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 125000004161 1,4-diazepinyl group Chemical group 0.000 claims description 10
- 125000002785 azepinyl group Chemical group 0.000 claims description 10
- 125000002393 azetidinyl group Chemical group 0.000 claims description 10
- 125000004069 aziridinyl group Chemical group 0.000 claims description 10
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 claims description 10
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 9
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 102100031983 Ephrin type-B receptor 4 Human genes 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- LXHHJLJPJDCURN-UHFFFAOYSA-N 1-(4-bromophenyl)-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC=CC=C1NC1=NC=NC2=C1C=NN2C1=CC=C(Br)C=C1 LXHHJLJPJDCURN-UHFFFAOYSA-N 0.000 claims description 4
- 241001377010 Pila Species 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- NEVKWSNYPQZDQX-UHFFFAOYSA-N 1-(4-methoxyphenyl)-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC=NC(NC=3C(=CC=CC=3)C)=C2C=N1 NEVKWSNYPQZDQX-UHFFFAOYSA-N 0.000 claims description 3
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- OTUFKAPFRAKZOU-UHFFFAOYSA-N n-(5-fluoro-2-methylphenyl)-1-(4-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC=NC(NC=3C(=CC=C(F)C=3)C)=C2C=N1 OTUFKAPFRAKZOU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 3
- PTAVYJBCZAPEBZ-UHFFFAOYSA-N 1-(3-methoxyphenyl)-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(N2C3=NC=NC(NC=4C(=CC=CC=4)C)=C3C=N2)=C1 PTAVYJBCZAPEBZ-UHFFFAOYSA-N 0.000 claims description 2
- PLCARNJOQDDPQG-UHFFFAOYSA-N 1-[4-(4-methyl-1,4-diazepan-1-yl)phenyl]-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=CC=4)C)=C3C=N2)C=C1 PLCARNJOQDDPQG-UHFFFAOYSA-N 0.000 claims description 2
- KYWKYEDMARGTEE-HXUWFJFHSA-N 1-[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=CC=4)C)=C3C=N2)C=C1 KYWKYEDMARGTEE-HXUWFJFHSA-N 0.000 claims description 2
- TVWFORVJOUCMDU-OAQYLSRUSA-N 1-[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(4-fluoro-2,6-dimethylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4C)C)=C3C=N2)C=C1 TVWFORVJOUCMDU-OAQYLSRUSA-N 0.000 claims description 2
- QPKJZZHUKMYDIO-HXUWFJFHSA-N 1-[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(4-fluoro-2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4)C)=C3C=N2)C=C1 QPKJZZHUKMYDIO-HXUWFJFHSA-N 0.000 claims description 2
- XOPGFBHSOGPXQT-HXUWFJFHSA-N 1-[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(5-fluoro-2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=C(F)C=4)C)=C3C=N2)C=C1 XOPGFBHSOGPXQT-HXUWFJFHSA-N 0.000 claims description 2
- KYWKYEDMARGTEE-FQEVSTJZSA-N 1-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=CC=4)C)=C3C=N2)C=C1 KYWKYEDMARGTEE-FQEVSTJZSA-N 0.000 claims description 2
- TVWFORVJOUCMDU-NRFANRHFSA-N 1-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(4-fluoro-2,6-dimethylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4C)C)=C3C=N2)C=C1 TVWFORVJOUCMDU-NRFANRHFSA-N 0.000 claims description 2
- QPKJZZHUKMYDIO-FQEVSTJZSA-N 1-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(4-fluoro-2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4)C)=C3C=N2)C=C1 QPKJZZHUKMYDIO-FQEVSTJZSA-N 0.000 claims description 2
- XOPGFBHSOGPXQT-FQEVSTJZSA-N 1-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]-n-(5-fluoro-2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=C(F)C=4)C)=C3C=N2)C=C1 XOPGFBHSOGPXQT-FQEVSTJZSA-N 0.000 claims description 2
- STTLIMCCZAVEAI-UHFFFAOYSA-N 1-[4-[4-(diethylamino)piperidin-1-yl]phenyl]-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CC(N(CC)CC)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=CC=4)C)=C3C=N2)C=C1 STTLIMCCZAVEAI-UHFFFAOYSA-N 0.000 claims description 2
- VVPCINGESYBUDF-UHFFFAOYSA-N 1-[4-[4-(diethylamino)piperidin-1-yl]phenyl]-n-(4-fluoro-2,6-dimethylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CC(N(CC)CC)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4C)C)=C3C=N2)C=C1 VVPCINGESYBUDF-UHFFFAOYSA-N 0.000 claims description 2
- RAIDNOWHKFNFBB-UHFFFAOYSA-N 1-[4-[4-(diethylamino)piperidin-1-yl]phenyl]-n-(5-fluoro-2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical class C1CC(N(CC)CC)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=C(F)C=4)C)=C3C=N2)C=C1 RAIDNOWHKFNFBB-UHFFFAOYSA-N 0.000 claims description 2
- XVUXZMNJKZLDKD-UHFFFAOYSA-N 1-[4-[4-(dipropylamino)piperidin-1-yl]phenyl]-n-(2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CC(N(CCC)CCC)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=CC=4)C)=C3C=N2)C=C1 XVUXZMNJKZLDKD-UHFFFAOYSA-N 0.000 claims description 2
- KYOZWCSXZJWVLH-UHFFFAOYSA-N 1-[4-[4-(dipropylamino)piperidin-1-yl]phenyl]-n-(4-fluoro-2-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CC(N(CCC)CCC)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4)C)=C3C=N2)C=C1 KYOZWCSXZJWVLH-UHFFFAOYSA-N 0.000 claims description 2
- PECBBVVSFRZZQH-UHFFFAOYSA-N 6-[3-(dimethylamino)propyl]-n-(2,6-dimethylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C=12C=NN(C=3C=CC=CC=3)C2=NC(CCCN(C)C)=NC=1NC1=C(C)C=CC=C1C PECBBVVSFRZZQH-UHFFFAOYSA-N 0.000 claims description 2
- SWJUELRUGYLLPX-UHFFFAOYSA-N 6-[3-(dimethylamino)propyl]-n-(2-methylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C=12C=NN(C=3C=CC=CC=3)C2=NC(CCCN(C)C)=NC=1NC1=CC=CC=C1C SWJUELRUGYLLPX-UHFFFAOYSA-N 0.000 claims description 2
- LRSPQPJJXJVMGW-UHFFFAOYSA-N 6-methyl-n-(2-methylphenyl)-1-[3-(4-methylpiperazin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC=CC(N2C3=NC(C)=NC(NC=4C(=CC=CC=4)C)=C3C=N2)=C1 LRSPQPJJXJVMGW-UHFFFAOYSA-N 0.000 claims description 2
- CMNDCBIFZSELPL-UHFFFAOYSA-N 6-methyl-n-(2-methylphenyl)-1-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC=C(N2C3=NC(C)=NC(NC=4C(=CC=CC=4)C)=C3C=N2)C=C1 CMNDCBIFZSELPL-UHFFFAOYSA-N 0.000 claims description 2
- NGDTXTYEHLAOFU-UHFFFAOYSA-N 6-methyl-n-(2-methylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC=CC=C1NC1=NC(C)=NC2=C1C=NN2C1=CC=CC=C1 NGDTXTYEHLAOFU-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 2
- HSQBWCUIAJYDBO-UHFFFAOYSA-N n',n'-dimethyl-n-[4-[4-(2-methylanilino)pyrazolo[3,4-d]pyrimidin-1-yl]phenyl]ethane-1,2-diamine Chemical compound C1=CC(NCCN(C)C)=CC=C1N1C2=NC=NC(NC=3C(=CC=CC=3)C)=C2C=N1 HSQBWCUIAJYDBO-UHFFFAOYSA-N 0.000 claims description 2
- UJABTMNLNHAXGJ-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-(3-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(N2C3=NC=NC(NC=4C(=CC=CC=4C)C)=C3C=N2)=C1 UJABTMNLNHAXGJ-UHFFFAOYSA-N 0.000 claims description 2
- YCVUOIXNXLTWDT-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-(4-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC=NC(NC=3C(=CC=CC=3C)C)=C2C=N1 YCVUOIXNXLTWDT-UHFFFAOYSA-N 0.000 claims description 2
- ANYQRKAGBILOFB-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-[3-(4-methylpiperazin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC=CC(N2C3=NC=NC(NC=4C(=CC=CC=4C)C)=C3C=N2)=C1 ANYQRKAGBILOFB-UHFFFAOYSA-N 0.000 claims description 2
- UYZYWKQEPGKFSS-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC=CC=4C)C)=C3C=N2)C=C1 UYZYWKQEPGKFSS-UHFFFAOYSA-N 0.000 claims description 2
- YZSCAIVAROZMMD-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-[4-(4-morpholin-4-ylpiperidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(C)=C1NC1=NC=NC2=C1C=NN2C1=CC=C(N2CCC(CC2)N2CCOCC2)C=C1 YZSCAIVAROZMMD-UHFFFAOYSA-N 0.000 claims description 2
- YHOOFFGHGKFSSD-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-[4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(C)=C1NC1=NC=NC2=C1C=NN2C1=CC=C(N2CCC(CC2)N2CCCC2)C=C1 YHOOFFGHGKFSSD-UHFFFAOYSA-N 0.000 claims description 2
- VBPYYEWVIMVIDY-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-[4-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCC1N1CCN(C=2C=CC(=CC=2)N2C3=NC=NC(NC=4C(=CC=CC=4C)C)=C3C=N2)CC1 VBPYYEWVIMVIDY-UHFFFAOYSA-N 0.000 claims description 2
- UFRSWHYPQXDDPS-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1CCN(C=2C=CC(=CC=2)N2C3=NC=NC(NC=4C(=CC=CC=4C)C)=C3C=N2)CC1 UFRSWHYPQXDDPS-UHFFFAOYSA-N 0.000 claims description 2
- UTRRBNFCMUJPQL-UHFFFAOYSA-N n-(2-chloro-4-fluorophenyl)-1-[4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC(F)=CC=C1NC1=NC=NC2=C1C=NN2C1=CC=C(N2CCC(CC2)N2CCCC2)C=C1 UTRRBNFCMUJPQL-UHFFFAOYSA-N 0.000 claims description 2
- RZBHKDAWWCLQPS-GOSISDBHSA-N n-(2-chloro-4-fluorophenyl)-1-[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4)Cl)=C3C=N2)C=C1 RZBHKDAWWCLQPS-GOSISDBHSA-N 0.000 claims description 2
- RZBHKDAWWCLQPS-SFHVURJKSA-N n-(2-chloro-4-fluorophenyl)-1-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=C(N2C3=NC=NC(NC=4C(=CC(F)=CC=4)Cl)=C3C=N2)C=C1 RZBHKDAWWCLQPS-SFHVURJKSA-N 0.000 claims description 2
- NAFKUFNOOOUZBN-UHFFFAOYSA-N n-(2-chloro-4-fluorophenyl)-1-[4-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]phenyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCC1N1CCN(C=2C=CC(=CC=2)N2C3=NC=NC(NC=4C(=CC(F)=CC=4)Cl)=C3C=N2)CC1 NAFKUFNOOOUZBN-UHFFFAOYSA-N 0.000 claims description 2
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Landscapes
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| GB0425035A GB0425035D0 (en) | 2004-11-12 | 2004-11-12 | Organic compounds |
| PCT/EP2005/012045 WO2006050946A1 (en) | 2004-11-12 | 2005-11-10 | 1,4 substituted pyrazolopyrimidines as kinase inhibitors |
Publications (2)
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| JP2008519790A true JP2008519790A (ja) | 2008-06-12 |
| JP2008519790A5 JP2008519790A5 (enExample) | 2008-12-25 |
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| EP (1) | EP1812441A1 (enExample) |
| JP (1) | JP2008519790A (enExample) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011004610A1 (ja) * | 2009-07-10 | 2011-01-13 | 大鵬薬品工業株式会社 | アザ二環式化合物又はその塩 |
| JP2013542966A (ja) * | 2010-11-19 | 2013-11-28 | エフ．ホフマン−ラ ロシュ アーゲー | ピラゾロピリジンならびにｔｙｋ２阻害剤としてのピラゾロピリジン及びそれらの使用 |
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| EP1599468B1 (en) | 2003-01-14 | 2007-10-03 | Arena Pharmaceuticals, Inc. | 1,2,3-trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| WO2006068760A2 (en) | 2004-11-19 | 2006-06-29 | The Regents Of The University Of California | Anti-inflammatory pyrazolopyrimidines |
| AU2005323311A1 (en) * | 2004-11-23 | 2006-07-13 | Venkateswara Rao Batchu | Novel bicyclic heterocyclic compounds, process for their preparation and compositions containing them |
| DOP2006000009A (es) * | 2005-01-13 | 2006-08-15 | Arena Pharm Inc | Procedimiento para preparar eteres de pirazolo [3,4-d] pirimidina |
| CA2909277A1 (en) | 2006-04-04 | 2007-10-11 | Kevan M. Shokat | Kinase antagonists |
| US8093259B2 (en) | 2006-05-25 | 2012-01-10 | Novartis Ag | 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-N-[5-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)phenyl]-benzamide for treatment of melanoma |
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| TW200840581A (en) * | 2007-02-28 | 2008-10-16 | Astrazeneca Ab | Novel pyrimidine derivatives |
| US20120101114A1 (en) | 2007-03-28 | 2012-04-26 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| WO2009046448A1 (en) | 2007-10-04 | 2009-04-09 | Intellikine, Inc. | Chemical entities and therapeutic uses thereof |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| DK2240451T3 (da) | 2008-01-04 | 2017-11-20 | Intellikine Llc | Isoquinolinonderivater substitueret med en purin, der er anvendelig som pi3k-inhibitorer |
| EP2252293B1 (en) | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
| WO2009114874A2 (en) | 2008-03-14 | 2009-09-17 | Intellikine, Inc. | Benzothiazole kinase inhibitors and methods of use |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
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| US20100015141A1 (en) * | 2008-07-21 | 2010-01-21 | Wyeth | 4-phenoxy-6-aryl-1h-pyrazolo[3,4-d]pyrimidine and n-aryl-6-aryl-1h-pyrazolo[3,4-d]pyrimidin-4-amine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
| WO2010036380A1 (en) | 2008-09-26 | 2010-04-01 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| US8697709B2 (en) * | 2008-10-16 | 2014-04-15 | The Regents Of The University Of California | Fused ring heteroaryl kinase inhibitors |
| US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
| EP2427195B1 (en) | 2009-05-07 | 2019-05-01 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
| KR101721280B1 (ko) | 2009-08-17 | 2017-03-29 | 인텔리카인, 엘엘씨 | 헤테로사이클릭 화합물 및 이의 용도 |
| WO2011047384A2 (en) | 2009-10-16 | 2011-04-21 | The Regents Of The University Of California | Methods of inhibiting ire1 |
| EP2571357B1 (en) | 2010-05-21 | 2016-07-06 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
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- 2005-11-10 EP EP05819276A patent/EP1812441A1/en not_active Withdrawn
- 2005-11-10 RU RU2007121846/04A patent/RU2007121846A/ru not_active Application Discontinuation
- 2005-11-10 US US11/718,730 patent/US20080096868A1/en not_active Abandoned
- 2005-11-10 CN CNA2005800464109A patent/CN101098873A/zh active Pending
- 2005-11-10 MX MX2007005644A patent/MX2007005644A/es not_active Application Discontinuation
- 2005-11-10 AU AU2005303965A patent/AU2005303965A1/en not_active Abandoned
- 2005-11-10 BR BRPI0517803-7A patent/BRPI0517803A/pt not_active IP Right Cessation
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- 2005-11-10 KR KR1020077010778A patent/KR20070084191A/ko not_active Withdrawn
- 2005-11-10 CA CA002585660A patent/CA2585660A1/en not_active Abandoned
- 2005-11-11 TW TW094139701A patent/TW200621783A/zh unknown
- 2005-11-11 AR ARP050104725A patent/AR051485A1/es not_active Application Discontinuation
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| WO2003099820A1 (en) * | 2002-05-20 | 2003-12-04 | Bristol-Myers Squibb Company | Pyrazolo-pyrimidine aniline compounds |
| JP2007210887A (ja) * | 2004-06-21 | 2007-08-23 | Astellas Pharma Inc | 縮合二環性ピリミジン誘導体 |
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| WO2011004610A1 (ja) * | 2009-07-10 | 2011-01-13 | 大鵬薬品工業株式会社 | アザ二環式化合物又はその塩 |
| JPWO2011004610A1 (ja) * | 2009-07-10 | 2012-12-20 | 大鵬薬品工業株式会社 | アザ二環式化合物又はその塩 |
| US8779142B2 (en) | 2009-07-10 | 2014-07-15 | Taiho Pharmaceutical Co., Ltd. | Azabicyclo compound and salt thereof |
| US9273045B2 (en) | 2009-07-10 | 2016-03-01 | Taiho Pharmaceutical Co., Ltd. | Azabicyclo compound and salt thereof |
| JP2013542966A (ja) * | 2010-11-19 | 2013-11-28 | エフ．ホフマン−ラ ロシュ アーゲー | ピラゾロピリジンならびにｔｙｋ２阻害剤としてのピラゾロピリジン及びそれらの使用 |
Also Published As
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| GT200500325A (es) | 2006-05-22 |
| US20080096868A1 (en) | 2008-04-24 |
| WO2006050946A1 (en) | 2006-05-18 |
| EP1812441A1 (en) | 2007-08-01 |
| CA2585660A1 (en) | 2006-05-18 |
| AR051485A1 (es) | 2007-01-17 |
| CN101098873A (zh) | 2008-01-02 |
| MX2007005644A (es) | 2007-06-05 |
| AU2005303965A1 (en) | 2006-05-18 |
| GB0425035D0 (en) | 2004-12-15 |
| BRPI0517803A (pt) | 2008-10-21 |
| TW200621783A (en) | 2006-07-01 |
| RU2007121846A (ru) | 2008-12-20 |
| KR20070084191A (ko) | 2007-08-24 |
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