ES2744541T3 - Inhibidores de imidazopirazina Syk - Google Patents
Inhibidores de imidazopirazina Syk Download PDFInfo
- Publication number
- ES2744541T3 ES2744541T3 ES09832229T ES09832229T ES2744541T3 ES 2744541 T3 ES2744541 T3 ES 2744541T3 ES 09832229 T ES09832229 T ES 09832229T ES 09832229 T ES09832229 T ES 09832229T ES 2744541 T3 ES2744541 T3 ES 2744541T3
- Authority
- ES
- Spain
- Prior art keywords
- indazol
- alkyl
- imidazo
- pyrazin
- amino
- 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.)
- Active
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- 239000003112 inhibitor Substances 0.000 title description 8
- ZKAMEFMDQNTDFK-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyrazine Chemical compound C1=CN=C2NC=NC2=N1 ZKAMEFMDQNTDFK-UHFFFAOYSA-N 0.000 title description 3
- -1 2,3-dimethyl-2H-indazol-6-yl Chemical group 0.000 claims abstract description 195
- 150000005829 chemical entities Chemical class 0.000 claims abstract description 103
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 125000003118 aryl group Chemical group 0.000 claims abstract description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 13
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
- 125000004429 atom Chemical group 0.000 claims abstract description 10
- 125000006413 ring segment Chemical group 0.000 claims abstract description 7
- KEZHRKOVLKUYCQ-UHFFFAOYSA-N 3,3-dimethyl-1h-indol-2-one Chemical compound C1=CC=C2C(C)(C)C(=O)NC2=C1 KEZHRKOVLKUYCQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims abstract description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 62
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 54
- 230000000694 effects Effects 0.000 claims description 54
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 51
- 210000004027 cell Anatomy 0.000 claims description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 37
- 230000005764 inhibitory process Effects 0.000 claims description 27
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 208000010668 atopic eczema Diseases 0.000 claims description 16
- 201000011510 cancer Diseases 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 208000023275 Autoimmune disease Diseases 0.000 claims description 14
- 230000000172 allergic effect Effects 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 208000027866 inflammatory disease Diseases 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 8
- 230000004054 inflammatory process Effects 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 4
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- XPDZPDKSEGYLDL-UHFFFAOYSA-N 2-[[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]-methylamino]ethanol Chemical compound C1=NC(N(CCO)C)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 XPDZPDKSEGYLDL-UHFFFAOYSA-N 0.000 claims description 3
- LDLAEUFQUOXALI-UHFFFAOYSA-N 3-methylazetidin-3-ol Chemical compound CC1(O)CNC1 LDLAEUFQUOXALI-UHFFFAOYSA-N 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- MFNFCABYKPLVLW-UHFFFAOYSA-N 5-n-[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]-2-n-(2-methoxyethyl)-2-n-methylpyridine-2,5-diamine Chemical compound C1=NC(N(C)CCOC)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 MFNFCABYKPLVLW-UHFFFAOYSA-N 0.000 claims description 3
- BLAURGSMVPJHCW-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1COCCN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 BLAURGSMVPJHCW-UHFFFAOYSA-N 0.000 claims description 3
- JJJFPCRLZYYNSS-UHFFFAOYSA-N 6-(2,3-dimethylindazol-6-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=CC2=C(C)N(C)N=C2C=C1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 JJJFPCRLZYYNSS-UHFFFAOYSA-N 0.000 claims description 3
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 3
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 208000026935 allergic disease Diseases 0.000 claims description 3
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- WBMQTECYFWQKRK-DEOSSOPVSA-N (3s)-1-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]-3-methylpiperidin-3-ol Chemical compound C1[C@@](C)(O)CCCN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 WBMQTECYFWQKRK-DEOSSOPVSA-N 0.000 claims description 2
- CVWASLZLFGDNNU-UHFFFAOYSA-N 1-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]-3-methylazetidin-3-ol Chemical compound C1C(C)(O)CN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 CVWASLZLFGDNNU-UHFFFAOYSA-N 0.000 claims description 2
- WBMQTECYFWQKRK-UHFFFAOYSA-N 1-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]-3-methylpiperidin-3-ol Chemical compound C1C(C)(O)CCCN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 WBMQTECYFWQKRK-UHFFFAOYSA-N 0.000 claims description 2
- BTQPMALBGWIQPN-UHFFFAOYSA-N 1-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]-4-methylpiperidin-4-ol Chemical compound C1CC(C)(O)CCN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 BTQPMALBGWIQPN-UHFFFAOYSA-N 0.000 claims description 2
- WSRTZAWLYQAAAB-UHFFFAOYSA-N 1-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]oxy-2-methylpropan-2-ol Chemical compound C1=NC(OCC(C)(O)C)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 WSRTZAWLYQAAAB-UHFFFAOYSA-N 0.000 claims description 2
- AQWARLFPYXVRKX-UHFFFAOYSA-N 1-[5-[[6-(3,4-dihydro-2h-1,4-benzoxazin-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]-4-methylpiperidin-4-ol Chemical compound C1CC(C)(O)CCN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NCCOC3=CC=2)=CN2C1=NC=C2 AQWARLFPYXVRKX-UHFFFAOYSA-N 0.000 claims description 2
- SLQZHBCBHXYHRO-UHFFFAOYSA-N 1-[5-[[6-(3,4-dihydro-2h-1,4-benzoxazin-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]azetidin-3-ol Chemical compound C1C(O)CN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NCCOC3=CC=2)=CN2C1=NC=C2 SLQZHBCBHXYHRO-UHFFFAOYSA-N 0.000 claims description 2
- CHMNAIGUJLWODD-UHFFFAOYSA-N 2-[4-[[6-(1,3-benzothiazol-5-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyrazol-1-yl]ethanol Chemical compound C1=NN(CCO)C=C1NC1=NC(C=2C=C3N=CSC3=CC=2)=CN2C1=NC=C2 CHMNAIGUJLWODD-UHFFFAOYSA-N 0.000 claims description 2
- FDBCUIMAOSMMPA-UHFFFAOYSA-N 2-[4-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyrazol-1-yl]ethanol Chemical compound C1=NN(CCO)C=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 FDBCUIMAOSMMPA-UHFFFAOYSA-N 0.000 claims description 2
- KRVYWBSYHNTNST-UHFFFAOYSA-N 2-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]oxyethanol Chemical compound C1=NC(OCCO)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 KRVYWBSYHNTNST-UHFFFAOYSA-N 0.000 claims description 2
- SBWBNCVVYPXVJY-UHFFFAOYSA-N 2-[[5-[[6-(3,4-dihydro-2h-1,4-benzoxazin-7-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]-methylamino]ethanol Chemical compound C1=NC(N(CCO)C)=CC=C1NC1=NC(C=2C=C3OCCNC3=CC=2)=CN2C1=NC=C2 SBWBNCVVYPXVJY-UHFFFAOYSA-N 0.000 claims description 2
- DTVSNTCXJLLUTG-UHFFFAOYSA-N 2-[[6-[[5-(1h-indazol-6-yl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]pyridin-3-yl]-methylamino]ethanol Chemical compound N1=CC(N(CCO)C)=CC=C1NC1=CC(C=2C=C3NN=CC3=CC=2)=NC2=CC=NN12 DTVSNTCXJLLUTG-UHFFFAOYSA-N 0.000 claims description 2
- ZZEQEKFGMMZTKM-UHFFFAOYSA-N 3,3-dimethyl-6-[8-[(6-morpholin-4-ylpyridin-3-yl)amino]imidazo[1,2-a]pyrazin-6-yl]-1h-indol-2-one Chemical compound C=1C=C2C(C)(C)C(=O)NC2=CC=1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 ZZEQEKFGMMZTKM-UHFFFAOYSA-N 0.000 claims description 2
- RVWUJQUKULSUKG-UHFFFAOYSA-N 3-[4-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyrazol-1-yl]propan-1-ol Chemical compound C1=NN(CCCO)C=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 RVWUJQUKULSUKG-UHFFFAOYSA-N 0.000 claims description 2
- LLDKGUNKYFJNPV-UHFFFAOYSA-N 3-methylpiperidin-3-ol Chemical compound CC1(O)CCCNC1 LLDKGUNKYFJNPV-UHFFFAOYSA-N 0.000 claims description 2
- CXBLQEIODBBSQD-UHFFFAOYSA-N 4-methylpiperidin-4-ol Chemical compound CC1(O)CCNCC1 CXBLQEIODBBSQD-UHFFFAOYSA-N 0.000 claims description 2
- YYHKIHMXDFCULT-UHFFFAOYSA-N 5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]-1h-pyridin-2-one Chemical compound C1=NC(O)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 YYHKIHMXDFCULT-UHFFFAOYSA-N 0.000 claims description 2
- MFSOZUSXQDDCNB-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-(1-propan-2-ylpyrazol-4-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=NN(C(C)C)C=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 MFSOZUSXQDDCNB-UHFFFAOYSA-N 0.000 claims description 2
- OXAWWNWLWPJGSD-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-(1h-indol-5-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2C=NNC2=CC(C=2N=C(C3=NC=CN3C=2)NC=2C=C3C=CNC3=CC=2)=C1 OXAWWNWLWPJGSD-UHFFFAOYSA-N 0.000 claims description 2
- REGRKEPTFXYWPD-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-(1h-indol-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2C=NNC2=CC(C=2N=C(C3=NC=CN3C=2)NC=2C=C3NC=CC3=CC=2)=C1 REGRKEPTFXYWPD-UHFFFAOYSA-N 0.000 claims description 2
- LOZAVAJLPYYTML-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-(2-methoxypyridin-4-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=NC(OC)=CC(NC=2C3=NC=CN3C=C(N=2)C=2C=C3NN=CC3=CC=2)=C1 LOZAVAJLPYYTML-UHFFFAOYSA-N 0.000 claims description 2
- QVALNOBDSBSJDA-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-(3-methylbenzimidazol-5-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2C=NNC2=CC(C=2N=C(C3=NC=CN3C=2)NC2=CC=C3N=CN(C3=C2)C)=C1 QVALNOBDSBSJDA-UHFFFAOYSA-N 0.000 claims description 2
- ILGMJEFGESPHHU-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-[1-(2-methoxyethyl)pyrazol-4-yl]imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=NN(CCOC)C=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 ILGMJEFGESPHHU-UHFFFAOYSA-N 0.000 claims description 2
- YRFVCAQTEKISHD-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-[6-(2-methoxyethoxy)pyridin-3-yl]imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=NC(OCCOC)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 YRFVCAQTEKISHD-UHFFFAOYSA-N 0.000 claims description 2
- MSOZVQWIBDYXLI-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-[6-(4-propan-2-ylpiperazin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyrazin-8-amine Chemical compound C1CN(C(C)C)CCN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 MSOZVQWIBDYXLI-UHFFFAOYSA-N 0.000 claims description 2
- JAIQINBVDXBDCL-UHFFFAOYSA-N 6-(2,3-dihydro-1h-indol-6-yl)-n-(2-methoxypyridin-4-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=NC(OC)=CC(NC=2C3=NC=CN3C=C(N=2)C=2C=C3NCCC3=CC=2)=C1 JAIQINBVDXBDCL-UHFFFAOYSA-N 0.000 claims description 2
- RJRRMFGLMTXVCJ-UHFFFAOYSA-N 6-(3,4-dihydro-2h-1,4-benzoxazin-6-yl)-n-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2C=NNC2=CC(NC=2C3=NC=CN3C=C(N=2)C2=CC=C3OCCNC3=C2)=C1 RJRRMFGLMTXVCJ-UHFFFAOYSA-N 0.000 claims description 2
- UVVDMEJUOQLGNU-UHFFFAOYSA-N 6-(3,4-dihydro-2h-1,4-benzoxazin-6-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2NCCOC2=CC=C1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 UVVDMEJUOQLGNU-UHFFFAOYSA-N 0.000 claims description 2
- HEDRGLFIFIZNRZ-UHFFFAOYSA-N 6-(3,4-dihydro-2h-1,4-benzoxazin-7-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C=1C=C2NCCOC2=CC=1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 HEDRGLFIFIZNRZ-UHFFFAOYSA-N 0.000 claims description 2
- FFIRAJURARWRBR-UHFFFAOYSA-N 6-(4-fluoro-1h-indazol-6-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C=1C=2NN=CC=2C(F)=CC=1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 FFIRAJURARWRBR-UHFFFAOYSA-N 0.000 claims description 2
- FXWKJRPKFLLYCP-UHFFFAOYSA-N 6-(5-fluoro-1h-indazol-6-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound FC1=CC=2C=NNC=2C=C1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 FXWKJRPKFLLYCP-UHFFFAOYSA-N 0.000 claims description 2
- YJSOTIZELLALLH-UHFFFAOYSA-N 6-[8-[(2-methoxypyridin-4-yl)amino]imidazo[1,2-a]pyrazin-6-yl]-4h-1,4-benzoxazin-3-one Chemical compound C1=NC(OC)=CC(NC=2C3=NC=CN3C=C(N=2)C=2C=C3NC(=O)COC3=CC=2)=C1 YJSOTIZELLALLH-UHFFFAOYSA-N 0.000 claims description 2
- GVHAQVNWVMWREB-UHFFFAOYSA-N 6-[8-[(6-morpholin-4-ylpyridin-3-yl)amino]imidazo[1,2-a]pyrazin-6-yl]-1,3-dihydroindol-2-one Chemical compound C1=C2NC(=O)CC2=CC=C1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 GVHAQVNWVMWREB-UHFFFAOYSA-N 0.000 claims description 2
- KBSDNGMTLHBUAW-UHFFFAOYSA-N 6-[8-[(6-morpholin-4-ylpyridin-3-yl)amino]imidazo[1,2-a]pyrazin-6-yl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)COC2=CC=C1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 KBSDNGMTLHBUAW-UHFFFAOYSA-N 0.000 claims description 2
- CPVHSKNQELNOSO-UHFFFAOYSA-N 6-[8-[(6-morpholin-4-ylpyridin-3-yl)amino]imidazo[1,2-a]pyrazin-6-yl]quinazolin-2-amine Chemical compound C1=CC2=NC(N)=NC=C2C=C1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 CPVHSKNQELNOSO-UHFFFAOYSA-N 0.000 claims description 2
- 208000004736 B-Cell Leukemia Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- FTZDSFCLGHITMM-GOSISDBHSA-N [(2r)-4-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]morpholin-2-yl]methanol Chemical compound C1CO[C@@H](CO)CN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 FTZDSFCLGHITMM-GOSISDBHSA-N 0.000 claims description 2
- FTZDSFCLGHITMM-SFHVURJKSA-N [(2s)-4-[5-[[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]amino]pyridin-2-yl]morpholin-2-yl]methanol Chemical compound C1CO[C@H](CO)CN1C(N=C1)=CC=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 FTZDSFCLGHITMM-SFHVURJKSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 230000007815 allergy Effects 0.000 claims description 2
- 125000004540 benzothiazol-5-yl group Chemical group S1C=NC2=C1C=CC(=C2)* 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical group C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- TVXBXCYRWQVAHC-UHFFFAOYSA-N n,6-bis(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2C=NNC2=CC(C=2N=C(C3=NC=CN3C=2)NC=2C=C3NN=CC3=CC=2)=C1 TVXBXCYRWQVAHC-UHFFFAOYSA-N 0.000 claims description 2
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Families Citing this family (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2714414A1 (en) | 2008-02-13 | 2009-08-20 | Cgi Pharmaceuticals, Inc. | Certain substituted amides, method of making, and method of use thereof |
| CN104059073B (zh) * | 2008-12-08 | 2017-04-12 | 吉利德康涅狄格公司 | 咪唑并哌嗪syk抑制剂 |
| US8450321B2 (en) | 2008-12-08 | 2013-05-28 | Gilead Connecticut, Inc. | 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor |
| ES2590804T3 (es) | 2008-12-08 | 2016-11-23 | Gilead Connecticut, Inc. | Inhibidores de Imidazopyrazine Syk |
| US9951008B2 (en) * | 2009-11-03 | 2018-04-24 | University Of Notre Dame Du Lac | Ionic liquids comprising heteraromatic anions |
| US9181255B2 (en) | 2009-12-23 | 2015-11-10 | Takeda Pharmaceutical Company Limited | Fused heteroaromatic pyrrolidinones as SYK inhibitors |
| WO2011100341A1 (en) * | 2010-02-09 | 2011-08-18 | Drexel University | New signaling molecule involved in ultraviolet damage to skin |
| JP5938352B2 (ja) | 2010-03-11 | 2016-06-22 | ギリアード コネチカット, インコーポレイテッド | イミダゾピリジンsyk阻害剤 |
| AU2012244550C1 (en) | 2011-04-21 | 2017-06-22 | Origenis Gmbh | Pyrazolo [4, 3-d] pyrimidines useful as kinase inhibitors |
| JP2014513687A (ja) | 2011-05-10 | 2014-06-05 | メルク・シャープ・アンド・ドーム・コーポレーション | Syk阻害薬としてのピリジルアミノピリジン |
| US9145391B2 (en) | 2011-05-10 | 2015-09-29 | Merck Sharp & Dohme Corp. | Bipyridylaminopyridines as Syk inhibitors |
| WO2012177714A1 (en) | 2011-06-22 | 2012-12-27 | Takeda Pharmaceutical Company Limited | Substituted 6-aza-isoindolin-1-one derivatives |
| WO2013052391A1 (en) | 2011-10-05 | 2013-04-11 | Merck Sharp & Dohme Corp. | PHENYL CARBOXAMIDE-CONTAINING SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| EP2763975B1 (en) | 2011-10-05 | 2016-04-06 | Merck Sharp & Dohme Corp. | 3-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors |
| US9216173B2 (en) | 2011-10-05 | 2015-12-22 | Merck Sharp & Dohme Corp. | 2-Pyridyl carboxamide-containing spleen tyrosine kinase (SYK) inhibitors |
| RU2662443C2 (ru) * | 2011-11-01 | 2018-07-26 | Ф. Хоффманн-Ля Рош Аг | Имидазопиридазины |
| KR101994381B1 (ko) | 2011-12-09 | 2019-06-28 | 키에시 파르마슈티시 엣스. 피. 에이. | 키나아제 억제제 |
| RU2623734C9 (ru) | 2011-12-09 | 2017-09-18 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Ингибиторы киназы |
| CN104159891B (zh) | 2012-01-10 | 2016-09-07 | 霍夫曼-拉罗奇有限公司 | 哒嗪酰胺化合物和它们作为syk 抑制剂的用途 |
| WO2013188856A1 (en) * | 2012-06-14 | 2013-12-19 | Gilead Connecticut, Inc. | Imidazopyrazine syk inhibitors |
| WO2013192128A1 (en) | 2012-06-20 | 2013-12-27 | Merck Sharp & Dohme Corp. | Imidazolyl analogs as syk inhibitors |
| EP2863914B1 (en) | 2012-06-20 | 2018-10-03 | Merck Sharp & Dohme Corp. | Pyrazolyl derivatives as syk inhibitors |
| WO2013192098A1 (en) | 2012-06-22 | 2013-12-27 | Merck Sharp & Dohme Corp. | SUBSTITUTED PYRIDINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| EP2863915B1 (en) | 2012-06-22 | 2017-12-06 | Merck Sharp & Dohme Corp. | SUBSTITUTED DIAZINE AND TRIAZINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| WO2014031438A2 (en) | 2012-08-20 | 2014-02-27 | Merck Sharp & Dohme Corp. | SUBSTITUTED PHENYL SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| US9469654B2 (en) | 2012-09-27 | 2016-10-18 | Portola Pharmaceuticals, Inc. | Bicyclic oxa-lactam kinase inhibitors |
| US9586931B2 (en) | 2012-09-28 | 2017-03-07 | Merck Sharp & Dohme Corp. | Triazolyl derivatives as Syk inhibitors |
| US9637491B2 (en) | 2012-10-19 | 2017-05-02 | Origenis Gmbh | Pyrazolo[4,3-D]pyrimidines as kinase inhibitors |
| HRP20181367T4 (hr) | 2012-11-01 | 2021-11-26 | Infinity Pharmaceuticals, Inc. | Liječenje raka korištenjem modulatora izoforme pi3 kinaze |
| WO2014093191A1 (en) | 2012-12-12 | 2014-06-19 | Merck Sharp & Dohme Corp. | AMINO-PYRIMIDINE-CONTAINING SPLEEN TYROSINE KINASE (Syk) INHIBITORS |
| WO2014100314A1 (en) | 2012-12-21 | 2014-06-26 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors |
| US20160024051A1 (en) | 2013-03-15 | 2016-01-28 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| EP2988744A4 (en) | 2013-04-26 | 2016-11-02 | Merck Sharp & Dohme | THIAZOLSUBSTITUTED AMINOHETEROARYLE AS MILZTYROSINKINASE INHIBITOR |
| EP2988749B1 (en) | 2013-04-26 | 2019-08-14 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyrimidines as spleen tyrosine kinase inhibitors |
| EP3003309B1 (en) | 2013-05-30 | 2020-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| WO2014195402A1 (en) | 2013-06-06 | 2014-12-11 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| EA029281B1 (ru) | 2013-07-30 | 2018-03-30 | Джилид Коннектикут, Инк. | Полиморф ингибиторов syk |
| WO2015017466A1 (en) | 2013-07-30 | 2015-02-05 | Gilead Connecticut, Inc. | Formulation of syk inhibitors |
| US9376441B2 (en) | 2013-07-31 | 2016-06-28 | Gilead Sciences, Inc. | Substituted pyrrolidines as SYK inhibitors |
| WO2015048765A1 (en) | 2013-09-30 | 2015-04-02 | University Of Notre Dame Du Lac | Compounds, complexes, compositions, methods and systems for heating and cooling |
| MX389256B (es) | 2013-10-04 | 2025-03-20 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos. |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US20160244452A1 (en) | 2013-10-21 | 2016-08-25 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2015069799A1 (en) | 2013-11-05 | 2015-05-14 | University Of Notre Dame Du Lac | Carbon dioxide capture using phase change ionic liquids |
| KR20160090903A (ko) | 2013-12-04 | 2016-08-01 | 길리애드 사이언시즈, 인코포레이티드 | 암을 치료하는 방법 |
| WO2015094997A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| WO2015095444A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| WO2015095445A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| US9290505B2 (en) | 2013-12-23 | 2016-03-22 | Gilead Sciences, Inc. | Substituted imidazo[1,2-a]pyrazines as Syk inhibitors |
| UY35898A (es) | 2013-12-23 | 2015-07-31 | Gilead Sciences Inc | ?compuestos inhibidores de syk y composiciones que los comprenden?. |
| EP3116506B1 (en) | 2014-03-13 | 2019-04-17 | Merck Sharp & Dohme Corp. | 2-pyrazine carboxamides as spleen tyrosine kinase inhibitors |
| CN113616656B (zh) | 2014-03-19 | 2023-02-17 | 无限药品股份有限公司 | 用于治疗PI3K-γ介导的障碍的杂环化合物 |
| WO2015160986A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| WO2015157955A1 (en) | 2014-04-17 | 2015-10-22 | Abbvie Inc. | Heterocyclic btk inhibit ors |
| TW201617074A (zh) | 2014-07-14 | 2016-05-16 | 吉李德科學股份有限公司 | Syk(脾酪胺酸激酶)抑制劑 |
| CA2955180A1 (en) | 2014-07-14 | 2016-01-21 | Gilead Sciences, Inc. | Combinations comprising entospletinib and a vinca-alkaloid for treating cancers |
| US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
| CN107709336B (zh) * | 2015-06-12 | 2021-06-22 | 杭州英创医药科技有限公司 | 作为Syk抑制剂和/或Syk-HDAC双重抑制剂的杂环化合物 |
| PL3347353T3 (pl) * | 2015-09-11 | 2020-01-31 | Boehringer Ingelheim International Gmbh | Heteroaryle podstawione pirazolilem i ich zastosowanie jako leki |
| CN114230571B (zh) | 2015-09-14 | 2025-07-08 | 无限药品股份有限公司 | 异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法 |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CA3028718A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| EP3512519A1 (en) | 2016-09-14 | 2019-07-24 | Gilead Sciences, Inc. | Syk inhibitors |
| TW201822764A (zh) | 2016-09-14 | 2018-07-01 | 美商基利科學股份有限公司 | Syk抑制劑 |
| EP3553065A4 (en) * | 2016-12-12 | 2020-07-01 | Hangzhou Innogate Pharma Co., Ltd. | HETEROCYCLIC COMPOUND AS SYK INHIBITOR AND / OR DUAL SYK-HDAC INHIBITOR |
| WO2018195471A1 (en) | 2017-04-21 | 2018-10-25 | Gilead Sciences, Inc. | Syk inhibitors in combination with hypomethylating agents |
| EP3672974A1 (en) | 2017-08-25 | 2020-07-01 | Gilead Sciences, Inc. | Polymorphs of syk inhibitors |
| WO2019191667A1 (en) * | 2018-03-29 | 2019-10-03 | Board Of Regents, The University Of Texas System | Imidazopiperazine inhibitors of transcription activating proteins |
| AU2020225455A1 (en) | 2019-02-22 | 2021-09-09 | Kronos Bio, Inc. | Solid forms of condensed pyrazines as Syk inhibitors |
| CN114364798A (zh) | 2019-03-21 | 2022-04-15 | 欧恩科斯欧公司 | 用于治疗癌症的Dbait分子与激酶抑制剂的组合 |
| US20220401436A1 (en) | 2019-11-08 | 2022-12-22 | INSERM (Institute National de la Santé et de la Recherche Médicale) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| WO2024110342A1 (en) | 2022-11-23 | 2024-05-30 | Koninklijke Philips N.V. | Controlling a tactile breathing guidance device |
Family Cites Families (98)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4337609A (en) | 1980-09-17 | 1982-07-06 | Pitney Bowes Inc. | Envelope stuffing apparatus |
| FR2607813B1 (fr) | 1986-12-05 | 1989-03-31 | Montpellier I Universite | Alkylamino-8 imidazo (1,2-a) pyrazines et derives, leur preparation et leur application en therapeutique |
| US5137876A (en) | 1990-10-12 | 1992-08-11 | Merck & Co., Inc. | Nucleoside antiviral and anti-inflammatory compounds and compositions and methods for using same |
| DE4327027A1 (de) * | 1993-02-15 | 1994-08-18 | Bayer Ag | Imidazoazine |
| DE4337656C2 (de) | 1993-11-04 | 1996-01-18 | Audi Ag | Insassenschutzvorrichtung für Kraftfahrzeuge |
| DE4337611A1 (de) * | 1993-11-04 | 1995-05-11 | Boehringer Ingelheim Kg | Neue Benzoylguanidine, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| DE4337609A1 (de) | 1993-11-04 | 1995-05-11 | Boehringer Ingelheim Kg | Neue Pyrazincarboxamidderivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| FR2711993B1 (fr) | 1993-11-05 | 1995-12-01 | Rhone Poulenc Rorer Sa | Médicaments contenant des dérivés de 7H-imidazol[1,2-a]pyrazine-8-one, les nouveaux composés et leur préparation. |
| BR9507200A (pt) * | 1994-03-25 | 1997-09-16 | Isotechnika Inc | Melhora da eficácia de drogas por deuteração |
| US6334997B1 (en) * | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| FR2723373B1 (fr) | 1994-08-02 | 1996-09-13 | Rhone Poulenc Rorer Sa | Forme purifiee de streptogramines, sa preparation et les compositions pharmaceutiques qui la contiennent |
| JPH11505524A (ja) | 1995-05-01 | 1999-05-21 | 藤沢薬品工業株式会社 | イミダゾ1,2−aピリジンおよびイミダゾ1,2−aピリデジン誘導体、および骨吸収阻害剤としてのその用途 |
| US5593997A (en) * | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
| US6249495B1 (en) | 1997-02-27 | 2001-06-19 | Matsushita Electric Industrial Co., Ltd. | Stepping motor control method and disk drive apparatus |
| SE9704404D0 (sv) | 1997-11-28 | 1997-11-28 | Astra Ab | New compounds |
| DE19948434A1 (de) | 1999-10-08 | 2001-06-07 | Gruenenthal Gmbh | Substanzbibliothek enthaltend bicyclische Imidazo-5-amine und/oder bicyclische Imidazo-3-amine |
| JP2001302667A (ja) | 2000-04-28 | 2001-10-31 | Bayer Ag | イミダゾピリミジン誘導体およびトリアゾロピリミジン誘導体 |
| AU2001275076A1 (en) | 2000-06-19 | 2002-01-02 | Armin S. Tay | Axial position changing transmission mechanism |
| GB0018473D0 (en) | 2000-07-27 | 2000-09-13 | Merck Sharp & Dohme | Therapeutic agents |
| DE10050663A1 (de) | 2000-10-13 | 2002-04-18 | Gruenenthal Gmbh | Verwendung von substituierten Imidazo[1,2-a]pyridin-, -pyrimidin- und pyrazin-3-yl-amin-Derivaten zur Herstellung von Medikamenten zur NOS-Inhibierung |
| US20030089434A1 (en) | 2000-11-20 | 2003-05-15 | Flynn Thomas M. | Method and apparatus for the preparation and usage of a cryogenic propellant or explosive system |
| DK174233B1 (da) | 2000-12-27 | 2002-10-07 | Dss Danish Separation Systems | Sanitært spiralfilteranlæg |
| US20040102455A1 (en) | 2001-01-30 | 2004-05-27 | Burns Christopher John | Method of inhibiting kinases |
| GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| WO2002076985A1 (en) | 2001-03-23 | 2002-10-03 | Smithkline Beecham Corporation | Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases |
| US7230941B2 (en) | 2001-04-26 | 2007-06-12 | Qualcomm Incorporated | Preamble channel decoding |
| FR2824092B1 (fr) | 2001-04-30 | 2004-04-09 | Camille Jim Riviere | Ensemble d'elements de construction |
| US7003125B2 (en) | 2001-09-12 | 2006-02-21 | Seung-Hwan Yi | Micromachined piezoelectric microspeaker and fabricating method thereof |
| EP1308716A1 (en) * | 2001-10-03 | 2003-05-07 | Avantium International B.V. | Method for performing a transmission diffraction analysis |
| US6858613B2 (en) | 2002-02-19 | 2005-02-22 | Pfizer Inc. | Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease |
| IL164703A0 (en) * | 2002-04-19 | 2005-12-18 | Cellular Genomics Inc | ImidazoÄ1,2-AÜpyrazin-8-ylamines method of making and method of use thereof |
| US20040072081A1 (en) | 2002-05-14 | 2004-04-15 | Coleman Thomas P. | Methods for etching photolithographic reticles |
| JP2004053714A (ja) | 2002-07-17 | 2004-02-19 | Fuji Xerox Co Ltd | 画像定着装置及び画像定着方法 |
| US20040026867A1 (en) | 2002-08-09 | 2004-02-12 | Adams David J. | Bearing seal |
| US6761361B2 (en) | 2002-08-09 | 2004-07-13 | Credo Technology Corporation | Drill and drive apparatus with improved tool holder |
| AU2003270489A1 (en) | 2002-09-09 | 2004-03-29 | Cellular Genomics, Inc. | 6-ARYL-IMIDAZO(1,2-a)PYRAZIN-8-YLAMINES, METHOD OF MAKING, AND METHOD OF USE THEREOF |
| ATE378336T1 (de) | 2002-09-19 | 2007-11-15 | Schering Corp | Imidazopyridine als hemmstoffe cyclin abhängiger kinasen |
| MXPA05003120A (es) | 2002-09-23 | 2005-06-22 | Schering Corp | Imidazopirazinas como inhibidores de cinasa dependientes de ciclinas. |
| KR20060010709A (ko) * | 2002-09-23 | 2006-02-02 | 쉐링 코포레이션 | 사이클린 의존성 키나제 억제제로서의 신규한 이미다조피라진 |
| JP4056346B2 (ja) | 2002-09-30 | 2008-03-05 | 三洋電機株式会社 | 非水電解質二次電池 |
| MX353044B (es) | 2002-10-29 | 2017-12-18 | Insmed Inc | Liberacion sostenida de anti-infecciosos. |
| WO2004072080A1 (en) | 2003-02-10 | 2004-08-26 | Cellular Genomics, Inc. | Certain 8-heteroaryl-6-phenyl-imidazo[1,2-a]pyrazines as modulators of hsp90 complex activity |
| AR043002A1 (es) | 2003-02-18 | 2005-07-13 | Altana Pharma Ag | Imidazopirazinas 6-substituidos |
| US7157460B2 (en) * | 2003-02-20 | 2007-01-02 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| US7186832B2 (en) | 2003-02-20 | 2007-03-06 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| US7456393B2 (en) | 2003-04-10 | 2008-11-25 | Ge Homeland Protection, Inc. | Device for testing surfaces of articles for traces of explosives and/or drugs |
| US20060183746A1 (en) * | 2003-06-04 | 2006-08-17 | Currie Kevin S | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
| US7405295B2 (en) * | 2003-06-04 | 2008-07-29 | Cgi Pharmaceuticals, Inc. | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
| WO2005005429A1 (en) | 2003-06-30 | 2005-01-20 | Cellular Genomics, Inc. | Certain heterocyclic substituted imidazo[1,2-a]pyrazin-8-ylamines and methods of inhibition of bruton’s tyrosine kinase by such compounds |
| US20050009632A1 (en) * | 2003-07-08 | 2005-01-13 | Karsten Manufacturing Corporation | Iron type golf club head with low profile tuning port |
| US7259164B2 (en) * | 2003-08-11 | 2007-08-21 | Cgi Pharmaceuticals, Inc. | Certain substituted imidazo[1,2-a]pyrazines, as modulators of kinase activity |
| US7144907B2 (en) | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| US7236749B2 (en) | 2003-10-15 | 2007-06-26 | Honeywell International Inc. | Stuck microphone deselection system and method |
| WO2005047290A2 (en) * | 2003-11-11 | 2005-05-26 | Cellular Genomics Inc. | Imidazo[1,2-a] pyrazin-8-ylamines as kinase inhibitors |
| WO2005085252A1 (en) | 2004-03-04 | 2005-09-15 | Biofocus Discovery Limited | Imidazo ‘1,2-a’ pyrazine compounds which interact with protein kinases |
| JP2006099930A (ja) | 2004-09-01 | 2006-04-13 | Tdk Corp | 情報記録媒体、記録再生装置およびスタンパー |
| US8145601B2 (en) | 2004-09-09 | 2012-03-27 | Microsoft Corporation | Method, system, and apparatus for providing resilient data transfer in a data protection system |
| WO2006044687A2 (en) * | 2004-10-15 | 2006-04-27 | Takeda San Diego, Inc. | Kinase inhibitors |
| KR20070119606A (ko) | 2004-11-10 | 2007-12-20 | 씨지아이 파마슈티칼스, 인크. | 특정 이미다조[1,2-a]피라진-8-일아민, 그의 제조 방법및 용도 |
| CN101124227A (zh) | 2004-11-10 | 2008-02-13 | Cgi制药有限公司 | 可用作激酶活性调节剂的咪唑并[1,2-a]吡嗪-8-基胺 |
| WO2007008541A2 (en) | 2005-07-08 | 2007-01-18 | Kalypsys, Inc. | Cellular cholesterol absorption modifiers |
| JP4883959B2 (ja) | 2005-08-17 | 2012-02-22 | Ntn株式会社 | 回転検出装置および回転検出装置付き軸受 |
| GB0520838D0 (en) * | 2005-10-13 | 2005-11-23 | Glaxo Group Ltd | Novel compounds |
| US20070105864A1 (en) | 2005-11-10 | 2007-05-10 | Schering Corporation | Methods for inhibiting protein kinases |
| US20070117804A1 (en) * | 2005-11-10 | 2007-05-24 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| JP4837378B2 (ja) | 2006-01-04 | 2011-12-14 | 株式会社日立製作所 | データの改竄を防止する記憶装置 |
| US7446352B2 (en) | 2006-03-09 | 2008-11-04 | Tela Innovations, Inc. | Dynamic array architecture |
| DE102006032495A1 (de) | 2006-07-13 | 2008-02-07 | Nokia Siemens Networks Gmbh & Co.Kg | Verfahren und Vorrichtung zur Vermeidung von Interferenzen in einem zellulären Funkkommunikationssystem |
| US20080025821A1 (en) | 2006-07-25 | 2008-01-31 | Applied Materials, Inc. | Octagon transfer chamber |
| JP5336375B2 (ja) | 2006-08-30 | 2013-11-06 | セルゾーム リミテッド | キナーゼ阻害剤としてのトリアゾール誘導体 |
| ES2307402B1 (es) | 2006-10-30 | 2009-09-30 | Archivel Farma, S.L. | Vacuna profilactica contra la tuberculosis. |
| EP2099798A1 (en) | 2006-12-01 | 2009-09-16 | Galapagos N.V. | Imidazolopyridine compounds useful for the treatment of degenerative and inflammatory diseases |
| US7657023B2 (en) | 2007-06-08 | 2010-02-02 | At&T Intellectual Property I, L.P. | Splitter wall plates for digital subscriber line (DSL) communication systems and methods to use the same |
| WO2009077334A1 (en) | 2007-12-14 | 2009-06-25 | F. Hoffmann-La Roche Ag | Novel imidazo[1,2-a]pyridine and imidazo[1,2-b]pyridazine derivatives |
| CA2714414A1 (en) | 2008-02-13 | 2009-08-20 | Cgi Pharmaceuticals, Inc. | Certain substituted amides, method of making, and method of use thereof |
| CN102131805A (zh) | 2008-06-20 | 2011-07-20 | 百时美施贵宝公司 | 用作激酶抑制剂的咪唑并吡啶和咪唑并吡嗪化合物 |
| JP5318952B2 (ja) | 2008-07-15 | 2013-10-16 | エフ.ホフマン−ラ ロシュ アーゲー | 新規なフェニル−イミダゾピリジン類及びピリダジン類 |
| JP5341187B2 (ja) * | 2008-07-18 | 2013-11-13 | エフ.ホフマン−ラ ロシュ アーゲー | 新規なフェニルイミダゾピラジン類 |
| TWI453207B (zh) | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶,其組合物及使用其之治療方法 |
| CN104059073B (zh) | 2008-12-08 | 2017-04-12 | 吉利德康涅狄格公司 | 咪唑并哌嗪syk抑制剂 |
| ES2590804T3 (es) | 2008-12-08 | 2016-11-23 | Gilead Connecticut, Inc. | Inhibidores de Imidazopyrazine Syk |
| US8450321B2 (en) | 2008-12-08 | 2013-05-28 | Gilead Connecticut, Inc. | 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor |
| US20110112995A1 (en) | 2009-10-28 | 2011-05-12 | Industrial Technology Research Institute | Systems and methods for organizing collective social intelligence information using an organic object data model |
| JP5938352B2 (ja) | 2010-03-11 | 2016-06-22 | ギリアード コネチカット, インコーポレイテッド | イミダゾピリジンsyk阻害剤 |
| US20140148430A1 (en) | 2012-11-26 | 2014-05-29 | Gilead Connecticut, Inc. | Imidazopyridines syk inhibitors |
| WO2015017466A1 (en) | 2013-07-30 | 2015-02-05 | Gilead Connecticut, Inc. | Formulation of syk inhibitors |
| EA029281B1 (ru) | 2013-07-30 | 2018-03-30 | Джилид Коннектикут, Инк. | Полиморф ингибиторов syk |
| US9376441B2 (en) | 2013-07-31 | 2016-06-28 | Gilead Sciences, Inc. | Substituted pyrrolidines as SYK inhibitors |
| KR20160090903A (ko) | 2013-12-04 | 2016-08-01 | 길리애드 사이언시즈, 인코포레이티드 | 암을 치료하는 방법 |
| US9290505B2 (en) | 2013-12-23 | 2016-03-22 | Gilead Sciences, Inc. | Substituted imidazo[1,2-a]pyrazines as Syk inhibitors |
| UY35898A (es) | 2013-12-23 | 2015-07-31 | Gilead Sciences Inc | ?compuestos inhibidores de syk y composiciones que los comprenden?. |
| TW201617074A (zh) | 2014-07-14 | 2016-05-16 | 吉李德科學股份有限公司 | Syk(脾酪胺酸激酶)抑制劑 |
| CA2955180A1 (en) | 2014-07-14 | 2016-01-21 | Gilead Sciences, Inc. | Combinations comprising entospletinib and a vinca-alkaloid for treating cancers |
| TW201639573A (zh) | 2015-02-03 | 2016-11-16 | 吉李德科學股份有限公司 | 有關治療癌症之合併治療 |
| KR20170137200A (ko) | 2015-04-21 | 2017-12-12 | 길리애드 사이언시즈, 인코포레이티드 | Syk 억제제를 사용한 만성 이식편 대 숙주 질환의 치료 |
| ES2674236T3 (es) | 2015-07-07 | 2018-06-28 | Swiss Coffee Innovation Ag | Cápsula que contiene bebida en polvo instantánea, en especial para la preparación de café hervido |
| TW201822764A (zh) | 2016-09-14 | 2018-07-01 | 美商基利科學股份有限公司 | Syk抑制劑 |
| EP3512519A1 (en) | 2016-09-14 | 2019-07-24 | Gilead Sciences, Inc. | Syk inhibitors |
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