SG171993A1 - Imidazopyrazine syk inhibitors - Google Patents
Imidazopyrazine syk inhibitors Download PDFInfo
- Publication number
- SG171993A1 SG171993A1 SG2011041266A SG2011041266A SG171993A1 SG 171993 A1 SG171993 A1 SG 171993A1 SG 2011041266 A SG2011041266 A SG 2011041266A SG 2011041266 A SG2011041266 A SG 2011041266A SG 171993 A1 SG171993 A1 SG 171993A1
- Authority
- SG
- Singapore
- Prior art keywords
- imidazo
- pyrazin
- indazol
- pyridin
- alkyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 10
- ZKAMEFMDQNTDFK-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyrazine Chemical compound C1=CN=C2NC=NC2=N1 ZKAMEFMDQNTDFK-UHFFFAOYSA-N 0.000 title description 2
- 150000005829 chemical entities Chemical class 0.000 claims abstract description 84
- 230000000694 effects Effects 0.000 claims abstract description 65
- 238000000034 method Methods 0.000 claims abstract description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 51
- 230000005764 inhibitory process Effects 0.000 claims abstract description 37
- 201000010099 disease Diseases 0.000 claims abstract description 36
- 208000035475 disorder Diseases 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- -1 2-methoxy-pyridin-5-yl Chemical group 0.000 claims description 169
- 125000000217 alkyl group Chemical group 0.000 claims description 133
- 150000001875 compounds Chemical class 0.000 claims description 95
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 49
- 210000004027 cell Anatomy 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 208000023275 Autoimmune disease Diseases 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 208000010668 atopic eczema Diseases 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 208000027866 inflammatory disease Diseases 0.000 claims description 15
- 230000000172 allergic effect Effects 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 9
- 230000001154 acute effect Effects 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 claims description 9
- 230000004054 inflammatory process Effects 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 238000000338 in vitro Methods 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 7
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 6
- 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 6
- 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
- 238000001514 detection method Methods 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- ORNSLMJWQDGQFF-UHFFFAOYSA-N 1h-pyrido[2,3-b][1,4]oxazin-2-one Chemical compound C1=CC=C2NC(=O)COC2=N1 ORNSLMJWQDGQFF-UHFFFAOYSA-N 0.000 claims description 4
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 208000026935 allergic disease 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
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 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
- UBQKCCHYAOITMY-UHFFFAOYSA-N 2-hydroxy-pyridine Natural products OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-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
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 3
- 230000007815 allergy Effects 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 3
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 3
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 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 description 2
- LLDKGUNKYFJNPV-UHFFFAOYSA-N 3-methylpiperidin-3-ol Chemical compound CC1(O)CCCNC1 LLDKGUNKYFJNPV-UHFFFAOYSA-N 0.000 claims description 2
- QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-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
- CGUPZIZXXGKGNQ-UHFFFAOYSA-N 5-(3,4-dihydro-2h-1,4-benzoxazin-6-yl)-n-(5-morpholin-4-ylpyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C2NCCOC2=CC=C1C(=NC1=CC=NN11)C=C1NC(N=C1)=CC=C1N1CCOCC1 CGUPZIZXXGKGNQ-UHFFFAOYSA-N 0.000 claims description 2
- UVNKRRHSMNYXBP-UHFFFAOYSA-N 5-(3-methylbenzimidazol-5-yl)-n-(5-morpholin-4-ylpyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=C2N(C)C=NC2=CC=C1C(=NC1=CC=NN11)C=C1NC(N=C1)=CC=C1N1CCOCC1 UVNKRRHSMNYXBP-UHFFFAOYSA-N 0.000 claims description 2
- XFCQRUDDAVRMRJ-UHFFFAOYSA-N 6-(1-methylbenzimidazol-5-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C=1C=C2N(C)C=NC2=CC=1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 XFCQRUDDAVRMRJ-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
- SMDZVMZCRFMZLC-UHFFFAOYSA-N 6-(1h-indazol-6-yl)-n-(6-morpholin-4-ylpyridazin-3-yl)imidazo[1,2-a]pyridin-8-amine Chemical compound C1COCCN1C(N=N1)=CC=C1NC1=CC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 SMDZVMZCRFMZLC-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
- LKPBCEATGKFYLL-UHFFFAOYSA-N 6-(1h-indol-6-yl)-n-(5-morpholin-4-ylpyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine Chemical compound C1COCCN1C(C=N1)=CC=C1NC1=CC(C=2C=C3NC=CC3=CC=2)=NN2C1=NC=C2 LKPBCEATGKFYLL-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
- 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 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
- FJCFYHNLUHAOEQ-UHFFFAOYSA-N 6-(3-amino-1h-indazol-6-yl)-n-(5-morpholin-4-ylpyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine Chemical compound C=1C=C2C(N)=NNC2=CC=1C(=NN1C=CN=C11)C=C1NC(N=C1)=CC=C1N1CCOCC1 FJCFYHNLUHAOEQ-UHFFFAOYSA-N 0.000 claims description 2
- NVNCYDLJZPDTJU-UHFFFAOYSA-N 6-(3-methylbenzimidazol-5-yl)-n-(6-morpholin-4-ylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2N(C)C=NC2=CC=C1C(N=1)=CN2C=CN=C2C=1NC(C=N1)=CC=C1N1CCOCC1 NVNCYDLJZPDTJU-UHFFFAOYSA-N 0.000 claims description 2
- XMIBZUXAYJDEPJ-UHFFFAOYSA-N 6-(3h-benzimidazol-5-yl)-n-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2N=CNC2=CC(C=2N=C(C3=NC=CN3C=2)NC=2C=C3NN=CC3=CC=2)=C1 XMIBZUXAYJDEPJ-UHFFFAOYSA-N 0.000 claims description 2
- UBIGVLDELBKURT-UHFFFAOYSA-N 6-(3h-benzimidazol-5-yl)-n-(5-morpholin-4-ylpyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine Chemical compound C1COCCN1C(C=N1)=CC=C1NC1=CC(C=2C=C3NC=NC3=CC=2)=NN2C1=NC=C2 UBIGVLDELBKURT-UHFFFAOYSA-N 0.000 claims description 2
- RSURYJHTBIMKJB-UHFFFAOYSA-N 6-(3h-benzimidazol-5-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=C3NC=NC3=CC=2)=CN2C1=NC=C2 RSURYJHTBIMKJB-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
- ACTDGIAISBVOBA-UHFFFAOYSA-N 6-[8-(3h-benzimidazol-5-ylamino)imidazo[1,2-a]pyrazin-6-yl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC=NC2=CC(NC=2C3=NC=CN3C=C(N=2)C2=CC=C3OCC(NC3=C2)=O)=C1 ACTDGIAISBVOBA-UHFFFAOYSA-N 0.000 claims description 2
- BAAULUYTQPWZKP-UHFFFAOYSA-N 6-[8-[[6-[2-hydroxyethyl(methyl)amino]pyridin-3-yl]amino]imidazo[1,2-a]pyrazin-6-yl]-4h-1,4-benzoxazin-3-one Chemical compound C1=NC(N(CCO)C)=CC=C1NC1=NC(C=2C=C3NC(=O)COC3=CC=2)=CN2C1=NC=C2 BAAULUYTQPWZKP-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
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000004540 benzothiazol-5-yl group Chemical group S1C=NC2=C1C=CC(=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 125000005434 dihydrobenzoxazinyl group Chemical group O1N(CCC2=C1C=CC=C2)* 0.000 claims description 2
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Substances CC(C)CO ZXEKIIBDNHEJCQ-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
- XMUVBXMTSPNLPS-UHFFFAOYSA-N n-(1-ethyl-5-methylpyrazol-3-yl)-6-(1h-indazol-6-yl)imidazo[1,2-a]pyridin-8-amine Chemical compound C1=C(C)N(CC)N=C1NC1=CC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 XMUVBXMTSPNLPS-UHFFFAOYSA-N 0.000 claims description 2
- VDWUKUJNGKUJRK-UHFFFAOYSA-N n-(1-ethylpyrazol-4-yl)-6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=NN(CC)C=C1NC1=NC(C=2C=C3NN=CC3=CC=2)=CN2C1=NC=C2 VDWUKUJNGKUJRK-UHFFFAOYSA-N 0.000 claims description 2
- GMVKFRBATNDGIQ-UHFFFAOYSA-N n-(1-ethylpyrazol-4-yl)-6-(1h-pyrrolo[3,2-b]pyridin-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=NN(CC)C=C1NC1=NC(C=2C=C3NC=CC3=NC=2)=CN2C1=NC=C2 GMVKFRBATNDGIQ-UHFFFAOYSA-N 0.000 claims description 2
- XVPSBTQBKHTHAA-UHFFFAOYSA-N n-(1h-indazol-5-yl)-6-(1-methylindazol-5-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2NN=CC2=CC(NC=2C3=NC=CN3C=C(N=2)C=2C=C3C=NN(C3=CC=2)C)=C1 XVPSBTQBKHTHAA-UHFFFAOYSA-N 0.000 claims description 2
- VMFCOXUYVZFXMW-UHFFFAOYSA-N n-(1h-indazol-5-yl)-6-(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=C3C=NNC3=CC=2)=C1 VMFCOXUYVZFXMW-UHFFFAOYSA-N 0.000 claims description 2
- CHFMKCITFBGXOU-UHFFFAOYSA-N n-(3-methylbenzimidazol-5-yl)-6-(1-methylindazol-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2C=NN(C)C2=CC(C=2N=C(C3=NC=CN3C=2)NC2=CC=C3N=CN(C3=C2)C)=C1 CHFMKCITFBGXOU-UHFFFAOYSA-N 0.000 claims description 2
- BNCKTNDSKXWEAE-UHFFFAOYSA-N n-(3h-benzimidazol-5-yl)-6-(1,3-benzoxazol-6-yl)imidazo[1,2-a]pyrazin-8-amine Chemical compound C1=C2N=COC2=CC(C=2N=C(C3=NC=CN3C=2)NC=2C=C3NC=NC3=CC=2)=C1 BNCKTNDSKXWEAE-UHFFFAOYSA-N 0.000 claims description 2
- QETBUDBNKCLIMS-UHFFFAOYSA-N n-(3h-benzimidazol-5-yl)-6-(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=C3NC=NC3=CC=2)=C1 QETBUDBNKCLIMS-UHFFFAOYSA-N 0.000 claims description 2
- ACIGLWSVXQNOCW-UHFFFAOYSA-N n-[6-(1h-indazol-6-yl)imidazo[1,2-a]pyrazin-8-yl]-1,3-benzothiazol-6-amine Chemical compound C1=C2C=NNC2=CC(C=2N=C(C3=NC=CN3C=2)NC=2C=C3SC=NC3=CC=2)=C1 ACIGLWSVXQNOCW-UHFFFAOYSA-N 0.000 claims description 2
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Landscapes
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| PCT/US2009/006446 WO2010068258A1 (en) | 2008-12-08 | 2009-12-07 | Imidazopyrazine syk inhibitors |
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Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009102468A1 (en) | 2008-02-13 | 2009-08-20 | Cgi Pharmaceuticals, Inc. | 6-aryl-imidaz0[l, 2-a] pyrazine derivatives, method of making, and method of use thereof |
| 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 |
| PE20120121A1 (es) | 2008-12-08 | 2012-02-20 | Gilead Connecticut Inc | Derivados de imidazopirazina como inhibidores de syk |
| PL2716157T3 (pl) | 2008-12-08 | 2017-06-30 | Gilead Connecticut, Inc. | Imidazopirazynowe inhibitory Syk |
| WO2011056895A1 (en) * | 2009-11-03 | 2011-05-12 | University Of Notre Dame Du Lac | Ionic liquids comprising heteraromatic anions |
| NZ601267A (en) * | 2009-12-23 | 2014-03-28 | Takeda Pharmaceutical | Fused heteroaromatic pyrrolidinones as syk inhibitors |
| CA2789276A1 (en) * | 2010-02-09 | 2011-08-18 | Drexel University | New signaling molecule involved in ultraviolet damage to skin |
| AU2011226689B2 (en) | 2010-03-11 | 2016-09-01 | Kronos Bio, Inc. | Imidazopyridines Syk inhibitors |
| AP2013007253A0 (en) | 2011-04-21 | 2013-11-30 | Origenis Gmbh | Pyrazolo [4,3-D] pyrimidines useful as kinase inhibitors |
| US9145391B2 (en) | 2011-05-10 | 2015-09-29 | Merck Sharp & Dohme Corp. | Bipyridylaminopyridines as Syk inhibitors |
| CA2834062A1 (en) | 2011-05-10 | 2012-11-15 | Merck Sharp & Dohme Corp. | Pyridyl aminopyridines as syk inhibitors |
| EP2723739B1 (en) | 2011-06-22 | 2016-08-24 | 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 |
| US9216173B2 (en) | 2011-10-05 | 2015-12-22 | Merck Sharp & Dohme Corp. | 2-Pyridyl 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 |
| KR20140095513A (ko) | 2011-11-01 | 2014-08-01 | 에프. 호프만-라 로슈 아게 | 이미다조피리다진 화합물 |
| MY167216A (en) | 2011-12-09 | 2018-08-14 | Chiesi Farm Spa | Kinase inhibitors |
| UA115320C2 (uk) | 2011-12-09 | 2017-10-25 | К'Єзі Фармачеутічі С.П.А. | Інгібітори кінази |
| 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 |
| EP2863913B1 (en) | 2012-06-20 | 2018-09-12 | 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 |
| EP2863916B1 (en) | 2012-06-22 | 2018-07-18 | 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 |
| US9353066B2 (en) | 2012-08-20 | 2016-05-31 | Merck Sharp & Dohme Corp. | Substituted phenyl-Spleen Tyrosine Kinase (Syk) inhibitors |
| WO2014051654A2 (en) * | 2012-09-27 | 2014-04-03 | Portola Pharmaceuticals, Inc. | Bicyclic oxa-lactam kinase inhibitors |
| WO2014048065A1 (en) | 2012-09-28 | 2014-04-03 | Merck Sharp & Dohme Corp. | Triazolyl derivatives as syk inhibitors |
| WO2014060112A1 (en) * | 2012-10-19 | 2014-04-24 | Origenis Gmbh | Pyrazolo[4,3-d]pyrimidines as kinase inhibitors |
| AU2013337717B2 (en) | 2012-11-01 | 2018-10-25 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using PI3 kinase isoform modulators |
| EP2931281B1 (en) | 2012-12-12 | 2018-01-17 | Merck Sharp & Dohme Corp. | Amino-pyrimidine-containing spleen tyrosine kinase inhibitors |
| EP2934525B1 (en) | 2012-12-21 | 2019-05-08 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors |
| WO2014151386A1 (en) | 2013-03-15 | 2014-09-25 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| WO2014176210A1 (en) | 2013-04-26 | 2014-10-30 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| EP2988749B1 (en) | 2013-04-26 | 2019-08-14 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminopyrimidines as spleen tyrosine kinase inhibitors |
| CA2914284A1 (en) | 2013-05-30 | 2014-12-04 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| RU2015151886A (ru) | 2013-06-06 | 2017-06-08 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Ингибиторы киназ |
| KR101810798B1 (ko) | 2013-07-30 | 2017-12-19 | 질레드 코네티컷 인코포레이티드 | Ｓｙｋ 억제제의 다형체 |
| PE20160605A1 (es) | 2013-07-30 | 2016-07-20 | Gilead Connecticut Inc | Formulaciones de inhibidores de la syk |
| SG11201600373YA (en) | 2013-07-31 | 2016-02-26 | Gilead Sciences Inc | Syk inhibitors |
| US10385251B2 (en) | 2013-09-30 | 2019-08-20 | University Of Notre Dame Du Lac | Compounds, complexes, compositions, methods and systems for heating and cooling |
| PT3052485T (pt) | 2013-10-04 | 2021-10-22 | Infinity Pharmaceuticals Inc | Compostos heterocíclicos e suas utilizações |
| 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 |
| US10086331B2 (en) | 2013-11-05 | 2018-10-02 | 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 |
| WO2015095444A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| US9822107B2 (en) | 2013-12-20 | 2017-11-21 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| WO2015094997A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| TWI735853B (zh) | 2013-12-23 | 2021-08-11 | 美商克洛諾斯生技有限公司 | 脾酪胺酸激酶抑制劑 |
| US9290505B2 (en) | 2013-12-23 | 2016-03-22 | Gilead Sciences, Inc. | Substituted imidazo[1,2-a]pyrazines as Syk inhibitors |
| WO2015138273A1 (en) | 2014-03-13 | 2015-09-17 | Merck Sharp & Dohme Corp. | 2-pyrazine carboxamides as spleen tyrosine kinase inhibitors |
| MX382033B (es) | 2014-03-19 | 2025-03-13 | Infinity Pharmaceuticals Inc | Compuestos heterocíclicos para utilizarlos en el tratamiento de trastornos mediados por pi3k-gamma. |
| US20150320754A1 (en) | 2014-04-16 | 2015-11-12 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| WO2015157955A1 (en) * | 2014-04-17 | 2015-10-22 | Abbvie Inc. | Heterocyclic btk inhibit ors |
| SG11201610551TA (en) | 2014-07-14 | 2017-01-27 | Gilead Sciences Inc | Combinations for treating cancers |
| 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 |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds 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 |
| EP3347353B1 (en) * | 2015-09-11 | 2019-07-17 | Boehringer Ingelheim International GmbH | Pyrazolyl-substituted heteroaryls and their use as medicaments |
| WO2017048702A1 (en) | 2015-09-14 | 2017-03-23 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| SG11201811237WA (en) | 2016-06-24 | 2019-01-30 | Infinity Pharmaceuticals Inc | Combination therapies |
| AU2017325844A1 (en) | 2016-09-14 | 2019-03-07 | 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 |
| CN110099909B (zh) * | 2016-12-12 | 2021-11-19 | 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 |
| 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 |
| RU2020131507A (ru) * | 2018-03-29 | 2022-05-04 | Боард Оф Реджентс, Де Юниверсити Оф Техас Систем | Имидазопиперазиновые ингибиторы белков-активаторов транскрипции |
| US11339168B2 (en) | 2019-02-22 | 2022-05-24 | Kronos Bio, Inc. | Crystalline forms of 6-(6-aminopyrazin-2-yl)-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine as Syk inhibitors |
| EA202192575A1 (ru) | 2019-03-21 | 2022-01-14 | Онксео | Соединения dbait в сочетании с ингибиторами киназ для лечения рака |
| CN114761006A (zh) | 2019-11-08 | 2022-07-15 | Inserm(法国国家健康医学研究院) | 对激酶抑制剂产生耐药性的癌症的治疗方法 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| WO2022019920A1 (en) | 2020-07-24 | 2022-01-27 | Verastem, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| 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 |
| DE4337609A1 (de) | 1993-11-04 | 1995-05-11 | Boehringer Ingelheim Kg | Neue Pyrazincarboxamidderivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| DE4337611A1 (de) | 1993-11-04 | 1995-05-11 | Boehringer Ingelheim Kg | Neue Benzoylguanidine, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| DE4337656C2 (de) | 1993-11-04 | 1996-01-18 | Audi Ag | Insassenschutzvorrichtung für Kraftfahrzeuge |
| 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. |
| ES2293638T3 (es) | 1994-03-25 | 2008-03-16 | Isotechnika, Inc. | Mejora de la eficacia de farmacos por deuteracion. |
| 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 |
| AU2001297846A1 (en) | 2000-11-20 | 2002-12-23 | Cryoco, Inc. | A 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 |
| CA2476681A1 (en) | 2002-02-19 | 2003-08-28 | Bruce N. Rogers | Fused bicyclic-n-bridged-heteroaromatic carboxamides for the treatment of disease |
| KR20050008691A (ko) | 2002-04-19 | 2005-01-21 | 셀룰러 지노믹스 아이엔씨 | 이미다조[1,2-ａ]피라진-8-일 아민, 그의 제조방법 및사용방법 |
| KR20040012451A (ko) | 2002-05-14 | 2004-02-11 | 어플라이드 머티어리얼스, 인코포레이티드 | 포토리소그래픽 레티클을 에칭하는 방법 |
| 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 |
| MY133311A (en) | 2002-09-19 | 2007-11-30 | Schering Corp | Novel imidazopyridines as cyclin dependent kinase inhibitors |
| NZ538685A (en) | 2002-09-23 | 2008-02-29 | Schering Corp | Imidazopyrazines as cyclin dependent kinase inhibitors |
| NZ538686A (en) | 2002-09-23 | 2008-01-31 | Schering Corp | Novel imidazopyrazines as cyclin dependent kinase inhibitors |
| 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 |
| PT1581236E (pt) | 2002-10-29 | 2013-12-24 | Insmed Inc | Libertação prolongada 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 |
| EP1812439B2 (en) | 2004-10-15 | 2017-12-06 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| AU2005304473A1 (en) | 2004-11-10 | 2006-05-18 | Cgi Pharmaceuticals, Inc. | Imidazo[1 , 2-a] pyrazin-8-ylamines useful as modulators of kinase activity |
| 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 |
| TW200803863A (en) | 2005-11-10 | 2008-01-16 | Schering Corp | Method 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 |
| BRPI0716239A2 (pt) | 2006-08-30 | 2013-08-13 | Cellzome Ltd | derivados de triazol como inibidores de cinase |
| ES2307402B1 (es) | 2006-10-30 | 2009-09-30 | Archivel Farma, S.L. | Vacuna profilactica contra la tuberculosis. |
| JP2010511019A (ja) | 2006-12-01 | 2010-04-08 | ガラパゴス・ナムローゼ・フェンノートシャップ | 変性疾患及び炎症性疾患の治療に有用なイミダゾロピリジン化合物 |
| 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 |
| JP5643105B2 (ja) | 2007-12-14 | 2014-12-17 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 新規イミダゾ［１，２−ａ］ピリジン及びイミダゾ［１，２−ｂ］ピリダジン誘導体 |
| WO2009102468A1 (en) | 2008-02-13 | 2009-08-20 | Cgi Pharmaceuticals, Inc. | 6-aryl-imidaz0[l, 2-a] pyrazine derivatives, 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 |
| WO2010006947A1 (en) | 2008-07-15 | 2010-01-21 | F. Hoffmann-La Roche Ag | Novel phenyl-imidazopyridines and pyridazines |
| ES2461494T3 (es) * | 2008-07-18 | 2014-05-20 | F. Hoffmann-La Roche Ag | Nuevas fenilimidazopirazinas |
| 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 |
| PL2716157T3 (pl) | 2008-12-08 | 2017-06-30 | Gilead Connecticut, Inc. | Imidazopirazynowe inhibitory Syk |
| PE20120121A1 (es) | 2008-12-08 | 2012-02-20 | Gilead Connecticut Inc | Derivados de imidazopirazina como inhibidores de 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 |
| US20110099133A1 (en) | 2009-10-28 | 2011-04-28 | Industrial Technology Research Institute | Systems and methods for capturing and managing collective social intelligence information |
| AU2011226689B2 (en) | 2010-03-11 | 2016-09-01 | Kronos Bio, Inc. | Imidazopyridines Syk inhibitors |
| US20140148430A1 (en) | 2012-11-26 | 2014-05-29 | Gilead Connecticut, Inc. | Imidazopyridines syk inhibitors |
| KR101810798B1 (ko) | 2013-07-30 | 2017-12-19 | 질레드 코네티컷 인코포레이티드 | Ｓｙｋ 억제제의 다형체 |
| PE20160605A1 (es) | 2013-07-30 | 2016-07-20 | Gilead Connecticut Inc | Formulaciones de inhibidores de la syk |
| SG11201600373YA (en) | 2013-07-31 | 2016-02-26 | Gilead Sciences Inc | 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 |
| TWI735853B (zh) | 2013-12-23 | 2021-08-11 | 美商克洛諾斯生技有限公司 | 脾酪胺酸激酶抑制劑 |
| 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 |
| SG11201610551TA (en) | 2014-07-14 | 2017-01-27 | Gilead Sciences Inc | Combinations 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 |
| CA2983611A1 (en) | 2015-04-21 | 2016-10-27 | Gilead Sciences, Inc. | Treatment of chronic graft versus host disease with syk inhibitors |
| HUE039356T2 (hu) | 2015-07-07 | 2018-12-28 | Swiss Coffee Innovation Ag | Italport tartalmazó kapszula, különösen forrázott kávé készítéséhez |
| AU2017325844A1 (en) | 2016-09-14 | 2019-03-07 | 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 |
-
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