DK2265607T3 - PYRIMIDIN-2-AMINE COMPOUNDS AND THEIR USE AS INHIBITORS OF JAK KINASES - Google Patents
PYRIMIDIN-2-AMINE COMPOUNDS AND THEIR USE AS INHIBITORS OF JAK KINASES Download PDFInfo
- Publication number
- DK2265607T3 DK2265607T3 DK09710734.6T DK09710734T DK2265607T3 DK 2265607 T3 DK2265607 T3 DK 2265607T3 DK 09710734 T DK09710734 T DK 09710734T DK 2265607 T3 DK2265607 T3 DK 2265607T3
- Authority
- DK
- Denmark
- Prior art keywords
- optionally substituted
- substitueret
- eventuelt
- alkyl
- heterocyclyl
- Prior art date
Links
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical class NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 title description 561
- 239000003112 inhibitor Substances 0.000 title description 13
- 108091000080 Phosphotransferase Proteins 0.000 title description 4
- 102000020233 phosphotransferase Human genes 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 361
- -1 halogenalkynyl Chemical group 0.000 claims description 328
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 256
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 232
- 239000001257 hydrogen Substances 0.000 claims description 228
- 229910052739 hydrogen Inorganic materials 0.000 claims description 228
- 125000001188 haloalkyl group Chemical group 0.000 claims description 227
- 125000001072 heteroaryl group Chemical group 0.000 claims description 197
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 174
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 165
- 229910052757 nitrogen Inorganic materials 0.000 claims description 159
- 125000001424 substituent group Chemical group 0.000 claims description 159
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 149
- 125000000623 heterocyclic group Chemical group 0.000 claims description 147
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 122
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 112
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 110
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 107
- 125000003118 aryl group Chemical group 0.000 claims description 102
- 125000003342 alkenyl group Chemical group 0.000 claims description 100
- 125000000304 alkynyl group Chemical group 0.000 claims description 99
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 94
- 125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 94
- 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 90
- 150000003839 salts Chemical class 0.000 claims description 85
- 125000004076 pyridyl group Chemical group 0.000 claims description 67
- 125000004043 oxo group Chemical group O=* 0.000 claims description 47
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 32
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 32
- 125000001041 indolyl group Chemical group 0.000 claims description 29
- 125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 28
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 27
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 claims description 27
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 24
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 24
- 125000005876 benzo[b][1,4]oxazinyl group Chemical group 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 22
- 125000000335 thiazolyl group Chemical group 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 230000027455 binding Effects 0.000 claims description 6
- 238000009739 binding Methods 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims 17
- 150000002367 halogens Chemical class 0.000 claims 17
- 150000001875 compounds Chemical class 0.000 description 331
- 125000005843 halogen group Chemical group 0.000 description 203
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 161
- 125000003107 substituted aryl group Chemical group 0.000 description 157
- 125000002947 alkylene group Chemical group 0.000 description 118
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 106
- 125000000232 haloalkynyl group Chemical group 0.000 description 85
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 79
- 210000004027 cell Anatomy 0.000 description 67
- 125000000547 substituted alkyl group Chemical group 0.000 description 61
- 102000042838 JAK family Human genes 0.000 description 60
- 108091082332 JAK family Proteins 0.000 description 60
- 201000010099 disease Diseases 0.000 description 52
- 150000003254 radicals Chemical class 0.000 description 46
- 238000000034 method Methods 0.000 description 43
- 230000000694 effects Effects 0.000 description 40
- 125000004450 alkenylene group Chemical group 0.000 description 36
- 230000001404 mediated effect Effects 0.000 description 36
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 30
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 30
- 125000004419 alkynylene group Chemical group 0.000 description 30
- 208000035475 disorder Diseases 0.000 description 27
- 125000004429 atom Chemical group 0.000 description 25
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 24
- 241000124008 Mammalia Species 0.000 description 23
- 230000002062 proliferating effect Effects 0.000 description 23
- 238000003556 assay Methods 0.000 description 21
- 230000037361 pathway Effects 0.000 description 20
- 230000019491 signal transduction Effects 0.000 description 19
- 206010052779 Transplant rejections Diseases 0.000 description 18
- 208000023275 Autoimmune disease Diseases 0.000 description 17
- 108010024121 Janus Kinases Proteins 0.000 description 17
- 102000015617 Janus Kinases Human genes 0.000 description 17
- 210000001744 T-lymphocyte Anatomy 0.000 description 16
- 125000002757 morpholinyl group Chemical group 0.000 description 16
- 125000004193 piperazinyl group Chemical group 0.000 description 16
- 125000003386 piperidinyl group Chemical group 0.000 description 16
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 15
- 241000282414 Homo sapiens Species 0.000 description 15
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 14
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 14
- 150000005840 aryl radicals Chemical class 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 13
- 125000005961 oxazepanyl group Chemical group 0.000 description 13
- 125000002785 azepinyl group Chemical group 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 230000004913 activation Effects 0.000 description 11
- 125000005605 benzo group Chemical group 0.000 description 11
- 208000032839 leukemia Diseases 0.000 description 11
- 239000000427 antigen Substances 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 206010020751 Hypersensitivity Diseases 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 208000024908 graft versus host disease Diseases 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000002054 transplantation Methods 0.000 description 8
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 8
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 7
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 7
- 208000014767 Myeloproliferative disease Diseases 0.000 description 7
- 230000001154 acute effect Effects 0.000 description 7
- 150000001721 carbon Chemical group 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 125000003003 spiro group Chemical group 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 125000003831 tetrazolyl group Chemical group 0.000 description 7
- 125000000464 thioxo group Chemical group S=* 0.000 description 7
- 208000032027 Essential Thrombocythemia Diseases 0.000 description 6
- 208000017604 Hodgkin disease Diseases 0.000 description 6
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 description 6
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 6
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 6
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 6
- 208000017733 acquired polycythemia vera Diseases 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 210000003630 histaminocyte Anatomy 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 208000037244 polycythemia vera Diseases 0.000 description 6
- 208000003476 primary myelofibrosis Diseases 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 230000003827 upregulation Effects 0.000 description 6
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 5
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 5
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 5
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 5
- 108010002335 Interleukin-9 Proteins 0.000 description 5
- 102000000585 Interleukin-9 Human genes 0.000 description 5
- 206010025323 Lymphomas Diseases 0.000 description 5
- 102000000551 Syk Kinase Human genes 0.000 description 5
- 108010016672 Syk Kinase Proteins 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000007815 allergy Effects 0.000 description 5
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 210000002443 helper t lymphocyte Anatomy 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 206010028537 myelofibrosis Diseases 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 5
- 210000000130 stem cell Anatomy 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
- 108010036949 Cyclosporine Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 4
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010073148 Multiple endocrine neoplasia type 2A Diseases 0.000 description 4
- 208000034578 Multiple myelomas Diseases 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 229960002930 sirolimus Drugs 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102100030703 Interleukin-22 Human genes 0.000 description 3
- 102100021592 Interleukin-7 Human genes 0.000 description 3
- 108010002586 Interleukin-7 Proteins 0.000 description 3
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 102000001253 Protein Kinase Human genes 0.000 description 3
- 206010042971 T-cell lymphoma Diseases 0.000 description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 3
- 229960002170 azathioprine Drugs 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 230000008512 biological response Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229930182912 cyclosporin Natural products 0.000 description 3
- 108010057085 cytokine receptors Proteins 0.000 description 3
- 102000003675 cytokine receptors Human genes 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 230000001861 immunosuppressant effect Effects 0.000 description 3
- 238000002650 immunosuppressive therapy Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 108010074108 interleukin-21 Proteins 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 201000005962 mycosis fungoides Diseases 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 210000004986 primary T-cell Anatomy 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108060006633 protein kinase Proteins 0.000 description 3
- 125000002098 pyridazinyl group Chemical group 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229910052717 sulfur Chemical group 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229960001967 tacrolimus Drugs 0.000 description 3
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical compound CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 108091006112 ATPases Proteins 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 2
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 2
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000031404 Chromosome Aberrations Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- 201000006850 Familial medullary thyroid carcinoma Diseases 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 108010073816 IgE Receptors Proteins 0.000 description 2
- 102000009438 IgE Receptors Human genes 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- 102000003812 Interleukin-15 Human genes 0.000 description 2
- 108090000172 Interleukin-15 Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102000000646 Interleukin-3 Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- 208000006876 Multiple Endocrine Neoplasia Type 2b Diseases 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical group C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical group C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000003969 blast cell Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 239000002771 cell marker Substances 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 125000003636 chemical group Chemical group 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000010250 cytokine signaling pathway Effects 0.000 description 2
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 201000009277 hairy cell leukemia Diseases 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 125000005020 hydroxyalkenyl group Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 210000000244 kidney pelvis Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229960001428 mercaptopurine Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229940014456 mycophenolate Drugs 0.000 description 2
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 2
- 229960004866 mycophenolate mofetil Drugs 0.000 description 2
- QKMCCZNSUKDKIE-UHFFFAOYSA-N n-[5-[2-[3-methyl-4-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)anilino]pyrimidin-4-yl]pyridin-2-yl]methanesulfonamide Chemical compound CN1C(C2)CCC1CN2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(NS(C)(=O)=O)N=C1 QKMCCZNSUKDKIE-UHFFFAOYSA-N 0.000 description 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 125000005593 norbornanyl group Chemical group 0.000 description 2
- 210000004287 null lymphocyte Anatomy 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical group C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000005951 type IV hypersensitivity Effects 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- TUCIOBMMDDOEMM-RIYZIHGNSA-N tyrphostin B42 Chemical compound C1=C(O)C(O)=CC=C1\C=C(/C#N)C(=O)NCC1=CC=CC=C1 TUCIOBMMDDOEMM-RIYZIHGNSA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- 125000005960 1,4-diazepanyl group Chemical group 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- DUXFREOBYRRERX-OALUTQOASA-N 1-[(1s,4s)-5-[4-[[4-(6-aminopyridin-3-yl)pyrimidin-2-yl]amino]-2-methylphenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]propan-1-one Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)CC)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(N)N=C1 DUXFREOBYRRERX-OALUTQOASA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- 125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- YFLOLTUGVIYIAD-UHFFFAOYSA-N 4-(4-tert-butylphenyl)-n-[3-methyl-4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl]pyrimidin-2-amine Chemical compound CN1CC2CC1CN2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(C(C)(C)C)C=C1 YFLOLTUGVIYIAD-UHFFFAOYSA-N 0.000 description 1
- OFLWOYGHVVIMLP-ROUUACIJSA-N 4-(6-aminopyridin-3-yl)-n-[3-methyl-4-[(1s,4s)-2-methylsulfonyl-2,5-diazabicyclo[2.2.1]heptan-5-yl]phenyl]pyrimidin-2-amine Chemical compound C([C@]1(N(C[C@@]2(C1)[H])S(C)(=O)=O)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(N)N=C1 OFLWOYGHVVIMLP-ROUUACIJSA-N 0.000 description 1
- QXYVDYVKSSMFBR-UHFFFAOYSA-N 4-(6-aminopyridin-3-yl)-n-[5-methyl-6-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyridin-3-yl]pyrimidin-2-amine Chemical compound CN1CC2CC1CN2C(C(=C1)C)=NC=C1NC(N=1)=NC=CC=1C1=CC=C(N)N=C1 QXYVDYVKSSMFBR-UHFFFAOYSA-N 0.000 description 1
- ZPYUCJRJSSKXQT-VXKWHMMOSA-N 4-[4-(dimethylamino)phenyl]-n-[3-methyl-4-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]pyrimidin-2-amine Chemical compound C([C@]1(N(C[C@]2([H])C1)C)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(N(C)C)C=C1 ZPYUCJRJSSKXQT-VXKWHMMOSA-N 0.000 description 1
- YBROWKWXWXJJFF-UHFFFAOYSA-N 4-[6-(cyclohexylamino)pyridin-3-yl]-n-[3-methyl-4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl]pyrimidin-2-amine Chemical compound CN1CC2CC1CN2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C(C=N1)=CC=C1NC1CCCCC1 YBROWKWXWXJJFF-UHFFFAOYSA-N 0.000 description 1
- OVRYDJPBNPHKPD-GOTSBHOMSA-N 4-[6-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridin-3-yl]-n-[3-methyl-4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine Chemical compound C([C@]1(N(C[C@]2([H])C1)C)[H])N2C(N=C1)=CC=C1C(N=1)=CC=NC=1NC(C=C1C)=CC=C1N1CCN(C)CC1 OVRYDJPBNPHKPD-GOTSBHOMSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- 206010068532 5q minus syndrome Diseases 0.000 description 1
- HEOQXHNKRXRCTO-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-benzo[7]annulene Chemical group C1CCCCC2=CC=CC=C21 HEOQXHNKRXRCTO-UHFFFAOYSA-N 0.000 description 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000016557 Acute basophilic leukemia Diseases 0.000 description 1
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 1
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
- 208000016585 Acute panmyelosis with myelofibrosis Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 206010001413 Adult T-cell lymphoma/leukaemia Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010060971 Astrocytoma malignant Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 1
- 206010003908 B-cell small lymphocytic lymphoma Diseases 0.000 description 1
- 208000033775 Basophilic Acute Leukemia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 208000030808 Clear cell renal carcinoma Diseases 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000006402 Ductal Carcinoma Diseases 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 208000002460 Enteropathy-Associated T-Cell Lymphoma Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010051841 Exposure to allergen Diseases 0.000 description 1
- 208000033371 Extranodal NK/T-cell lymphoma, nasal type Diseases 0.000 description 1
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 206010061187 Haematopoietic neoplasm Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 1
- 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 description 1
- 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 description 1
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 description 1
- 208000020875 Idiopathic pulmonary arterial hypertension Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003815 Interleukin-11 Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102100020870 La-related protein 6 Human genes 0.000 description 1
- 108050008265 La-related protein 6 Proteins 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 206010062038 Lip neoplasm Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010073099 Lobular breast carcinoma in situ Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 201000003791 MALT lymphoma Diseases 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 208000032271 Malignant tumor of penis Diseases 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 1
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 206010027761 Mixed hepatocellular cholangiocarcinoma Diseases 0.000 description 1
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100351501 Mus musculus Cbfb gene Proteins 0.000 description 1
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 1
- 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028767 Nasal sinus cancer Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
- 208000033755 Neutrophilic Chronic Leukemia Diseases 0.000 description 1
- 241000080590 Niso Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 1
- 208000019569 Nodular lymphocyte predominant Hodgkin lymphoma Diseases 0.000 description 1
- 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000004140 Oncostatin M Human genes 0.000 description 1
- 108090000630 Oncostatin M Proteins 0.000 description 1
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 239000012826 P38 inhibitor Substances 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 206010033661 Pancytopenia Diseases 0.000 description 1
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 1
- 208000003937 Paranasal Sinus Neoplasms Diseases 0.000 description 1
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 201000008199 Pleuropulmonary blastoma Diseases 0.000 description 1
- 208000017414 Precursor T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000032758 Precursor T-lymphoblastic lymphoma/leukaemia Diseases 0.000 description 1
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 1
- 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038272 Refractory anaemia with ringed sideroblasts Diseases 0.000 description 1
- 208000009527 Refractory anemia Diseases 0.000 description 1
- 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 description 1
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000010502 Subcutaneous panniculitis-like T-cell lymphoma Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 1
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 1
- JVDOKQYTTYUYDV-UHFFFAOYSA-N TG101209 Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C)C(NC=2C=C(C=CC=2)S(=O)(=O)NC(C)(C)C)=N1 JVDOKQYTTYUYDV-UHFFFAOYSA-N 0.000 description 1
- 102000003714 TNF receptor-associated factor 6 Human genes 0.000 description 1
- 108090000009 TNF receptor-associated factor 6 Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 201000009365 Thymic carcinoma Diseases 0.000 description 1
- 206010062129 Tongue neoplasm Diseases 0.000 description 1
- 102000000887 Transcription factor STAT Human genes 0.000 description 1
- 108050007918 Transcription factor STAT Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 101710112792 Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 208000035868 Vascular inflammations Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- KYIKRXIYLAGAKQ-UHFFFAOYSA-N abcn Chemical compound C1CCCCC1(C#N)N=NC1(C#N)CCCCC1 KYIKRXIYLAGAKQ-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Natural products C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000013685 acquired idiopathic sideroblastic anemia Diseases 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 1
- 208000026784 acute myeloblastic leukemia with maturation Diseases 0.000 description 1
- 208000010816 acute myeloblastic leukemia without maturation Diseases 0.000 description 1
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 229960000250 adipic acid Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000015230 aggressive NK-cell leukemia Diseases 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 206010002449 angioimmunoblastic T-cell lymphoma Diseases 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 230000000781 anti-lymphocytic effect Effects 0.000 description 1
- 230000001494 anti-thymocyte effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- KNNXFYIMEYKHBZ-UHFFFAOYSA-N as-indacene Chemical group C1=CC2=CC=CC2=C2C=CC=C21 KNNXFYIMEYKHBZ-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229940022777 azasan Drugs 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229960004669 basiliximab Drugs 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000005870 benzindolyl group Chemical group 0.000 description 1
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 125000005878 benzonaphthofuranyl group Chemical group 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 201000005389 breast carcinoma in situ Diseases 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 229940046731 calcineurin inhibitors Drugs 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 230000005961 cardioprotection Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229940107810 cellcept Drugs 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 201000007335 cerebellar astrocytoma Diseases 0.000 description 1
- 208000030239 cerebral astrocytoma Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 231100000005 chromosome aberration Toxicity 0.000 description 1
- 208000021668 chronic eosinophilic leukemia Diseases 0.000 description 1
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 1
- 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 206010073251 clear cell renal cell carcinoma Diseases 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 208000011588 combined hepatocellular carcinoma and cholangiocarcinoma Diseases 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 108010010201 core binding factor alpha Proteins 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 210000000448 cultured tumor cell Anatomy 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 208000024389 cytopenia Diseases 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000005509 dibenzothiophenyl group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 208000023437 ependymal tumor Diseases 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 208000019995 familial amyotrophic lateral sclerosis Diseases 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical group C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000003844 furanonyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940062737 gengraf Drugs 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000009033 hematopoietic malignancy Effects 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 208000027671 high grade ependymoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 102000055229 human IL4 Human genes 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 229940073062 imuran Drugs 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 235000013902 inosinic acid Nutrition 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 201000008893 intraocular retinoblastoma Diseases 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 201000006721 lip cancer Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000011059 lobular neoplasia Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 208000037652 lymphocytic-histiocytic predominance Hodgkin lymphoma Diseases 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000030883 malignant astrocytoma Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000006178 malignant mesothelioma Diseases 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000037524 mixed cellularity Hodgkin lymphoma Diseases 0.000 description 1
- 229950007856 mofetil Drugs 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 229940083410 myfortic Drugs 0.000 description 1
- ZOZRKNRDIIBFSH-VXKWHMMOSA-N n-(4,5-dihydro-1,3-thiazol-2-yl)-4-[2-[3-methyl-4-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]pyrimidin-4-yl]benzamide Chemical compound C([C@]1(N(C[C@]2([H])C1)C)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C(C=C1)=CC=C1C(=O)NC1=NCCS1 ZOZRKNRDIIBFSH-VXKWHMMOSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- LZWSNXJCTUJJGI-UHFFFAOYSA-N n-[3-fluoro-4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl]-4-(3-fluoro-2-morpholin-4-ylpyridin-4-yl)pyrimidin-2-amine Chemical compound CN1CC2CC1CN2C(C(=C1)F)=CC=C1NC(N=1)=NC=CC=1C(C=1F)=CC=NC=1N1CCOCC1 LZWSNXJCTUJJGI-UHFFFAOYSA-N 0.000 description 1
- FINLQJXRZOGZLB-SFTDATJTSA-N n-[3-methyl-4-[(1s,4s)-2-methylsulfonyl-2,5-diazabicyclo[2.2.1]heptan-5-yl]phenyl]-4-[6-(propylamino)pyridin-3-yl]pyrimidin-2-amine Chemical compound C([C@]1(N(C[C@@]2(C1)[H])S(C)(=O)=O)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(NCCC)N=C1 FINLQJXRZOGZLB-SFTDATJTSA-N 0.000 description 1
- NNZZTUSEJJHFDQ-PMACEKPBSA-N n-[3-methyl-4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]phenyl]-4-(2-morpholin-4-ylpyrimidin-5-yl)pyrimidin-2-amine Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C(C=N1)=CN=C1N1CCOCC1 NNZZTUSEJJHFDQ-PMACEKPBSA-N 0.000 description 1
- IZIBTLHFWKBENU-OALUTQOASA-N n-[5-[2-[3-methyl-4-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]pyrimidin-4-yl]pyridin-2-yl]methanesulfonamide Chemical compound C([C@]1(N(C[C@]2([H])C1)C)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(NS(C)(=O)=O)N=C1 IZIBTLHFWKBENU-OALUTQOASA-N 0.000 description 1
- FFXFRJNZYPZNCG-UHFFFAOYSA-N n-[5-[2-[[5-methyl-6-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyridin-3-yl]amino]pyrimidin-4-yl]pyridin-2-yl]methanesulfonamide Chemical compound CN1CC2CC1CN2C(C(=C1)C)=NC=C1NC(N=1)=NC=CC=1C1=CC=C(NS(C)(=O)=O)N=C1 FFXFRJNZYPZNCG-UHFFFAOYSA-N 0.000 description 1
- FFXFRJNZYPZNCG-ROUUACIJSA-N n-[5-[2-[[5-methyl-6-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridin-3-yl]amino]pyrimidin-4-yl]pyridin-2-yl]methanesulfonamide Chemical compound C([C@]1(N(C[C@]2([H])C1)C)[H])N2C(C(=C1)C)=NC=C1NC(N=1)=NC=CC=1C1=CC=C(NS(C)(=O)=O)N=C1 FFXFRJNZYPZNCG-ROUUACIJSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- GQOXEXVTDZYHNL-VXKWHMMOSA-N n-methyl-2-[4-[2-[3-methyl-4-[(1s,4s)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]pyrimidin-4-yl]phenyl]acetamide Chemical compound C([C@]1(N(C[C@]2([H])C1)C)[H])N2C(C(=C1)C)=CC=C1NC(N=1)=NC=CC=1C1=CC=C(CC(=O)NC)C=C1 GQOXEXVTDZYHNL-VXKWHMMOSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 208000025275 nodular sclerosis classical Hodgkin lymphoma Diseases 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000000683 nonmetastatic effect Effects 0.000 description 1
- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Chemical group C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- UZGLIIJVICEWHF-UHFFFAOYSA-N octogen Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)CN([N+]([O-])=O)C1 UZGLIIJVICEWHF-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960005010 orotic acid Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 208000021284 ovarian germ cell tumor Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 229940098695 palmitic acid Drugs 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 201000002530 pancreatic endocrine carcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 201000007052 paranasal sinus cancer Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- NQFOGDIWKQWFMN-UHFFFAOYSA-N phenalene Chemical group C1=CC([CH]C=C2)=C3C2=CC=CC3=C1 NQFOGDIWKQWFMN-UHFFFAOYSA-N 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 201000008312 primary pulmonary hypertension Diseases 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940072288 prograf Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 229940117820 purinethol Drugs 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000005495 pyridazyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 229940099538 rapamune Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 108091008726 retinoic acid receptors α Proteins 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- WEMQMWWWCBYPOV-UHFFFAOYSA-N s-indacene Chemical group C=1C2=CC=CC2=CC2=CC=CC2=1 WEMQMWWWCBYPOV-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229940063122 sandimmune Drugs 0.000 description 1
- 229940116353 sebacic acid Drugs 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229940115586 simulect Drugs 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 201000009373 spindle cell thymoma Diseases 0.000 description 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
- 208000037969 squamous neck cancer Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000005985 thienyl[1,3]dithianyl group Chemical group 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000002750 tryptase inhibitor Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 208000037965 uterine sarcoma Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000003156 vasculitic effect Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2926508P | 2008-02-15 | 2008-02-15 | |
| US3867208P | 2008-03-21 | 2008-03-21 | |
| US11204608P | 2008-11-06 | 2008-11-06 | |
| PCT/US2009/034159 WO2009103032A1 (en) | 2008-02-15 | 2009-02-13 | Pyrimidine-2-amine compounds and their use as inhibitors of jak kinases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2265607T3 true DK2265607T3 (en) | 2017-03-13 |
Family
ID=40591956
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK09710734.6T DK2265607T3 (en) | 2008-02-15 | 2009-02-13 | PYRIMIDIN-2-AMINE COMPOUNDS AND THEIR USE AS INHIBITORS OF JAK KINASES |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US8309566B2 (enExample) |
| EP (1) | EP2265607B1 (enExample) |
| JP (2) | JP5711537B2 (enExample) |
| KR (1) | KR101700454B1 (enExample) |
| CN (1) | CN102007124B (enExample) |
| AU (1) | AU2009214440B2 (enExample) |
| CA (1) | CA2715658C (enExample) |
| CY (1) | CY1118969T1 (enExample) |
| DK (1) | DK2265607T3 (enExample) |
| ES (1) | ES2617622T3 (enExample) |
| HR (1) | HRP20170317T1 (enExample) |
| HU (1) | HUE030912T2 (enExample) |
| IL (1) | IL207609A (enExample) |
| LT (1) | LT2265607T (enExample) |
| MX (1) | MX2010008926A (enExample) |
| NZ (1) | NZ587589A (enExample) |
| PL (1) | PL2265607T3 (enExample) |
| PT (1) | PT2265607T (enExample) |
| SI (1) | SI2265607T1 (enExample) |
| WO (1) | WO2009103032A1 (enExample) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2074115B1 (en) * | 2006-12-29 | 2018-03-07 | Rigel Pharmaceuticals, Inc. | N3-heteroaryl substituted triazoles and n5-heteroaryl substituted triazoles useful as axl inhibitors |
| US8012965B2 (en) | 2006-12-29 | 2011-09-06 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| AU2007342007A1 (en) | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Substituted triazoles useful as Axl inhibitors |
| WO2008083353A1 (en) | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| EP2078010B1 (en) | 2006-12-29 | 2014-01-29 | Rigel Pharmaceuticals, Inc. | Polycyclic heteroaryl substituted triazoles useful as axl inhibitors |
| WO2009032861A1 (en) | 2007-09-04 | 2009-03-12 | The Scripps Research Institute | Substituted pyrimidinyl-amines as protein kinase inhibitors |
| ES2424259T3 (es) * | 2007-10-26 | 2013-09-30 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos con arilo policíclico y heteroarilo policíclico, útiles como agentes inhibidores del Axl |
| LT2265607T (lt) | 2008-02-15 | 2017-03-27 | Rigel Pharmaceuticals, Inc. | Pirimidin-2-amino junginiai ir jų panaudojimas kaip jak kinazių slopiklių |
| JP5592884B2 (ja) | 2008-07-09 | 2014-09-17 | ライジェル ファーマシューティカルズ， インコーポレイテッド | Ａｘｌ阻害剤として有用な多環式ヘテロアリール置換トリアゾール |
| WO2010005879A1 (en) | 2008-07-09 | 2010-01-14 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| CA2749843C (en) | 2009-01-16 | 2017-09-05 | Rigel Pharmaceuticals, Inc. | Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer |
| EP2512246B1 (en) | 2009-12-17 | 2015-09-30 | Merck Sharp & Dohme Corp. | Aminopyrimidines as syk inhibitors |
| MX2012007154A (es) | 2009-12-17 | 2012-08-01 | Merck Sharp & Dohme | Aminopirimidinas como inhibidores de syk. |
| MX2012014158A (es) | 2010-06-04 | 2013-02-07 | Hoffmann La Roche | Derivados de aminopirimidina como moduladores de proteina cinasa rica repeticiones leucina 2 (lrrk2). |
| EP2593434A1 (en) | 2010-07-16 | 2013-05-22 | Purdue Pharma LP | Pyridine compounds as sodium channel blockers |
| PH12013500880A1 (en) | 2010-11-10 | 2013-07-01 | Hoffmann La Roche | Pyrazole aminopyrimidine derivatives as lrrk2 modulators |
| CN103619172A (zh) | 2011-05-10 | 2014-03-05 | 默沙东公司 | 作为syk抑制剂的氨基嘧啶 |
| US9145391B2 (en) | 2011-05-10 | 2015-09-29 | Merck Sharp & Dohme Corp. | Bipyridylaminopyridines as Syk 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 |
| US9206127B2 (en) | 2012-03-16 | 2015-12-08 | Purdue Pharm, L.P. | Substituted pyridines as sodium channel blockers |
| WO2013173506A2 (en) | 2012-05-16 | 2013-11-21 | Rigel Pharmaceuticals, Inc. | Method of treating muscular degradation |
| US8809359B2 (en) * | 2012-06-29 | 2014-08-19 | Ym Biosciences Australia Pty Ltd | Phenyl amino pyrimidine bicyclic compounds and uses thereof |
| CN103709172B (zh) * | 2012-09-28 | 2018-02-13 | 江苏先声药业有限公司 | 取代呋喃并哌啶衍生物及其应用 |
| US9714252B2 (en) | 2012-12-20 | 2017-07-25 | Purdue Pharma L.P. | Cyclic sulfonamides as sodium channel blockers |
| GB201303109D0 (en) | 2013-02-21 | 2013-04-10 | Domainex Ltd | Novel pyrimidine compounds |
| ES2618072T3 (es) * | 2013-08-07 | 2017-06-20 | Cadila Healthcare Limited | N-Cianometilamidas como inhibidores de la quinasa Janus |
| CN111493682A (zh) * | 2013-08-26 | 2020-08-07 | 皇家飞利浦有限公司 | 用于准备食物的具有带滑动机构的抽屉的装置 |
| CN104860941B (zh) * | 2014-02-25 | 2017-03-22 | 上海海雁医药科技有限公司 | 2,4‑二取代苯‑1,5‑二胺衍生物及其应用以及由其制备的药物组合物和药用组合物 |
| US10730866B2 (en) | 2014-04-07 | 2020-08-04 | Purdue Pharma L.P. | Indole derivatives and use thereof |
| BR112017019286B1 (pt) * | 2015-03-11 | 2023-02-14 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Derivados de 2h-pirazol substituídos ou um sal farmacêuticamente aceitável dos mesmos |
| WO2017007658A1 (en) * | 2015-07-07 | 2017-01-12 | Rigel Pharmaceuticals, Inc. | A combination for immune mediated cancer treatment |
| CN106810536A (zh) * | 2015-11-30 | 2017-06-09 | 甘李药业股份有限公司 | 一种蛋白激酶抑制剂及其制备方法和医药用途 |
| GB201702947D0 (en) | 2017-02-23 | 2017-04-12 | Domainex Ltd | Novel compounds |
| US12171764B2 (en) | 2018-06-20 | 2024-12-24 | Biora Therapeutics, Inc. | Treatment of a disease of the gastrointestinal tract with a JAK or other kinase inhibitor |
| CN114364675A (zh) | 2019-05-05 | 2022-04-15 | 上海齐鲁锐格医药研发有限公司 | Cdk抑制剂 |
| US20220372135A1 (en) | 2019-09-27 | 2022-11-24 | Disc Medicine, Inc. | Methods for treating myelofibrosis and related conditions |
| IL297437A (en) | 2020-05-13 | 2022-12-01 | Disc Medicine Inc | Anti-hemojuvelin (hjv) antibodies for treating myelofibrosis |
| CN113880813B (zh) * | 2020-07-01 | 2024-05-28 | 杭州百诚医药科技股份有限公司 | 一种2-氨基嘧啶类杂环化合物及应用 |
| CN116113628A (zh) * | 2020-08-31 | 2023-05-12 | 甘李药业股份有限公司 | 一种含cdk4/6抑制剂的药物组合物 |
| JP2024502175A (ja) * | 2021-01-07 | 2024-01-17 | オンタリオ・インスティテュート・フォー・キャンサー・リサーチ（オーアイシーアール） | Ｎｕａｋキナーゼの阻害剤としてのイソインドリノンアミノピリミジン化合物、その組成物及び使用 |
| CN115073425B (zh) * | 2021-03-16 | 2023-11-14 | 中国科学院上海药物研究所 | 一类作为tbk1抑制剂的化合物、包含其的药物组合物及其用途 |
| CN115160341B (zh) * | 2022-07-18 | 2023-07-18 | 中国医学科学院医学实验动物研究所 | 苯并噁嗪类化合物及其药物用途 |
Family Cites Families (116)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4788195A (en) * | 1986-01-13 | 1988-11-29 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
| US4876252A (en) * | 1986-01-13 | 1989-10-24 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
| US5728536A (en) * | 1993-07-29 | 1998-03-17 | St. Jude Children's Research Hospital | Jak kinases and regulation of Cytokine signal transduction |
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| WO1995010506A1 (en) | 1993-10-12 | 1995-04-20 | The Du Pont Merck Pharmaceutical Company | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
| US6316635B1 (en) * | 1995-06-07 | 2001-11-13 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| US6696448B2 (en) * | 1996-06-05 | 2004-02-24 | Sugen, Inc. | 3-(piperazinylbenzylidenyl)-2-indolinone compounds and derivatives as protein tyrosine kinase inhibitors |
| GB9619284D0 (en) | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| US6486185B1 (en) * | 1997-05-07 | 2002-11-26 | Sugen, Inc. | 3-heteroarylidene-2-indolinone protein kinase inhibitors |
| US6316429B1 (en) * | 1997-05-07 | 2001-11-13 | Sugen, Inc. | Bicyclic protein kinase inhibitors |
| CA2296014A1 (en) * | 1997-07-03 | 1999-01-14 | Frank W. Hobbs | Aryl-and arylamino-substituted heterocycles as corticotropin releasing hormone antagonists |
| GB9718913D0 (en) | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
| US6133305A (en) * | 1997-09-26 | 2000-10-17 | Sugen, Inc. | 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity |
| CA2337999A1 (en) | 1998-06-30 | 2000-01-06 | Parker Hughes Institute | Method for inhibiting c-jun expression using jak-3 inhibitors |
| IL141434A0 (en) | 1998-08-21 | 2002-03-10 | Parker Hughes Inst | Quinazoline derivatives |
| US6841567B1 (en) | 1999-02-12 | 2005-01-11 | Cephalon, Inc. | Cyclic substituted fused pyrrolocarbazoles and isoindolones |
| GB9904995D0 (en) | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Substituted aza-oxindole derivatives |
| US6624171B1 (en) * | 1999-03-04 | 2003-09-23 | Smithkline Beecham Corporation | Substituted aza-oxindole derivatives |
| US6080747A (en) * | 1999-03-05 | 2000-06-27 | Hughes Institute | JAK-3 inhibitors for treating allergic disorders |
| US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| AR032130A1 (es) | 1999-08-13 | 2003-10-29 | Vertex Pharma | Un compuesto inhibidor de quinasas proteicas, una composicion farmaceutica que lo incluye, y un metodo para tratar afecciones con dicho compuesto |
| GB9924862D0 (en) * | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2003518023A (ja) * | 1999-11-30 | 2003-06-03 | パーカー ヒューズ インスティテュート | トロンビン誘導血小板凝集の阻害剤 |
| AU777911B2 (en) | 1999-12-10 | 2004-11-04 | Pfizer Products Inc. | Pyrrolo(2,3-d)pyrimidine compounds |
| US6610688B2 (en) * | 1999-12-21 | 2003-08-26 | Sugen, Inc. | 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors |
| CA2397774A1 (en) | 2000-01-24 | 2001-07-26 | Genzyme Corporation | Jak/stat pathway inhibitors and the uses thereof |
| JP4739632B2 (ja) | 2000-02-05 | 2011-08-03 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｅｒｋのインヒビターとして有用なピラゾール組成物 |
| IL145757A (en) * | 2000-02-05 | 2007-12-03 | Vertex Pharma | History of pyrazole and pharmaceutical preparations containing them |
| AR028261A1 (es) | 2000-03-28 | 2003-04-30 | Wyeth Corp | Inhibidores triciclicos de la proteina quinasa |
| US6608048B2 (en) * | 2000-03-28 | 2003-08-19 | Wyeth Holdings | Tricyclic protein kinase inhibitors |
| UA74370C2 (uk) | 2000-06-26 | 2005-12-15 | Пфайзер Продактс Інк. | Піроло(2,3-d)піримідинові сполуки як імуносупресори |
| GB0022438D0 (en) * | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| AU2001229722A1 (en) | 2000-11-29 | 2002-06-11 | Parker Hughes Institute | Inhibitors of thrombin induced platelet aggregation |
| EP1343781B1 (en) | 2000-12-05 | 2008-09-03 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| US20020115173A1 (en) * | 2000-12-11 | 2002-08-22 | Children's Medical Center Corporation | Short peptides from the 'A-region' of protein kinases which selectively modulate protein kinase activity |
| CA2432114A1 (en) * | 2000-12-20 | 2002-07-18 | Sugen, Inc. | 4-(hetero)aryl substituted indolinones |
| WO2002060492A1 (en) | 2001-01-30 | 2002-08-08 | Cytopia Pty Ltd | Methods of inhibiting kinases |
| AUPR279101A0 (en) * | 2001-01-30 | 2001-02-22 | Cytopia Pty Ltd | Protein kinase signalling |
| MY130778A (en) | 2001-02-09 | 2007-07-31 | Vertex Pharma | Heterocyclic inhibitiors of erk2 and uses thereof |
| DE60230160D1 (de) | 2001-02-20 | 2009-01-15 | Astrazeneca Ab | 2-arylaminopyrimidine zur behandlung von mit gsk3 in zusammenhang stehenden erkrankungen |
| CA2441733A1 (en) * | 2001-03-29 | 2002-10-10 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| EP1389206B1 (en) | 2001-04-13 | 2006-09-13 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
| WO2002096905A1 (en) | 2001-06-01 | 2002-12-05 | Vertex Pharmaceuticals Incorporated | Thiazole compounds useful as inhibitors of protein kinases |
| US7301023B2 (en) | 2001-05-31 | 2007-11-27 | Pfizer Inc. | Chiral salt resolution |
| US6825190B2 (en) * | 2001-06-15 | 2004-11-30 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors and uses thereof |
| US6689778B2 (en) | 2001-07-03 | 2004-02-10 | Vertex Pharmaceuticals Incorporated | Inhibitors of Src and Lck protein kinases |
| WO2003011837A1 (en) | 2001-08-01 | 2003-02-13 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6433018B1 (en) * | 2001-08-31 | 2002-08-13 | The Research Foundation Of State University Of New York | Method for reducing hypertrophy and ischemia |
| WO2003020698A2 (en) | 2001-09-06 | 2003-03-13 | Prochon Biotech Ltd. | Protein tyrosine kinase inhibitors |
| US6777417B2 (en) * | 2001-09-10 | 2004-08-17 | Sugen, Inc. | 3-(4,5,6,7-tetrahydroindol-2-ylmethylidiene-2-indolinone derivatives as kinase inhibitors |
| WO2003030909A1 (en) | 2001-09-25 | 2003-04-17 | Bayer Pharmaceuticals Corporation | 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer |
| GT200200234A (es) | 2001-12-06 | 2003-06-27 | Compuestos cristalinos novedosos | |
| EP1463730B1 (en) | 2001-12-17 | 2006-04-19 | SmithKline Beecham Corporation | Pyrazolopyridazine derivatives |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| US6998391B2 (en) * | 2002-02-07 | 2006-02-14 | Supergen.Inc. | Method for treating diseases associated with abnormal kinase activity |
| EP1501829B1 (en) | 2002-05-06 | 2010-11-24 | Vertex Pharmaceuticals Incorporated | Thiadiazoles or oxadiazoles and their use as inhibitors of jak protein kinase |
| WO2003101989A1 (en) * | 2002-05-30 | 2003-12-11 | Vertex Pharmaceuticals Incorporated | Inhibitors of jak and cdk2 protein kinases |
| GB0215844D0 (en) | 2002-07-09 | 2002-08-14 | Novartis Ag | Organic compounds |
| JP4570955B2 (ja) | 2002-07-09 | 2010-10-27 | バーテクス ファーマスーティカルズ インコーポレイテッド | プロテインキナーゼ阻害活性を持つイミダゾール類 |
| IL166241A0 (en) * | 2002-07-29 | 2006-01-15 | Rigel Pharmaceuticals Inc | Method of treating or preventing autoimmune diseases with 2,4-pyrimidinedinediamine compounds |
| MXPA05001804A (es) | 2002-08-14 | 2005-05-27 | Vertex Pharma | Inhibidores de proteinas cinasas y usos de los mismos. |
| CA2506772A1 (en) | 2002-11-01 | 2004-05-21 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of jak and other protein kinases |
| ATE371656T1 (de) * | 2002-11-04 | 2007-09-15 | Vertex Pharma | Heteroaryl-pyrimidinderivate als jak-inhibitoren |
| AU2003286895A1 (en) * | 2002-11-05 | 2004-06-07 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of jak and other protein kinases |
| GB0226583D0 (en) | 2002-11-14 | 2002-12-18 | Cyclacel Ltd | Compounds |
| AR042052A1 (es) * | 2002-11-15 | 2005-06-08 | Vertex Pharma | Diaminotriazoles utiles como inhibidores de proteinquinasas |
| BR0316470A (pt) | 2002-11-21 | 2005-10-11 | Pfizer Prod Inc | Derivados de 3-amino-piperadina e métodos de preparação |
| BR0316487A (pt) | 2002-11-26 | 2005-10-11 | Pfizer Prod Inc | Método todo de tratamento da rejeição de transplantes |
| AU2003297160A1 (en) | 2002-12-18 | 2004-07-22 | Vertex Pharmaceuticals Incorporated | Benzisoxazole derivatives useful as inhibitors of protein kinases |
| CA2523126A1 (en) | 2003-03-25 | 2004-10-14 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
| EP1610793A2 (en) | 2003-03-25 | 2006-01-04 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
| JP2006522124A (ja) | 2003-04-03 | 2006-09-28 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼのインヒビターとして有用な組成物 |
| EP1620437B1 (en) | 2003-04-29 | 2009-06-17 | Pfizer Limited | 5,7-diaminopyrazolo¬4,3-d pyrimidines useful in the traetment of hypertension |
| WO2004099186A1 (en) * | 2003-05-06 | 2004-11-18 | Il Yang Pharm Co., Ltd. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
| JP2006528629A (ja) | 2003-07-24 | 2006-12-21 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼ阻害薬 |
| US8178671B2 (en) | 2003-07-30 | 2012-05-15 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2, 4-pyrimidinediamine compounds |
| AU2004261482A1 (en) | 2003-07-30 | 2005-02-10 | Cyclacel Limited | Pyridinylamino-pyrimidine derivatives as protein kinase inhibitors |
| JP2007500179A (ja) | 2003-07-30 | 2007-01-11 | サイクラセル・リミテッド | キナーゼ阻害剤としての２−アミノフェニル−４−フェニルピリミジン |
| OA13235A (en) | 2003-08-14 | 2006-12-13 | Pfizer | Piperazine derivatives for the treatment of HIV infections. |
| AR045595A1 (es) | 2003-09-04 | 2005-11-02 | Vertex Pharma | Composiciones utiles como inhibidores de proteinas quinasas |
| ES2295924T3 (es) | 2003-10-03 | 2008-04-16 | Pfizer, Inc. | Derivados de tropano imidazopirina sustituidos con actividad antagonista de los receptores ccr5 para el tratamiento de vih y de la inflamacion. |
| US7169781B2 (en) | 2003-10-17 | 2007-01-30 | Hoffmann-La Roche Inc. | Imidazole derivatives and their use as pharmaceutical agents |
| TW200528101A (en) | 2004-02-03 | 2005-09-01 | Astrazeneca Ab | Chemical compounds |
| GB0402653D0 (en) | 2004-02-06 | 2004-03-10 | Cyclacel Ltd | Compounds |
| ES2505090T3 (es) * | 2004-05-07 | 2014-10-09 | Amgen Inc. | Derivados heterocíclicos nitrogenados como moduladores de proteína cinasas y su uso para el tratamiento de angiogénesis y cáncer |
| GB0411791D0 (en) | 2004-05-26 | 2004-06-30 | Cyclacel Ltd | Compounds |
| WO2006021458A2 (en) | 2004-08-27 | 2006-03-02 | Gpc Biotech Ag | Pyrimidine derivatives |
| EP1814878B1 (en) * | 2004-11-24 | 2012-01-04 | Rigel Pharmaceuticals, Inc. | Spiro-2, 4-pyrimidinediamine compounds and their uses |
| EP1828185B1 (en) | 2004-12-21 | 2009-05-06 | SmithKline Beecham Corporation | 2-pyrimidinyl pyrazolopyridine erbb kinase inhibitors |
| EP1856135B1 (en) * | 2005-01-19 | 2009-12-09 | Rigel Pharmaceuticals, Inc. | Prodrugs of 2,4-pyrimidinediamine compounds and their uses |
| GB0504753D0 (en) | 2005-03-08 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| EP1907385A4 (en) | 2005-07-26 | 2009-05-06 | Smithkline Beecham Corp | LINKS |
| JP2009506040A (ja) | 2005-08-26 | 2009-02-12 | スミスクライン・ビーチャム・コーポレイション | オーロラキナーゼのピリミジニル−ピラゾール阻害剤 |
| US7884119B2 (en) | 2005-09-07 | 2011-02-08 | Rigel Pharmaceuticals, Inc. | Triazole derivatives useful as Axl inhibitors |
| DE102005048072A1 (de) | 2005-09-24 | 2007-04-05 | Bayer Cropscience Ag | Thiazole als Fungizide |
| GB0520955D0 (en) | 2005-10-14 | 2005-11-23 | Cyclacel Ltd | Compound |
| JP2009519218A (ja) | 2005-11-03 | 2009-05-14 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | ピリミジニル−チオフェンキナーゼモジュレータ |
| WO2007067506A2 (en) | 2005-12-05 | 2007-06-14 | Smithkline Beecham Corporation | 2-pyrimidinyl pyrazolopyridine erbb kinase inhibitors |
| WO2007089768A2 (en) * | 2006-01-30 | 2007-08-09 | Exelixis, Inc. | 4-aryl-2-amino-pyrimidines or 4-aryl-2-aminoalkyl-pyrimidines as jak-2 modulators and pharmaceutical compositions containing them |
| WO2007132221A1 (en) | 2006-05-12 | 2007-11-22 | Cyclacel Limited | Combined anticancer pyrimidine-thiazole aurora kinase inhibitors |
| US8258129B2 (en) * | 2006-07-06 | 2012-09-04 | Boehringer Ingelheim International Gmbh | 4-heterocycloalkylpyri(mi)dines, process for the preparation thereof and their use as medicaments |
| US8097630B2 (en) | 2006-10-10 | 2012-01-17 | Rigel Pharmaceuticals, Inc. | Pinane-substituted pyrimidinediamine derivatives useful as Axl inhibitors |
| US7879856B2 (en) | 2006-12-22 | 2011-02-01 | Rigel Pharmaceuticals, Inc. | Diaminothiazoles useful as Axl inhibitors |
| EP2074115B1 (en) | 2006-12-29 | 2018-03-07 | Rigel Pharmaceuticals, Inc. | N3-heteroaryl substituted triazoles and n5-heteroaryl substituted triazoles useful as axl inhibitors |
| EP2078010B1 (en) | 2006-12-29 | 2014-01-29 | Rigel Pharmaceuticals, Inc. | Polycyclic heteroaryl substituted triazoles useful as axl inhibitors |
| AU2007342007A1 (en) | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Substituted triazoles useful as Axl inhibitors |
| WO2008083353A1 (en) | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| US8012965B2 (en) | 2006-12-29 | 2011-09-06 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| HUE029188T2 (en) * | 2007-03-12 | 2017-03-28 | Ym Biosciences Australia Pty | Phenylamino-pyrimidine compounds and their use |
| US20100216779A1 (en) * | 2007-06-01 | 2010-08-26 | Glaxosmithkline Llc | Imidazopyridine Kinase Inhibitors |
| ES2424259T3 (es) | 2007-10-26 | 2013-09-30 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos con arilo policíclico y heteroarilo policíclico, útiles como agentes inhibidores del Axl |
| LT2265607T (lt) * | 2008-02-15 | 2017-03-27 | Rigel Pharmaceuticals, Inc. | Pirimidin-2-amino junginiai ir jų panaudojimas kaip jak kinazių slopiklių |
| JP5592884B2 (ja) | 2008-07-09 | 2014-09-17 | ライジェル ファーマシューティカルズ， インコーポレイテッド | Ａｘｌ阻害剤として有用な多環式ヘテロアリール置換トリアゾール |
| WO2010005879A1 (en) | 2008-07-09 | 2010-01-14 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| CA2749843C (en) | 2009-01-16 | 2017-09-05 | Rigel Pharmaceuticals, Inc. | Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer |
-
2009
- 2009-02-13 LT LTEP09710734.6T patent/LT2265607T/lt unknown
- 2009-02-13 HU HUE09710734A patent/HUE030912T2/en unknown
- 2009-02-13 CN CN200980113512.6A patent/CN102007124B/zh not_active Expired - Fee Related
- 2009-02-13 WO PCT/US2009/034159 patent/WO2009103032A1/en not_active Ceased
- 2009-02-13 JP JP2010546945A patent/JP5711537B2/ja not_active Expired - Fee Related
- 2009-02-13 DK DK09710734.6T patent/DK2265607T3/en active
- 2009-02-13 KR KR1020107020561A patent/KR101700454B1/ko not_active Expired - Fee Related
- 2009-02-13 NZ NZ587589A patent/NZ587589A/xx not_active IP Right Cessation
- 2009-02-13 CA CA2715658A patent/CA2715658C/en active Active
- 2009-02-13 EP EP09710734.6A patent/EP2265607B1/en active Active
- 2009-02-13 AU AU2009214440A patent/AU2009214440B2/en not_active Ceased
- 2009-02-13 HR HRP20170317TT patent/HRP20170317T1/hr unknown
- 2009-02-13 US US12/371,550 patent/US8309566B2/en not_active Expired - Fee Related
- 2009-02-13 PT PT97107346T patent/PT2265607T/pt unknown
- 2009-02-13 ES ES09710734.6T patent/ES2617622T3/es active Active
- 2009-02-13 SI SI200931620A patent/SI2265607T1/sl unknown
- 2009-02-13 MX MX2010008926A patent/MX2010008926A/es active IP Right Grant
- 2009-02-13 PL PL09710734T patent/PL2265607T3/pl unknown
-
2010
- 2010-08-12 IL IL207609A patent/IL207609A/en active IP Right Grant
-
2012
- 2012-09-14 US US13/619,843 patent/US8735418B2/en active Active
-
2014
- 2014-04-02 US US14/243,579 patent/US9624229B2/en not_active Expired - Fee Related
- 2014-11-04 JP JP2014224663A patent/JP2015061846A/ja active Pending
-
2017
- 2017-03-13 CY CY20171100312T patent/CY1118969T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2715658C (en) | 2016-07-19 |
| US20140213585A1 (en) | 2014-07-31 |
| JP5711537B2 (ja) | 2015-05-07 |
| LT2265607T (lt) | 2017-03-27 |
| EP2265607B1 (en) | 2016-12-14 |
| US8735418B2 (en) | 2014-05-27 |
| AU2009214440B2 (en) | 2014-09-25 |
| IL207609A0 (en) | 2010-12-30 |
| MX2010008926A (es) | 2011-02-23 |
| HRP20170317T1 (hr) | 2017-04-21 |
| PL2265607T3 (pl) | 2017-07-31 |
| PT2265607T (pt) | 2017-03-08 |
| CN102007124A (zh) | 2011-04-06 |
| KR20100124292A (ko) | 2010-11-26 |
| SI2265607T1 (sl) | 2017-06-30 |
| ES2617622T3 (es) | 2017-06-19 |
| NZ587589A (en) | 2012-10-26 |
| CY1118969T1 (el) | 2018-01-10 |
| AU2009214440A1 (en) | 2009-08-20 |
| KR101700454B1 (ko) | 2017-01-26 |
| US8309566B2 (en) | 2012-11-13 |
| JP2011512361A (ja) | 2011-04-21 |
| IL207609A (en) | 2015-08-31 |
| US9624229B2 (en) | 2017-04-18 |
| HUE030912T2 (en) | 2017-06-28 |
| CN102007124B (zh) | 2014-06-18 |
| WO2009103032A1 (en) | 2009-08-20 |
| US20130018041A1 (en) | 2013-01-17 |
| CA2715658A1 (en) | 2009-08-20 |
| JP2015061846A (ja) | 2015-04-02 |
| US20090258864A1 (en) | 2009-10-15 |
| EP2265607A1 (en) | 2010-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2265607T3 (en) | PYRIMIDIN-2-AMINE COMPOUNDS AND THEIR USE AS INHIBITORS OF JAK KINASES | |
| US10577380B2 (en) | MK2 inhibitors and uses thereof | |
| US11053215B2 (en) | Heterocyclic compounds useful as Pim kinase inhibitors | |
| CA2779105C (en) | Kinase inhibitors | |
| ME00811B (me) | JEDINJENJA l KOMPOZICIJE KAO INHIBITORI PROTEIN KINAZE | |
| WO2015038417A1 (en) | Compounds for regulating fak and/or src pathways | |
| AU2008312631A1 (en) | Thienopyrimidine and pyrazolopyrimidine compounds and their use as mTOR kinase and PI3 kinase inhibitors | |
| TW201008949A (en) | Triazine compounds as PI3 kinase and mTOR inhibitors | |
| CA2942636A1 (en) | Macrocylic pyrimidine derivatives | |
| CA3187566A1 (en) | Quaternary indazole glucocorticoid receptor antagonists | |
| JP2023542042A (ja) | Ｅｇｆｒ阻害剤としてのインドリン化合物及び誘導体 | |
| KR102669660B1 (ko) | 키나아제 억제 활성을 가진 방향족 헤테로고리 화합물 | |
| US12037330B2 (en) | Heteroaryl derivative compounds, and uses thereof | |
| HK1150606B (en) | Pyrimidine-2-amine compounds and their use as inhibitors of jak kinases | |
| HK1150606A (en) | Pyrimidine-2-amine compounds and their use as inhibitors of jak kinases |