JP2002526500A - プロテインキナーゼ阻害剤としてのピロロピリミジン - Google Patents
プロテインキナーゼ阻害剤としてのピロロピリミジンInfo
- Publication number
- JP2002526500A JP2002526500A JP2000574112A JP2000574112A JP2002526500A JP 2002526500 A JP2002526500 A JP 2002526500A JP 2000574112 A JP2000574112 A JP 2000574112A JP 2000574112 A JP2000574112 A JP 2000574112A JP 2002526500 A JP2002526500 A JP 2002526500A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- pyrrolo
- amino
- pyrimidin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title 1
- 239000003909 protein kinase inhibitor Substances 0.000 title 1
- 150000004944 pyrrolopyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 259
- 238000000034 method Methods 0.000 claims abstract description 107
- 230000000694 effects Effects 0.000 claims abstract description 81
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
- 201000010099 disease Diseases 0.000 claims abstract description 57
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 49
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 41
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 41
- 230000033115 angiogenesis Effects 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 201000011510 cancer Diseases 0.000 claims abstract description 20
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 11
- 206010052779 Transplant rejections Diseases 0.000 claims abstract description 7
- 239000002207 metabolite Substances 0.000 claims abstract description 7
- 230000004054 inflammatory process Effects 0.000 claims abstract description 5
- 206010061218 Inflammation Diseases 0.000 claims abstract description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 4
- -1 trifluoromethylcarbonylamino Chemical group 0.000 claims description 255
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 125
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 108
- 125000000217 alkyl group Chemical group 0.000 claims description 90
- 125000003118 aryl group Chemical group 0.000 claims description 89
- 125000001072 heteroaryl group Chemical group 0.000 claims description 86
- 229910052757 nitrogen Inorganic materials 0.000 claims description 79
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 60
- 102000001253 Protein Kinase Human genes 0.000 claims description 58
- 108060006633 protein kinase Proteins 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 50
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 45
- 125000001931 aliphatic group Chemical group 0.000 claims description 39
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 38
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 38
- 101100481410 Mus musculus Tek gene Proteins 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 101100481408 Danio rerio tie2 gene Proteins 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 206010030113 Oedema Diseases 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 27
- 230000001404 mediated effect Effects 0.000 claims description 26
- 230000002401 inhibitory effect Effects 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 22
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims description 21
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
- 229940124530 sulfonamide Drugs 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- 230000014509 gene expression Effects 0.000 claims description 16
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 13
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 12
- 230000002491 angiogenic effect Effects 0.000 claims description 12
- 239000003102 growth factor Substances 0.000 claims description 12
- CTHYLYWLCPLBHO-UKFGXMPHSA-N C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(C1=CC=CC=C1)#N Chemical compound C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(C1=CC=CC=C1)#N CTHYLYWLCPLBHO-UKFGXMPHSA-N 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 claims description 9
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 claims description 9
- 208000025865 Ulcer Diseases 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 208000028867 ischemia Diseases 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 231100000397 ulcer Toxicity 0.000 claims description 9
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims description 8
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims description 8
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 206010003445 Ascites Diseases 0.000 claims description 7
- 206010016654 Fibrosis Diseases 0.000 claims description 7
- 201000004681 Psoriasis Diseases 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 208000006673 asthma Diseases 0.000 claims description 7
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 230000001023 pro-angiogenic effect Effects 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 claims description 5
- 206010048962 Brain oedema Diseases 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 claims description 5
- 206010021143 Hypoxia Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 206010040047 Sepsis Diseases 0.000 claims description 5
- 230000006044 T cell activation Effects 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 208000006752 brain edema Diseases 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 230000004761 fibrosis Effects 0.000 claims description 5
- 230000007954 hypoxia Effects 0.000 claims description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 5
- 208000002780 macular degeneration Diseases 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- 125000005504 styryl group Chemical group 0.000 claims description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
- 230000008728 vascular permeability Effects 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 claims description 4
- 208000010412 Glaucoma Diseases 0.000 claims description 4
- 206010061216 Infarction Diseases 0.000 claims description 4
- 102100040681 Platelet-derived growth factor C Human genes 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 4
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 claims description 4
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
- 150000008378 aryl ethers Chemical class 0.000 claims description 4
- 125000004421 aryl sulphonamide group Chemical group 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
- 150000002475 indoles Chemical class 0.000 claims description 4
- 230000007574 infarction Effects 0.000 claims description 4
- 230000028709 inflammatory response Effects 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 210000005087 mononuclear cell Anatomy 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000005541 phosphonamide group Chemical group 0.000 claims description 4
- 108010017992 platelet-derived growth factor C Proteins 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- 230000008733 trauma Effects 0.000 claims description 4
- 201000009273 Endometriosis Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010025538 Malignant ascites Diseases 0.000 claims description 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
- BSCFDQRAZKSKOV-RJWLIWLUSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(C)CCN1[C@@H]1CC[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)C)=C2)CC1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(C)CCN1[C@@H]1CC[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)C)=C2)CC1 BSCFDQRAZKSKOV-RJWLIWLUSA-N 0.000 claims description 3
- 208000010191 Osteitis Deformans Diseases 0.000 claims description 3
- 206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 claims description 3
- 208000027868 Paget disease Diseases 0.000 claims description 3
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 3
- 206010046788 Uterine haemorrhage Diseases 0.000 claims description 3
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 claims description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000005124 aminocycloalkyl group Chemical group 0.000 claims description 3
- 230000001580 bacterial effect Effects 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 230000007882 cirrhosis Effects 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 210000000416 exudates and transudate Anatomy 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 230000028993 immune response Effects 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 208000027202 mammary Paget disease Diseases 0.000 claims description 3
- 201000011461 pre-eclampsia Diseases 0.000 claims description 3
- 208000005333 pulmonary edema Diseases 0.000 claims description 3
- 201000000306 sarcoidosis Diseases 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 230000009885 systemic effect Effects 0.000 claims description 3
- 206010043778 thyroiditis Diseases 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- KQYMKXFMYBEGGV-HOOFBURESA-N (z)-but-2-enedioic acid;7-[(1s,3s)-3-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(C)CCN1[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CCC1 KQYMKXFMYBEGGV-HOOFBURESA-N 0.000 claims description 2
- VERVXQHJOXBEON-UKFGXMPHSA-N (z)-but-2-enedioic acid;7-[3-(4-methylpiperazin-1-yl)cyclopentyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(C)CCN1C1CC(N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CC1 VERVXQHJOXBEON-UKFGXMPHSA-N 0.000 claims description 2
- FNQJDLTXOVEEFB-UHFFFAOYSA-N 1,2,3-benzothiadiazole Chemical class C1=CC=C2SN=NC2=C1 FNQJDLTXOVEEFB-UHFFFAOYSA-N 0.000 claims description 2
- SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical class C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 claims description 2
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical class C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 claims description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical class C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- CUVKCBQMMTYQDV-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7-piperidin-4-ylpyrrolo[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1=2C(N)=NC=NC=2N(C2CCNCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 CUVKCBQMMTYQDV-UHFFFAOYSA-N 0.000 claims description 2
- RIYCTZNNVAPBTP-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7-pyrrolidin-3-ylpyrrolo[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1=2C(N)=NC=NC=2N(C2CNCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 RIYCTZNNVAPBTP-UHFFFAOYSA-N 0.000 claims description 2
- XXVMQVGMHJTNNM-GOTSBHOMSA-N 7-[(1s,3s)-3-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CCC1 XXVMQVGMHJTNNM-GOTSBHOMSA-N 0.000 claims description 2
- RAFDMAREGMMOIL-USLJDWOKSA-N 7-[(1s,3s)-3-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(C)CCN1[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CCC1 RAFDMAREGMMOIL-USLJDWOKSA-N 0.000 claims description 2
- 239000005964 Acibenzolar-S-methyl Substances 0.000 claims description 2
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- MKEROYXTJIGURE-JVUUZWNBSA-N C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(N)(O)=O Chemical compound C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.C(N)(O)=O MKEROYXTJIGURE-JVUUZWNBSA-N 0.000 claims description 2
- FMUOXVONZMGWIG-SOAUALDESA-N CC(C)N1CCN(CC1)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 Chemical compound CC(C)N1CCN(CC1)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 FMUOXVONZMGWIG-SOAUALDESA-N 0.000 claims description 2
- VDRZDUSWGNJJPK-RQNOJGIXSA-N CCN1CCN(CC1)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 Chemical compound CCN1CCN(CC1)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 VDRZDUSWGNJJPK-RQNOJGIXSA-N 0.000 claims description 2
- VITHMKRAFXZBHC-MXVIHJGJSA-N CN(C)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 Chemical compound CN(C)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 VITHMKRAFXZBHC-MXVIHJGJSA-N 0.000 claims description 2
- YHGKQELKHNKVTG-SOAUALDESA-N COCCN1CCN(CC1)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 Chemical compound COCCN1CCN(CC1)[C@H]1CC[C@@H](CC1)n1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc12 YHGKQELKHNKVTG-SOAUALDESA-N 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 206010010741 Conjunctivitis Diseases 0.000 claims description 2
- 206010054044 Diabetic microangiopathy Diseases 0.000 claims description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 2
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 claims description 2
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 claims description 2
- 206010017533 Fungal infection Diseases 0.000 claims description 2
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 2
- 102100021866 Hepatocyte growth factor Human genes 0.000 claims description 2
- 208000009889 Herpes Simplex Diseases 0.000 claims description 2
- 208000007514 Herpes zoster Diseases 0.000 claims description 2
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 2
- 206010051151 Hyperviscosity syndrome Diseases 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 208000016604 Lyme disease Diseases 0.000 claims description 2
- 206010025421 Macule Diseases 0.000 claims description 2
- 208000031888 Mycoses Diseases 0.000 claims description 2
- OITSZLJUQJSVJD-HZCBDIJESA-N Nc1ncnc2n(cc(-c3ccc(Oc4ccccc4)cc3)c12)[C@H]1CC[C@@H](CC1)N1CCCC1 Chemical compound Nc1ncnc2n(cc(-c3ccc(Oc4ccccc4)cc3)c12)[C@H]1CC[C@@H](CC1)N1CCCC1 OITSZLJUQJSVJD-HZCBDIJESA-N 0.000 claims description 2
- 206010028851 Necrosis Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- VBIOZKAWUKJTGU-XTRVKEAMSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1=2C(N)=NC=NC=2N([C@@H]2CC[C@H](CC2)N2CCCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1=2C(N)=NC=NC=2N([C@@H]2CC[C@H](CC2)N2CCCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 VBIOZKAWUKJTGU-XTRVKEAMSA-N 0.000 claims description 2
- ROCPMRNTUHWNAA-IHLMUMEFSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.N1([C@@H]2CC[C@H](CC2)n2c3ncnc(N)c3c(c2)-c2ccc(cc2)Oc2ccccc2)CCCCC1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.N1([C@@H]2CC[C@H](CC2)n2c3ncnc(N)c3c(c2)-c2ccc(cc2)Oc2ccccc2)CCCCC1 ROCPMRNTUHWNAA-IHLMUMEFSA-N 0.000 claims description 2
- DHINWTJZDYEBDZ-HEQCVELZSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(C(C)C)CCN1[C@@H]1CC[C@@H](N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CC1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(C(C)C)CCN1[C@@H]1CC[C@@H](N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CC1 DHINWTJZDYEBDZ-HEQCVELZSA-N 0.000 claims description 2
- OBEVZOQOHFEYGJ-HEQCVELZSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(CCOC)CCN1[C@@H]1CC[C@@H](N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CC1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(CCOC)CCN1[C@@H]1CC[C@@H](N2C3=NC=NC(N)=C3C(C=3C=CC(OC=4C=CC=CC=4)=CC=3)=C2)CC1 OBEVZOQOHFEYGJ-HEQCVELZSA-N 0.000 claims description 2
- YAFKBXAUONFNGP-UQBLWFTISA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.N1([C@@H]2CC[C@H](CC2)n2c3ncnc(N)c3c(c2)-c2ccc(cc2)Oc2ccccc2)CCNCC1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.N1([C@@H]2CC[C@H](CC2)n2c3ncnc(N)c3c(c2)-c2ccc(cc2)Oc2ccccc2)CCNCC1 YAFKBXAUONFNGP-UQBLWFTISA-N 0.000 claims description 2
- 206010053869 POEMS syndrome Diseases 0.000 claims description 2
- 241000700639 Parapoxvirus Species 0.000 claims description 2
- 241000721454 Pemphigus Species 0.000 claims description 2
- 206010063837 Reperfusion injury Diseases 0.000 claims description 2
- 206010038848 Retinal detachment Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 201000000582 Retinoblastoma Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 206010039705 Scleritis Diseases 0.000 claims description 2
- 208000027073 Stargardt disease Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 201000005485 Toxoplasmosis Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- 206010053648 Vascular occlusion Diseases 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 150000005215 alkyl ethers Chemical class 0.000 claims description 2
- 125000005360 alkyl sulfoxide group Chemical group 0.000 claims description 2
- 125000005012 alkyl thioether group Chemical group 0.000 claims description 2
- 125000006356 alkylene carbonyl group Chemical group 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 208000007502 anemia Diseases 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
- 125000005362 aryl sulfone group Chemical group 0.000 claims description 2
- 125000005361 aryl sulfoxide group Chemical group 0.000 claims description 2
- 150000004832 aryl thioethers Chemical class 0.000 claims description 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
- 150000008316 benzisoxazoles Chemical class 0.000 claims description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 2
- 239000012964 benzotriazole Substances 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- 230000020411 cell activation Effects 0.000 claims description 2
- KDRZYBZCBYKLPL-YHBQERECSA-N chembl431342 Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CC[C@H](CC2)N2CCCCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 KDRZYBZCBYKLPL-YHBQERECSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 208000037976 chronic inflammation Diseases 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 201000009101 diabetic angiopathy Diseases 0.000 claims description 2
- 150000002012 dioxanes Chemical class 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 230000009033 hematopoietic malignancy Effects 0.000 claims description 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 2
- 210000003630 histaminocyte Anatomy 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 2
- 150000002537 isoquinolines Chemical class 0.000 claims description 2
- 150000002545 isoxazoles Chemical class 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 208000001491 myopia Diseases 0.000 claims description 2
- 230000004379 myopia Effects 0.000 claims description 2
- 230000017074 necrotic cell death Effects 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 150000003248 quinolines Chemical class 0.000 claims description 2
- 150000003252 quinoxalines Chemical class 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 230000004264 retinal detachment Effects 0.000 claims description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 2
- 208000007056 sickle cell anemia Diseases 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 150000003456 sulfonamides Chemical class 0.000 claims description 2
- 201000004595 synovitis Diseases 0.000 claims description 2
- 150000003557 thiazoles Chemical class 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 claims description 2
- 239000013638 trimer Substances 0.000 claims description 2
- 208000021331 vascular occlusion disease Diseases 0.000 claims description 2
- 201000009371 venous hemangioma Diseases 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims 5
- 239000000651 prodrug Substances 0.000 claims 5
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 claims 2
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 claims 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 2
- 210000005252 bulbus oculi Anatomy 0.000 claims 2
- 230000003844 B-cell-activation Effects 0.000 claims 1
- 208000026372 Congenital cystic kidney disease Diseases 0.000 claims 1
- 208000026292 Cystic Kidney disease Diseases 0.000 claims 1
- 208000019878 Eales disease Diseases 0.000 claims 1
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 claims 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims 1
- 201000008808 Fibrosarcoma Diseases 0.000 claims 1
- 206010017711 Gangrene Diseases 0.000 claims 1
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 0.000 claims 1
- 208000017604 Hodgkin disease Diseases 0.000 claims 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 1
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 claims 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 claims 1
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 claims 1
- YIFDJTICUMKHHX-SPIKMXEPSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.NS(=O)(=O)c1cccc(F)c1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.NS(=O)(=O)c1cccc(F)c1 YIFDJTICUMKHHX-SPIKMXEPSA-N 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 208000002151 Pleural effusion Diseases 0.000 claims 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 claims 1
- 102000009521 Vascular Endothelial Growth Factor B Human genes 0.000 claims 1
- 102000009519 Vascular Endothelial Growth Factor D Human genes 0.000 claims 1
- 206010052428 Wound Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 150000001565 benzotriazoles Chemical class 0.000 claims 1
- 125000004965 chloroalkyl group Chemical group 0.000 claims 1
- 230000035558 fertility Effects 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 201000000050 myeloid neoplasm Diseases 0.000 claims 1
- 208000008798 osteoma Diseases 0.000 claims 1
- 150000003217 pyrazoles Chemical class 0.000 claims 1
- 101150035983 str1 gene Proteins 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 230000002195 synergetic effect Effects 0.000 claims 1
- 208000001608 teratocarcinoma Diseases 0.000 claims 1
- 125000005309 thioalkoxy group Chemical group 0.000 claims 1
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 35
- 102000020233 phosphotransferase Human genes 0.000 abstract description 35
- 239000003112 inhibitor Substances 0.000 abstract description 31
- 210000002889 endothelial cell Anatomy 0.000 abstract description 15
- 230000008569 process Effects 0.000 abstract description 13
- 230000035755 proliferation Effects 0.000 abstract description 10
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 abstract description 6
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 abstract description 5
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 abstract description 5
- 210000000987 immune system Anatomy 0.000 abstract description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004473 Threonine Substances 0.000 abstract description 3
- 230000001575 pathological effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 204
- 239000000203 mixture Substances 0.000 description 173
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 93
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 77
- 210000004027 cell Anatomy 0.000 description 74
- 235000019439 ethyl acetate Nutrition 0.000 description 68
- 239000007787 solid Substances 0.000 description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 50
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 50
- 239000000243 solution Substances 0.000 description 49
- 230000002792 vascular Effects 0.000 description 43
- 238000002844 melting Methods 0.000 description 41
- 230000008018 melting Effects 0.000 description 41
- 238000003756 stirring Methods 0.000 description 38
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 37
- 239000002904 solvent Substances 0.000 description 35
- 238000005160 1H NMR spectroscopy Methods 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 31
- 102000005962 receptors Human genes 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 238000001914 filtration Methods 0.000 description 28
- 239000003446 ligand Substances 0.000 description 28
- 230000005764 inhibitory process Effects 0.000 description 27
- 108020003175 receptors Proteins 0.000 description 27
- 239000000047 product Substances 0.000 description 26
- 108090000623 proteins and genes Proteins 0.000 description 26
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 25
- 102000004190 Enzymes Human genes 0.000 description 24
- 108090000790 Enzymes Proteins 0.000 description 24
- 229940088598 enzyme Drugs 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 23
- 102000004169 proteins and genes Human genes 0.000 description 22
- 239000003814 drug Substances 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 18
- 241000282414 Homo sapiens Species 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 238000003818 flash chromatography Methods 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000000872 buffer Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 238000006366 phosphorylation reaction Methods 0.000 description 15
- 239000000758 substrate Substances 0.000 description 15
- 101150012716 CDK1 gene Proteins 0.000 description 14
- 239000006185 dispersion Substances 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 14
- 239000002480 mineral oil Substances 0.000 description 14
- 235000010446 mineral oil Nutrition 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 206010015866 Extravasation Diseases 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 13
- 230000036251 extravasation Effects 0.000 description 13
- 230000009826 neoplastic cell growth Effects 0.000 description 13
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- 230000004044 response Effects 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- 230000000638 stimulation Effects 0.000 description 13
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 230000033228 biological regulation Effects 0.000 description 12
- 230000026731 phosphorylation Effects 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 230000001105 regulatory effect Effects 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- DCBBIJFOBUXCIV-UHFFFAOYSA-N 5-(4-amino-3-methoxyphenyl)-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=C(N)C(OC)=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=C1 DCBBIJFOBUXCIV-UHFFFAOYSA-N 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 9
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 9
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 9
- QWJCULDQFSFIEW-UHFFFAOYSA-N phenyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OC1=CC=CC=C1 QWJCULDQFSFIEW-UHFFFAOYSA-N 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 230000002441 reversible effect Effects 0.000 description 9
- 241000701447 unidentified baculovirus Species 0.000 description 9
- 210000003556 vascular endothelial cell Anatomy 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 8
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 8
- 102000003923 Protein Kinase C Human genes 0.000 description 8
- 108090000315 Protein Kinase C Proteins 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 230000001413 cellular effect Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- NFSWHYRUVWRUDN-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OC1=CC=CC=C1 NFSWHYRUVWRUDN-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 7
- 102000000588 Interleukin-2 Human genes 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 108091008605 VEGF receptors Proteins 0.000 description 7
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 7
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 150000001413 amino acids Chemical group 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000006184 cosolvent Substances 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 7
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 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 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 101100464293 Caenorhabditis elegans plk-1 gene Proteins 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- 102000002427 Cyclin B Human genes 0.000 description 6
- 108010068150 Cyclin B Proteins 0.000 description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 6
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 230000004663 cell proliferation Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 150000004292 cyclic ethers Chemical class 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 238000011081 inoculation Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 235000011007 phosphoric acid Nutrition 0.000 description 6
- 230000002062 proliferating effect Effects 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 5
- 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 108700020796 Oncogene Proteins 0.000 description 5
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 5
- 235000011613 Pinus brutia Nutrition 0.000 description 5
- 241000018646 Pinus brutia Species 0.000 description 5
- 102100035194 Placenta growth factor Human genes 0.000 description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 5
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 125000002541 furyl group Chemical group 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 229940014259 gelatin Drugs 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 229940043355 kinase inhibitor Drugs 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000001613 neoplastic effect Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- WWCNXHYRAKUQDB-UHFFFAOYSA-N oxolan-3-yl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1COCC1 WWCNXHYRAKUQDB-UHFFFAOYSA-N 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 102100034594 Angiopoietin-1 Human genes 0.000 description 4
- 102100034608 Angiopoietin-2 Human genes 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 206010061818 Disease progression Diseases 0.000 description 4
- 108091008794 FGF receptors Proteins 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 108010057466 NF-kappa B Proteins 0.000 description 4
- 102000003945 NF-kappa B Human genes 0.000 description 4
- 206010029113 Neovascularisation Diseases 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 4
- 108091005682 Receptor kinases Proteins 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 101100234062 Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770) cmk gene Proteins 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 235000019445 benzyl alcohol Nutrition 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004891 communication Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 230000005750 disease progression Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 230000003511 endothelial effect Effects 0.000 description 4
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 4
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 4
- SYRILXALXISPJM-UHFFFAOYSA-N ethyl 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]acetate Chemical compound C12=C(N)N=CN=C2N(CC(=O)OCC)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 SYRILXALXISPJM-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- AKQZEFRALAUBFS-UHFFFAOYSA-N ilamine Natural products COC(C)C(O)(C(=O)OCC1=CCN2CCCC12)C(C)(C)O AKQZEFRALAUBFS-UHFFFAOYSA-N 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 231100000682 maximum tolerated dose Toxicity 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 210000004291 uterus Anatomy 0.000 description 4
- 210000005166 vasculature Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- KDMYXTBGUWUKHT-UHFFFAOYSA-N (2,4-dibromo-1,3-thiazol-5-yl)methanol Chemical compound OCC=1SC(Br)=NC=1Br KDMYXTBGUWUKHT-UHFFFAOYSA-N 0.000 description 3
- RDCLVZNNBVGGFW-UHFFFAOYSA-N (4-bromo-1,3-thiazol-5-yl)methanol Chemical compound OCC=1SC=NC=1Br RDCLVZNNBVGGFW-UHFFFAOYSA-N 0.000 description 3
- RXIQKSZSJLADAQ-UHFFFAOYSA-N (4-nitrophenyl) pyridin-3-ylmethyl carbonate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)OCC1=CC=CN=C1 RXIQKSZSJLADAQ-UHFFFAOYSA-N 0.000 description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 3
- BXPALDBXOXQZPT-UHFFFAOYSA-N 2-[4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]benzaldehyde Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1C=O BXPALDBXOXQZPT-UHFFFAOYSA-N 0.000 description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 3
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 3
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 3
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 3
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 3
- AOJAKVAHBPZCGH-UHFFFAOYSA-N 4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenol Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C1=CC=C(O)C=C1 AOJAKVAHBPZCGH-UHFFFAOYSA-N 0.000 description 3
- PUCKZOLRLPDMCL-UHFFFAOYSA-N 4-[4-chloro-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyaniline Chemical compound C1=C(N)C(OC)=CC(C=2C3=C(Cl)N=CN=C3N(C3CCOCC3)C=2)=C1 PUCKZOLRLPDMCL-UHFFFAOYSA-N 0.000 description 3
- WHYFIQVWNTXZNI-UHFFFAOYSA-N 4-chloro-5-iodo-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidine Chemical compound C1=C(I)C=2C(Cl)=NC=NC=2N1C1CCOC1 WHYFIQVWNTXZNI-UHFFFAOYSA-N 0.000 description 3
- CBWBJFJMNBPWAL-UHFFFAOYSA-N 4-chloro-5-iodo-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C(I)=CN2 CBWBJFJMNBPWAL-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 101000924552 Homo sapiens Angiopoietin-1 Proteins 0.000 description 3
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 description 3
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 3
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 3
- 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 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 3
- 208000001132 Osteoporosis Diseases 0.000 description 3
- 108700020978 Proto-Oncogene Proteins 0.000 description 3
- 102000052575 Proto-Oncogene Human genes 0.000 description 3
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 3
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 3
- 206010062662 Uterine mass Diseases 0.000 description 3
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 3
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 3
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000035578 autophosphorylation Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000006369 cell cycle progression Effects 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 230000007783 downstream signaling Effects 0.000 description 3
- 201000002491 encephalomyelitis Diseases 0.000 description 3
- 229940011871 estrogen Drugs 0.000 description 3
- 239000000262 estrogen Substances 0.000 description 3
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 102000058223 human VEGFA Human genes 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000002596 lactones Chemical class 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 3
- 108010052968 leupeptin Proteins 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000000394 mitotic effect Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 3
- MHTSXBUIUUOYDC-UHFFFAOYSA-N n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]-2,2-dimethylpropanamide Chemical compound C1=C(NC(=O)C(C)(C)C)C(OC)=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=C1 MHTSXBUIUUOYDC-UHFFFAOYSA-N 0.000 description 3
- RHTYPJAOPJSRAJ-UHFFFAOYSA-N oxan-4-yl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1CCOCC1 RHTYPJAOPJSRAJ-UHFFFAOYSA-N 0.000 description 3
- SQLSLZYOHOYFJB-UHFFFAOYSA-N oxolan-3-yl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OC1CCOC1 SQLSLZYOHOYFJB-UHFFFAOYSA-N 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 230000007115 recruitment Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- YQKDTZYYROHLMB-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(CO)C=C1 YQKDTZYYROHLMB-UHFFFAOYSA-N 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 230000009385 viral infection Effects 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- HKAOKULCDBIFIW-UHFFFAOYSA-N (4-aminophenyl)methyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OCC1=CC=C(N)C=C1 HKAOKULCDBIFIW-UHFFFAOYSA-N 0.000 description 2
- LOSOTFPNPJEFOL-UHFFFAOYSA-N (4-bromo-1,3-thiazol-5-yl)methyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OCC=1SC=NC=1Br LOSOTFPNPJEFOL-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- QHZSJKGSCFBJEX-UHFFFAOYSA-N 2,2-dimethylpropyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound C1=C(NC(=O)OCC(C)(C)C)C(OC)=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=C1 QHZSJKGSCFBJEX-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- YBOMYWFVQPMAAK-UHFFFAOYSA-N 2-(4-iodophenoxy)benzaldehyde Chemical compound C1=CC(I)=CC=C1OC1=CC=CC=C1C=O YBOMYWFVQPMAAK-UHFFFAOYSA-N 0.000 description 2
- ZHKCKKMMBOHRCY-UHFFFAOYSA-N 2-(tert-butylamino)-1-(4-phenoxyphenyl)ethanone;hydrochloride Chemical compound Cl.C1=CC(C(=O)CNC(C)(C)C)=CC=C1OC1=CC=CC=C1 ZHKCKKMMBOHRCY-UHFFFAOYSA-N 0.000 description 2
- HNTMGMVTTWQPSK-UHFFFAOYSA-N 2-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]benzonitrile Chemical compound C1=2C(N)=NC=NC=2N(C2CCOCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1C#N HNTMGMVTTWQPSK-UHFFFAOYSA-N 0.000 description 2
- MRHJHDFCEZIYCO-UHFFFAOYSA-N 2-[4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]-6-(2-pyridin-4-ylethylamino)benzonitrile Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC(C=1C#N)=CC=CC=1NCCC1=CC=NC=C1 MRHJHDFCEZIYCO-UHFFFAOYSA-N 0.000 description 2
- LQIMOVGYJMTARP-UHFFFAOYSA-N 2-[4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]-6-(3-imidazol-1-ylpropylamino)benzonitrile Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC(C=1C#N)=CC=CC=1NCCCN1C=CN=C1 LQIMOVGYJMTARP-UHFFFAOYSA-N 0.000 description 2
- QQEBAIXEUQBUBU-UHFFFAOYSA-N 2-[4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]-6-(3-methoxypropylamino)benzonitrile Chemical compound COCCCNC1=CC=CC(OC=2C=CC(=CC=2)C=2C3=C(N)N=CN=C3N(C3COCC3)C=2)=C1C#N QQEBAIXEUQBUBU-UHFFFAOYSA-N 0.000 description 2
- WWNVZPOLPBITMW-UHFFFAOYSA-N 2-[4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]benzonitrile Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1C#N WWNVZPOLPBITMW-UHFFFAOYSA-N 0.000 description 2
- LXMPKWBCNAXNPL-UHFFFAOYSA-N 2-[4-[4-chloro-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]benzaldehyde Chemical compound C1=2C(Cl)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1C=O LXMPKWBCNAXNPL-UHFFFAOYSA-N 0.000 description 2
- OQQLCGMCYLNBAC-UHFFFAOYSA-N 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-methylpropanamide Chemical compound C12=C(N)N=CN=C2N(C(C)(C(N)=O)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 OQQLCGMCYLNBAC-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- WTRIMJTZOOLIFZ-UHFFFAOYSA-N 2-bromo-2-methylpropanamide Chemical compound CC(C)(Br)C(N)=O WTRIMJTZOOLIFZ-UHFFFAOYSA-N 0.000 description 2
- KESZCYFLBJZEPA-UHFFFAOYSA-N 2-fluoro-6-(3-methoxypropylamino)benzonitrile Chemical compound COCCCNC1=CC=CC(F)=C1C#N KESZCYFLBJZEPA-UHFFFAOYSA-N 0.000 description 2
- WLHQLBRPPRSGSH-UHFFFAOYSA-N 2-morpholin-4-ylethyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OCCN1CCOCC1 WLHQLBRPPRSGSH-UHFFFAOYSA-N 0.000 description 2
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 2
- XUBKRVPXTJMKLB-UHFFFAOYSA-N 3-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]oxolan-2-one Chemical compound C1=2C(N)=NC=NC=2N(C2C(OCC2)=O)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XUBKRVPXTJMKLB-UHFFFAOYSA-N 0.000 description 2
- KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 2
- LZXRKNFGAZGMRP-UHFFFAOYSA-N 4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-one Chemical compound C1=2C(N)=NC=NC=2N(C2CCC(=O)CC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 LZXRKNFGAZGMRP-UHFFFAOYSA-N 0.000 description 2
- LUZMRHZVQFTJEO-UHFFFAOYSA-N 4-chloro-5-iodo-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidine Chemical compound C1=C(I)C=2C(Cl)=NC=NC=2N1C1CCOCC1 LUZMRHZVQFTJEO-UHFFFAOYSA-N 0.000 description 2
- ROTVXDLCQVYQMO-UHFFFAOYSA-N 5-[4-[2-(diethylaminomethyl)phenoxy]phenyl]-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CCN(CC)CC1=CC=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C3COCC3)C=2)C=C1 ROTVXDLCQVYQMO-UHFFFAOYSA-N 0.000 description 2
- SKPPGUKRJWUUHJ-UHFFFAOYSA-N 5-[4-[2-[(2-methoxyethylamino)methyl]phenoxy]phenyl]-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COCCNCC1=CC=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C3COCC3)C=2)C=C1 SKPPGUKRJWUUHJ-UHFFFAOYSA-N 0.000 description 2
- ICCKABOUVDEALX-UHFFFAOYSA-N 7-(1,2-oxazolidin-4-yl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1=2C(N)=NC=NC=2N(C2CONC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 ICCKABOUVDEALX-UHFFFAOYSA-N 0.000 description 2
- WOOFRRZKRYQTJQ-UHFFFAOYSA-N 7-(2-aminoethyl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine;hydrochloride Chemical compound Cl.C12=C(N)N=CN=C2N(CCN)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 WOOFRRZKRYQTJQ-UHFFFAOYSA-N 0.000 description 2
- BCWVVERKADMJGG-UHFFFAOYSA-N 7-(oxan-4-yl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2CCOCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 BCWVVERKADMJGG-UHFFFAOYSA-N 0.000 description 2
- GONCOGHZCWCVGP-UHFFFAOYSA-N 7-(oxolan-3-yl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 GONCOGHZCWCVGP-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- HIDBZNBOXBSWKS-UHFFFAOYSA-N C=1C=C(C=2N=C3NC=CC3=CN=2)C=CC=1OC1=CC=CC=C1 Chemical compound C=1C=C(C=2N=C3NC=CC3=CN=2)C=CC=1OC1=CC=CC=C1 HIDBZNBOXBSWKS-UHFFFAOYSA-N 0.000 description 2
- 108091007914 CDKs Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 2
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 102000002554 Cyclin A Human genes 0.000 description 2
- 108010068192 Cyclin A Proteins 0.000 description 2
- 102000003909 Cyclin E Human genes 0.000 description 2
- 108090000257 Cyclin E Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 208000037147 Hypercalcaemia Diseases 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
- 208000001344 Macular Edema Diseases 0.000 description 2
- 206010025415 Macular oedema Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001024304 Mino Species 0.000 description 2
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 102100028762 Neuropilin-1 Human genes 0.000 description 2
- 108090000772 Neuropilin-1 Proteins 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 241000700635 Orf virus Species 0.000 description 2
- 101150093908 PDGFRB gene Proteins 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 101000852966 Rattus norvegicus Interleukin-1 receptor-like 1 Proteins 0.000 description 2
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 2
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 230000003527 anti-angiogenesis Effects 0.000 description 2
- 230000001772 anti-angiogenic effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- OTBHHUPVCYLGQO-UHFFFAOYSA-N bis(3-aminopropyl)amine Chemical group NCCCNCCCN OTBHHUPVCYLGQO-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 208000001969 capillary hemangioma Diseases 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- WCSZJWMDHCJPSX-UHFFFAOYSA-N ethyl 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]propanoate Chemical compound C12=C(N)N=CN=C2N(C(C)C(=O)OCC)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 WCSZJWMDHCJPSX-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000001030 gas--liquid chromatography Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 238000005734 heterodimerization reaction Methods 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- VIPHVHVAGBKHGR-UHFFFAOYSA-N hydron;pyridine-2-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CC=N1 VIPHVHVAGBKHGR-UHFFFAOYSA-N 0.000 description 2
- 230000000148 hypercalcaemia Effects 0.000 description 2
- 208000030915 hypercalcemia disease Diseases 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000006525 intracellular process Effects 0.000 description 2
- 239000011630 iodine Chemical group 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 201000010230 macular retinal edema Diseases 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229940087646 methanolamine Drugs 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000003226 mitogen Substances 0.000 description 2
- 230000002297 mitogenic effect Effects 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- HVXSGVSDDTWEJC-UHFFFAOYSA-N n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]-2,5-dimethylpyrazole-3-carboxamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)C1=CC(C)=NN1C HVXSGVSDDTWEJC-UHFFFAOYSA-N 0.000 description 2
- ZKJSKUBEPVMSPP-UHFFFAOYSA-N n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]benzamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)C1=CC=CC=C1 ZKJSKUBEPVMSPP-UHFFFAOYSA-N 0.000 description 2
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- 208000002865 osteopetrosis Diseases 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- RKKSMJJUSLCQCH-UHFFFAOYSA-N oxan-4-yl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OC1CCOCC1 RKKSMJJUSLCQCH-UHFFFAOYSA-N 0.000 description 2
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 229940080469 phosphocellulose Drugs 0.000 description 2
- 208000030761 polycystic kidney disease Diseases 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- HEIHVJQRVYTWCG-UHFFFAOYSA-N pyridin-2-ylmethyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OCC1=CC=CC=N1 HEIHVJQRVYTWCG-UHFFFAOYSA-N 0.000 description 2
- DVLOLDYTPHYPSL-UHFFFAOYSA-N pyridin-3-ylmethyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OCC1=CC=CN=C1 DVLOLDYTPHYPSL-UHFFFAOYSA-N 0.000 description 2
- QUOHETBONYWGKO-UHFFFAOYSA-N pyridin-3-ylmethyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate;hydrochloride Chemical compound Cl.COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OCC1=CC=CN=C1 QUOHETBONYWGKO-UHFFFAOYSA-N 0.000 description 2
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 2
- 230000000552 rheumatic effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000002511 suppository base Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 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
- 238000001890 transfection Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000005740 tumor formation Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 230000006711 vascular endothelial growth factor production Effects 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-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
- AXKGIPZJYUNAIW-UHFFFAOYSA-N (4-aminophenyl)methanol Chemical compound NC1=CC=C(CO)C=C1 AXKGIPZJYUNAIW-UHFFFAOYSA-N 0.000 description 1
- MDYHWQQHEWDJKR-UHFFFAOYSA-N (5-methyl-1,2-oxazol-3-yl)methanol Chemical compound CC1=CC(CO)=NO1 MDYHWQQHEWDJKR-UHFFFAOYSA-N 0.000 description 1
- OOCVANXBTXQYQK-UHFFFAOYSA-N (5-methyl-1,2-oxazol-3-yl)methyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OCC=1C=C(C)ON=1 OOCVANXBTXQYQK-UHFFFAOYSA-N 0.000 description 1
- HOBJEFOCIRXQKH-BYPYZUCNSA-N (5s)-5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OC[C@@H]1CCC(=O)N1 HOBJEFOCIRXQKH-BYPYZUCNSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- BBWJIHMTJCJDKJ-UHFFFAOYSA-N 1,2-oxazolidin-4-ol Chemical compound OC1CNOC1 BBWJIHMTJCJDKJ-UHFFFAOYSA-N 0.000 description 1
- NQPJDJVGBDHCAD-UHFFFAOYSA-N 1,3-diazinan-2-one Chemical compound OC1=NCCCN1 NQPJDJVGBDHCAD-UHFFFAOYSA-N 0.000 description 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 1
- OWOKCUXVMOFUSP-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-yl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1CCC2(OCCO2)CC1 OWOKCUXVMOFUSP-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- FRUWMYWEARDNTC-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-indole Chemical compound C1C=CC=C2NCCC21 FRUWMYWEARDNTC-UHFFFAOYSA-N 0.000 description 1
- FDBMZERYWBZSQS-UHFFFAOYSA-N 2,4-dibromo-1,3-thiazole-5-carbaldehyde Chemical compound BrC1=NC(Br)=C(C=O)S1 FDBMZERYWBZSQS-UHFFFAOYSA-N 0.000 description 1
- OJTMHIMQUQOLJV-UHFFFAOYSA-N 2,5-difluorobenzonitrile Chemical compound FC1=CC=C(F)C(C#N)=C1 OJTMHIMQUQOLJV-UHFFFAOYSA-N 0.000 description 1
- GIAFURWZWWWBQT-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanol Chemical compound NCCOCCO GIAFURWZWWWBQT-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 1
- QTPCNKOBARGZNB-UHFFFAOYSA-N 2-(4-bromophenoxy)benzonitrile Chemical compound C1=CC(Br)=CC=C1OC1=CC=CC=C1C#N QTPCNKOBARGZNB-UHFFFAOYSA-N 0.000 description 1
- PPGIPCCRKURSST-UHFFFAOYSA-N 2-(4-trimethylstannylphenoxy)benzaldehyde Chemical compound C1=CC([Sn](C)(C)C)=CC=C1OC1=CC=CC=C1C=O PPGIPCCRKURSST-UHFFFAOYSA-N 0.000 description 1
- XFZSRFRTOZKTQL-UHFFFAOYSA-N 2-(4-trimethylstannylphenoxy)benzonitrile Chemical compound C1=CC([Sn](C)(C)C)=CC=C1OC1=CC=CC=C1C#N XFZSRFRTOZKTQL-UHFFFAOYSA-N 0.000 description 1
- LAMUQORCSIHVMC-UHFFFAOYSA-N 2-(8-bromooctyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCCCCCBr)C(=O)C2=C1 LAMUQORCSIHVMC-UHFFFAOYSA-N 0.000 description 1
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
- IKWVRXHMXGIHKU-UHFFFAOYSA-N 2-(tert-butylamino)-1-(4-phenoxyphenyl)ethanone Chemical compound C1=CC(C(=O)CNC(C)(C)C)=CC=C1OC1=CC=CC=C1 IKWVRXHMXGIHKU-UHFFFAOYSA-N 0.000 description 1
- RMHSPGDPXRFDSK-UHFFFAOYSA-N 2-[4-[2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]acetyl]piperazin-1-yl]-1-morpholin-4-ylethanone Chemical compound C1=C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C=2C(N)=NC=NC=2N1CC(=O)N(CC1)CCN1CC(=O)N1CCOCC1 RMHSPGDPXRFDSK-UHFFFAOYSA-N 0.000 description 1
- ZDYDISPFNXABMS-UHFFFAOYSA-N 2-[4-[4-chloro-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]benzonitrile Chemical compound C1=2C(Cl)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1C#N ZDYDISPFNXABMS-UHFFFAOYSA-N 0.000 description 1
- XYAWVANHFCQANC-UHFFFAOYSA-N 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-1-[4-(2-morpholin-4-ylethyl)piperazin-1-yl]ethanone Chemical compound C1=C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C=2C(N)=NC=NC=2N1CC(=O)N(CC1)CCN1CCN1CCOCC1 XYAWVANHFCQANC-UHFFFAOYSA-N 0.000 description 1
- ZWXBQDPTMDRRPD-UHFFFAOYSA-N 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]propanoic acid Chemical compound C12=C(N)N=CN=C2N(C(C(O)=O)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 ZWXBQDPTMDRRPD-UHFFFAOYSA-N 0.000 description 1
- SRQPYXNCRBXSLK-UHFFFAOYSA-N 2-[8-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]octyl]isoindole-1,3-dione Chemical compound C1=2C(N)=NC=NC=2N(CCCCCCCCN2C(C3=CC=CC=C3C2=O)=O)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 SRQPYXNCRBXSLK-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 description 1
- SUGIXUOLQCWZSX-UHFFFAOYSA-N 2-amino-1-tert-butyl-4-(4-phenoxyphenyl)pyrrole-3-carbonitrile Chemical compound N#CC1=C(N)N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 SUGIXUOLQCWZSX-UHFFFAOYSA-N 0.000 description 1
- RAXTYMXDSNWNJS-UHFFFAOYSA-N 2-bromo-1-(4-phenoxyphenyl)ethanone Chemical compound C1=CC(C(=O)CBr)=CC=C1OC1=CC=CC=C1 RAXTYMXDSNWNJS-UHFFFAOYSA-N 0.000 description 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- ZJMLDNRAZWLIIK-UHFFFAOYSA-N 2-fluoro-6-(3-imidazol-1-ylpropylamino)benzonitrile Chemical compound FC1=CC=CC(NCCCN2C=NC=C2)=C1C#N ZJMLDNRAZWLIIK-UHFFFAOYSA-N 0.000 description 1
- JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- WIQRSJOCVVPMPS-UHFFFAOYSA-N 3-(1h-indol-2-yl)pyrrole-2,5-dione Chemical class O=C1NC(=O)C(C=2NC3=CC=CC=C3C=2)=C1 WIQRSJOCVVPMPS-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- NUFBIAUZAMHTSP-UHFFFAOYSA-N 3-(n-morpholino)-2-hydroxypropanesulfonic acid Chemical compound OS(=O)(=O)CC(O)CN1CCOCC1 NUFBIAUZAMHTSP-UHFFFAOYSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
- MQPXWLANVDGUEL-UHFFFAOYSA-N 3-[4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]benzaldehyde Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC(C=O)=C1 MQPXWLANVDGUEL-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LFJJGHGXHXXDFT-UHFFFAOYSA-N 3-bromooxolan-2-one Chemical compound BrC1CCOC1=O LFJJGHGXHXXDFT-UHFFFAOYSA-N 0.000 description 1
- XDPCNPCKDGQBAN-UHFFFAOYSA-N 3-hydroxytetrahydrofuran Chemical compound OC1CCOC1 XDPCNPCKDGQBAN-UHFFFAOYSA-N 0.000 description 1
- UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
- MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
- SINQIEAULQKUPD-UHFFFAOYSA-N 4-[4-(6-methoxy-2-naphthalenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C=1N=C(C=2C=CC(=CC=2)S(C)=O)NC=1C1=CC=NC=C1 SINQIEAULQKUPD-UHFFFAOYSA-N 0.000 description 1
- BZVBDHWDCSNGRM-UHFFFAOYSA-N 4-[4-[4-amino-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]benzaldehyde Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=C(C=O)C=C1 BZVBDHWDCSNGRM-UHFFFAOYSA-N 0.000 description 1
- WOAWCSRPZUJFSP-UHFFFAOYSA-N 4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]oxolan-3-ol Chemical compound C1=2C(N)=NC=NC=2N(C2C(COC2)O)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 WOAWCSRPZUJFSP-UHFFFAOYSA-N 0.000 description 1
- LSOXASSQYIYLFU-UHFFFAOYSA-N 4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenol Chemical compound C1=2C(N)=NC=NC=2N(C2CCOCC2)C=C1C1=CC=C(O)C=C1 LSOXASSQYIYLFU-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 description 1
- DGYXMFAYEGJBOH-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)C1=CNC=2N=CN=CC=21 DGYXMFAYEGJBOH-UHFFFAOYSA-N 0.000 description 1
- OBMGVMWHMBYZJC-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrobromide Chemical compound Br.C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OC1=CC=CC=C1 OBMGVMWHMBYZJC-UHFFFAOYSA-N 0.000 description 1
- UHDSSJJGBUOKBN-UHFFFAOYSA-N 5-(4-phenylmethoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 UHDSSJJGBUOKBN-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- HURSAXUOBNDDRV-UHFFFAOYSA-N 5-[4-(4-fluorophenoxy)phenyl]-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=C(F)C=C1 HURSAXUOBNDDRV-UHFFFAOYSA-N 0.000 description 1
- LQQNGIJVMPTKNM-UHFFFAOYSA-N 5-[4-[2-(morpholin-4-ylmethyl)phenoxy]phenyl]-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1CN1CCOCC1 LQQNGIJVMPTKNM-UHFFFAOYSA-N 0.000 description 1
- VUBBUEQZRLFHJJ-UHFFFAOYSA-N 5-[4-[4-(morpholin-4-ylmethyl)phenoxy]phenyl]-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC(C=C1)=CC=C1CN1CCOCC1 VUBBUEQZRLFHJJ-UHFFFAOYSA-N 0.000 description 1
- VRNJWKISMWDTAY-UHFFFAOYSA-N 5-chloro-2,1,3-benzothiadiazole Chemical compound C1=C(Cl)C=CC2=NSN=C21 VRNJWKISMWDTAY-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- PDTHYCGQHARBOW-UHFFFAOYSA-N 6-bromo-5-(4-phenoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2NC(Br)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 PDTHYCGQHARBOW-UHFFFAOYSA-N 0.000 description 1
- OAPIRERJQZQJHA-UHFFFAOYSA-N 6-bromo-7-(oxolan-3-yl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound BrC1=C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C=2C(N)=NC=NC=2N1C1CCOC1 OAPIRERJQZQJHA-UHFFFAOYSA-N 0.000 description 1
- QODOIYQAHJZCLD-UHFFFAOYSA-N 7-(1,4-dioxaspiro[4.5]decan-8-yl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2CCC3(CC2)OCCO3)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 QODOIYQAHJZCLD-UHFFFAOYSA-N 0.000 description 1
- ABIMTHAQGHGFTF-UHFFFAOYSA-N 7-(8-aminooctyl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine;dihydrate;dihydrochloride Chemical compound O.O.Cl.Cl.C12=C(N)N=CN=C2N(CCCCCCCCN)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 ABIMTHAQGHGFTF-UHFFFAOYSA-N 0.000 description 1
- DEVGVVFEQFTMOA-UHFFFAOYSA-N 7-(oxan-4-yl)-5-(4-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2CCOCC2)C=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 DEVGVVFEQFTMOA-UHFFFAOYSA-N 0.000 description 1
- UXAQEJWTKUGECL-UHFFFAOYSA-N 7-(oxolan-3-yl)-5-[4-[2-(piperidin-1-ylmethyl)phenoxy]phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2COCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1CN1CCCCC1 UXAQEJWTKUGECL-UHFFFAOYSA-N 0.000 description 1
- WFAHCBGQSRNACC-UHFFFAOYSA-N 7-cyclopentylsulfonyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(S(=O)(=O)C2CCCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 WFAHCBGQSRNACC-UHFFFAOYSA-N 0.000 description 1
- MYSJNRWPLKEUQT-UHFFFAOYSA-N 7-tert-butyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 MYSJNRWPLKEUQT-UHFFFAOYSA-N 0.000 description 1
- HPKBIUNLYQDWDJ-UHFFFAOYSA-N 7a-(bromomethyl)-3ah-isoindole-1,3-dione Chemical compound C1=CC=CC2C(=O)NC(=O)C21CBr HPKBIUNLYQDWDJ-UHFFFAOYSA-N 0.000 description 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 108010048154 Angiopoietin-1 Proteins 0.000 description 1
- 108010048036 Angiopoietin-2 Proteins 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 201000002909 Aspergillosis Diseases 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 208000036641 Aspergillus infections Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- OGBVRMYSNSKIEF-UHFFFAOYSA-N Benzylphosphonic acid Chemical class OP(O)(=O)CC1=CC=CC=C1 OGBVRMYSNSKIEF-UHFFFAOYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- MZRZRVHMRKDXKD-UHFFFAOYSA-N C(C(C)C)(=O)Cl.C(C(C)C)(=O)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)OC2=CC=CC=C2 Chemical compound C(C(C)C)(=O)Cl.C(C(C)C)(=O)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)OC2=CC=CC=C2 MZRZRVHMRKDXKD-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- JYHAPUSHXOPSAS-UHFFFAOYSA-N CC(C)C(=O)N1C=C(C2=CN=CN=C21)C3=CC=C(C=C3)OC4=CC=CC=C4 Chemical compound CC(C)C(=O)N1C=C(C2=CN=CN=C21)C3=CC=C(C=C3)OC4=CC=CC=C4 JYHAPUSHXOPSAS-UHFFFAOYSA-N 0.000 description 1
- 101150047144 CDC28 gene Proteins 0.000 description 1
- MIODUYDSGXUAGH-DIVCQZSQSA-N COc1cc(ccc1NC(=O)CCc1ccccc1)-c1cn([C@H]2CC[C@@H](CC2)N2CCN(C)CC2)c2ncnc(N)c12 Chemical compound COc1cc(ccc1NC(=O)CCc1ccccc1)-c1cn([C@H]2CC[C@@H](CC2)N2CCN(C)CC2)c2ncnc(N)c12 MIODUYDSGXUAGH-DIVCQZSQSA-N 0.000 description 1
- 101100290380 Caenorhabditis elegans cel-1 gene Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010048964 Carotid artery occlusion Diseases 0.000 description 1
- 208000003732 Cat-scratch disease Diseases 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- 208000037088 Chromosome Breakage Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102000003910 Cyclin D Human genes 0.000 description 1
- 108090000259 Cyclin D Proteins 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 1
- 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 1
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 206010063045 Effusion Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical group CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 102000038624 GSKs Human genes 0.000 description 1
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 1
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 1
- 101150087426 Gnal gene Proteins 0.000 description 1
- 206010018498 Goitre Diseases 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101001005128 Homo sapiens LIM domain kinase 1 Proteins 0.000 description 1
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 1
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 description 1
- 101001092185 Homo sapiens Regulator of cell cycle RGCC Proteins 0.000 description 1
- 108010070875 Human Immunodeficiency Virus tat Gene Products Proteins 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 description 1
- 101710199015 Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 1
- 102100036433 Interleukin-1 receptor-associated kinase-like 2 Human genes 0.000 description 1
- 101710182491 Interleukin-1 receptor-associated kinase-like 2 Proteins 0.000 description 1
- 208000002260 Keloid Diseases 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
- 102100026023 LIM domain kinase 1 Human genes 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 108010002481 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Proteins 0.000 description 1
- 102000036243 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Human genes 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
- 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 description 1
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 1
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101150024075 Mapk1 gene Proteins 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 206010027452 Metastases to bone Diseases 0.000 description 1
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 1
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
- 102100028194 Mitogen-activated protein kinase kinase kinase kinase 4 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100323232 Mus musculus Ang3 gene Proteins 0.000 description 1
- 101100216078 Mus musculus Ang4 gene Proteins 0.000 description 1
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
- 101000851005 Mus musculus Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- DHTIGDBTRPKRGJ-UHFFFAOYSA-N N-[[2-[4-[4-chloro-7-(oxolan-3-yl)pyrrolo[2,3-d]pyrimidin-5-yl]phenoxy]phenyl]methyl]-N-ethylethanamine Chemical compound CCN(CC)CC1=CC=CC=C1OC1=CC=C(C=2C3=C(Cl)N=CN=C3N(C3COCC3)C=2)C=C1 DHTIGDBTRPKRGJ-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 108040008091 NF-kappaB-inducing kinase activity proteins Proteins 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000008636 Neoplastic Processes Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001111421 Pannus Species 0.000 description 1
- 206010072078 Parapox virus infection Diseases 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010073214 Peptic ulcer helicobacter Diseases 0.000 description 1
- 206010034476 Pericardial haemorrhage Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 208000034708 Pleural haemorrhage Diseases 0.000 description 1
- 208000037062 Polyps Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 229940078123 Ras inhibitor Drugs 0.000 description 1
- 101000851003 Rattus norvegicus Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 230000010799 Receptor Interactions Effects 0.000 description 1
- 102100022501 Receptor-interacting serine/threonine-protein kinase 1 Human genes 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 102100035542 Regulator of cell cycle RGCC Human genes 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000037453 T cell priming 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
- 108091082333 TEC family Proteins 0.000 description 1
- 102000042834 TEC family Human genes 0.000 description 1
- 108010090091 TIE-2 Receptor Proteins 0.000 description 1
- 102000012753 TIE-2 Receptor Human genes 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010067269 Uterine fibrosis Diseases 0.000 description 1
- 206010047663 Vitritis Diseases 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- HCKOUYGJVYWAIQ-HNNXBMFYSA-N [(2s)-5-oxopyrrolidin-2-yl]methyl n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]carbamate Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)OC[C@@H]1CCC(=O)N1 HCKOUYGJVYWAIQ-HNNXBMFYSA-N 0.000 description 1
- AIZPLMDBAXQSOY-UHFFFAOYSA-N [2-(4-nitrophenyl)oxan-4-yl] hydrogen carbonate Chemical compound C1C(OC(=O)O)CCOC1C1=CC=C([N+]([O-])=O)C=C1 AIZPLMDBAXQSOY-UHFFFAOYSA-N 0.000 description 1
- 108700025690 abl Genes Proteins 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 208000008445 altitude sickness Diseases 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 125000006242 amine protecting group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000006427 angiogenic response Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003501 anti-edematous effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000007640 basal medium Substances 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000003354 benzotriazolyl group Chemical class N1N=NC2=C1C=CC=C2* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 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
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- XNRHTMDHGDWBGP-UHFFFAOYSA-N carbamic acid;hydrochloride Chemical compound Cl.NC(O)=O XNRHTMDHGDWBGP-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000010002 chemokinesis Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000003081 coactivator Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- WEPUZBYKXNKSDH-UHFFFAOYSA-N cyclopentanecarbonyl chloride Chemical compound ClC(=O)C1CCCC1 WEPUZBYKXNKSDH-UHFFFAOYSA-N 0.000 description 1
- HZVKYZHPDGEECE-UHFFFAOYSA-N cyclopentanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CCCC1 HZVKYZHPDGEECE-UHFFFAOYSA-N 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 239000002037 dichloromethane fraction Substances 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- UXDYOTXIGXWAGT-UHFFFAOYSA-L disodium carbonate trihydrate Chemical compound O.O.O.[Na+].[Na+].[O-]C([O-])=O UXDYOTXIGXWAGT-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000032692 embryo implantation Effects 0.000 description 1
- 230000000408 embryogenic effect Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- KKAGWINEAOLBNB-UHFFFAOYSA-N ethyl 4-[2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]acetyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)CN1C2=NC=NC(N)=C2C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 KKAGWINEAOLBNB-UHFFFAOYSA-N 0.000 description 1
- XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 239000002038 ethyl acetate fraction Substances 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 230000012953 feeding on blood of other organism Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940074076 glycerol formal Drugs 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000055590 human KDR Human genes 0.000 description 1
- 208000013653 hyalitis Diseases 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000003259 immunoinhibitory effect Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 230000002083 iodinating effect Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000005073 lymphatic endothelial cell Anatomy 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000004579 marble Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000031864 metaphase Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- DZFFVUPWZIKCDX-UHFFFAOYSA-N n,n-bis(2-aminoethyl)acetamide Chemical compound NCCN(C(=O)C)CCN DZFFVUPWZIKCDX-UHFFFAOYSA-N 0.000 description 1
- QMHRYTFRSVXTMK-UHFFFAOYSA-N n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]-3-phenylpropanamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)CCC1=CC=CC=C1 QMHRYTFRSVXTMK-UHFFFAOYSA-N 0.000 description 1
- MNMJLOYNSAMCAZ-UHFFFAOYSA-N n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]cyclopentanecarboxamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)C1CCCC1 MNMJLOYNSAMCAZ-UHFFFAOYSA-N 0.000 description 1
- PCKINMYIGQIANF-UHFFFAOYSA-N n-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,3-d]pyrimidin-5-yl]-2-methoxyphenyl]pyridine-2-carboxamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCOCC3)C=2)=CC=C1NC(=O)C1=CC=CC=N1 PCKINMYIGQIANF-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 230000009707 neogenesis Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- LMYJGUNNJIDROI-UHFFFAOYSA-N oxan-4-ol Chemical compound OC1CCOCC1 LMYJGUNNJIDROI-UHFFFAOYSA-N 0.000 description 1
- ZEERHWXRRLRIQO-UHFFFAOYSA-N oxan-4-yl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1CCOCC1 ZEERHWXRRLRIQO-UHFFFAOYSA-N 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 210000000496 pancreas Anatomy 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
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Chemical group 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000028742 placenta development Effects 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 230000017363 positive regulation of growth Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000009443 proangiogenesis Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000006884 regulation of angiogenesis Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003346 selenoethers Chemical class 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- RHVYVVCXRBJXTD-UHFFFAOYSA-N tert-butyl 4-(4-methylphenyl)sulfonyloxy-1,2-oxazolidine-2-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1CN(C(=O)OC(C)(C)C)OC1 RHVYVVCXRBJXTD-UHFFFAOYSA-N 0.000 description 1
- VSQPEDPYPBOLOK-UHFFFAOYSA-N tert-butyl 4-hydroxy-1,2-oxazolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(O)CO1 VSQPEDPYPBOLOK-UHFFFAOYSA-N 0.000 description 1
- HTNAUNFQAMHASO-UHFFFAOYSA-N tert-butyl n-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate Chemical compound C1=C(NC(=O)OC(C)(C)C)C(OC)=CC(B2OC(C)(C)C(C)(C)O2)=C1 HTNAUNFQAMHASO-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000004865 vascular response Effects 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 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
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- AIDS & HIV (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Obesity (AREA)
- Hematology (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10083298P | 1998-09-18 | 1998-09-18 | |
| US10083398P | 1998-09-18 | 1998-09-18 | |
| US10094698P | 1998-09-18 | 1998-09-18 | |
| US10083498P | 1998-09-18 | 1998-09-18 | |
| US60/100,834 | 1998-09-18 | ||
| US60/100,833 | 1998-09-18 | ||
| US60/100,946 | 1998-09-18 | ||
| US60/100,832 | 1998-09-18 | ||
| PCT/US1999/021560 WO2000017203A1 (en) | 1998-09-18 | 1999-09-17 | Pyrrolopyrimidines as protein kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002526500A true JP2002526500A (ja) | 2002-08-20 |
Family
ID=27493158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000574112A Pending JP2002526500A (ja) | 1998-09-18 | 1999-09-17 | プロテインキナーゼ阻害剤としてのピロロピリミジン |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1114053A1 (cs) |
| JP (1) | JP2002526500A (cs) |
| KR (1) | KR20010085824A (cs) |
| CN (1) | CN1335849A (cs) |
| AU (1) | AU753555C (cs) |
| BG (1) | BG105346A (cs) |
| BR (1) | BR9913887A (cs) |
| CA (1) | CA2344249A1 (cs) |
| CZ (1) | CZ2001960A3 (cs) |
| HK (1) | HK1039326A1 (cs) |
| HU (1) | HUP0200403A3 (cs) |
| ID (1) | ID29028A (cs) |
| IL (1) | IL141866A0 (cs) |
| NO (1) | NO20011356L (cs) |
| NZ (1) | NZ510588A (cs) |
| PL (1) | PL346700A1 (cs) |
| SK (1) | SK3842001A3 (cs) |
| TR (1) | TR200101186T2 (cs) |
| WO (1) | WO2000017203A1 (cs) |
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003519676A (ja) * | 2000-01-13 | 2003-06-24 | トゥラリック インコーポレイテッド | 抗菌剤 |
| JP2007520559A (ja) * | 2004-02-03 | 2007-07-26 | アボット・ラボラトリーズ | 治療薬としてのアミノベンゾオキサゾール類 |
| JP2008513500A (ja) * | 2004-09-21 | 2008-05-01 | グラクソ グループ リミテッド | 化学物質 |
| JP2008538773A (ja) * | 2005-04-25 | 2008-11-06 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | キナーゼ阻害剤としての新規アザ複素環化合物 |
| JP2009514882A (ja) * | 2005-11-02 | 2009-04-09 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | がんおよび他の過剰増殖性疾患の処置のためのピロロ［２，１−ｆ］［１，２，４］トリアジン−４−イルアミンＩＧＦ−１Ｒキナーゼ阻害剤 |
| JP2009528991A (ja) * | 2006-02-14 | 2009-08-13 | 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阻害剤として有用なピロロ（３，２−ｃ）ピリジン |
| WO2010084944A1 (ja) * | 2009-01-22 | 2010-07-29 | 田辺三菱製薬株式会社 | 新規ピロロ［２，３－ｄ］ピリミジン化合物 |
| JP2012505916A (ja) * | 2008-10-16 | 2012-03-08 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 融合環ヘテロアリールキナーゼ阻害剤 |
| JP2012525400A (ja) * | 2009-04-29 | 2012-10-22 | ローカス ファーマシューティカルズ インコーポレイテッド | ピロロトリアジン化合物 |
| JP2013507448A (ja) * | 2009-10-12 | 2013-03-04 | ファーマサイクリクス，インコーポレイテッド | ブルトン型チロシンキナーゼの阻害剤 |
| WO2014017659A1 (ja) * | 2012-07-27 | 2014-01-30 | 独立行政法人理化学研究所 | 急性骨髄性白血病の治療又は再発抑制剤 |
| JP2015509107A (ja) * | 2012-01-31 | 2015-03-26 | ナンジン アルゲン ファルマ カンパニー リミテッドＮａｎｊｉｎｇ Ａｌｌｇｅｎ Ｐｈａｒｍａ Ｃｏ． Ｌｔｄ． | ブルトンチロシンキナーゼ阻害薬としての環状分子 |
| US9321772B2 (en) | 2011-09-02 | 2016-04-26 | The Regents Of The University Of California | Substituted pyrazolo[3,4-D]pyrimidines and uses thereof |
| JPWO2015068767A1 (ja) * | 2013-11-08 | 2017-03-09 | 小野薬品工業株式会社 | ピロロピリミジン誘導体 |
| US10131668B2 (en) | 2012-09-26 | 2018-11-20 | The Regents Of The University Of California | Substituted imidazo[1,5-a]pYRAZINES for modulation of IRE1 |
| WO2020054788A1 (ja) * | 2018-09-13 | 2020-03-19 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物 |
| JP2021143175A (ja) * | 2020-03-12 | 2021-09-24 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物を含む医薬組成物 |
| JP2023518035A (ja) * | 2020-03-16 | 2023-04-27 | フラッシュ セラピューティクス，エルエルシー | 急性骨髄性白血病の再発を処置または阻害するための化合物 |
| JP2025511287A (ja) * | 2022-03-31 | 2025-04-15 | エースランド セラピューティクス（ホンコン）リミテッド | スピロビシクリック化合物 |
Families Citing this family (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| JP2002523498A (ja) | 1998-08-29 | 2002-07-30 | アストラゼネカ・アクチエボラーグ | ピリミジン化合物 |
| ATE342892T1 (de) | 1998-08-29 | 2006-11-15 | Astrazeneca Ab | Pyrimidine verbindungen |
| US6713474B2 (en) | 1998-09-18 | 2004-03-30 | Abbott Gmbh & Co. Kg | Pyrrolopyrimidines as therapeutic agents |
| GB9828511D0 (en) | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| GB9905075D0 (en) | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
| GB9907658D0 (en) | 1999-04-06 | 1999-05-26 | Zeneca Ltd | Chemical compounds |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| HU229671B1 (en) | 1999-12-10 | 2014-04-28 | Pfizer Prod Inc | Pyrrolo[2,3-d]pirimidine compounds |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004886D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0007371D0 (en) | 2000-03-28 | 2000-05-17 | Astrazeneca Uk Ltd | Chemical compounds |
| US7369946B2 (en) | 2000-03-29 | 2008-05-06 | Abbott Gmbh & Co. Kg | Method of identifying inhibitors of Tie-2 |
| WO2001072751A1 (en) * | 2000-03-29 | 2001-10-04 | Knoll Gesellschaft Mit Beschraenkter Haftung | Pyrrolopyrimidines as tyrosine kinase inhibitors |
| KR100516419B1 (ko) * | 2000-06-26 | 2005-09-23 | 화이자 프로덕츠 인크. | 면역억제제로서 피롤로[2,3-ｄ]피리미딘 화합물 |
| GB0016877D0 (en) | 2000-07-11 | 2000-08-30 | Astrazeneca Ab | Chemical compounds |
| GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| US7081454B2 (en) | 2001-03-28 | 2006-07-25 | Bristol-Myers Squibb Co. | Tyrosine kinase inhibitors |
| TWI238824B (en) | 2001-05-14 | 2005-09-01 | Novartis Ag | 4-amino-5-phenyl-7-cyclobutyl-pyrrolo[2,3-d]pyrimidine derivatives |
| GB0113041D0 (en) | 2001-05-30 | 2001-07-18 | Astrazeneca Ab | Chemical compounds |
| GB0121033D0 (en) * | 2001-08-30 | 2001-10-24 | Novartis Ag | Organic compounds |
| GB0205690D0 (en) | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| US7442697B2 (en) | 2002-03-09 | 2008-10-28 | Astrazeneca Ab | 4-imidazolyl substituted pyrimidine derivatives with CDK inhibitory activity |
| GB0205688D0 (en) | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| GB0205693D0 (en) | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| AU2003246972A1 (en) | 2002-08-06 | 2004-02-23 | Astrazeneca Ab | Condensed pyridines and pyrimidines with tie2 (tek) activity |
| GB0226370D0 (en) * | 2002-11-12 | 2002-12-18 | Novartis Ag | Organic compounds |
| CN1717236A (zh) | 2002-11-26 | 2006-01-04 | 辉瑞产品公司 | 治疗移植排斥的方法 |
| UA80171C2 (en) | 2002-12-19 | 2007-08-27 | Pfizer Prod Inc | Pyrrolopyrimidine derivatives |
| WO2004081007A1 (en) | 2003-03-12 | 2004-09-23 | Pfizer Products Inc. | Pyridyloxymethyl and benzisoxazole azabicyclic derivatives |
| GB0311276D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| GB0311274D0 (en) | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| AR045037A1 (es) | 2003-07-10 | 2005-10-12 | Aventis Pharma Sa | Tetrahidro-1h-pirazolo [3,4-c] piridinas sustituidas, composiciones que las contienen y su utilizacion. |
| US7312215B2 (en) | 2003-07-29 | 2007-12-25 | Bristol-Myers Squibb Company | Benzimidazole C-2 heterocycles as kinase inhibitors |
| US7338957B2 (en) * | 2003-08-28 | 2008-03-04 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| JP2007511596A (ja) * | 2003-11-17 | 2007-05-10 | ファイザー・プロダクツ・インク | 癌の治療において有用なピロロピリミジン化合物 |
| TW200528101A (en) | 2004-02-03 | 2005-09-01 | Astrazeneca Ab | Chemical compounds |
| EP2308879A1 (en) | 2004-04-02 | 2011-04-13 | OSI Pharmaceuticals, Inc. | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| WO2005116035A1 (en) | 2004-05-27 | 2005-12-08 | Pfizer Products Inc. | Pyrrolopyrimidine derivatives useful in cancer treatment |
| MY139689A (en) | 2004-07-20 | 2009-10-30 | Osi Pharm Inc | Imidazotriazines as protein kinase inhibitors |
| AU2006227447A1 (en) * | 2005-03-17 | 2006-09-28 | Novartis Ag | N- [3- (1-amin0-5, 6, 7, 8-tetrahydro-2 , 4, 4b-triazafluoren-9-yl)-phenyl] benzamides as tyrosine/threonine kinase inhibitors, in particular b-RAF kinase |
| WO2007035744A1 (en) | 2005-09-20 | 2007-03-29 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| CA2623374A1 (en) | 2005-09-30 | 2007-04-05 | Astrazeneca Ab | Imidazo [1,2-a] pyridine having anti-cell-proliferation activity |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| BRPI0711358A2 (pt) | 2006-05-09 | 2011-09-27 | Pfizer Prod Inc | derivados do ácido cicloalquilamino e suas composições farmacêuticas |
| US8217177B2 (en) * | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| EP2170830B1 (en) | 2007-07-17 | 2014-10-15 | Plexxikon, Inc. | 2-FLUORO-BENZENESULFONAMIDE COMPOUNDS AS Raf KINASE MODULATORS |
| JP4884570B2 (ja) | 2008-08-20 | 2012-02-29 | ファイザー・インク | ピロロ［２，３−ｄ］ピリミジン化合物 |
| MX2011004824A (es) | 2008-11-07 | 2012-01-12 | Triact Therapeutics Inc | Uso de derivados de butano catecólico en terapia contra el cáncer. |
| JP2012518657A (ja) | 2009-02-25 | 2012-08-16 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 併用抗癌治療 |
| WO2010099137A2 (en) | 2009-02-26 | 2010-09-02 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the emt status of tumor cells in vivo |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| WO2010099364A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519281A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| US20110275644A1 (en) | 2010-03-03 | 2011-11-10 | Buck Elizabeth A | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| CA2783665A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| EP2544672A1 (en) | 2010-03-09 | 2013-01-16 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| WO2012116040A1 (en) | 2011-02-22 | 2012-08-30 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| CN103492390A (zh) * | 2011-03-08 | 2014-01-01 | 诺瓦提斯公司 | 氟苯基双环杂芳基化合物 |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| BR112014000653A2 (pt) | 2011-07-13 | 2017-02-14 | Pharmacyclics Inc | inibidores de tirosina quinase de bruton |
| SMT202100729T1 (it) | 2011-07-19 | 2022-01-10 | Merck Sharp & Dohme | 4-imidazopiridazin-1-il-benzammidi e 4-imidazotriazin-1-ilbenzammidi come inibitori di btk |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| US9834575B2 (en) | 2013-02-26 | 2017-12-05 | Triact Therapeutics, Inc. | Cancer therapy |
| CA2923667A1 (en) | 2013-09-09 | 2015-03-12 | Triact Therapeutics, Inc. | Cancer therapy |
| JP2016531941A (ja) | 2013-09-30 | 2016-10-13 | ファーマサイクリックス エルエルシー | ブルトン型チロシンキナーゼの阻害剤 |
| CA2833701A1 (en) * | 2013-11-19 | 2015-05-19 | Pharmascience Inc. | Protein kinase inhibitors |
| CA2834528A1 (en) * | 2013-11-26 | 2015-05-26 | Pharmascience Inc. | Protein kinase inhibitors |
| AU2015225745B2 (en) * | 2014-02-03 | 2017-04-20 | Cadila Healthcare Limited | Heterocyclic compounds |
| SI3179991T1 (sl) | 2014-08-11 | 2022-04-29 | Acerta Pharma B.V. | Terapevtske kombinacije zaviralca BTK in zaviralca BCL-2 |
| US10112924B2 (en) | 2015-12-02 | 2018-10-30 | Astraea Therapeutics, Inc. | Piperdinyl nociceptin receptor compounds |
| CN108883103A (zh) * | 2015-12-02 | 2018-11-23 | 阿斯特来亚治疗有限责任公司 | 哌啶基痛敏肽受体化合物 |
| NL2022471B1 (en) | 2019-01-29 | 2020-08-18 | Vationpharma B V | Solid state forms of oclacitinib |
| WO2021030537A1 (en) | 2019-08-14 | 2021-02-18 | Incyte Corporation | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2021038540A1 (en) | 2019-08-31 | 2021-03-04 | Sun Pharma Advanced Research Company Limited | Cycloalkylidene carboxylic acids and derivatives as btk inhibitors |
| MX2022004390A (es) * | 2019-10-11 | 2022-08-08 | Incyte Corp | Aminas biciclicas como inhibidores de la cinasa dependiente de ciclina 2 (cdk2). |
| CN112961159B (zh) * | 2020-03-05 | 2022-07-01 | 四川大学华西医院 | 氨基嘧啶并吡唑/吡咯类衍生物及其制备方法和用途 |
| CN112961158B (zh) * | 2020-03-05 | 2022-07-01 | 四川大学华西医院 | 氨基嘧啶并吡唑/吡咯类衍生物及其制备方法和用途 |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| CN117402161A (zh) * | 2022-07-06 | 2024-01-16 | 上海科恩泰生物医药科技有限公司 | 一种具有fgfr抑制作用的亚砜亚胺类化合物、包含其的药物组合物及其用途 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3036390A1 (de) * | 1980-09-26 | 1982-05-13 | Troponwerke GmbH & Co KG, 5000 Köln | Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen |
| CA2100863A1 (en) * | 1991-01-23 | 1992-07-24 | David A. Bullough | Adenosine kinase inhibitors |
| IL108523A0 (en) * | 1993-02-03 | 1994-05-30 | Gensia Inc | Pharmaceutical compositions containing adenosine kinase inhibitors for preventing or treating conditions involving inflammatory responses and pain |
| DE69520282T2 (de) * | 1994-09-29 | 2001-08-09 | Novartis Ag, Basel | Pyrrolo[2,3-d]pyrimidinderivate und ihre verwendung |
| US5665721A (en) * | 1995-06-07 | 1997-09-09 | Abbott Laboratories | Heterocyclic substituted cyclopentane compounds |
| US6143749A (en) * | 1995-06-07 | 2000-11-07 | Abbott Laboratories | Heterocyclic substituted cyclopentane compounds |
| CH690773A5 (de) * | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| AU1794697A (en) * | 1996-03-06 | 1997-09-22 | Novartis Ag | 7-alkyl-pyrrolo{2,3-d}pyrimidines |
| ATE244719T1 (de) * | 1996-03-15 | 2003-07-15 | Novartis Pharma Gmbh | N-7 heterocyclyl-pyrrolo( 2,3-d)pyrimidine und ihre verwendung |
| HUP0001507A3 (en) * | 1997-03-19 | 2002-01-28 | Abbott Gmbh & Co Kg | Pyrrolo [2,3-d] pyrimidine derivatives, process for their preparation, their use and pharmaceutical compositions containing them |
-
1999
- 1999-09-17 BR BR9913887-5A patent/BR9913887A/pt not_active IP Right Cessation
- 1999-09-17 EP EP99969415A patent/EP1114053A1/en not_active Withdrawn
- 1999-09-17 HU HU0200403A patent/HUP0200403A3/hu unknown
- 1999-09-17 AU AU60484/99A patent/AU753555C/en not_active Ceased
- 1999-09-17 PL PL99346700A patent/PL346700A1/xx unknown
- 1999-09-17 WO PCT/US1999/021560 patent/WO2000017203A1/en not_active Application Discontinuation
- 1999-09-17 CZ CZ2001960A patent/CZ2001960A3/cs unknown
- 1999-09-17 IL IL14186699A patent/IL141866A0/xx unknown
- 1999-09-17 HK HK02100227.3A patent/HK1039326A1/zh unknown
- 1999-09-17 TR TR2001/01186T patent/TR200101186T2/xx unknown
- 1999-09-17 CA CA002344249A patent/CA2344249A1/en not_active Abandoned
- 1999-09-17 CN CN99813217A patent/CN1335849A/zh active Pending
- 1999-09-17 NZ NZ510588A patent/NZ510588A/en unknown
- 1999-09-17 ID IDW20010652A patent/ID29028A/id unknown
- 1999-09-17 KR KR1020017003532A patent/KR20010085824A/ko not_active Ceased
- 1999-09-17 SK SK384-2001A patent/SK3842001A3/sk unknown
- 1999-09-17 JP JP2000574112A patent/JP2002526500A/ja active Pending
-
2001
- 2001-03-15 BG BG105346A patent/BG105346A/xx unknown
- 2001-03-16 NO NO20011356A patent/NO20011356L/no not_active Application Discontinuation
Cited By (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003519676A (ja) * | 2000-01-13 | 2003-06-24 | トゥラリック インコーポレイテッド | 抗菌剤 |
| JP2007520559A (ja) * | 2004-02-03 | 2007-07-26 | アボット・ラボラトリーズ | 治療薬としてのアミノベンゾオキサゾール類 |
| JP2008513500A (ja) * | 2004-09-21 | 2008-05-01 | グラクソ グループ リミテッド | 化学物質 |
| JP2008538773A (ja) * | 2005-04-25 | 2008-11-06 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | キナーゼ阻害剤としての新規アザ複素環化合物 |
| JP2009514882A (ja) * | 2005-11-02 | 2009-04-09 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | がんおよび他の過剰増殖性疾患の処置のためのピロロ［２，１−ｆ］［１，２，４］トリアジン−４−イルアミンＩＧＦ−１Ｒキナーゼ阻害剤 |
| JP2009528991A (ja) * | 2006-02-14 | 2009-08-13 | 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阻害剤として有用なピロロ（３，２−ｃ）ピリジン |
| JP2014193925A (ja) * | 2008-10-16 | 2014-10-09 | Regents Of The Univ Of California | 融合環ヘテロアリールキナーゼ阻害剤 |
| JP2012505916A (ja) * | 2008-10-16 | 2012-03-08 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 融合環ヘテロアリールキナーゼ阻害剤 |
| WO2010084944A1 (ja) * | 2009-01-22 | 2010-07-29 | 田辺三菱製薬株式会社 | 新規ピロロ［２，３－ｄ］ピリミジン化合物 |
| JP2012525400A (ja) * | 2009-04-29 | 2012-10-22 | ローカス ファーマシューティカルズ インコーポレイテッド | ピロロトリアジン化合物 |
| JP2013507448A (ja) * | 2009-10-12 | 2013-03-04 | ファーマサイクリクス，インコーポレイテッド | ブルトン型チロシンキナーゼの阻害剤 |
| US9895373B2 (en) | 2011-09-02 | 2018-02-20 | The Regents Of The University Of California | Substituted pyrazolo[3,4-D]pyrimidines and uses thereof |
| US9321772B2 (en) | 2011-09-02 | 2016-04-26 | The Regents Of The University Of California | Substituted pyrazolo[3,4-D]pyrimidines and uses thereof |
| JP2015509107A (ja) * | 2012-01-31 | 2015-03-26 | ナンジン アルゲン ファルマ カンパニー リミテッドＮａｎｊｉｎｇ Ａｌｌｇｅｎ Ｐｈａｒｍａ Ｃｏ． Ｌｔｄ． | ブルトンチロシンキナーゼ阻害薬としての環状分子 |
| JPWO2014017659A1 (ja) * | 2012-07-27 | 2016-07-11 | 国立研究開発法人理化学研究所 | 急性骨髄性白血病の治療又は再発抑制剤 |
| US9604988B2 (en) | 2012-07-27 | 2017-03-28 | Riken | Agent for treating or inhibiting recurrence of acute myeloid leukemia |
| WO2014017659A1 (ja) * | 2012-07-27 | 2014-01-30 | 独立行政法人理化学研究所 | 急性骨髄性白血病の治療又は再発抑制剤 |
| US10131668B2 (en) | 2012-09-26 | 2018-11-20 | The Regents Of The University Of California | Substituted imidazo[1,5-a]pYRAZINES for modulation of IRE1 |
| US11613544B2 (en) | 2012-09-26 | 2023-03-28 | The Regents Of The University Of California | Substituted imidazo[1,5-a]pyrazines for modulation of IRE1 |
| US10822340B2 (en) | 2012-09-26 | 2020-11-03 | The Regents Of The University Of California | Substituted imidazolopyrazine compounds and methods of using same |
| JPWO2015068767A1 (ja) * | 2013-11-08 | 2017-03-09 | 小野薬品工業株式会社 | ピロロピリミジン誘導体 |
| JPWO2020054788A1 (ja) * | 2018-09-13 | 2021-08-30 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物 |
| WO2020054788A1 (ja) * | 2018-09-13 | 2020-03-19 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物 |
| JP7458987B2 (ja) | 2018-09-13 | 2024-04-01 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物 |
| US12077531B2 (en) | 2018-09-13 | 2024-09-03 | Kissei Pharmaceutical Co., Ltd. | Imidazopyridinone compound |
| JP2021143175A (ja) * | 2020-03-12 | 2021-09-24 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物を含む医薬組成物 |
| JP7504822B2 (ja) | 2020-03-12 | 2024-06-24 | キッセイ薬品工業株式会社 | イミダゾピリジノン化合物を含む医薬組成物 |
| JP2023518035A (ja) * | 2020-03-16 | 2023-04-27 | フラッシュ セラピューティクス，エルエルシー | 急性骨髄性白血病の再発を処置または阻害するための化合物 |
| JP7744358B2 (ja) | 2020-03-16 | 2025-09-25 | フラッシュ セラピューティクス，エルエルシー | 急性骨髄性白血病の再発を処置または阻害するための化合物 |
| JP2025511287A (ja) * | 2022-03-31 | 2025-04-15 | エースランド セラピューティクス（ホンコン）リミテッド | スピロビシクリック化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| TR200101186T2 (tr) | 2001-10-22 |
| NO20011356D0 (no) | 2001-03-16 |
| AU753555B2 (en) | 2002-10-24 |
| HUP0200403A2 (en) | 2002-06-29 |
| CA2344249A1 (en) | 2000-03-30 |
| ID29028A (id) | 2001-07-26 |
| KR20010085824A (ko) | 2001-09-07 |
| BR9913887A (pt) | 2001-10-23 |
| AU753555C (en) | 2003-07-03 |
| PL346700A1 (en) | 2002-02-25 |
| NO20011356L (no) | 2001-05-16 |
| WO2000017203A1 (en) | 2000-03-30 |
| CZ2001960A3 (cs) | 2001-10-17 |
| BG105346A (en) | 2001-12-29 |
| IL141866A0 (en) | 2002-03-10 |
| HUP0200403A3 (en) | 2004-07-28 |
| AU6048499A (en) | 2000-04-10 |
| NZ510588A (en) | 2003-08-29 |
| SK3842001A3 (en) | 2002-04-04 |
| EP1114053A1 (en) | 2001-07-11 |
| CN1335849A (zh) | 2002-02-13 |
| HK1039326A1 (zh) | 2002-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2002526500A (ja) | プロテインキナーゼ阻害剤としてのピロロピリミジン | |
| JP4707167B2 (ja) | キナーゼ阻害剤 | |
| US6713474B2 (en) | Pyrrolopyrimidines as therapeutic agents | |
| US7829570B2 (en) | Substituted 4-amino isoxazolo[5,4-d]pyrimidines as kinase inhibitors | |
| DE69928414T2 (de) | 4-aminopyrrolopyrimidine als kinaseinhibitoren | |
| US7863444B2 (en) | 4-aminopyrrolopyrimidines as kinase inhibitors | |
| DE60004685T2 (de) | Pyrazolopyrimidine als arzneimittel | |
| WO2001072751A1 (en) | Pyrrolopyrimidines as tyrosine kinase inhibitors | |
| KR20020063854A (ko) | 치료제로서의 키나제 억제제 | |
| US20040006083A1 (en) | Pyrazolopyrimidines as therapeutic agents | |
| KR20020084116A (ko) | 2-벤조티아졸릴 우레아 유도체 및 이의 단백질 키나제억제제로서의 용도 | |
| US7071199B1 (en) | Kinase inhibitors as therapeutic agents | |
| MXPA01002785A (en) | Pyrrolopyrimidines as protein kinase inhibitors |