ZA200202122B - Kinase inhibitors as therapeutic agents. - Google Patents
Kinase inhibitors as therapeutic agents. Download PDFInfo
- Publication number
- ZA200202122B ZA200202122B ZA200202122A ZA200202122A ZA200202122B ZA 200202122 B ZA200202122 B ZA 200202122B ZA 200202122 A ZA200202122 A ZA 200202122A ZA 200202122 A ZA200202122 A ZA 200202122A ZA 200202122 B ZA200202122 B ZA 200202122B
- Authority
- ZA
- South Africa
- Prior art keywords
- substituted
- unsubstituted
- group
- alkyl
- compound
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 11
- 229940043355 kinase inhibitor Drugs 0.000 title description 7
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 7
- 229940124597 therapeutic agent Drugs 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 150000001875 compounds Chemical class 0.000 claims description 110
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 125000003118 aryl group Chemical group 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 62
- -1 2,3-dihydrobenzofuranyl Chemical group 0.000 claims description 55
- 229910052757 nitrogen Inorganic materials 0.000 claims description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 47
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 43
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 41
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 150000002431 hydrogen Chemical class 0.000 claims description 34
- 239000000126 substance Substances 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 28
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 229910020008 S(O) Inorganic materials 0.000 claims description 24
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 22
- 102000001253 Protein Kinase Human genes 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 21
- 108060006633 protein kinase Proteins 0.000 claims description 21
- 206010028980 Neoplasm Diseases 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 239000002207 metabolite Substances 0.000 claims description 20
- 229940002612 prodrug Drugs 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 20
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 19
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 230000033115 angiogenesis Effects 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims description 12
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 claims description 12
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 claims description 12
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 230000004913 activation Effects 0.000 claims description 10
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 230000002792 vascular Effects 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 239000003102 growth factor Substances 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 230000003463 hyperproliferative effect Effects 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 102100040681 Platelet-derived growth factor C Human genes 0.000 claims description 7
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 208000028867 ischemia Diseases 0.000 claims description 7
- 108010017992 platelet-derived growth factor C Proteins 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 claims description 6
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 claims description 6
- 206010030113 Oedema Diseases 0.000 claims description 6
- 206010052779 Transplant rejections Diseases 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 claims description 5
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 claims description 5
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 claims description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 230000001023 pro-angiogenic effect Effects 0.000 claims description 5
- 125000005504 styryl group Chemical group 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 101100481403 Bos taurus TIE1 gene Proteins 0.000 claims description 4
- 101100481408 Danio rerio tie2 gene Proteins 0.000 claims description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 claims description 4
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 claims description 4
- 101150028321 Lck gene Proteins 0.000 claims description 4
- 101100481410 Mus musculus Tek gene Proteins 0.000 claims description 4
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000005518 carboxamido group Chemical group 0.000 claims description 4
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 4
- 230000028709 inflammatory response Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 208000002780 macular degeneration Diseases 0.000 claims description 4
- 210000001616 monocyte Anatomy 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010017533 Fungal infection Diseases 0.000 claims description 3
- 206010021143 Hypoxia Diseases 0.000 claims description 3
- 206010061216 Infarction Diseases 0.000 claims description 3
- 208000031888 Mycoses Diseases 0.000 claims description 3
- 241000700639 Parapoxvirus Species 0.000 claims description 3
- 241000700605 Viruses Species 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 3
- 230000007954 hypoxia Effects 0.000 claims description 3
- 230000007574 infarction Effects 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 230000004862 vasculogenesis Effects 0.000 claims description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
- 125000006356 alkylene carbonyl group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 14
- 208000025865 Ulcer Diseases 0.000 claims 13
- 231100000397 ulcer Toxicity 0.000 claims 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims 7
- 238000004519 manufacturing process Methods 0.000 claims 6
- 206010016654 Fibrosis Diseases 0.000 claims 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- 230000003844 B-cell-activation Effects 0.000 claims 3
- 101100503636 Danio rerio fyna gene Proteins 0.000 claims 3
- 101150018272 FYN gene Proteins 0.000 claims 3
- 208000019693 Lung disease Diseases 0.000 claims 3
- 101150058160 Lyn gene Proteins 0.000 claims 3
- 101150001535 SRC gene Proteins 0.000 claims 3
- 230000006044 T cell activation Effects 0.000 claims 3
- 208000006673 asthma Diseases 0.000 claims 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 3
- 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 3
- 230000003247 decreasing effect Effects 0.000 claims 3
- 230000035558 fertility Effects 0.000 claims 3
- 210000003630 histaminocyte Anatomy 0.000 claims 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims 2
- 206010010741 Conjunctivitis Diseases 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 206010054044 Diabetic microangiopathy Diseases 0.000 claims 2
- 208000019878 Eales disease Diseases 0.000 claims 2
- 201000009273 Endometriosis Diseases 0.000 claims 2
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 claims 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 2
- 201000008808 Fibrosarcoma Diseases 0.000 claims 2
- 206010017711 Gangrene Diseases 0.000 claims 2
- 208000010412 Glaucoma Diseases 0.000 claims 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims 2
- 102100021866 Hepatocyte growth factor Human genes 0.000 claims 2
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 0.000 claims 2
- 208000009889 Herpes Simplex Diseases 0.000 claims 2
- 208000007514 Herpes zoster Diseases 0.000 claims 2
- 208000017604 Hodgkin disease Diseases 0.000 claims 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 2
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 claims 2
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 claims 2
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 claims 2
- 206010051151 Hyperviscosity syndrome Diseases 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 2
- 208000016604 Lyme disease Diseases 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 206010025538 Malignant ascites Diseases 0.000 claims 2
- 206010027295 Menometrorrhagia Diseases 0.000 claims 2
- 208000024599 Mooren ulcer Diseases 0.000 claims 2
- 101100381649 Mus musculus Bik gene Proteins 0.000 claims 2
- 206010028851 Necrosis Diseases 0.000 claims 2
- 206010029260 Neuroblastoma Diseases 0.000 claims 2
- 208000010191 Osteitis Deformans Diseases 0.000 claims 2
- 206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 claims 2
- 101150038994 PDGFRA gene Proteins 0.000 claims 2
- 208000027868 Paget disease Diseases 0.000 claims 2
- 206010034277 Pemphigoid Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 claims 2
- 206010063837 Reperfusion injury Diseases 0.000 claims 2
- 206010038848 Retinal detachment Diseases 0.000 claims 2
- 208000017442 Retinal disease Diseases 0.000 claims 2
- 201000000582 Retinoblastoma Diseases 0.000 claims 2
- 206010038923 Retinopathy Diseases 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 206010039705 Scleritis Diseases 0.000 claims 2
- 206010040047 Sepsis Diseases 0.000 claims 2
- 208000027073 Stargardt disease Diseases 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- 201000005485 Toxoplasmosis Diseases 0.000 claims 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 2
- 206010064996 Ulcerative keratitis Diseases 0.000 claims 2
- 206010046851 Uveitis Diseases 0.000 claims 2
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 claims 2
- 102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 claims 2
- 102000009519 Vascular Endothelial Growth Factor D Human genes 0.000 claims 2
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 claims 2
- 206010047663 Vitritis Diseases 0.000 claims 2
- 206010052428 Wound Diseases 0.000 claims 2
- 208000027418 Wounds and injury Diseases 0.000 claims 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 208000007502 anemia Diseases 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 claims 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
- 208000037976 chronic inflammation Diseases 0.000 claims 2
- 230000006020 chronic inflammation Effects 0.000 claims 2
- 230000007882 cirrhosis Effects 0.000 claims 2
- 125000004966 cyanoalkyl group Chemical group 0.000 claims 2
- 201000009101 diabetic angiopathy Diseases 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 230000004761 fibrosis Effects 0.000 claims 2
- 208000005017 glioblastoma Diseases 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 230000009033 hematopoietic malignancy Effects 0.000 claims 2
- 208000013653 hyalitis Diseases 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 208000014674 injury Diseases 0.000 claims 2
- 238000013532 laser treatment Methods 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 206010025135 lupus erythematosus Diseases 0.000 claims 2
- 208000027202 mammary Paget disease Diseases 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims 2
- 208000001491 myopia Diseases 0.000 claims 2
- 230000004379 myopia Effects 0.000 claims 2
- 230000017074 necrotic cell death Effects 0.000 claims 2
- 230000000414 obstructive effect Effects 0.000 claims 2
- 201000008482 osteoarthritis Diseases 0.000 claims 2
- 208000008798 osteoma Diseases 0.000 claims 2
- 208000030761 polycystic kidney disease Diseases 0.000 claims 2
- 201000011461 pre-eclampsia Diseases 0.000 claims 2
- 230000005855 radiation Effects 0.000 claims 2
- 230000004264 retinal detachment Effects 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 201000000306 sarcoidosis Diseases 0.000 claims 2
- 208000007056 sickle cell anemia Diseases 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- 201000004595 synovitis Diseases 0.000 claims 2
- 230000009885 systemic effect Effects 0.000 claims 2
- 208000001608 teratocarcinoma Diseases 0.000 claims 2
- 206010043778 thyroiditis Diseases 0.000 claims 2
- 230000008733 trauma Effects 0.000 claims 2
- 208000006542 von Hippel-Lindau disease Diseases 0.000 claims 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims 1
- 241000725303 Human immunodeficiency virus Species 0.000 claims 1
- 206010061598 Immunodeficiency Diseases 0.000 claims 1
- 208000029462 Immunodeficiency disease Diseases 0.000 claims 1
- 208000001344 Macular Edema Diseases 0.000 claims 1
- 206010025415 Macular oedema Diseases 0.000 claims 1
- 101100381845 Mus musculus Blk gene Proteins 0.000 claims 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims 1
- 125000005181 hydroxyalkylaminoalkyl group Chemical group 0.000 claims 1
- 230000007813 immunodeficiency Effects 0.000 claims 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims 1
- 201000010230 macular retinal edema Diseases 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims 1
- 125000005309 thioalkoxy group Chemical group 0.000 claims 1
- 229930192474 thiophene Natural products 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 43
- 102000005962 receptors Human genes 0.000 description 28
- 108020003175 receptors Proteins 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 19
- 108091000080 Phosphotransferase Proteins 0.000 description 18
- 102000020233 phosphotransferase Human genes 0.000 description 18
- 108091007914 CDKs Proteins 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 239000003446 ligand Substances 0.000 description 10
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 9
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- 238000006366 phosphorylation reaction Methods 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 9
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 8
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 8
- 230000004663 cell proliferation Effects 0.000 description 8
- 230000026731 phosphorylation Effects 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 8
- 101150012716 CDK1 gene Proteins 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 7
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 7
- 101100464293 Caenorhabditis elegans plk-1 gene Proteins 0.000 description 6
- 230000033228 biological regulation Effects 0.000 description 6
- 230000008728 vascular permeability Effects 0.000 description 6
- 108010057466 NF-kappa B Proteins 0.000 description 5
- 102000003945 NF-kappa B Human genes 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
- 230000018199 S phase Effects 0.000 description 5
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 102000002427 Cyclin B Human genes 0.000 description 4
- 108010068150 Cyclin B Proteins 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 102100035194 Placenta growth factor Human genes 0.000 description 4
- 108091008605 VEGF receptors Proteins 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 230000003511 endothelial effect Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 102000016736 Cyclin Human genes 0.000 description 3
- 108050006400 Cyclin Proteins 0.000 description 3
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 3
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 3
- 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 3
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 description 3
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 3
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 3
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 3
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 3
- 238000004891 communication Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 229960002897 heparin Drugs 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 102000058223 human VEGFA Human genes 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 241000894007 species Species 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
- 210000003556 vascular endothelial cell Anatomy 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000005623 Carcinogenesis Diseases 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
- 206010063045 Effusion Diseases 0.000 description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 2
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100028762 Neuropilin-1 Human genes 0.000 description 2
- 108090000772 Neuropilin-1 Proteins 0.000 description 2
- 241000700635 Orf virus Species 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108091005682 Receptor kinases Proteins 0.000 description 2
- 108060006706 SRC Proteins 0.000 description 2
- 102000001332 SRC Human genes 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000001772 anti-angiogenic effect Effects 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000006369 cell cycle progression Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 210000000416 exudates and transudate Anatomy 0.000 description 2
- 230000003176 fibrotic effect Effects 0.000 description 2
- 238000005734 heterodimerization reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000003584 mesangial cell Anatomy 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000002297 mitogenic effect Effects 0.000 description 2
- 230000000394 mitotic effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000006884 regulation of angiogenesis Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 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
- 201000002909 Aspergillosis Diseases 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 208000036641 Aspergillus infections Diseases 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
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101150047144 CDC28 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 235000002566 Capsicum Nutrition 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 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
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000001267 GSK3 Human genes 0.000 description 1
- 108060006662 GSK3 Proteins 0.000 description 1
- 208000022461 Glomerular disease Diseases 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
- 241000282412 Homo Species 0.000 description 1
- 101001005128 Homo sapiens LIM domain kinase 1 Proteins 0.000 description 1
- 101001092185 Homo sapiens Regulator of cell cycle RGCC Proteins 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 102100026023 LIM domain kinase 1 Human genes 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
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101000851005 Mus musculus Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000006002 Pepper Substances 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 235000016761 Piper aduncum Nutrition 0.000 description 1
- 235000017804 Piper guineense Nutrition 0.000 description 1
- 244000203593 Piper nigrum Species 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- 108010082093 Placenta Growth Factor Proteins 0.000 description 1
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 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
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- 101000851003 Rattus norvegicus Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100035542 Regulator of cell cycle RGCC Human genes 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 108010034265 Vascular Endothelial Growth Factor Receptors Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 208000001969 capillary hemangioma Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 230000003081 coactivator Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000005073 lymphatic endothelial cell Anatomy 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000031864 metaphase Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 210000000479 mitotic spindle apparatus Anatomy 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 1
- CEONEQNQPCIIEY-UHFFFAOYSA-N n-phenylcinnolin-3-amine Chemical class C=1C2=CC=CC=C2N=NC=1NC1=CC=CC=C1 CEONEQNQPCIIEY-UHFFFAOYSA-N 0.000 description 1
- 201000009925 nephrosclerosis Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 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
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 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
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000006760 regulation of extracellular matrix disassembly Effects 0.000 description 1
- 150000003346 selenoethers Chemical class 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000006459 vascular development Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—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
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- 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
- A61P31/12—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
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- 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 System
- 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
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15461899P | 1999-09-17 | 1999-09-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200202122B true ZA200202122B (en) | 2003-08-27 |
Family
ID=22552056
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200202122A ZA200202122B (en) | 1999-09-17 | 2002-03-14 | Kinase inhibitors as therapeutic agents. |
Country Status (27)
| Country | Link |
|---|---|
| EP (1) | EP1268481B1 (tr) |
| JP (1) | JP2003509427A (tr) |
| KR (1) | KR20020063854A (tr) |
| CN (1) | CN1390220A (tr) |
| AR (1) | AR029766A1 (tr) |
| AT (1) | ATE380814T1 (tr) |
| AU (1) | AU7491400A (tr) |
| BG (1) | BG106585A (tr) |
| BR (1) | BR0014075A (tr) |
| CA (1) | CA2385769A1 (tr) |
| CY (1) | CY1107886T1 (tr) |
| CZ (1) | CZ2002934A3 (tr) |
| DE (1) | DE60037455T2 (tr) |
| DK (1) | DK1268481T3 (tr) |
| ES (1) | ES2299434T3 (tr) |
| HK (1) | HK1053831A1 (tr) |
| HU (1) | HUP0303363A2 (tr) |
| IL (1) | IL148719A0 (tr) |
| MX (1) | MXPA02002938A (tr) |
| NO (1) | NO20021329L (tr) |
| NZ (1) | NZ517759A (tr) |
| PL (1) | PL354241A1 (tr) |
| PT (1) | PT1268481E (tr) |
| SK (1) | SK3792002A3 (tr) |
| TR (1) | TR200201506T2 (tr) |
| WO (1) | WO2001019828A2 (tr) |
| ZA (1) | ZA200202122B (tr) |
Families Citing this family (117)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7235551B2 (en) | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| JP4524072B2 (ja) | 2000-10-23 | 2010-08-11 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 新規化合物 |
| EP1425284A2 (en) * | 2001-09-11 | 2004-06-09 | Smithkline Beecham Corporation | Furo- and thienopyrimidine derivatives as angiogenesis inhibitors |
| CN1646535A (zh) * | 2002-02-22 | 2005-07-27 | 帝人株式会社 | 吡咯并嘧啶衍生物 |
| US7560552B2 (en) | 2002-03-21 | 2009-07-14 | Abbott Laboratories | Thiopyrimidine and isothiazolopyrimidine kinase inhibitors |
| US20030225273A1 (en) * | 2002-03-21 | 2003-12-04 | Michaelides Michael R. | Thiopyrimidine and isothiazolopyrimidine kinase inhibitors |
| US7629350B2 (en) | 2002-04-19 | 2009-12-08 | Smithkline Beecham Corporation | Compounds |
| MXPA05001389A (es) | 2002-08-06 | 2005-04-28 | Astrazeneca Ab | Piridinas y pirimidinas condensadas con actividad tie2 (tek). |
| US7592352B2 (en) | 2003-05-06 | 2009-09-22 | Smithkline Beecham Corporation | Substituted thieno and furo-pyridines |
| US7297709B2 (en) | 2003-05-22 | 2007-11-20 | Abbott Laboratories | Indazole, benzisoxazole, and benzisothiazole kinase inhibitors |
| US7129260B2 (en) | 2003-06-02 | 2006-10-31 | Abbott Laboratories | Isoindolinone kinase inhibitors |
| US20050026944A1 (en) * | 2003-07-24 | 2005-02-03 | Patrick Betschmann | Thienopyridine and furopyridine kinase inhibitors |
| US7202363B2 (en) | 2003-07-24 | 2007-04-10 | Abbott Laboratories | Thienopyridine and furopyridine kinase inhibitors |
| US7371750B2 (en) * | 2003-07-29 | 2008-05-13 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| CA2548326A1 (en) * | 2003-12-23 | 2005-07-14 | Novartis Ag | Bicyclic heterocyclic p-38 kinase inhibitors |
| TW200530236A (en) * | 2004-02-23 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Heteroaryl phenylurea |
| JP2007538068A (ja) * | 2004-05-19 | 2007-12-27 | アストラゼネカ アクチボラグ | 新規な縮合複素環およびそれらの使用 |
| FR2871158A1 (fr) | 2004-06-04 | 2005-12-09 | Aventis Pharma Sa | Indazoles substitues, compositions les contenant, procede de fabrication et utilisation |
| US20070054916A1 (en) * | 2004-10-01 | 2007-03-08 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and methods of use |
| CA2585934C (en) * | 2004-10-29 | 2013-09-10 | Abbott Laboratories | Novel pyrazolopyridine urea kinase inhibitors |
| DE102004061288A1 (de) * | 2004-12-14 | 2006-06-29 | Schering Ag | 3-Amino-Pyrazolo[3,4b]pyridine als Inhibitoren von Proteintyrosinkinasen, deren Herstellung und Verwendung als Arzneimittel |
| PE20061119A1 (es) | 2005-01-19 | 2006-11-27 | Aventis Pharma Sa | PIRAZOLO PIRIDINAS SUSTITUIDAS COMO INHIBIDORES DE CINASAS FAK, KDR Y Tie |
| EP1683796A1 (en) * | 2005-01-24 | 2006-07-26 | Schering Aktiengesellschaft | Pyrazolopyridines, their preparation and their medical use |
| US7842809B2 (en) | 2005-01-24 | 2010-11-30 | Bayer Schering Pharma Ag | Pyrazolopyridines and salts thereof, a pharmaceutical composition comprising said compounds, a method of preparing same and use of same |
| AR053450A1 (es) | 2005-03-25 | 2007-05-09 | Glaxo Group Ltd | Derivados de 3,4-dihidro-pirimido(4,5-d)pirimidin-2-(1h)-ona 1,5,7 trisustituidos como inhibidores de la quinasa p38 |
| EA200702073A1 (ru) | 2005-03-25 | 2008-12-30 | Глэксо Груп Лимитед | Способ получения пиридо[2,3-d]пиримидин-7-оновых и 3,4-дигидропиримидо[4,5-d]пиримидин-2(1н)-оновых производных |
| EP1868612A4 (en) | 2005-03-25 | 2010-03-24 | Glaxo Group Ltd | NOVEL CONNECTIONS |
| AR053346A1 (es) | 2005-03-25 | 2007-05-02 | Glaxo Group Ltd | Compuesto derivado de 8h -pirido (2,3-d) pirimidin -7 ona 2,4,8- trisustituida composicion farmaceutica y uso para preparar una composicion para tratamiento y profilxis de una enfermedad mediada por la quinasa csbp/ rk/p38 |
| US7884109B2 (en) | 2005-04-05 | 2011-02-08 | Wyeth Llc | Purine and imidazopyridine derivatives for immunosuppression |
| US7795248B2 (en) * | 2005-05-18 | 2010-09-14 | Abbott Laboratories, Inc. | Substituted 7,8-dihydro-1H-pyrimido[4,5-B][1,4]diazepin-4-amines are novel kinase inhibitors |
| FR2889526B1 (fr) * | 2005-08-04 | 2012-02-17 | Aventis Pharma Sa | 7-aza-indazoles substitues, compositions les contenant, procede de fabrication et utilisation |
| DE102005042742A1 (de) * | 2005-09-02 | 2007-03-08 | Schering Ag | Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| TW200800983A (en) * | 2005-09-14 | 2008-01-01 | Janssen Pharmaceutica Nv | 5-oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of C-FMS kinase |
| WO2007033232A1 (en) * | 2005-09-14 | 2007-03-22 | Janssen Pharmaceutica, N.V. | 5-oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of c-fms kinase |
| PT1951724E (pt) | 2005-11-17 | 2011-08-02 | Osi Pharm Inc | Inibidores mtor fundidos bicíclicos |
| AU2006320440B2 (en) * | 2005-12-02 | 2012-04-05 | Bayer Healthcare Llc | Substituted 4-amino-pyrrolotriazine derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis |
| PE20070855A1 (es) * | 2005-12-02 | 2007-10-14 | Bayer Pharmaceuticals Corp | Derivados de 4-amino-pirrolotriazina sustituida como inhibidores de quinasas |
| TW200738725A (en) * | 2006-01-25 | 2007-10-16 | Osi Pharm Inc | Unsaturated mTOR inhibitors |
| NZ570530A (en) * | 2006-02-14 | 2011-09-30 | Vertex Pharma | Pharmaceutical compositions comprising 6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4)diazepine derivatives |
| US7989459B2 (en) | 2006-02-17 | 2011-08-02 | Pharmacopeia, Llc | Purinones and 1H-imidazopyridinones as PKC-theta inhibitors |
| EP1987037A2 (en) * | 2006-02-23 | 2008-11-05 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
| TW200815437A (en) * | 2006-06-13 | 2008-04-01 | Bayer Schering Pharma Ag | Substituted aminopyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| WO2008022060A2 (en) * | 2006-08-14 | 2008-02-21 | Novartis Ag | Imidazo-pyridine derivatives for modulating protein kinase activity |
| US7897762B2 (en) * | 2006-09-14 | 2011-03-01 | Deciphera Pharmaceuticals, Llc | Kinase inhibitors useful for the treatment of proliferative diseases |
| US7902187B2 (en) | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| AR063142A1 (es) | 2006-10-04 | 2008-12-30 | Pharmacopeia Inc | Derivados de 2-(bencimidazolil) purina y purinonas 6-sustituidas utiles como inmunosupresores,y composiciones farmaceuticas que los contienen. |
| WO2008043019A1 (en) | 2006-10-04 | 2008-04-10 | Pharmacopeia, Inc | 8-substituted 2-(benzimidazolyl) purine derivatives for immunosuppression |
| KR101157848B1 (ko) | 2007-03-22 | 2012-07-11 | 다케다 야쿠힌 고교 가부시키가이샤 | Ｐｌｋ１ 저해제로서 유용한 치환된 피리미도디아제핀 |
| EP2152708A1 (en) | 2007-05-23 | 2010-02-17 | Pharmacopeia, LLC | Purinones and 1h-imidazopyridinones as pkc-theta inhibitors |
| DE102007024470A1 (de) | 2007-05-24 | 2008-11-27 | Bayer Schering Pharma Aktiengesellschaft | Neue Sulfoximin-substituierte Chinolin- bzw. Chinazolinderivate als Kinase-Inhibitoren |
| MY152283A (en) | 2007-09-25 | 2014-09-15 | Takeda Pharmaceutical | Polo-like kinase inhibitirs |
| EP2072502A1 (de) | 2007-12-20 | 2009-06-24 | Bayer Schering Pharma Aktiengesellschaft | Sulfoximid-substituierte Chinolin- und Chinazolinderivate als Kinase-Inhibitoren |
| CN101239978A (zh) * | 2008-03-05 | 2008-08-13 | 南方医科大学 | 一种咪唑并吡啶类化合物 |
| US20100048524A1 (en) | 2008-03-14 | 2010-02-25 | Angela Brodie | Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens;Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity |
| JP5647098B2 (ja) | 2008-03-21 | 2014-12-24 | ザ ユニヴァーシティー オヴ シカゴ | オピオイド拮抗薬とｍＴＯＲ阻害薬を用いた治療 |
| EP2303889A1 (en) | 2008-06-18 | 2011-04-06 | F. Hoffmann-La Roche AG | Halo-substituted pyrimidodiazepines as plkl inhibitors |
| ES2524966T3 (es) | 2008-12-05 | 2014-12-16 | Abbvie Bahamas Ltd. | Derivados de tieno[3,2-c]piridina como inhibidores de quinasas para uso en el tratamiento del cáncer |
| CA2761389A1 (en) | 2009-02-05 | 2010-08-12 | Tokai Pharmaceuticals, Inc. | Novel prodrugs of steroidal cyp17 inhibitors/antiandrogens |
| EP2789615B1 (en) * | 2009-08-11 | 2017-05-03 | Bristol-Myers Squibb Company | Azaindazoles as Btk kinase modulators and use thereof |
| JP2013505927A (ja) | 2009-09-25 | 2013-02-21 | 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阻害剤として有用なピリミジン誘導体の調製方法 |
| SG179207A1 (en) | 2009-09-25 | 2012-04-27 | Vertex Pharma | Methods for preparing pyrimidine derivatives useful as protein kinase inhibitors |
| JP5764145B2 (ja) * | 2010-02-08 | 2015-08-12 | メルク・シャープ・エンド・ドーム・ベー・フェー | ８−メチル−１−フェニル−イミダゾル［１，５−ａ］ピラジン化合物 |
| AU2015202128B2 (en) * | 2010-05-31 | 2015-05-28 | Ono Pharmaceutical Co., Ltd. | Purinone derivative |
| PT2578585T (pt) | 2010-05-31 | 2016-09-23 | Ono Pharmaceutical Co | Derivado de purinona como inibidor da quinase btk |
| CN106243113B (zh) | 2011-07-19 | 2018-12-18 | 默沙东有限责任公司 | 作为btk抑制剂的选择的咪唑并吡嗪类 |
| EP2548877A1 (en) | 2011-07-19 | 2013-01-23 | MSD Oss B.V. | 4-(5-Membered fused pyridinyl)benzamides as BTK-inhibitors |
| WO2013012909A1 (en) | 2011-07-20 | 2013-01-24 | Abbott Laboratories | Kinase inhibitor with improved aqueous solubility |
| RS55542B1 (sr) * | 2011-11-29 | 2017-05-31 | Ono Pharmaceutical Co | Purinonski derivati hlorovodonika |
| JP6047582B2 (ja) | 2011-12-15 | 2016-12-21 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | 置換ベンゾチエニル−ピロロトリアジンおよび癌の処置におけるその使用 |
| UY34484A (es) | 2011-12-15 | 2013-07-31 | Bayer Ip Gmbh | Benzotienilo-pirrolotriazinas disustituidas y sus usos |
| US8501724B1 (en) * | 2012-01-31 | 2013-08-06 | Pharmacyclics, Inc. | Purinone compounds as kinase inhibitors |
| CA2865021C (en) | 2012-02-23 | 2020-06-30 | Bayer Intellectual Property Gmbh | Substituted benzothienyl-pyrrolotriazines and uses thereof |
| CA2874211A1 (en) | 2012-05-31 | 2013-12-05 | Pharmascience Inc. | Protein kinase inhibitors |
| CA2782774A1 (en) | 2012-07-06 | 2014-01-06 | Pharmascience Inc. | Protein kinase inhibitors |
| CN105796569A (zh) * | 2012-09-10 | 2016-07-27 | 杨子娇 | 化合物在制备防治青光眼病的药物中的用途 |
| CN105796562A (zh) * | 2012-09-10 | 2016-07-27 | 杨子娇 | 化合物在制备防治青光眼病的药物中的用途 |
| US20140206681A1 (en) | 2013-01-23 | 2014-07-24 | Ronald M. Kim | Btk inhibitors |
| WO2014113942A1 (en) | 2013-01-23 | 2014-07-31 | Merck Sharp & Dohme Corp. | Btk inhibitors |
| AU2014236135A1 (en) | 2013-03-14 | 2015-09-10 | Thomas Jefferson University | Androgen receptor down-regulating agents and uses thereof |
| US9637487B2 (en) * | 2013-07-02 | 2017-05-02 | Pharmacyclics Llc | Purinone compounds as kinase inhibitors |
| US9808472B2 (en) | 2013-08-12 | 2017-11-07 | Tokai Pharmaceuticals, Inc. | Biomarkers for treatment of neoplastic disorders using androgen-targeted therapies |
| CA2833701A1 (en) * | 2013-11-19 | 2015-05-19 | Pharmascience Inc. | Protein kinase inhibitors |
| CA2833867A1 (en) * | 2013-11-21 | 2015-05-21 | Pharmascience Inc. | Protein kinase inhibitors |
| EP3076974A1 (en) | 2013-12-05 | 2016-10-12 | Acerta Pharma B.V. | Therapeutic combination of a pi3k inhibitor and a btk inhibitor |
| US9834554B2 (en) | 2013-12-20 | 2017-12-05 | Merck Sharp & Dohme Corp. | BTK inhibitors |
| WO2015095099A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Btk inhibitors |
| US10428331B2 (en) | 2014-01-16 | 2019-10-01 | Musc Foundation For Research Development | Targeted nanocarriers for the administration of immunosuppressive agents |
| US10272083B2 (en) | 2014-01-21 | 2019-04-30 | Acerta Pharma B.V. | Methods of treating chronic lymphocytic leukemia and small lymphocytic leukemia using a BTK inhibitor |
| WO2015146159A1 (en) | 2014-03-25 | 2015-10-01 | Ono Pharmaceutical Co., Ltd. | Prophylactic agent and/or therapeutic agent for diffuse large b-cell lymphoma |
| US9937171B2 (en) | 2014-04-11 | 2018-04-10 | Acerta Pharma B.V. | Methods of blocking the CXCR-4/SDF-1 signaling pathway with inhibitors of bruton's tyrosine kinase |
| WO2015193740A2 (en) | 2014-06-17 | 2015-12-23 | Acerta Pharma B.V. | Therapeutic combinations of a btk inhibitor, a pi3k inhibitor and/or a jak-2 inhibitor |
| LT3179991T (lt) | 2014-08-11 | 2021-11-10 | Acerta Pharma B.V. | Terapiniai btk inhibitoriaus ir bcl-2 inhibitoriaus deriniai |
| WO2016106623A1 (en) | 2014-12-31 | 2016-07-07 | Merck Sharp & Dohme Corp. | Benzamide imidazopyrazine btk inhibitors |
| WO2016106626A1 (en) | 2014-12-31 | 2016-07-07 | Merck Sharp & Dohme Corp. | Imidazopyrazine analogs with 3-tertiary carbon substitutions as btk inhibitors |
| WO2016106629A1 (en) | 2014-12-31 | 2016-07-07 | Merck Sharp & Dohme Corp. | Btk inhibitors |
| WO2016106624A1 (en) | 2014-12-31 | 2016-07-07 | Merck Sharp & Dohme Corp. | Tertiary alcohol imidazopyrazine btk inhibitors |
| WO2016106628A1 (en) | 2014-12-31 | 2016-07-07 | Merck Sharp & Dohme Corp. | Btk inhibitors |
| WO2016163531A1 (ja) | 2015-04-09 | 2016-10-13 | 小野薬品工業株式会社 | プリノン誘導体の製造方法 |
| MA50817B1 (fr) | 2015-07-02 | 2021-10-29 | Acerta Pharma Bv | Formes et formulations solides de (s)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide |
| CN105130932B (zh) * | 2015-07-14 | 2017-06-16 | 中国科学院微生物研究所 | 化合物及其在制备ptp1b抑制剂和治疗和/或预防ⅱ型糖尿病的药物的用途 |
| WO2017035366A1 (en) | 2015-08-26 | 2017-03-02 | Incyte Corporation | Pyrrolopyrimidine derivatives as tam inhibitors |
| JP7034084B2 (ja) * | 2016-03-28 | 2022-03-11 | インサイト・コーポレイション | Ｔａｍ阻害剤としてのピロロトリアジン化合物 |
| WO2018049191A1 (en) | 2016-09-09 | 2018-03-15 | Incyte Corporation | Pyrazolopyridone derivatives as hpk1 modulators and uses thereof for the treatment of cancer |
| AR109595A1 (es) | 2016-09-09 | 2018-12-26 | Incyte Corp | Compuestos de pirazolopirimidina y usos de estos como inhibidores de hpk1 |
| US20180072718A1 (en) | 2016-09-09 | 2018-03-15 | Incyte Corporation | Pyrazolopyridine compounds and uses thereof |
| CN109923114B (zh) | 2016-09-09 | 2022-11-01 | 因赛特公司 | 作为hpk1调节剂的吡唑并吡啶衍生物和其用于治疗癌症的用途 |
| US20180228786A1 (en) | 2017-02-15 | 2018-08-16 | Incyte Corporation | Pyrazolopyridine compounds and uses thereof |
| US10722495B2 (en) | 2017-09-08 | 2020-07-28 | Incyte Corporation | Cyanoindazole compounds and uses thereof |
| TWI821200B (zh) | 2017-09-27 | 2023-11-11 | 美商英塞特公司 | Tam抑制劑之鹽 |
| US10752635B2 (en) | 2018-02-20 | 2020-08-25 | Incyte Corporation | Indazole compounds and uses thereof |
| MX2020008656A (es) | 2018-02-20 | 2020-12-09 | Incyte Corp | Derivados de n-(fenil)-2-(fenil)pirimidina-4-carboxamida y compuestos relacionados como inhibidores de la cinasa de progenitores hematopoyeticos 1 (hpk1) para tratar el cancer. |
| US10745388B2 (en) | 2018-02-20 | 2020-08-18 | Incyte Corporation | Indazole compounds and uses thereof |
| US11299473B2 (en) | 2018-04-13 | 2022-04-12 | Incyte Corporation | Benzimidazole and indole compounds and uses thereof |
| MX2021000127A (es) | 2018-06-29 | 2021-03-29 | Incyte Corp | Formulaciones de un inhibidor de axl/mer. |
| US10899755B2 (en) | 2018-08-08 | 2021-01-26 | Incyte Corporation | Benzothiazole compounds and uses thereof |
| JP7399968B2 (ja) | 2018-09-25 | 2023-12-18 | インサイト・コーポレイション | Ａｌｋ２及び／またはｆｇｆｒ調節剤としてのピラゾロ［４，３－ｄ］ピリミジン化合物 |
| KR20220059480A (ko) | 2019-08-06 | 2022-05-10 | 인사이트 코포레이션 | 고체 형태의 hpk1 억제제 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SK125999A3 (en) * | 1997-03-19 | 2000-05-16 | Knoll Ag | Pyrrolo[2,3d]pyrimidines and their use as tyrosine kinase inhibitors |
| UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
-
2000
- 2000-09-15 KR KR1020027003507A patent/KR20020063854A/ko not_active Application Discontinuation
- 2000-09-15 AU AU74914/00A patent/AU7491400A/en not_active Abandoned
- 2000-09-15 BR BR0014075-9A patent/BR0014075A/pt not_active IP Right Cessation
- 2000-09-15 MX MXPA02002938A patent/MXPA02002938A/es unknown
- 2000-09-15 DE DE60037455T patent/DE60037455T2/de not_active Expired - Lifetime
- 2000-09-15 SK SK379-2002A patent/SK3792002A3/sk unknown
- 2000-09-15 PT PT00963510T patent/PT1268481E/pt unknown
- 2000-09-15 NZ NZ517759A patent/NZ517759A/en unknown
- 2000-09-15 EP EP00963510A patent/EP1268481B1/en not_active Expired - Lifetime
- 2000-09-15 ES ES00963510T patent/ES2299434T3/es not_active Expired - Lifetime
- 2000-09-15 HU HU0303363A patent/HUP0303363A2/hu unknown
- 2000-09-15 WO PCT/US2000/025357 patent/WO2001019828A2/en active IP Right Grant
- 2000-09-15 CA CA002385769A patent/CA2385769A1/en not_active Abandoned
- 2000-09-15 AT AT00963510T patent/ATE380814T1/de active
- 2000-09-15 JP JP2001523405A patent/JP2003509427A/ja not_active Withdrawn
- 2000-09-15 IL IL14871900A patent/IL148719A0/xx unknown
- 2000-09-15 CN CN00815776A patent/CN1390220A/zh active Pending
- 2000-09-15 PL PL00354241A patent/PL354241A1/xx not_active Application Discontinuation
- 2000-09-15 TR TR2002/01506T patent/TR200201506T2/tr unknown
- 2000-09-15 CZ CZ2002934A patent/CZ2002934A3/cs unknown
- 2000-09-15 DK DK00963510T patent/DK1268481T3/da active
- 2000-09-18 AR ARP000104887A patent/AR029766A1/es unknown
-
2002
- 2002-03-14 ZA ZA200202122A patent/ZA200202122B/en unknown
- 2002-03-18 NO NO20021329A patent/NO20021329L/no not_active Application Discontinuation
- 2002-04-05 BG BG106585A patent/BG106585A/xx unknown
-
2003
- 2003-06-19 HK HK03104425.4A patent/HK1053831A1/zh unknown
-
2008
- 2008-02-14 CY CY20081100173T patent/CY1107886T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT1268481E (pt) | 2008-03-19 |
| AR029766A1 (es) | 2003-07-16 |
| CN1390220A (zh) | 2003-01-08 |
| DE60037455D1 (de) | 2008-01-24 |
| EP1268481A2 (en) | 2003-01-02 |
| WO2001019828A3 (en) | 2001-10-04 |
| NO20021329L (no) | 2002-05-21 |
| AU7491400A (en) | 2001-04-17 |
| HK1053831A1 (zh) | 2003-11-07 |
| CA2385769A1 (en) | 2001-03-22 |
| NZ517759A (en) | 2004-04-30 |
| TR200201506T2 (tr) | 2002-10-21 |
| BR0014075A (pt) | 2002-07-16 |
| WO2001019828A2 (en) | 2001-03-22 |
| CY1107886T1 (el) | 2013-06-19 |
| MXPA02002938A (es) | 2004-12-06 |
| IL148719A0 (en) | 2002-09-12 |
| SK3792002A3 (en) | 2003-09-11 |
| KR20020063854A (ko) | 2002-08-05 |
| ATE380814T1 (de) | 2007-12-15 |
| NO20021329D0 (no) | 2002-03-18 |
| DE60037455T2 (de) | 2008-11-27 |
| BG106585A (en) | 2003-03-31 |
| DK1268481T3 (da) | 2008-05-05 |
| PL354241A1 (en) | 2003-12-29 |
| HUP0303363A2 (hu) | 2004-07-28 |
| ES2299434T3 (es) | 2008-06-01 |
| EP1268481B1 (en) | 2007-12-12 |
| CZ2002934A3 (cs) | 2002-07-17 |
| JP2003509427A (ja) | 2003-03-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200202122B (en) | Kinase inhibitors as therapeutic agents. | |
| ZA200202123B (en) | Pyrazolopyrimidines as therapeutic agents. | |
| ZA200306887B (en) | Pyrazolopyrimidines as therapeutic agents. | |
| ZA200102201B (en) | 4-aminopyrrolopyrimidines as kinase inhibitors. | |
| JP4707167B2 (ja) | キナーゼ阻害剤 | |
| CN111757878B (zh) | 一种哒嗪类衍生物抑制剂、其制备方法和应用 | |
| ZA200206235B (en) | 2-Benzothiazolyl urea derivatives and their use as protein kinase inhibitors. | |
| US7829570B2 (en) | Substituted 4-amino isoxazolo[5,4-d]pyrimidines as kinase inhibitors | |
| KR20010085824A (ko) | 단백질 키나아제 억제제로서의 피롤로피리미딘 | |
| JP2004531513A (ja) | 治療剤としてのピラゾールピリミジン | |
| CN101917849A (zh) | Bcr-abl的小分子豆蔻酸酯抑制剂及其使用方法 | |
| US7071199B1 (en) | Kinase inhibitors as therapeutic agents | |
| CZ20013580A3 (cs) | Substituované 1,4-dihydroindeno[1,2-c]pyrazoly jako inhibitory tyrosin kinázy | |
| ZA200102204B (en) | Pyrrolopyrimidines as protein kinase inhibitors. | |
| AU2002258590A1 (en) | Pyrazolopyrimidines as Therapeutic Agents |