NO326409B1 - 1,5-disubstituerte 3,4-dihydro-1H-pyrimido[4,5-D]-pyrimidin-2-onforbindelser og deres anvendelse samt farmasoytisk preparat inneholdende en slik forbindelse - Google Patents
1,5-disubstituerte 3,4-dihydro-1H-pyrimido[4,5-D]-pyrimidin-2-onforbindelser og deres anvendelse samt farmasoytisk preparat inneholdende en slik forbindelse Download PDFInfo
- Publication number
- NO326409B1 NO326409B1 NO20024134A NO20024134A NO326409B1 NO 326409 B1 NO326409 B1 NO 326409B1 NO 20024134 A NO20024134 A NO 20024134A NO 20024134 A NO20024134 A NO 20024134A NO 326409 B1 NO326409 B1 NO 326409B1
- Authority
- NO
- Norway
- Prior art keywords
- pyrimidin
- pyrimido
- difluorophenyl
- dihydro
- fluoro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 150
- -1 1,5-disubstituted 3,4-dihydro-1H-pyrimido [4,5-D] -pyrimidin-2-one compounds Chemical class 0.000 title claims description 34
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 4
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 58
- 238000011282 treatment Methods 0.000 claims description 56
- 201000010099 disease Diseases 0.000 claims description 52
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 34
- 108010084680 Heterogeneous-Nuclear Ribonucleoprotein K Proteins 0.000 claims description 33
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 27
- 241000124008 Mammalia Species 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 21
- 238000011321 prophylaxis Methods 0.000 claims description 19
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- 230000001404 mediated effect Effects 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 208000006673 asthma Diseases 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 206010040070 Septic Shock Diseases 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 206010003246 arthritis Diseases 0.000 claims description 8
- 210000004556 brain Anatomy 0.000 claims description 8
- 150000003536 tetrazoles Chemical class 0.000 claims description 8
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 230000002685 pulmonary effect Effects 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- ALFUUHHEXQAFKA-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=CN=C2NC(=O)NCC2=C1 ALFUUHHEXQAFKA-UHFFFAOYSA-N 0.000 claims description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
- 201000005569 Gout Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 6
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 206010035664 Pneumonia Diseases 0.000 claims description 5
- 206010063837 Reperfusion injury Diseases 0.000 claims description 5
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 5
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 5
- 230000002917 arthritic effect Effects 0.000 claims description 5
- 206010022000 influenza Diseases 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 125000003178 carboxy group Chemical class [H]OC(*)=O 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- NHWQNBZGHWTZTF-UHFFFAOYSA-N 2-methoxy-4,8-diphenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(OC)=NC=2N(C=3C=CC=CC=3)C(=O)NCC=2C=1C1=CC=CC=C1 NHWQNBZGHWTZTF-UHFFFAOYSA-N 0.000 claims description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- 206010063094 Cerebral malaria Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 206010010741 Conjunctivitis Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
- 208000016988 Hemorrhagic Stroke Diseases 0.000 claims description 3
- 201000009906 Meningitis Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 3
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 3
- 208000033464 Reiter syndrome Diseases 0.000 claims description 3
- 201000010001 Silicosis Diseases 0.000 claims description 3
- 206010042496 Sunburn Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 206010048873 Traumatic arthritis Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 230000002491 angiogenic effect Effects 0.000 claims description 3
- 208000010668 atopic eczema Diseases 0.000 claims description 3
- 208000019664 bone resorption disease Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 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 description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- 208000002574 reactive arthritis Diseases 0.000 claims description 3
- 201000005404 rubella Diseases 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 201000004595 synovitis Diseases 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- FWIQAZGOXKXCIO-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-methoxy-4-phenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(OC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=CC=C1 FWIQAZGOXKXCIO-UHFFFAOYSA-N 0.000 claims description 2
- OWJIMCIWDXHGMZ-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-methylsulfonyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(S(C)(=O)=O)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F OWJIMCIWDXHGMZ-UHFFFAOYSA-N 0.000 claims description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 208000029028 brain injury Diseases 0.000 claims description 2
- 230000015556 catabolic process Effects 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
- 210000004351 coronary vessel Anatomy 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims description 2
- JPOJBQLUJAIHHL-UHFFFAOYSA-N 1h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=CN=C2NC(=O)N=CC2=C1 JPOJBQLUJAIHHL-UHFFFAOYSA-N 0.000 claims 7
- XFIVQPQXMLYMEL-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-pyridin-3-ylethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCC=2C=NC=CC=2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F XFIVQPQXMLYMEL-UHFFFAOYSA-N 0.000 claims 2
- SJDADHVFQGGIIK-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(4-methylpiperazin-1-yl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(C)CCN1C(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F SJDADHVFQGGIIK-UHFFFAOYSA-N 0.000 claims 2
- WSDQIHATCCOMLH-UHFFFAOYSA-N phenyl n-(3,5-dichlorophenyl)carbamate Chemical compound ClC1=CC(Cl)=CC(NC(=O)OC=2C=CC=CC=2)=C1 WSDQIHATCCOMLH-UHFFFAOYSA-N 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical class 0.000 claims 1
- INHFBBAQFRVOHD-UHFFFAOYSA-N 2-[2-(diethylamino)ethylamino]-8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(NCCN(CC)CC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C INHFBBAQFRVOHD-UHFFFAOYSA-N 0.000 claims 1
- ZMIKRTDSJYSRIQ-UHFFFAOYSA-N 2-[2-[bis(2-hydroxyethyl)amino]ethoxy]-8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(OCCN(CCO)CCO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F ZMIKRTDSJYSRIQ-UHFFFAOYSA-N 0.000 claims 1
- POIUUYBLAPDZRL-CQSZACIVSA-N 4-(4-fluoro-2-methylphenyl)-2-methylsulfanyl-8-[(1r)-1-phenylethyl]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1([C@@H](C)N2C=3N=C(N=C(C=3CNC2=O)C=2C(=CC(F)=CC=2)C)SC)=CC=CC=C1 POIUUYBLAPDZRL-CQSZACIVSA-N 0.000 claims 1
- POIUUYBLAPDZRL-AWEZNQCLSA-N 4-(4-fluoro-2-methylphenyl)-2-methylsulfanyl-8-[(1s)-1-phenylethyl]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1([C@H](C)N2C=3N=C(N=C(C=3CNC2=O)C=2C(=CC(F)=CC=2)C)SC)=CC=CC=C1 POIUUYBLAPDZRL-AWEZNQCLSA-N 0.000 claims 1
- ZRQQTBJJAHYZCN-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-methylsulfanyl-4-phenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=CC=C1 ZRQQTBJJAHYZCN-UHFFFAOYSA-N 0.000 claims 1
- RBKUFYXURQWVHJ-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-piperidin-1-ylethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCN2CCCCC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F RBKUFYXURQWVHJ-UHFFFAOYSA-N 0.000 claims 1
- HKPXJUXWLNGMFC-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-pyrrolidin-1-ylethylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NCCN2CCCC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F HKPXJUXWLNGMFC-UHFFFAOYSA-N 0.000 claims 1
- CGRTXKHCITVACI-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[(1-hydroxy-2-methylpropan-2-yl)amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(NC(C)(C)CO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F CGRTXKHCITVACI-UHFFFAOYSA-N 0.000 claims 1
- OWBLWOFCPKNBSN-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[(1-methylpiperidin-4-yl)amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(C)CCC1NC(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F OWBLWOFCPKNBSN-UHFFFAOYSA-N 0.000 claims 1
- SVZMXTLXWFBJSH-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[4-(hydroxymethyl)piperidin-1-yl]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound CC1=CC(F)=CC=C1C1=NC(N2CCC(CO)CC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F SVZMXTLXWFBJSH-UHFFFAOYSA-N 0.000 claims 1
- RYLOGURSYLZAJG-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-[methyl(1,1,2-trihydroxyethyl)amino]-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(N(C)C(O)(O)CO)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C RYLOGURSYLZAJG-UHFFFAOYSA-N 0.000 claims 1
- 206010012442 Dermatitis contact Diseases 0.000 claims 1
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims 1
- 230000001149 cognitive effect Effects 0.000 claims 1
- 208000010247 contact dermatitis Diseases 0.000 claims 1
- VBPRDTNZCVKPNV-UHFFFAOYSA-N ethyl 1-[8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-7-oxo-5,6-dihydropyrimido[4,5-d]pyrimidin-2-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F VBPRDTNZCVKPNV-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 description 75
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 62
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 62
- 102000004127 Cytokines Human genes 0.000 description 48
- 108090000695 Cytokines Proteins 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 102000000589 Interleukin-1 Human genes 0.000 description 44
- 108010002352 Interleukin-1 Proteins 0.000 description 44
- 239000000047 product Substances 0.000 description 43
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 36
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 36
- 108090001007 Interleukin-8 Proteins 0.000 description 31
- 102000004890 Interleukin-8 Human genes 0.000 description 31
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 31
- 229940096397 interleukin-8 Drugs 0.000 description 31
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 28
- 239000002158 endotoxin Substances 0.000 description 26
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- 229920006008 lipopolysaccharide Polymers 0.000 description 24
- 108090001005 Interleukin-6 Proteins 0.000 description 23
- 102000004889 Interleukin-6 Human genes 0.000 description 23
- 229940100601 interleukin-6 Drugs 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- 206010061218 Inflammation Diseases 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 206010011224 Cough Diseases 0.000 description 20
- 230000004054 inflammatory process Effects 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 19
- 208000015181 infectious disease Diseases 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 17
- 150000002825 nitriles Chemical class 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 230000002401 inhibitory effect Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 15
- 108091000080 Phosphotransferase Proteins 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 102000020233 phosphotransferase Human genes 0.000 description 14
- 150000003457 sulfones Chemical class 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 229960004106 citric acid Drugs 0.000 description 12
- 235000015165 citric acid Nutrition 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 239000000779 smoke Substances 0.000 description 12
- 241000430519 Human rhinovirus sp. Species 0.000 description 11
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 11
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 230000016396 cytokine production Effects 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 10
- 235000019504 cigarettes Nutrition 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 230000000770 proinflammatory effect Effects 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 210000000440 neutrophil Anatomy 0.000 description 9
- 230000006433 tumor necrosis factor production Effects 0.000 description 9
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 8
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 229940043355 kinase inhibitor Drugs 0.000 description 8
- 210000001616 monocyte Anatomy 0.000 description 8
- 239000012038 nucleophile Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 8
- 238000002953 preparative HPLC Methods 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 230000019491 signal transduction Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 206010006895 Cachexia Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 7
- 206010062106 Respiratory tract infection viral Diseases 0.000 description 7
- 208000030886 Traumatic Brain injury Diseases 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 230000021995 interleukin-8 production Effects 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 208000030507 AIDS Diseases 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 102000001253 Protein Kinase Human genes 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 208000036142 Viral infection Diseases 0.000 description 6
- 208000037883 airway inflammation Diseases 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 6
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 108060006633 protein kinase Proteins 0.000 description 6
- 150000003462 sulfoxides Chemical class 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000009529 traumatic brain injury Effects 0.000 description 6
- 230000009385 viral infection Effects 0.000 description 6
- SQSIKNPJLPNKJL-UHFFFAOYSA-N 4-amino-6-chloro-2-methylsulfanylpyrimidine-5-carbonitrile Chemical compound CSC1=NC(N)=C(C#N)C(Cl)=N1 SQSIKNPJLPNKJL-UHFFFAOYSA-N 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 239000012826 P38 inhibitor Substances 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 201000004897 cough variant asthma Diseases 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 210000002889 endothelial cell Anatomy 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 150000003568 thioethers Chemical class 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 206010001513 AIDS related complex Diseases 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 206010006458 Bronchitis chronic Diseases 0.000 description 4
- 241000700198 Cavia Species 0.000 description 4
- 206010009137 Chronic sinusitis Diseases 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 206010014950 Eosinophilia Diseases 0.000 description 4
- 241000713800 Feline immunodeficiency virus Species 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 102000043136 MAP kinase family Human genes 0.000 description 4
- 108091054455 MAP kinase family Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000000954 anitussive effect Effects 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 206010006451 bronchitis Diseases 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 208000007451 chronic bronchitis Diseases 0.000 description 4
- 208000024035 chronic otitis media Diseases 0.000 description 4
- 208000027157 chronic rhinosinusitis Diseases 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 230000018276 interleukin-1 production Effects 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 230000000241 respiratory effect Effects 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 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 3
- AEXCUJUYEZIWJV-UHFFFAOYSA-N 4-hydroxy-2-methylsulfanyl-1h-pyrimidin-6-one Chemical compound CSC1=NC(O)=CC(=O)N1 AEXCUJUYEZIWJV-UHFFFAOYSA-N 0.000 description 3
- DQJMEYBIBKRMNE-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-methylsulfanyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C DQJMEYBIBKRMNE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 102000029816 Collagenase Human genes 0.000 description 3
- 206010014824 Endotoxic shock Diseases 0.000 description 3
- 241000709661 Enterovirus Species 0.000 description 3
- 206010065563 Eosinophilic bronchitis Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010061598 Immunodeficiency Diseases 0.000 description 3
- 208000029462 Immunodeficiency disease Diseases 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
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 206010028289 Muscle atrophy Diseases 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 206010033078 Otitis media Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 241000725643 Respiratory syncytial virus Species 0.000 description 3
- 206010038997 Retroviral infections Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 210000003651 basophil Anatomy 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 229960004126 codeine Drugs 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 229960001985 dextromethorphan Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 3
- 230000007813 immunodeficiency Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 201000009240 nasopharyngitis Diseases 0.000 description 3
- 230000011242 neutrophil chemotaxis Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 201000009890 sinusitis Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- QPZMKCAFTCXOLA-UHFFFAOYSA-N 2-methylsulfanyl-4,8-diphenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(SC)=NC=2N(C=3C=CC=CC=3)C(=O)NCC=2C=1C1=CC=CC=C1 QPZMKCAFTCXOLA-UHFFFAOYSA-N 0.000 description 2
- XAVYPWCOJBGECR-UHFFFAOYSA-N 2-pyrimidin-2-ylsulfonylpyrimidine Chemical class N=1C=CC=NC=1S(=O)(=O)C1=NC=CC=N1 XAVYPWCOJBGECR-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- YOELZIQOLWZLQC-UHFFFAOYSA-N 6-(4-fluorophenyl)-5-pyridin-4-yl-2,3-dihydroimidazo[2,1-b]thiazole Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N2CCSC2=N1 YOELZIQOLWZLQC-UHFFFAOYSA-N 0.000 description 2
- YUCRDXYBZKOOOM-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(piperidin-4-ylamino)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CC(F)=CC=C1C1=NC(NC2CCNCC2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F YUCRDXYBZKOOOM-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 208000037487 Endotoxemia Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 206010018634 Gouty Arthritis Diseases 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102000013967 Monokines Human genes 0.000 description 2
- 108010050619 Monokines Proteins 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 206010029379 Neutrophilia Diseases 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 2
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 102100023132 Transcription factor Jun Human genes 0.000 description 2
- 208000010094 Visna Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003434 antitussive agent Substances 0.000 description 2
- 229940124584 antitussives Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000014564 chemokine production Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 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 2
- 238000001035 drying Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000003090 exacerbative effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 125000005241 heteroarylamino group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000017306 interleukin-6 production Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 208000011379 keloid formation Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 239000000865 liniment Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 210000004457 myocytus nodalis Anatomy 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 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 2
- 239000006072 paste Substances 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000003880 polar aprotic solvent Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229920002994 synthetic fiber Polymers 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000009772 tissue formation Effects 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical group 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- IQMLIVUHMSIOQP-UHFFFAOYSA-N (4-fluoro-2-methylphenyl)boronic acid Chemical compound CC1=CC(F)=CC=C1B(O)O IQMLIVUHMSIOQP-UHFFFAOYSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WPRAXAOJIODQJR-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(C)C(C)=C1 WPRAXAOJIODQJR-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- GFPULOWPXJKUAA-UHFFFAOYSA-N 1-[8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-7-oxo-5,6-dihydropyrimido[4,5-d]pyrimidin-2-yl]piperidine-4-carboxylic acid Chemical compound CC1=CC(F)=CC=C1C1=NC(N2CCC(CC2)C(O)=O)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F GFPULOWPXJKUAA-UHFFFAOYSA-N 0.000 description 1
- AMWMZCQZVOTUKT-UHFFFAOYSA-N 1-[8-(2,6-difluorophenyl)-4-(4-fluorophenyl)-7-oxo-5,6-dihydropyrimido[4,5-d]pyrimidin-2-yl]piperidine-4-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CC(C(=O)O)CCN1C(N=C1C=2C=CC(F)=CC=2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F AMWMZCQZVOTUKT-UHFFFAOYSA-N 0.000 description 1
- LNQYIYWXSSCTLH-UHFFFAOYSA-N 1-[8-(2,6-difluorophenyl)-7-oxo-4-phenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-2-yl]piperidine-4-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CC(C(=O)O)CCN1C(N=C1C=2C=CC=CC=2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F LNQYIYWXSSCTLH-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- FOJNDKAWSIJVQL-UHFFFAOYSA-N 1-ethylpiperidin-4-amine;hydrochloride Chemical compound Cl.CCN1CCC(N)CC1 FOJNDKAWSIJVQL-UHFFFAOYSA-N 0.000 description 1
- BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- SZXUTTGMFUSMCE-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)pyridine Chemical class C1=CNC(C=2N=CC=CC=2)=N1 SZXUTTGMFUSMCE-UHFFFAOYSA-N 0.000 description 1
- MPEQTHOUWIOMQG-UHFFFAOYSA-N 2-[(1-ethylpiperidin-4-yl)amino]-4-(4-fluoro-2-methylphenyl)-8-(2-fluorophenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(CC)CCC1NC(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=CC=CC=C1F MPEQTHOUWIOMQG-UHFFFAOYSA-N 0.000 description 1
- UNPHZUNSDAOXER-UHFFFAOYSA-N 2-[2-[bis(2-hydroxyethyl)amino]ethoxy]-8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CC(F)=CC=C1C1=NC(OCCN(CCO)CCO)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F UNPHZUNSDAOXER-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ULRPISSMEBPJLN-UHFFFAOYSA-N 2h-tetrazol-5-amine Chemical compound NC1=NN=NN1 ULRPISSMEBPJLN-UHFFFAOYSA-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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- GLOOTGZVAHKTJS-UHFFFAOYSA-N 4,6-dichloro-2-methylsulfanylpyrimidine-5-carbonitrile Chemical compound CSC1=NC(Cl)=C(C#N)C(Cl)=N1 GLOOTGZVAHKTJS-UHFFFAOYSA-N 0.000 description 1
- FADCQFNQOBILLC-UHFFFAOYSA-N 4-(2,6-difluoroanilino)-6-(4-fluoro-2-methylphenyl)-2-methylsulfanylpyrimidine-5-carbonitrile Chemical compound N#CC=1C(C=2C(=CC(F)=CC=2)C)=NC(SC)=NC=1NC1=C(F)C=CC=C1F FADCQFNQOBILLC-UHFFFAOYSA-N 0.000 description 1
- NGMJPCDQNZGUIQ-UHFFFAOYSA-N 4-anilino-2-methylsulfanyl-6-phenylpyrimidine-5-carbonitrile Chemical compound N#CC=1C(C=2C=CC=CC=2)=NC(SC)=NC=1NC1=CC=CC=C1 NGMJPCDQNZGUIQ-UHFFFAOYSA-N 0.000 description 1
- CODSYMVFPMSBOL-UHFFFAOYSA-N 7-methylsulfanyl-1,5-diphenylpyrimido[4,5-d]pyrimidin-2-one Chemical compound C=12C=NC(=O)N(C=3C=CC=CC=3)C2=NC(SC)=NC=1C1=CC=CC=C1 CODSYMVFPMSBOL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GGVWISLSGVRPFO-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-(4-methylpiperazin-1-yl)-4-phenyl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound C1CN(C)CCN1C(N=C1C=2C=CC=CC=2)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F GGVWISLSGVRPFO-UHFFFAOYSA-N 0.000 description 1
- PCFPYNZFGKMKFH-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-[2-(dimethylamino)ethylamino]-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C(NCCN(C)C)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C PCFPYNZFGKMKFH-UHFFFAOYSA-N 0.000 description 1
- HURHZCBUJLSHOW-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-2-ethoxy-4-(4-fluoro-2-methylphenyl)-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(OCC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C HURHZCBUJLSHOW-UHFFFAOYSA-N 0.000 description 1
- DMJBMCYQCLHNFX-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(1-methylpiperidin-4-yl)oxy-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CN(C)CCC1OC(N=C1C=2C(=CC(F)=CC=2)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F DMJBMCYQCLHNFX-UHFFFAOYSA-N 0.000 description 1
- XBMJNGQHEOTKET-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-methoxy-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound N=1C(OC)=NC=2N(C=3C(=CC=CC=3F)F)C(=O)NCC=2C=1C1=CC=C(F)C=C1C XBMJNGQHEOTKET-UHFFFAOYSA-N 0.000 description 1
- JYKUFJDHBSZXAQ-UHFFFAOYSA-N 8-(2,6-difluorophenyl)-4-phenyl-2-piperazin-1-yl-5,6-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound FC1=CC=CC(F)=C1N1C(N=C(N=C2C=3C=CC=CC=3)N3CCNCC3)=C2CNC1=O JYKUFJDHBSZXAQ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 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 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 108091008038 CHOP Proteins 0.000 description 1
- 101150071146 COX2 gene Proteins 0.000 description 1
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 1
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- 208000018652 Closed Head injury Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- 102100023033 Cyclic AMP-dependent transcription factor ATF-2 Human genes 0.000 description 1
- 102100029145 DNA damage-inducible transcript 3 protein Human genes 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010020164 HIV infection CDC Group III Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 description 1
- 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101000578774 Homo sapiens MAP kinase-activated protein kinase 5 Proteins 0.000 description 1
- 101100456626 Homo sapiens MEF2A gene Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 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 1
- 239000004166 Lanolin Substances 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229940122696 MAP kinase inhibitor Drugs 0.000 description 1
- 102100034069 MAP kinase-activated protein kinase 2 Human genes 0.000 description 1
- 102100028397 MAP kinase-activated protein kinase 3 Human genes 0.000 description 1
- 102100028396 MAP kinase-activated protein kinase 5 Human genes 0.000 description 1
- 108010041955 MAP-kinase-activated kinase 2 Proteins 0.000 description 1
- 108010041980 MAP-kinase-activated kinase 3 Proteins 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 241000282346 Meles meles Species 0.000 description 1
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 101100079042 Mus musculus Myef2 gene Proteins 0.000 description 1
- 102100021148 Myocyte-specific enhancer factor 2A Human genes 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 208000025157 Oral disease Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 101150000187 PTGS2 gene Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 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
- 101710096328 Phospholipase A2 Proteins 0.000 description 1
- 102100026918 Phospholipase A2 Human genes 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Chemical class 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000021063 Respiratory fume inhalation disease Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 206010061494 Rhinovirus infection Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 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
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 241000011102 Thera Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 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
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 210000001056 activated astrocyte Anatomy 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 150000001356 alkyl thiols Chemical class 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 229940127225 asthma medication Drugs 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000005815 base catalysis Methods 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000010083 bronchial hyperresponsiveness Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 244000309464 bull Species 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
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000001889 chemoattractive effect Effects 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 229960002152 chlorhexidine acetate Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000013116 chronic cough Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000000463 effect on translation Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 208000009724 equine infectious anemia Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 239000002803 fossil fuel Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- DXMYKAREPXBRHQ-UHFFFAOYSA-N hydron;1-methylpiperidin-4-amine;chloride Chemical compound Cl.CN1CCC(N)CC1 DXMYKAREPXBRHQ-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 229940125369 inhaled corticosteroids Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 210000002660 insulin-secreting cell Anatomy 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000002555 ionophore Substances 0.000 description 1
- 230000000236 ionophoric effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 101150014102 mef-2 gene Proteins 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
- 229960002329 methacholine Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- NKAAEMMYHLFEFN-UHFFFAOYSA-M monosodium tartrate Chemical compound [Na+].OC(=O)C(O)C(O)C([O-])=O NKAAEMMYHLFEFN-UHFFFAOYSA-M 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 230000011234 negative regulation of signal transduction Effects 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 210000000929 nociceptor Anatomy 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000008723 osmotic stress Effects 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 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
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 238000009527 percussion Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000009719 regenerative response Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000019254 respiratory burst Effects 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical compound I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013125 spirometry Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose 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
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical group CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- NRNJRTKIZVHDKL-UHFFFAOYSA-N tert-butyl 4-[[8-(2,6-difluorophenyl)-4-(4-fluoro-2-methylphenyl)-7-oxo-5,6-dihydropyrimido[4,5-d]pyrimidin-2-yl]amino]piperidine-1-carboxylate Chemical compound CC1=CC(F)=CC=C1C1=NC(NC2CCN(CC2)C(=O)OC(C)(C)C)=NC2=C1CNC(=O)N2C1=C(F)C=CC=C1F NRNJRTKIZVHDKL-UHFFFAOYSA-N 0.000 description 1
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000001993 wax Substances 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- A61P33/06—Antimalarials
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US18641900P | 2000-03-02 | 2000-03-02 | |
PCT/US2001/006688 WO2001064679A1 (fr) | 2000-03-02 | 2001-03-02 | Composes de 3,4 dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one a disubstitution en position 1,5 et leur utilisation pour traiter des maladies mediees par des kinases csbp/p38 |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20024134D0 NO20024134D0 (no) | 2002-08-30 |
NO20024134L NO20024134L (no) | 2002-10-24 |
NO326409B1 true NO326409B1 (no) | 2008-12-01 |
Family
ID=22684876
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20024134A NO326409B1 (no) | 2000-03-02 | 2002-08-30 | 1,5-disubstituerte 3,4-dihydro-1H-pyrimido[4,5-D]-pyrimidin-2-onforbindelser og deres anvendelse samt farmasoytisk preparat inneholdende en slik forbindelse |
Country Status (26)
Country | Link |
---|---|
EP (1) | EP1265900B1 (fr) |
JP (1) | JP2003525295A (fr) |
KR (1) | KR100806978B1 (fr) |
CN (1) | CN100482664C (fr) |
AR (2) | AR030053A1 (fr) |
AT (1) | ATE362473T1 (fr) |
AU (2) | AU3999201A (fr) |
BR (1) | BR0108715A (fr) |
CA (1) | CA2402092C (fr) |
CY (1) | CY1106816T1 (fr) |
CZ (1) | CZ20022933A3 (fr) |
DE (1) | DE60128457T2 (fr) |
DK (1) | DK1265900T3 (fr) |
ES (1) | ES2287107T3 (fr) |
HK (1) | HK1052932A1 (fr) |
HU (1) | HUP0204431A3 (fr) |
IL (3) | IL151426A0 (fr) |
MX (1) | MXPA02008588A (fr) |
MY (1) | MY141144A (fr) |
NO (1) | NO326409B1 (fr) |
NZ (1) | NZ520914A (fr) |
PL (1) | PL358280A1 (fr) |
PT (1) | PT1265900E (fr) |
TW (1) | TWI290926B (fr) |
WO (1) | WO2001064679A1 (fr) |
ZA (1) | ZA200207017B (fr) |
Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69939168D1 (de) | 1998-05-26 | 2008-09-04 | Warner Lambert Co | Bicyclische pyrimidine und bicyclische 3,4-dihydropyrimidine als inhibitoren der zellvermehrung |
DK1333833T3 (da) * | 2000-10-23 | 2011-12-12 | Glaxosmithkline Llc | Ny trisubstitueret 8H-pyridol[2,3-d]pyrimidin-7-on-forbindelse til behandling af CSBP/RK/p38-kinnasemedierede sygdomme |
EP1345603A4 (fr) | 2000-12-20 | 2004-09-08 | Merck & Co Inc | Agents inhibiteurs de p38 kinase (halo-benzo carbonyl)heterocyclo- fusionnes phenyl |
GB0124848D0 (en) | 2001-10-16 | 2001-12-05 | Celltech R&D Ltd | Chemical compounds |
DK1474395T3 (da) | 2002-02-12 | 2008-02-11 | Smithkline Beecham Corp | Nicotinamidderivater, der er nyttige som p38-inhibitorer |
JP4359146B2 (ja) * | 2002-02-13 | 2009-11-04 | エフ.ホフマン−ラ ロシュ アーゲー | 新規なピリジン−およびピリミジン−誘導体 |
CA2482022A1 (fr) * | 2002-04-19 | 2003-10-30 | Smithkline Beecham Corporation | Nouveaux composes |
GB0214268D0 (en) * | 2002-06-20 | 2002-07-31 | Celltech R&D Ltd | Chemical compounds |
PA8577501A1 (es) | 2002-07-25 | 2004-02-07 | Warner Lambert Co | Inhibidores de quinasas |
GB0218800D0 (en) * | 2002-08-13 | 2002-09-18 | Celltech R&D Ltd | Chemical compounds |
US7084270B2 (en) | 2002-08-14 | 2006-08-01 | Hoffman-La Roche Inc. | Pyrimido compounds having antiproliferative activity |
AU2003262911A1 (en) | 2002-08-29 | 2004-03-19 | Scios Inc. | Methods of promoting osteogenesis |
US7112676B2 (en) | 2002-11-04 | 2006-09-26 | Hoffmann-La Roche Inc. | Pyrimido compounds having antiproliferative activity |
US7384937B2 (en) | 2002-11-06 | 2008-06-10 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
US7098332B2 (en) | 2002-12-20 | 2006-08-29 | Hoffmann-La Roche Inc. | 5,8-Dihydro-6H-pyrido[2,3-d]pyrimidin-7-ones |
CA2521124A1 (fr) | 2003-04-10 | 2004-10-21 | F. Hoffmann-La Roche Ag | Composes pyrimido |
WO2005030091A2 (fr) | 2003-09-25 | 2005-04-07 | Scios Inc. | Stents et protheses intra-luminales contenant des inhibiteurs de kinase map |
PT1699800E (pt) * | 2003-12-23 | 2010-04-12 | Novartis Ag | Inibidores de quinase p-38 heterocíclicos bicíclicos |
AU2005316668B2 (en) * | 2004-12-13 | 2012-09-06 | Millennium Pharmaceuticals, Inc. | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors |
EP1676574A3 (fr) | 2004-12-30 | 2006-07-26 | Johnson & Johnson Vision Care, Inc. | Procédé favorisant la survie des tissus ou cellules griffées |
JP5201817B2 (ja) * | 2005-10-28 | 2013-06-05 | 大塚製薬株式会社 | 医薬組成物 |
JP2009542818A (ja) * | 2006-06-16 | 2009-12-03 | グラクソ グループ リミテッド | 新規化合物 |
JP2009542817A (ja) * | 2006-06-16 | 2009-12-03 | グラクソ グループ リミテッド | 新規化合物 |
KR101040394B1 (ko) * | 2010-05-18 | 2011-06-09 | (주)이성산업 | 역화 방지 기능을 갖는 야외용 가스 히터 |
CN102816162B (zh) * | 2011-06-10 | 2016-04-27 | 中国科学院广州生物医药与健康研究院 | 嘧啶并嘧啶酮类化合物及其药用组合物和应用 |
BR112015022191A8 (pt) | 2013-03-15 | 2018-01-23 | Celgene Avilomics Res Inc | compostos heteroarila e usos dos mesmos |
US9321786B2 (en) | 2013-03-15 | 2016-04-26 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
MY181020A (en) | 2013-03-15 | 2020-12-16 | Sanofi Sa | Heteroaryl compounds and uses thereof |
RU2663999C2 (ru) * | 2013-10-16 | 2018-08-14 | Шанхай Инли Фармасьютикал Ко., Лтд | Конденсированное гетероциклическое соединение, способ его получения, его фармацевтическая композиция и применения |
US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
WO2019071147A1 (fr) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | Inhibiteurs de la kinase p38 réduisant l'expression du gène dux4 et des gènes aval pour le traitement de la fshd |
IL312076A (en) | 2021-10-20 | 2024-06-01 | Insilico Medicine Ip Ltd | Methionine adenosyltransferase 2A inhibitors and their uses |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60226882A (ja) * | 1984-04-24 | 1985-11-12 | Nippon Zoki Pharmaceut Co Ltd | 新規ピリミドピリミジン誘導体 |
ES2191183T3 (es) * | 1996-08-06 | 2003-09-01 | Pfizer | Derivados 6,6- o 6,7-biciclicos que contienen pirido o pirimido sustituidos. |
DE69939168D1 (de) * | 1998-05-26 | 2008-09-04 | Warner Lambert Co | Bicyclische pyrimidine und bicyclische 3,4-dihydropyrimidine als inhibitoren der zellvermehrung |
EP1086085A1 (fr) * | 1998-06-12 | 2001-03-28 | Vertex Pharmaceuticals Incorporated | INHIBITEURS DE p38 |
JP3593035B2 (ja) * | 1998-10-23 | 2004-11-24 | エフ.ホフマン−ラ ロシュ アーゲー | 二環式窒素複素環化合物 |
-
2001
- 2001-02-28 AR ARP010100940A patent/AR030053A1/es unknown
- 2001-02-28 MY MYPI20010900A patent/MY141144A/en unknown
- 2001-03-02 CA CA2402092A patent/CA2402092C/fr not_active Expired - Fee Related
- 2001-03-02 WO PCT/US2001/006688 patent/WO2001064679A1/fr active Application Filing
- 2001-03-02 MX MXPA02008588A patent/MXPA02008588A/es active IP Right Grant
- 2001-03-02 AU AU3999201A patent/AU3999201A/xx active Pending
- 2001-03-02 DE DE60128457T patent/DE60128457T2/de not_active Expired - Lifetime
- 2001-03-02 BR BR0108715-0A patent/BR0108715A/pt not_active Application Discontinuation
- 2001-03-02 AU AU2001239992A patent/AU2001239992B2/en not_active Ceased
- 2001-03-02 EP EP01914625A patent/EP1265900B1/fr not_active Expired - Lifetime
- 2001-03-02 NZ NZ520914A patent/NZ520914A/en not_active IP Right Cessation
- 2001-03-02 CZ CZ20022933A patent/CZ20022933A3/cs unknown
- 2001-03-02 IL IL15142601A patent/IL151426A0/xx active IP Right Grant
- 2001-03-02 AT AT01914625T patent/ATE362473T1/de active
- 2001-03-02 PL PL01358280A patent/PL358280A1/xx not_active Application Discontinuation
- 2001-03-02 KR KR1020027011408A patent/KR100806978B1/ko not_active IP Right Cessation
- 2001-03-02 HU HU0204431A patent/HUP0204431A3/hu unknown
- 2001-03-02 TW TW090104783A patent/TWI290926B/zh not_active IP Right Cessation
- 2001-03-02 CN CNB018076866A patent/CN100482664C/zh not_active Expired - Fee Related
- 2001-03-02 DK DK01914625T patent/DK1265900T3/da active
- 2001-03-02 JP JP2001564176A patent/JP2003525295A/ja active Pending
- 2001-03-02 PT PT01914625T patent/PT1265900E/pt unknown
- 2001-03-02 ES ES01914625T patent/ES2287107T3/es not_active Expired - Lifetime
-
2002
- 2002-08-22 IL IL151426A patent/IL151426A/en not_active IP Right Cessation
- 2002-08-30 NO NO20024134A patent/NO326409B1/no not_active IP Right Cessation
- 2002-09-02 ZA ZA200207017A patent/ZA200207017B/en unknown
-
2003
- 2003-05-07 AR ARP030101602A patent/AR040075A2/es unknown
- 2003-05-27 HK HK03103782A patent/HK1052932A1/xx not_active IP Right Cessation
-
2007
- 2007-08-13 CY CY20071101080T patent/CY1106816T1/el unknown
-
2008
- 2008-02-28 IL IL189865A patent/IL189865A0/en unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO326409B1 (no) | 1,5-disubstituerte 3,4-dihydro-1H-pyrimido[4,5-D]-pyrimidin-2-onforbindelser og deres anvendelse samt farmasoytisk preparat inneholdende en slik forbindelse | |
US7700768B2 (en) | Compounds | |
JP4500161B2 (ja) | フタラジノン誘導体 | |
EP1333833B1 (fr) | Nouveau composé 8H-pyrido[2,3-d]pyrimidin-7-one trisubstituté pour le traitement des maladies faisant intervenir les kinases CSBP/p38 | |
AU2001239992A1 (en) | 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 | |
EP1126852B1 (fr) | Pyrazines substitues pyridin-4-yle ou pyrimidin-4-yle | |
EA012875B1 (ru) | ПРОИЗВОДНЫЕ ПИРИМИДИНА И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ В КАЧЕСТВЕ ИНГИБИТОРОВ КИНАЗЫ CSBP/RK/p38 | |
EP1499320B1 (fr) | Nouveaux composes | |
US6982270B1 (en) | 3,4-dihydro-(1H)quinazolin-2-one compounds as CSBP/p38 kinase inhibitors | |
AU2024205090A1 (en) | Methods of use for trisubstituted benzotriazole derivatives as dihydroorotate oxygenase inhibitors | |
JP2003517471A (ja) | 3,4−ジヒドロ−(1H)−キナゾリン−2−オンおよびそのCSBP/p38キナーゼ阻害剤としての使用 | |
EP1235814B1 (fr) | COMPOSES DE 3,4-DIHYDRO-(1H)QUINAZOLINE-2-ONE UTILISES COMME INHIBITEURS DE LA KINASE CSBP/p38 | |
EP1842851A2 (fr) | Nouveaux composés |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |