JP5037487B2 - 新規化合物 - Google Patents
新規化合物 Download PDFInfo
- Publication number
- JP5037487B2 JP5037487B2 JP2008503238A JP2008503238A JP5037487B2 JP 5037487 B2 JP5037487 B2 JP 5037487B2 JP 2008503238 A JP2008503238 A JP 2008503238A JP 2008503238 A JP2008503238 A JP 2008503238A JP 5037487 B2 JP5037487 B2 JP 5037487B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- heteroaryl
- hydrogen
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims description 78
- -1 2,6-difluorophenyl Chemical group 0.000 claims description 172
- 150000003839 salts Chemical class 0.000 claims description 56
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 43
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 43
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 108010084680 Heterogeneous-Nuclear Ribonucleoprotein K Proteins 0.000 claims description 14
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 206010040070 Septic Shock Diseases 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 201000005569 Gout Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 3
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 201000005404 rubella Diseases 0.000 claims description 3
- 201000004595 synovitis Diseases 0.000 claims description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
- 206010063094 Cerebral malaria Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 206010014824 Endotoxic shock Diseases 0.000 claims description 2
- 241001529936 Murinae Species 0.000 claims description 2
- 206010028289 Muscle atrophy Diseases 0.000 claims description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
- 208000033464 Reiter syndrome Diseases 0.000 claims description 2
- 206010063837 Reperfusion injury Diseases 0.000 claims description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
- 201000010001 Silicosis Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 208000024908 graft versus host disease Diseases 0.000 claims description 2
- 206010022000 influenza Diseases 0.000 claims description 2
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 2
- 208000002574 reactive arthritis Diseases 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 2
- 208000002780 macular degeneration Diseases 0.000 claims 2
- IVYSYNYIZLRQPL-UHFFFAOYSA-N 3-[2-[3-(diethylamino)propylamino]-8-(2,6-difluorophenyl)-7-oxopyrido[2,3-d]pyrimidin-4-yl]-5-fluoro-4-methyl-n-propan-2-ylbenzamide Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3F)F)C2=NC(NCCCN(CC)CC)=NC=1C1=CC(C(=O)NC(C)C)=CC(F)=C1C IVYSYNYIZLRQPL-UHFFFAOYSA-N 0.000 claims 1
- XLNBGXSUYFKJFF-UHFFFAOYSA-N 4-methyl-n-(1,3-thiazol-2-yl)benzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=NC=CS1 XLNBGXSUYFKJFF-UHFFFAOYSA-N 0.000 claims 1
- 208000006386 Bone Resorption Diseases 0.000 claims 1
- 206010010741 Conjunctivitis Diseases 0.000 claims 1
- 201000004624 Dermatitis Diseases 0.000 claims 1
- 206010012442 Dermatitis contact Diseases 0.000 claims 1
- 206010018364 Glomerulonephritis Diseases 0.000 claims 1
- 206010019196 Head injury Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 208000016988 Hemorrhagic Stroke Diseases 0.000 claims 1
- 208000032382 Ischaemic stroke Diseases 0.000 claims 1
- 201000009906 Meningitis Diseases 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 206010042496 Sunburn Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 230000002491 angiogenic effect Effects 0.000 claims 1
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 208000010668 atopic eczema Diseases 0.000 claims 1
- 230000024279 bone resorption Effects 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 208000020832 chronic kidney disease Diseases 0.000 claims 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims 1
- 208000010247 contact dermatitis Diseases 0.000 claims 1
- 210000004351 coronary vessel Anatomy 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 210000002216 heart Anatomy 0.000 claims 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- WRVJRPQBHOZCQZ-UHFFFAOYSA-N n-cyclopropyl-3-[2-[3-(diethylamino)propylamino]-8-(2,6-difluorophenyl)-7-oxopyrido[2,3-d]pyrimidin-4-yl]-5-fluoro-4-methylbenzamide Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3F)F)C2=NC(NCCCN(CC)CC)=NC=1C(C(=C(F)C=1)C)=CC=1C(=O)NC1CC1 WRVJRPQBHOZCQZ-UHFFFAOYSA-N 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 208000013223 septicemia Diseases 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 description 1339
- 229910052739 hydrogen Inorganic materials 0.000 description 475
- 239000001257 hydrogen Substances 0.000 description 458
- 125000001072 heteroaryl group Chemical group 0.000 description 449
- 125000000623 heterocyclic group Chemical group 0.000 description 438
- 125000003118 aryl group Chemical group 0.000 description 425
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 423
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 302
- 150000002431 hydrogen Chemical group 0.000 description 288
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 233
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 220
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 165
- 229910052757 nitrogen Inorganic materials 0.000 description 158
- 229910052717 sulfur Inorganic materials 0.000 description 116
- 125000005842 heteroatom Chemical group 0.000 description 113
- 125000000392 cycloalkenyl group Chemical group 0.000 description 104
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 103
- 229910052760 oxygen Inorganic materials 0.000 description 100
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 93
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 83
- 239000001301 oxygen Substances 0.000 description 83
- 239000011593 sulfur Chemical group 0.000 description 83
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 74
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 67
- 229910052736 halogen Inorganic materials 0.000 description 66
- 150000002367 halogens Chemical class 0.000 description 66
- 125000000304 alkynyl group Chemical group 0.000 description 60
- 125000003545 alkoxy group Chemical group 0.000 description 57
- 125000003342 alkenyl group Chemical group 0.000 description 55
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 51
- 125000004093 cyano group Chemical group *C#N 0.000 description 48
- 125000004122 cyclic group Chemical group 0.000 description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 38
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 35
- 125000005843 halogen group Chemical group 0.000 description 35
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 34
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 33
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 33
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 31
- 239000012453 solvate Substances 0.000 description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 22
- 125000001424 substituent group Chemical group 0.000 description 22
- 125000003107 substituted aryl group Chemical group 0.000 description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 16
- 102000004127 Cytokines Human genes 0.000 description 16
- 108090000695 Cytokines Proteins 0.000 description 16
- 125000003282 alkyl amino group Chemical group 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 102000000589 Interleukin-1 Human genes 0.000 description 12
- 108010002352 Interleukin-1 Proteins 0.000 description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 239000011737 fluorine Substances 0.000 description 11
- 229910052731 fluorine Inorganic materials 0.000 description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 10
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 10
- 125000000335 thiazolyl group Chemical group 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 125000004193 piperazinyl group Chemical group 0.000 description 9
- 125000003386 piperidinyl group Chemical group 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 125000004076 pyridyl group Chemical group 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- 108090001007 Interleukin-8 Proteins 0.000 description 8
- 102000004890 Interleukin-8 Human genes 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 8
- 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 8
- 229940096397 interleukin-8 Drugs 0.000 description 8
- 210000000440 neutrophil Anatomy 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 102000004889 Interleukin-6 Human genes 0.000 description 7
- 108090001005 Interleukin-6 Proteins 0.000 description 7
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 7
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 125000003710 aryl alkyl group Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229940100601 interleukin-6 Drugs 0.000 description 7
- 230000037361 pathway Effects 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 125000001422 pyrrolinyl group Chemical group 0.000 description 7
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000002632 imidazolidinyl group Chemical group 0.000 description 6
- 125000002636 imidazolinyl group Chemical group 0.000 description 6
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 230000000770 proinflammatory effect Effects 0.000 description 6
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 6
- 125000002755 pyrazolinyl group Chemical group 0.000 description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 6
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 108010074051 C-Reactive Protein Proteins 0.000 description 5
- 102100032752 C-reactive protein Human genes 0.000 description 5
- 125000004069 aziridinyl group Chemical group 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 125000002883 imidazolyl group Chemical group 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 5
- 125000005505 thiomorpholino group Chemical group 0.000 description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 239000012826 P38 inhibitor Substances 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 125000000842 isoxazolyl group Chemical group 0.000 description 4
- 229940043355 kinase inhibitor Drugs 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000002971 oxazolyl group Chemical group 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 125000003373 pyrazinyl group Chemical group 0.000 description 4
- 125000003226 pyrazolyl group Chemical group 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 125000001425 triazolyl group Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 206010006895 Cachexia Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 108010055166 Chemokine CCL5 Proteins 0.000 description 3
- 102000001327 Chemokine CCL5 Human genes 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 102000029816 Collagenase Human genes 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 3
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 235000013985 cinnamic acid Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000021995 interleukin-8 production Effects 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001786 isothiazolyl group Chemical group 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- QOHMWDJIBGVPIF-UHFFFAOYSA-N n',n'-diethylpropane-1,3-diamine Chemical compound CCN(CC)CCCN QOHMWDJIBGVPIF-UHFFFAOYSA-N 0.000 description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 3
- 125000002098 pyridazinyl group Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 2
- RUYZJEIKQYLEGZ-UHFFFAOYSA-N 1-fluoro-4-phenylbenzene Chemical group C1=CC(F)=CC=C1C1=CC=CC=C1 RUYZJEIKQYLEGZ-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 2
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 125000004864 4-thiomethylphenyl group Chemical group 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
- 241000711286 Heterosais Species 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 2
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 230000003090 exacerbative effect Effects 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000018276 interleukin-1 production Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 2
- 125000004316 oxathiadiazolyl group Chemical group O1SNN=C1* 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
- 150000003235 pyrrolidines Chemical class 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000003938 response to stress Effects 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 108091007196 stromelysin Proteins 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- KQTIIICEAUMSDG-UHFFFAOYSA-N tricarballylic acid Chemical compound OC(=O)CC(C(O)=O)CC(O)=O KQTIIICEAUMSDG-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 230000009385 viral infection Effects 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
- SDOFMBGMRVAJNF-SLPGGIOYSA-N (2r,3r,4r,5s)-6-aminohexane-1,2,3,4,5-pentol Chemical compound NC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO SDOFMBGMRVAJNF-SLPGGIOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- AFDXODALSZRGIH-QPJJXVBHSA-N (E)-3-(4-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1 AFDXODALSZRGIH-QPJJXVBHSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- AAFXQFIGKBLKMC-KQQUZDAGSA-N (e)-3-[4-[(e)-2-carboxyethenyl]phenyl]prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=C(\C=C\C(O)=O)C=C1 AAFXQFIGKBLKMC-KQQUZDAGSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- HVCDMQWLANAJMW-UHFFFAOYSA-N 1-[amino-[2-(dimethylamino)ethyl]amino]propan-2-ol Chemical compound OC(CN(CCN(C)C)N)C HVCDMQWLANAJMW-UHFFFAOYSA-N 0.000 description 1
- YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- WHOYVSQXYWBSLY-UHFFFAOYSA-N 1-ethyl-2-propan-2-ylhydrazine Chemical compound CCNNC(C)C WHOYVSQXYWBSLY-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- CAPCBAYULRXQAN-UHFFFAOYSA-N 1-n,1-n-diethylpentane-1,4-diamine Chemical compound CCN(CC)CCCC(C)N CAPCBAYULRXQAN-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- DCYGAPKNVCQNOE-UHFFFAOYSA-N 2,2,2-triphenylacetic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)O)C1=CC=CC=C1 DCYGAPKNVCQNOE-UHFFFAOYSA-N 0.000 description 1
- PNHGJPJOMCXSKN-UHFFFAOYSA-N 2-(1-methylpyrrolidin-2-yl)ethanamine Chemical compound CN1CCCC1CCN PNHGJPJOMCXSKN-UHFFFAOYSA-N 0.000 description 1
- CXEJMFLWEVKOGS-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)ethanamine Chemical compound C1CN(CCN)CCN1CC1=CC=CC=C1 CXEJMFLWEVKOGS-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-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
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[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
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-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
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- JDQDSEVNMTYMOC-UHFFFAOYSA-N 3-methylbenzenesulfonic acid Chemical compound CC1=CC=CC(S(O)(=O)=O)=C1 JDQDSEVNMTYMOC-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- KWGPBDBAAXYWOJ-UHFFFAOYSA-N 3-naphthalen-2-ylprop-2-enoic acid Chemical compound C1=CC=CC2=CC(C=CC(=O)O)=CC=C21 KWGPBDBAAXYWOJ-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- RURHILYUWQEGOS-VOTSOKGWSA-N 4-Methylcinnamic acid Chemical group CC1=CC=C(\C=C\C(O)=O)C=C1 RURHILYUWQEGOS-VOTSOKGWSA-N 0.000 description 1
- QVMIDACOQMEXHV-UHFFFAOYSA-N 4-[2-[3-(diethylamino)propylamino]-8-(2,6-difluorophenyl)-7-oxopyrido[2,3-d]pyrimidin-4-yl]-n-(1,3-thiazol-2-yl)benzamide Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3F)F)C2=NC(NCCCN(CC)CC)=NC=1C(C=C1)=CC=C1C(=O)NC1=NC=CS1 QVMIDACOQMEXHV-UHFFFAOYSA-N 0.000 description 1
- JPQHOAKVOYRXPZ-UHFFFAOYSA-N 4-[2-[3-(diethylamino)propylamino]-8-(2,6-difluorophenyl)-7-oxopyrido[2,3-d]pyrimidin-4-yl]-n-(4-fluorophenyl)benzamide Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3F)F)C2=NC(NCCCN(CC)CC)=NC=1C(C=C1)=CC=C1C(=O)NC1=CC=C(F)C=C1 JPQHOAKVOYRXPZ-UHFFFAOYSA-N 0.000 description 1
- RFOLOMRDZMTVOU-UHFFFAOYSA-N 4-[2-[3-(diethylamino)propylamino]-8-(2,6-difluorophenyl)-7-oxopyrido[2,3-d]pyrimidin-4-yl]-n-propan-2-ylbenzamide Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3F)F)C2=NC(NCCCN(CC)CC)=NC=1C1=CC=C(C(=O)NC(C)C)C=C1 RFOLOMRDZMTVOU-UHFFFAOYSA-N 0.000 description 1
- UVRMBQSPRZJBDG-UHFFFAOYSA-N 4-[2-[3-(diethylamino)propylamino]-8-(2,6-difluorophenyl)-7-oxopyrido[2,3-d]pyrimidin-4-yl]-n-propylbenzamide Chemical compound C1=CC(C(=O)NCCC)=CC=C1C1=NC(NCCCN(CC)CC)=NC2=C1C=CC(=O)N2C1=C(F)C=CC=C1F UVRMBQSPRZJBDG-UHFFFAOYSA-N 0.000 description 1
- NJJRVKRWZLSTKM-UHFFFAOYSA-N 4-[2-[3-(diethylamino)propylamino]-8-(2,6-difluorophenyl)-7-oxopyrido[2,3-d]pyrimidin-4-yl]benzoic acid Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3F)F)C2=NC(NCCCN(CC)CC)=NC=1C1=CC=C(C(O)=O)C=C1 NJJRVKRWZLSTKM-UHFFFAOYSA-N 0.000 description 1
- PDTYLGXVBIWRIM-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-methoxypyrimidine Chemical compound COC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCNCC2)=N1 PDTYLGXVBIWRIM-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
- XDTYUYVIGLIFCW-UHFFFAOYSA-N 4-phenylbenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1=CC=CC=C1 XDTYUYVIGLIFCW-UHFFFAOYSA-N 0.000 description 1
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 1
- KQTGCJMBUBYSLL-UHFFFAOYSA-N 4-piperidin-1-ylmorpholine Chemical compound C1CCCCN1N1CCOCC1 KQTGCJMBUBYSLL-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 1
- WDHAAJIGSXNPFO-UHFFFAOYSA-N 8h-pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=CN=C2NC(=O)C=CC2=C1 WDHAAJIGSXNPFO-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000012124 AIDS-related disease Diseases 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 108091008038 CHOP Proteins 0.000 description 1
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-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
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 102100021246 DDIT3 upstream open reading frame protein Human genes 0.000 description 1
- 101100339887 Drosophila melanogaster Hsp27 gene Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 206010048554 Endothelial dysfunction Diseases 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102100022086 GRB2-related adapter protein 2 Human genes 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101150096895 HSPB1 gene Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 108010033040 Histones Proteins 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
- 101001046686 Homo sapiens Integrin alpha-M 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
- 101000945096 Homo sapiens Ribosomal protein S6 kinase alpha-5 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
- 102100026299 MAP kinase-interacting serine/threonine-protein kinase 1 Human genes 0.000 description 1
- 101710139011 MAP kinase-interacting serine/threonine-protein kinase 1 Proteins 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
- 235000011430 Malus pumila Nutrition 0.000 description 1
- 235000015103 Malus silvestris Nutrition 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- YXOLAZRVSSWPPT-UHFFFAOYSA-N Morin Chemical compound OC1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 YXOLAZRVSSWPPT-UHFFFAOYSA-N 0.000 description 1
- 101100079042 Mus musculus Myef2 gene Proteins 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 102100021148 Myocyte-specific enhancer factor 2A Human genes 0.000 description 1
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 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
- 208000007542 Paresis Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 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
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-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
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 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
- 241000219061 Rheum Species 0.000 description 1
- 102100033645 Ribosomal protein S6 kinase alpha-5 Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108091005735 TGF-beta receptors Proteins 0.000 description 1
- 229920002253 Tannate Polymers 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
- 241000011102 Thera Species 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010398 acute inflammatory response Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 210000005091 airway smooth muscle Anatomy 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 201000005008 bacterial sepsis Diseases 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008235 cell cycle pathway Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000014564 chemokine production Effects 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- TXKMVPPZCYKFAC-UHFFFAOYSA-N disulfur monoxide Inorganic materials O=S=S TXKMVPPZCYKFAC-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 230000009144 enzymatic modification Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 125000001145 hydrido group Chemical group *[H] 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 101150014102 mef-2 gene Proteins 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 235000007708 morin Nutrition 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- ULDIVZQLPBUHAG-UHFFFAOYSA-N n',n',2,2-tetramethylpropane-1,3-diamine Chemical compound CN(C)CC(C)(C)CN ULDIVZQLPBUHAG-UHFFFAOYSA-N 0.000 description 1
- KYCGURZGBKFEQB-UHFFFAOYSA-N n',n'-dibutylpropane-1,3-diamine Chemical compound CCCCN(CCCC)CCCN KYCGURZGBKFEQB-UHFFFAOYSA-N 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 1
- KFDIDIIKNMZLRZ-UHFFFAOYSA-N n'-propan-2-ylpropane-1,3-diamine Chemical compound CC(C)NCCCN KFDIDIIKNMZLRZ-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- AAXKMXAEFVWFDC-UHFFFAOYSA-N naphthalene;prop-2-enoic acid Chemical compound OC(=O)C=C.C1=CC=CC2=CC=CC=C21 AAXKMXAEFVWFDC-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004957 naphthylene group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 230000011242 neutrophil chemotaxis Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000008723 osmotic stress Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- AFDXODALSZRGIH-UHFFFAOYSA-N p-coumaric acid methyl ether Natural products COC1=CC=C(C=CC(O)=O)C=C1 AFDXODALSZRGIH-UHFFFAOYSA-N 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 235000019161 pantothenic acid Nutrition 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
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- QPMDWIOUHQWKHV-ODZAUARKSA-M potassium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound [K+].OC(=O)\C=C/C([O-])=O QPMDWIOUHQWKHV-ODZAUARKSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
- 229940076788 pyruvate Drugs 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000019254 respiratory burst Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 231100000241 scar Toxicity 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
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical compound S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-N trans-cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
-
- 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
-
- 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
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- 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
-
- 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)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Toxicology (AREA)
- Otolaryngology (AREA)
- Transplantation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66531505P | 2005-03-25 | 2005-03-25 | |
| US60/665,315 | 2005-03-25 | ||
| PCT/US2006/010855 WO2006104915A2 (en) | 2005-03-25 | 2006-03-24 | 8-PHENYL-7,8-DIHYDROPYRIDO[2,3-d]PYRIMIDIN-7-ONES AND THEIR USE AS PHARMACEUTICALS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008534513A JP2008534513A (ja) | 2008-08-28 |
| JP2008534513A5 JP2008534513A5 (enExample) | 2010-01-14 |
| JP5037487B2 true JP5037487B2 (ja) | 2012-09-26 |
Family
ID=37053943
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008503238A Expired - Fee Related JP5037487B2 (ja) | 2005-03-25 | 2006-03-24 | 新規化合物 |
Country Status (24)
| Country | Link |
|---|---|
| US (3) | US8207176B2 (enExample) |
| EP (3) | EP2436686A1 (enExample) |
| JP (1) | JP5037487B2 (enExample) |
| KR (1) | KR101235497B1 (enExample) |
| CN (4) | CN101258148A (enExample) |
| AR (1) | AR053346A1 (enExample) |
| AU (1) | AU2006229993B2 (enExample) |
| BR (1) | BRPI0609437A2 (enExample) |
| CA (1) | CA2602553C (enExample) |
| EA (1) | EA012875B1 (enExample) |
| ES (2) | ES2426251T3 (enExample) |
| IL (1) | IL185870A (enExample) |
| MA (1) | MA29341B1 (enExample) |
| MX (1) | MX2007011856A (enExample) |
| MY (2) | MY145281A (enExample) |
| NO (1) | NO20075275L (enExample) |
| NZ (1) | NZ561237A (enExample) |
| PE (2) | PE20061351A1 (enExample) |
| SG (1) | SG166771A1 (enExample) |
| TW (1) | TWI389690B (enExample) |
| UA (1) | UA95444C2 (enExample) |
| UY (1) | UY29440A1 (enExample) |
| WO (1) | WO2006104915A2 (enExample) |
| ZA (1) | ZA200707564B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7235551B2 (en) * | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| AU2002246855B2 (en) * | 2000-10-23 | 2005-12-22 | Smithkline Beecham Corporation | Novel compounds |
| KR20040103972A (ko) * | 2002-04-19 | 2004-12-09 | 스미스클라인 비참 코포레이션 | 신규 화합물 |
| AU2006229995A1 (en) * | 2005-03-25 | 2006-10-05 | Glaxo Group Limited | Process for preparing pyrido(2,3-d)pyrimidin-7-one and 3,4-dihydropyrimido(4,5-d)pyrimidin-2(1H)-one derivatives |
| JP2008535822A (ja) * | 2005-03-25 | 2008-09-04 | グラクソ グループ リミテッド | 新規化合物 |
| MY145281A (en) * | 2005-03-25 | 2012-01-13 | Glaxo Group Ltd | Novel compounds |
| UY29439A1 (es) * | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| WO2007147109A2 (en) * | 2006-06-16 | 2007-12-21 | Glaxo Group Limited | Novel compounds |
| WO2007147103A2 (en) * | 2006-06-16 | 2007-12-21 | Glaxo Group Limited | Novel compounds |
| GB0621830D0 (en) * | 2006-11-02 | 2006-12-13 | Chroma Therapeutics Ltd | Inhibitors of p38 mitogen-activated protein kinase |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| WO2012158197A2 (en) * | 2010-11-11 | 2012-11-22 | Lyndor Biosciences L.L.C. | Compounds useful as akt/pkb modulators and uses thereof |
| LT2748147T (lt) * | 2011-08-25 | 2017-10-25 | St. Jude Children`S Research Hospital | 2-alkil-1-okso-n-fenil-3-heteroaril-1,2,3,4-tetrahidroizochinolin-4-karboksamidai, skirti antimaliarinei terapijai |
| ES2927715T3 (es) | 2017-10-05 | 2022-11-10 | Fulcrum Therapeutics Inc | Inhibidores de la quinasa p38 reducen la expresión de dux4 y de los genes que le siguen para el tratamiento de la FSHD |
Family Cites Families (208)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US25386A (en) | 1859-09-13 | Fastening fob | ||
| US2833779A (en) | 1956-10-29 | 1958-05-06 | American Cyanamid Co | Substituted pyrazoles |
| US2918408A (en) | 1957-04-08 | 1959-12-22 | Lakeside Lab Inc | Anti-spasmodic compositions specific for treating spasm of the colon |
| US3631045A (en) | 1969-11-04 | 1971-12-28 | American Home Prod | 4 5-diamino-7h-pyrrolo(2 3-d)pyrimidine derivatives |
| US3910913A (en) | 1969-11-04 | 1975-10-07 | American Home Prod | 4,5-Diamino-7H-pyrrolo{8 2,3-d{9 pyrimidine derivatives |
| US3707475A (en) | 1970-11-16 | 1972-12-26 | Pfizer | Antiinflammatory imidazoles |
| US3929807A (en) | 1971-05-10 | 1975-12-30 | Ciba Geigy Corp | 2-Substituted-4(5)-(aryl)-5(4)-(2,3 or -4-pyridyl)-imidazoles |
| US3940486A (en) | 1971-05-10 | 1976-02-24 | Ciba-Geigy Corporation | Imidazole derivatives in the treatment of pain |
| CA966134A (en) | 1972-05-05 | 1975-04-15 | Haydn W.R. Williams | 1,8-naphthyridine compounds |
| US4058614A (en) | 1973-12-04 | 1977-11-15 | Merck & Co., Inc. | Substituted imidazole compounds and therapeutic compositions therewith |
| US4199592A (en) | 1978-08-29 | 1980-04-22 | E. I. Du Pont De Nemours And Company | Antiinflammatory 4,5-diaryl-2-nitroimidazoles |
| JPS5618982A (en) | 1979-06-14 | 1981-02-23 | Wellcome Found | Pyrimidine derivatives and medicinal drug containing them |
| CY1308A (en) | 1979-12-06 | 1985-12-06 | Glaxo Group Ltd | Device for dispensing medicaments |
| GR75287B (enExample) | 1980-07-25 | 1984-07-13 | Ciba Geigy Ag | |
| US4353656A (en) | 1980-10-14 | 1982-10-12 | Xerox Corporation | Moving coil, multiple energy print hammer system including a closed loop servo |
| EP0069715B1 (en) | 1981-07-08 | 1986-11-05 | Aktiebolaget Draco | Powder inhalator |
| WO1983002613A1 (fr) | 1981-07-20 | 1983-08-04 | Sallmann, Alfred | Composes oxazoiques a triple substitution |
| US4503065A (en) | 1982-08-03 | 1985-03-05 | E. I. Du Pont De Nemours And Company | Antiinflammatory 4,5-diaryl 1-2-halo imidazoles |
| US4778054A (en) | 1982-10-08 | 1988-10-18 | Glaxo Group Limited | Pack for administering medicaments to patients |
| GB2169265B (en) | 1982-10-08 | 1987-08-12 | Glaxo Group Ltd | Pack for medicament |
| DK172541B1 (da) | 1982-10-08 | 1998-12-07 | Glaxo Group Ltd | Apparat til administrering af medikamenter til patienter og en medikamentpakning til brug i apparatet |
| 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 |
| US4565875A (en) | 1984-06-27 | 1986-01-21 | Fmc Corporation | Imidazole plant growth regulators |
| US4560691A (en) | 1984-07-13 | 1985-12-24 | Sterling Drug Inc. | 5-(Phenyl)-1,6-naphthyridin-2(1H)-ones, their cardiotonic use and preparation |
| AU591152B2 (en) | 1985-07-30 | 1989-11-30 | Glaxo Group Limited | Devices for administering medicaments to patients |
| US4686231A (en) | 1985-12-12 | 1987-08-11 | Smithkline Beckman Corporation | Inhibition of 5-lipoxygenase products |
| IL83467A0 (en) | 1986-08-15 | 1988-01-31 | Fujisawa Pharmaceutical Co | Imidazole derivatives,processes for their preparation and pharmaceutical compositions containing the same |
| EP0278686A1 (en) | 1987-02-07 | 1988-08-17 | The Wellcome Foundation Limited | Pyridopyrimidines methods for their preparation and pharmaceutical formulations thereof |
| JPH01261306A (ja) | 1988-04-13 | 1989-10-18 | Nippon Kayaku Co Ltd | ２−アルキルチオ−４−アミノピリミジン誘導体を有効成分とする開花促進剤 |
| GB9004781D0 (en) | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| BG94957A (bg) | 1990-08-10 | 1993-12-24 | Ciba - Geigy Ag | Пиримидинови производни и средство за борба срещу вредители по растенията |
| FR2665898B1 (fr) | 1990-08-20 | 1994-03-11 | Sanofi | Derives d'amido-3 pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| IE913473A1 (en) | 1990-10-15 | 1992-04-22 | Fujisawa Pharmaceutical Co | Quinazoline derivatives and their preparation |
| WO1992012154A1 (en) | 1990-12-31 | 1992-07-23 | Fujisawa Pharmaceutical Co., Ltd. | Imidazotriazine derivatives |
| JP3375659B2 (ja) | 1991-03-28 | 2003-02-10 | テキサス インスツルメンツ インコーポレイテツド | 静電放電保護回路の形成方法 |
| DE69222637T2 (de) | 1991-05-10 | 1998-02-26 | Rhone Poulenc Rorer Int | Bis mono- und bicyclische aryl- und heteroarylderivate mit inhibierender wirkung auf die egf und/oder pdgf-rezeptor tyrosinkinase |
| FR2676734B1 (fr) | 1991-05-23 | 1995-05-19 | Roussel Uclaf | Nouveaux derives de la pyrimidine, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant. |
| IL102764A0 (en) | 1991-08-16 | 1993-01-31 | Merck & Co Inc | Quinazoline derivatives,and pharmaceutical compositions containing them |
| DE4131029A1 (de) | 1991-09-18 | 1993-07-29 | Basf Ag | Substituierte pyrido (2,3-d) pyrimidine als antidots |
| GB9127376D0 (en) | 1991-12-24 | 1992-02-19 | Wellcome Found | Amidino derivatives |
| US5716972A (en) | 1993-01-13 | 1998-02-10 | Smithkline Beecham Corporation | Pyridyl substituted imidazoles |
| US6008235A (en) | 1992-01-13 | 1999-12-28 | Smithkline Beecham Corporation | Pyridyl substituted imidazoles |
| US5916891A (en) | 1992-01-13 | 1999-06-29 | Smithkline Beecham Corporation | Pyrimidinyl imidazoles |
| US5656644A (en) | 1994-07-20 | 1997-08-12 | Smithkline Beecham Corporation | Pyridyl imidazoles |
| IL104369A0 (en) | 1992-01-13 | 1993-05-13 | Smithkline Beecham Corp | Novel compounds and compositions |
| FI944549L (fi) | 1992-04-02 | 1994-11-30 | Smithkline Beecham Corp | Allergisten ja tulehdussairauksien hoidossa käyttökelpoiset yhdisteet |
| GB9303993D0 (en) | 1993-02-26 | 1993-04-14 | Fujisawa Pharmaceutical Co | New heterocyclic derivatives |
| US5466692A (en) | 1993-03-24 | 1995-11-14 | American Home Products Corporation | Substituted pyridopyrimidines and antihypertensives |
| US5593992A (en) | 1993-07-16 | 1997-01-14 | Smithkline Beecham Corporation | Compounds |
| US5670527A (en) | 1993-07-16 | 1997-09-23 | Smithkline Beecham Corporation | Pyridyl imidazole compounds and compositions |
| US5593991A (en) | 1993-07-16 | 1997-01-14 | Adams; Jerry L. | Imidazole compounds, use and process of making |
| US5783664A (en) | 1993-09-17 | 1998-07-21 | Smithkline Beecham Corporation | Cytokine suppressive anit-inflammatory drug binding proteins |
| US5869043A (en) | 1993-09-17 | 1999-02-09 | Smithkline Beecham Corporation | Drug binding protein |
| US5871934A (en) | 1993-09-17 | 1999-02-16 | Smithkline Beecham Corporation | Screening methods using cytokine suppressive anti-inflammatory drug (CSAID) binding proteins |
| US5426110A (en) | 1993-10-06 | 1995-06-20 | Eli Lilly And Company | Pyrimidinyl-glutamic acid derivatives |
| EP1306377A3 (en) | 1993-11-08 | 2003-05-07 | Smithkline Beecham Corporation | Pyridyl-oxazoles and their use as cytokines inhibitors |
| GB9325217D0 (en) | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| US5559137A (en) | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
| US5547954A (en) | 1994-05-26 | 1996-08-20 | Fmc Corporation | 2,4-Diamino-5,6-disubstituted-and 5,6,7-trisubstituted-5-deazapteridines as insecticides |
| US5545669A (en) | 1994-06-02 | 1996-08-13 | Adams; Jerry L. | Anti-inflammatory compounds |
| TW574214B (en) | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
| EP0957087B1 (en) | 1994-06-15 | 2002-12-04 | The Wellcome Foundation Limited | Intermediates useful in the preparation of enzyme inhibitors |
| US5998428A (en) | 1995-05-31 | 1999-12-07 | Smithkline Beecham Corporation | Compounds and methods for treating PDE IV-related diseases |
| WO1996006843A1 (en) | 1994-08-29 | 1996-03-07 | Yamanouchi Pharmaceutical Co., Ltd. | Novel naphthyridine derivative and medicinal composition thereof |
| IL115256A0 (en) | 1994-11-14 | 1995-12-31 | Warner Lambert Co | 6-Aryl pyrido (2,3-d) pyrimidines and naphthyridines and their use |
| JPH11501892A (ja) | 1995-03-10 | 1999-02-16 | ミネソタ マイニング アンド マニュファクチャリング カンパニー | エアロゾルバルブ |
| US5620981A (en) | 1995-05-03 | 1997-04-15 | Warner-Lambert Company | Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation |
| EP0846117B1 (en) | 1995-06-07 | 2003-05-14 | Wyeth | Process for preparation of biphenyl derivatives |
| US5760220A (en) | 1995-06-07 | 1998-06-02 | American Home Products Corporation | Process for preparation of biphenyl derivatives |
| IL118544A (en) | 1995-06-07 | 2001-08-08 | Smithkline Beecham Corp | History of imidazole, the process for their preparation and the pharmaceutical preparations containing them |
| US5739143A (en) | 1995-06-07 | 1998-04-14 | Smithkline Beecham Corporation | Imidazole compounds and compositions |
| ZA9610687B (en) | 1995-12-22 | 1997-09-29 | Smithkline Beecham Corp | Novel synthesis. |
| ZA97175B (en) | 1996-01-11 | 1997-11-04 | Smithkline Beecham Corp | Novel substituted imidazole compounds. |
| US5756499A (en) | 1996-01-11 | 1998-05-26 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| US6150337A (en) | 1996-01-23 | 2000-11-21 | Icn Pharmaceuticals, Inc. | Specific modulation of Th1/Th2 cytokine expression by Ribavirin in activated T-lymphocytes |
| US5767097A (en) | 1996-01-23 | 1998-06-16 | Icn Pharmaceuticals, Inc. | Specific modulation of Th1/Th2 cytokine expression by ribavirin in activated T-lymphocytes |
| US20020137696A1 (en) | 1996-01-23 | 2002-09-26 | Robert Tam | Specific modulation of TH1/TH2 cytokine expression by ribavirin in activated T-lymphocytes |
| EP1005343A4 (en) | 1996-03-08 | 2000-06-07 | Smithkline Beecham Corp | USE OF CSAIDS AS ANGIOGENESIS INHIBITORS |
| WO1997035855A1 (en) | 1996-03-25 | 1997-10-02 | Smithkline Beecham Corporation | Novel treatment for cns injuries |
| WO1997035856A1 (en) | 1996-03-25 | 1997-10-02 | Smithkline Beecham Corporation | Novel treatment for cns injuries |
| ATE230740T1 (de) | 1996-04-12 | 2003-01-15 | Sumitomo Pharma | Piperidinylpyrimidine derivate |
| ZA973884B (en) | 1996-05-23 | 1998-11-06 | Du Pont Merck Pharma | Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders |
| US6875769B2 (en) | 1996-05-23 | 2005-04-05 | Pfizer Inc. | Substituted6,6-hetero-bicyclicderivatives |
| DK0920429T3 (da) | 1996-08-06 | 2003-05-12 | Pfizer | Substituerede pyrido- eller pyrimidoholdige, 6,6- eller 6,7-bicykliske derivater |
| TW477787B (en) | 1996-08-27 | 2002-03-01 | Pfizer | Pyrido six-membered nitrogen-containing cyclic ring derivatives having corticotropin releasing factor antagonist activity and pharmaceutical composition containing same |
| US6509320B1 (en) | 1996-10-16 | 2003-01-21 | Icn Pharmaceuticals, Inc. | Purine L-nucleosides, analogs and uses thereof |
| US6455690B1 (en) | 1996-10-16 | 2002-09-24 | Robert Tam | L-8-oxo-7-propyl-7,8-dihydro-(9H)-guanosine |
| AU727177B2 (en) | 1996-10-16 | 2000-12-07 | Icn Pharmaceuticals, Inc. | Purine L-nucleosides, analogs and uses thereof |
| US6147080A (en) | 1996-12-18 | 2000-11-14 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| GB9700226D0 (en) | 1997-01-08 | 1997-02-26 | Glaxo Group Ltd | Inhalation device |
| US5929076A (en) | 1997-01-10 | 1999-07-27 | Smithkline Beecham Corporation | Cycloalkyl substituted imidazoles |
| MY117948A (en) | 1997-01-13 | 2004-08-30 | Glaxo Group Ltd | Nitride oxide synthase inhibitors. |
| US6268310B1 (en) | 1997-01-28 | 2001-07-31 | Nippon Soda Co., Ltd. | Oxazole derivative, process for producing the same, and herbicide |
| ES2301194T3 (es) | 1997-02-05 | 2008-06-16 | Warner-Lambert Company Llc | Pirido 2,3-d pirimidinas y 4-aminopirimidinas como inhibidores de la proliferacion celular. |
| US6498163B1 (en) | 1997-02-05 | 2002-12-24 | Warner-Lambert Company | Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation |
| US5945422A (en) | 1997-02-05 | 1999-08-31 | Warner-Lambert Company | N-oxides of amino containing pyrido 2,3-D! pyrimidines |
| DE19723722A1 (de) | 1997-05-30 | 1998-12-10 | Schering Ag | Nichtsteroidale Gestagene |
| WO1999016766A1 (en) | 1997-10-01 | 1999-04-08 | Kyowa Hakko Kogyo Co., Ltd. | Benzodioxole derivatives |
| US6362193B1 (en) | 1997-10-08 | 2002-03-26 | Smithkline Beecham Corporation | Cycloalkenyl substituted compounds |
| JP2001526230A (ja) | 1997-12-19 | 2001-12-18 | スミスクライン・ビーチャム・コーポレイション | ヘテロアリール置換イミダゾール化合物、その医薬組成物および使用 |
| US6423695B1 (en) | 1998-01-13 | 2002-07-23 | Ribapharm, Inc. | Cytokine related treatments of disease |
| US6506766B1 (en) | 1998-02-13 | 2003-01-14 | Abbott Laboratories | Glucocortiocoid-selective antinflammatory agents |
| ATE245641T1 (de) | 1998-02-17 | 2003-08-15 | Tularik Inc | Antivirale pyrimidinderivate |
| US6306866B1 (en) | 1998-03-06 | 2001-10-23 | American Cyanamid Company | Use of aryl-substituted pyrimidines as insecticidal and acaricidal agents |
| SI1070056T1 (en) | 1998-03-14 | 2004-12-31 | Altana Pharma Ag | Phthalazinone pde iii/iv inhibitors |
| JP2000038350A (ja) | 1998-05-18 | 2000-02-08 | Yoshitomi Pharmaceut Ind Ltd | 糖尿病治療薬 |
| US6423425B1 (en) | 1998-05-26 | 2002-07-23 | Ppg Industries Ohio, Inc. | Article having a chip-resistant electrodeposited coating and a process for forming an electrodeposited coating |
| DE69939168D1 (de) | 1998-05-26 | 2008-09-04 | Warner Lambert Co | Bicyclische pyrimidine und bicyclische 3,4-dihydropyrimidine als inhibitoren der zellvermehrung |
| US6248225B1 (en) | 1998-05-26 | 2001-06-19 | Ppg Industries Ohio, Inc. | Process for forming a two-coat electrodeposited composite coating the composite coating and chip resistant electrodeposited coating composition |
| US20040044012A1 (en) | 1998-05-26 | 2004-03-04 | Dobrusin Ellen Myra | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
| GB9811599D0 (en) | 1998-05-30 | 1998-07-29 | Glaxo Group Ltd | Nitric oxide synthase inhibitors |
| AU4429799A (en) | 1998-06-12 | 1999-12-30 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| US5907465A (en) | 1998-08-13 | 1999-05-25 | Sensormatic Electronics Corporation | Circuit for energizing EAS marker deactivation device with DC pulses of alternating polarity |
| US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| AU762245B2 (en) | 1998-09-18 | 2003-06-19 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| CN1158266C (zh) | 1998-10-01 | 2004-07-21 | 阿斯特拉曾尼卡有限公司 | 化合物 |
| WO2000023444A1 (en) | 1998-10-21 | 2000-04-27 | Abbott Laboratories | 5,7-disubstituted-4-aminopyrido[2,3-d]pyrimidine compounds |
| PL347432A1 (en) | 1998-10-23 | 2002-04-08 | Hoffmann La Roche | Bicyclic nitrogen heterocycles |
| US6358959B1 (en) | 1999-01-26 | 2002-03-19 | Merck & Co., Inc. | Polyazanaphthalenone derivatives useful as alpha 1a adrenoceptor antagonists |
| AR035987A1 (es) | 1999-03-01 | 2004-08-04 | Smithkline Beecham Corp | Uso de un compuesto inhibidor de la pde 4 para la manufactura de un medicamento y el medicamento para tratar asma inducida por ejercicio |
| EP1040831A3 (en) | 1999-04-02 | 2003-05-02 | Pfizer Products Inc. | Use of corticotropin releasing factor (CRF) antagonists to prevent sudden death |
| AU4501800A (en) | 1999-05-04 | 2000-11-17 | American Home Products Corporation | Tetracyclic progesterone receptor modulator compounds and methods |
| DE60027431T2 (de) | 1999-07-02 | 2007-07-12 | Stuart A. Rancho Santa Fe Lipton | Verwendung von p38 MAPK Inhibitoren in der Behandlung von Augenkrankheiten |
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| US6263209B1 (en) | 1999-07-28 | 2001-07-17 | Motorola, Inc. | Method and apparatus in a wireless communication system for creating a learning function |
| PL200923B1 (pl) | 1999-08-21 | 2009-02-27 | Nycomed Gmbh | Lek zawierający inhibitor PDE w połączeniu z agonistą receptoraß₂ -adrenergicznego oraz zastosowanie połączenia roflumilastu i salmeterolu |
| CO5180649A1 (es) | 1999-09-01 | 2002-07-30 | Abbott Lab | Antagonistas de los receptores de los glucocorticoides para el tratamiento de la diabetes para el tratamiento de la diabetes |
| KR20020032591A (ko) | 1999-09-17 | 2002-05-03 | 스튜어트 알. 수터, 스티븐 베네티아너, 피터 존 기딩스 | 라이노바이러스 감염에서의 ｃｓａｉｄ의 용도 |
| HK1053831A1 (zh) | 1999-09-17 | 2003-11-07 | Basf Aktiengesellschaft | 作为治疗药物的激酶抑制剂 |
| OA11558A (en) | 1999-12-08 | 2004-06-03 | Advanced Medicine Inc | Beta 2-adrenergic receptor agonists. |
| AU2576501A (en) | 1999-12-08 | 2001-06-18 | Advanced Medicine, Inc. | Protein kinase inhibitors |
| US6632666B2 (en) | 2000-01-14 | 2003-10-14 | Biolife Solutions, Inc. | Normothermic, hypothermic and cryopreservation maintenance and storage of cells, tissues and organs in gel-based media |
| ATE385421T1 (de) | 2000-01-21 | 2008-02-15 | Novartis Pharma Gmbh | Zusammensetzungen bestehend aus dipeptidylpeptidase-iv inhibitoren und antidiabetica |
| WO2001055147A1 (en) | 2000-01-25 | 2001-08-02 | Warner-Lambert Company | PYRIDO[2,3-d]PYRIMIDINE-2,7-DIAMINE KINASE INHIBITORS |
| SK10772002A3 (sk) | 2000-01-27 | 2004-01-08 | Warner-Lambert Company | Pyridopyrimidinónové deriváty na liečbu neurodegeneratívnych ochorení |
| US7235551B2 (en) | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| AP2002002643A0 (en) | 2000-03-06 | 2002-12-31 | Warner Lambert Co | 5-alkylpyrido[2,3-d]pyrimidines tyrosine kinase inhibitors |
| AR035205A1 (es) | 2000-09-29 | 2004-05-05 | Glaxo Group Ltd | Compuestos utiles en el tratamiento de enfermedades inflamatorias, proceso para su preparacion, intermediarios y composiciones farmaceuticas |
| AU2002248269A1 (en) | 2000-10-19 | 2002-08-12 | Smithkline Beecham Corporation | Use of p38 inhibitors for the treatment of inflammation-enhanced cough |
| AU2002246855B2 (en) | 2000-10-23 | 2005-12-22 | Smithkline Beecham Corporation | Novel compounds |
| JP2002205986A (ja) | 2000-11-08 | 2002-07-23 | Takeda Chem Ind Ltd | ピリミジン誘導体およびそれを含有する除草剤 |
| US6945422B2 (en) * | 2000-11-08 | 2005-09-20 | Delphi Technologies, Inc. | In-tank fuel line quick connector assembly |
| JP2004521892A (ja) | 2000-12-20 | 2004-07-22 | メルク エンド カムパニー インコーポレーテッド | （ハロ−ベンゾカルボニル）複素環縮合フェニル系ｐ３８キナーゼ阻害剤 |
| GB0031179D0 (en) | 2000-12-21 | 2001-01-31 | Glaxo Group Ltd | Nitric oxide synthase inhibitors |
| US6484903B2 (en) | 2001-01-09 | 2002-11-26 | Riverwood International Corporation | Carton with an improved dispensing feature in combination with a unique handle |
| GB0103630D0 (en) | 2001-02-14 | 2001-03-28 | Glaxo Group Ltd | Chemical compounds |
| AU2002258400A1 (en) | 2001-02-16 | 2002-08-28 | Tularik Inc. | Methods of using pyrimidine-based antiviral agents |
| DE10108481A1 (de) | 2001-02-22 | 2002-10-24 | Bayer Ag | Pyridylpyrimidine |
| JP2004526720A (ja) | 2001-03-08 | 2004-09-02 | グラクソ グループ リミテッド | βアドレナリン受容体のアゴニスト |
| ATE381537T1 (de) | 2001-03-22 | 2008-01-15 | Glaxo Group Ltd | Formanilid-derivative als beta2-adrenorezeptor- agonisten |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| US7105667B2 (en) | 2001-05-01 | 2006-09-12 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
| CA2450934A1 (en) | 2001-06-19 | 2002-12-27 | Marco Dodier | Pyrimidine inhibitors of phosphodiesterase (pde) 7 |
| PE20030008A1 (es) | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| ES2438985T3 (es) | 2001-09-14 | 2014-01-21 | Glaxo Group Limited | Formulación de inhalación que comprende derivados de fenetanolamina para el tratamiento de enfermedades respiratorias |
| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| JP4178783B2 (ja) | 2001-10-19 | 2008-11-12 | 三菱化学株式会社 | 光学記録媒体 |
| US6653323B2 (en) | 2001-11-13 | 2003-11-25 | Theravance, Inc. | Aryl aniline β2 adrenergic receptor agonists |
| US7019002B2 (en) | 2001-12-11 | 2006-03-28 | Pharmacia & Upjohn, S.P.A. | Pyridopyrimidinones derivatives as telomerase inhibitors |
| EP1467982B8 (en) | 2002-01-14 | 2007-04-11 | Boehringer Ingelheim Pharmaceuticals Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical formulations containing them, and uses thereof |
| CA2473886C (en) | 2002-01-22 | 2012-08-21 | The Regents Of The University Of California | Non-steroidal ligands for the glucocorticoid receptor, compositions and uses thereof |
| NZ534069A (en) | 2002-01-22 | 2007-03-30 | Warner Lambert Co | 2-(Pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-ones to be used to treat neurodegenerative disorders, viruses and cancer |
| GB0204719D0 (en) | 2002-02-28 | 2002-04-17 | Glaxo Group Ltd | Medicinal compounds |
| EP1490317A1 (en) | 2002-03-26 | 2004-12-29 | Boehringer Ingelheim Pharmaceuticals Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| JP4324480B2 (ja) | 2002-03-26 | 2009-09-02 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | グルココルチコイドミメティクス、その製法、医薬組成物、及び使用 |
| DE10215316C1 (de) | 2002-04-02 | 2003-12-18 | Schering Ag | Chinolin- und Isochinolin-Derivate, ein pharmazeutisches Mittel und ihre Verwendung als Entzündungshemmer |
| WO2003086294A2 (en) | 2002-04-11 | 2003-10-23 | Merck & Co., Inc. | 1h-benzo[f]indazol-5-yl derivatives as selective glucocorticoid receptor modulators |
| ATE381535T1 (de) | 2002-04-25 | 2008-01-15 | Glaxo Group Ltd | Phenethanolaminderivate |
| BR0309581A (pt) | 2002-05-06 | 2005-03-29 | Genelabs Tech Inc | Derivados de nucleosìdeo para tratamento de infecção por vìrus de hepatite c |
| ITBO20020304A1 (it) | 2002-05-17 | 2003-11-17 | Magneti Marelli Powertrain Spa | Nuovi condotti in materiale polimerico |
| US7186864B2 (en) | 2002-05-29 | 2007-03-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| US7074806B2 (en) | 2002-06-06 | 2006-07-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| AR040456A1 (es) * | 2002-06-27 | 2005-04-06 | Bristol Myers Squibb Co | Piridina n-oxidos 2,4 -disubstituidos utiles como inhibidores de transcriptasa inversa del virus de inmunodeficiencia humana |
| WO2004005229A1 (en) | 2002-07-08 | 2004-01-15 | Pfizer Products Inc. | Modulators of the glucocorticoid receptor |
| ATE456100T1 (de) | 2002-07-18 | 2010-02-15 | Bristol Myers Squibb Co | Zusammensetzungen und verfahren im zusammenhang mit der nuklearen hormon-rezeptor-stelle ii |
| JP2006508042A (ja) | 2002-07-18 | 2006-03-09 | ブリストル−マイヤーズ スクイブ カンパニー | グルココルチコイド受容体の修飾物質および方法 |
| GB0217225D0 (en) | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicinal compounds |
| CA2496175A1 (en) | 2002-08-21 | 2004-03-04 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted hihydroquinolines as glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| GB0220730D0 (en) | 2002-09-06 | 2002-10-16 | Glaxo Group Ltd | Medicinal compounds |
| AU2003270783C1 (en) | 2002-09-20 | 2010-05-20 | Merck Sharp & Dohme Corp. | Octahydro-2-H-naphtho[1,2-F] indole-4-carboxamide derivatives as selective glucocorticoid receptor modulators |
| AU2003298094A1 (en) | 2002-10-22 | 2004-05-13 | Glaxo Group Limited | Medicinal arylethanolamine compounds |
| DE60320007T2 (de) | 2002-10-28 | 2009-06-18 | Glaxo Group Ltd., Greenford | Phenthanolamin-Derivate zur Behandlung von Atemwegserkrankungen |
| GB0225030D0 (en) | 2002-10-28 | 2002-12-04 | Glaxo Group Ltd | Medicinal compounds |
| GB0225535D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Medicinal compounds |
| GB0225540D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Medicinal compounds |
| TW200413381A (en) | 2002-11-04 | 2004-08-01 | Hoffmann La Roche | Novel amino-substituted dihydropyrimido [4,5-d]pyrimidinone derivatives, their manufacture and use as pharmaceutical agents |
| US7384937B2 (en) | 2002-11-06 | 2008-06-10 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
| JP2004203751A (ja) | 2002-12-24 | 2004-07-22 | Pfizer Inc | 置換６，６−ヘテロ二環式誘導体 |
| EP1590341B1 (en) | 2003-01-17 | 2009-06-17 | Warner-Lambert Company LLC | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
| CA2515939A1 (en) | 2003-02-14 | 2004-09-02 | Smithkline Beecham Corporation | Novel compounds |
| US7138412B2 (en) | 2003-03-11 | 2006-11-21 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives useful as serine protease inhibitors |
| EP1636195A1 (en) | 2003-05-27 | 2006-03-22 | Pfizer Products Inc. | Quinazolines and pyrido[3,4-d]pyrimidines as receptor tyrosine kinase inhibitors |
| EP1663994B1 (en) | 2003-08-05 | 2012-03-07 | Vertex Pharmaceuticals Incorporated | Tetrahydroquinazoline compounds as inhibitors of voltage-gated ion channels |
| DE102004020908A1 (de) | 2004-04-28 | 2005-11-17 | Grünenthal GmbH | Substituierte 5,6,7,8,-Tetrahydro-pyrido[4,3-d]pyrimidin-2-yl- und 5,6,7,8,-Tetrahydro-chinazolin-2-yl-Verbindungen |
| US7098222B2 (en) | 2004-05-12 | 2006-08-29 | Abbott Laboratories | Bicyclic-substituted amines having cyclic-substituted monocyclic substituents |
| JP2008535822A (ja) | 2005-03-25 | 2008-09-04 | グラクソ グループ リミテッド | 新規化合物 |
| AU2006229995A1 (en) | 2005-03-25 | 2006-10-05 | Glaxo Group Limited | Process for preparing pyrido(2,3-d)pyrimidin-7-one and 3,4-dihydropyrimido(4,5-d)pyrimidin-2(1H)-one derivatives |
| MY145281A (en) * | 2005-03-25 | 2012-01-13 | Glaxo Group Ltd | Novel compounds |
| UY29439A1 (es) | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| WO2006127678A2 (en) | 2005-05-23 | 2006-11-30 | Smithkline Beecham Corporation | Inhibition of p38 mark for treatment of obesity |
| EP1931667A1 (en) * | 2005-09-28 | 2008-06-18 | Ranbaxy Laboratories Limited | Pyrido-pyridimidine derivatives useful as antiinflammatory agents |
| HRP20130902T1 (hr) * | 2005-10-07 | 2013-11-08 | Exelixis Inc. | PIRIDOPIRIMIDINONSKI INHIBITORI PI3Kalfa |
| PE20070823A1 (es) | 2005-11-15 | 2007-08-09 | Glaxo Group Ltd | Sal tosilato de 8-(2,6-difluorofenil)-4-(4-fluoro-2-metilfenil)-2-{[2-hidroxi-1-(hidroximetil)etil]amino}pirido[2,3-]pirimidin-7(8h)-ona |
| US20090170834A1 (en) * | 2005-12-22 | 2009-07-02 | Prolexys Pharmaceuticals, Inc. | Fused Pyrimidones and Thiopyrimidones, and Uses Thereof |
| TW200800997A (en) * | 2006-03-22 | 2008-01-01 | Astrazeneca Ab | Chemical compounds |
| CN101595109B (zh) * | 2006-11-20 | 2012-09-05 | 百时美施贵宝公司 | 作为二肽基肽酶ⅳ抑制剂的7，8-二氢-1，6-二氮杂萘-5（6h）-酮和相关二环化合物及方法 |
| WO2009132980A1 (en) * | 2008-04-29 | 2009-11-05 | F. Hoffmann-La Roche Ag | Pyrimidinyl pyridone inhibitors of jnk. |
-
2006
- 2006-03-23 MY MYPI20093567A patent/MY145281A/en unknown
- 2006-03-23 PE PE2006000330A patent/PE20061351A1/es not_active Application Discontinuation
- 2006-03-23 PE PE2010000197A patent/PE20100737A1/es not_active Application Discontinuation
- 2006-03-23 AR ARP060101147A patent/AR053346A1/es not_active Application Discontinuation
- 2006-03-23 TW TW095109978A patent/TWI389690B/zh not_active IP Right Cessation
- 2006-03-23 UY UY29440A patent/UY29440A1/es unknown
- 2006-03-23 MY MYPI20061295A patent/MY145343A/en unknown
- 2006-03-24 CN CNA2006800182268A patent/CN101258148A/zh active Pending
- 2006-03-24 WO PCT/US2006/010855 patent/WO2006104915A2/en not_active Ceased
- 2006-03-24 UA UAA200710645A patent/UA95444C2/ru unknown
- 2006-03-24 AU AU2006229993A patent/AU2006229993B2/en not_active Ceased
- 2006-03-24 EP EP11176337A patent/EP2436686A1/en not_active Withdrawn
- 2006-03-24 SG SG201007027-4A patent/SG166771A1/en unknown
- 2006-03-24 EA EA200702071A patent/EA012875B1/ru not_active IP Right Cessation
- 2006-03-24 KR KR1020077021881A patent/KR101235497B1/ko not_active Expired - Fee Related
- 2006-03-24 JP JP2008503238A patent/JP5037487B2/ja not_active Expired - Fee Related
- 2006-03-24 CN CN2012102458960A patent/CN102746301A/zh active Pending
- 2006-03-24 ES ES11176338T patent/ES2426251T3/es not_active Expired - Lifetime
- 2006-03-24 NZ NZ561237A patent/NZ561237A/en not_active IP Right Cessation
- 2006-03-24 BR BRPI0609437-6A patent/BRPI0609437A2/pt not_active IP Right Cessation
- 2006-03-24 US US11/908,440 patent/US8207176B2/en not_active Expired - Fee Related
- 2006-03-24 CN CN201210245827XA patent/CN102746299A/zh active Pending
- 2006-03-24 ES ES06748672T patent/ES2398246T3/es not_active Expired - Lifetime
- 2006-03-24 US US11/388,968 patent/US7678801B2/en not_active Expired - Fee Related
- 2006-03-24 CA CA2602553A patent/CA2602553C/en not_active Expired - Fee Related
- 2006-03-24 EP EP06748672A patent/EP1868611B1/en not_active Expired - Lifetime
- 2006-03-24 MX MX2007011856A patent/MX2007011856A/es active IP Right Grant
- 2006-03-24 EP EP11176338.9A patent/EP2447266B1/en not_active Expired - Lifetime
- 2006-03-24 CN CN2012102458299A patent/CN102746300A/zh active Pending
-
2007
- 2007-09-03 ZA ZA200707564A patent/ZA200707564B/xx unknown
- 2007-09-10 IL IL185870A patent/IL185870A/en not_active IP Right Cessation
- 2007-09-24 MA MA30237A patent/MA29341B1/fr unknown
- 2007-10-15 NO NO20075275A patent/NO20075275L/no not_active Application Discontinuation
-
2008
- 2008-06-04 US US12/132,793 patent/US8354416B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8354416B2 (en) | 7,8-dihydropyrido[2,3-d]pyrimidin-4-yl substituted compounds as inhibitors of p38 kinase | |
| US20100093766A1 (en) | Novel compounds | |
| US20090005401A1 (en) | Novel Compounds | |
| US20100144755A1 (en) | Novel Compounds | |
| JP2009542818A (ja) | 新規化合物 | |
| HK1111422B (en) | 8-phenyl-7,8-dihydropyrido[2,3-d]pyrimidin-7-ones |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081210 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081210 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091119 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111115 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120215 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120222 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20120309 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120315 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120323 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120416 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120423 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120514 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120605 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120704 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150713 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |