KR100749566B1 - Alk5 및/또는 alk4 억제제로 유효한 2-피리딜이치환된 이미다졸 유도체 - Google Patents
Alk5 및/또는 alk4 억제제로 유효한 2-피리딜이치환된 이미다졸 유도체 Download PDFInfo
- Publication number
- KR100749566B1 KR100749566B1 KR1020040027591A KR20040027591A KR100749566B1 KR 100749566 B1 KR100749566 B1 KR 100749566B1 KR 1020040027591 A KR1020040027591 A KR 1020040027591A KR 20040027591 A KR20040027591 A KR 20040027591A KR 100749566 B1 KR100749566 B1 KR 100749566B1
- Authority
- KR
- South Korea
- Prior art keywords
- group
- imidazol
- benzamide
- quinoxalin
- methyl
- Prior art date
Links
- -1 2-PYRIDYL Chemical group 0.000 title abstract description 31
- 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 title abstract description 24
- 102100034134 Activin receptor type-1B Human genes 0.000 title abstract description 21
- 239000003112 inhibitor Substances 0.000 title description 4
- 150000002460 imidazoles Chemical class 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 15
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 82
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 56
- 239000000126 substance Substances 0.000 claims description 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 206010016654 Fibrosis Diseases 0.000 claims description 17
- 230000004761 fibrosis Effects 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 206010052428 Wound Diseases 0.000 claims description 6
- 208000027418 Wounds and injury Diseases 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 5
- 125000004419 alkynylene group Chemical group 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 4
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- SJSMOYGIHVJAIM-UHFFFAOYSA-N 4-[3-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]propyl]benzonitrile Chemical compound CC1=CC=CC(C2=C(N=C(CCCC=3C=CC(=CC=3)C#N)N2)C=2C=C3OCOC3=CC=2)=N1 SJSMOYGIHVJAIM-UHFFFAOYSA-N 0.000 claims description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 206010039710 Scleroderma Diseases 0.000 claims description 3
- 208000002847 Surgical Wound Diseases 0.000 claims description 3
- 206010057469 Vascular stenosis Diseases 0.000 claims description 3
- 230000009787 cardiac fibrosis Effects 0.000 claims description 3
- 210000004207 dermis Anatomy 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 230000001969 hypertrophic effect Effects 0.000 claims description 3
- 201000001881 impotence Diseases 0.000 claims description 3
- 230000002458 infectious effect Effects 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 231100000614 poison Toxicity 0.000 claims description 3
- 230000000750 progressive effect Effects 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 239000003440 toxic substance Substances 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- RWHPWZMVKYEXTO-UHFFFAOYSA-N 3-[[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]methyl]benzonitrile Chemical compound CC1=CC=CC(C2=C(N=C(CC=3C=C(C=CC=3)C#N)N2)C=2C=C3OCOC3=CC=2)=N1 RWHPWZMVKYEXTO-UHFFFAOYSA-N 0.000 claims description 2
- RYKSGWSKILPDDY-UHFFFAOYSA-N 3-[[5-(6-methylpyridin-2-yl)-4-quinoxalin-6-yl-1h-imidazol-2-yl]methyl]benzamide Chemical compound CC1=CC=CC(C2=C(N=C(CC=3C=C(C=CC=3)C(N)=O)N2)C=2C=C3N=CC=NC3=CC=2)=N1 RYKSGWSKILPDDY-UHFFFAOYSA-N 0.000 claims description 2
- VZXJZMWRNFVXEG-UHFFFAOYSA-N 4-[2-[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]ethyl]benzonitrile Chemical compound CC1=CC=CC(C2=C(N=C(CCC=3C=CC(=CC=3)C#N)N2)C=2C=C3OCOC3=CC=2)=N1 VZXJZMWRNFVXEG-UHFFFAOYSA-N 0.000 claims description 2
- HVULDQJYDNNWIM-UHFFFAOYSA-N 4-[[4-(1,3-benzodioxol-5-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]methyl]benzonitrile Chemical compound CC1=CC=CC(C2=C(N=C(CC=3C=CC(=CC=3)C#N)N2)C=2C=C3OCOC3=CC=2)=N1 HVULDQJYDNNWIM-UHFFFAOYSA-N 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 2
- 208000034189 Sclerosis Diseases 0.000 claims description 2
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 230000006510 metastatic growth Effects 0.000 claims description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 abstract description 27
- 108090001012 Transforming Growth Factor beta Proteins 0.000 abstract description 27
- 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 abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 15
- 230000002401 inhibitory effect Effects 0.000 abstract description 14
- 108020003175 receptors Proteins 0.000 abstract description 14
- 108010059616 Activins Proteins 0.000 abstract description 13
- 102000005606 Activins Human genes 0.000 abstract description 13
- 239000000488 activin Substances 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 13
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 239000000460 chlorine Substances 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 239000012141 concentrate Substances 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 10
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 9
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 102000049939 Smad3 Human genes 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 210000002744 extracellular matrix Anatomy 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 7
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 7
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 230000026731 phosphorylation Effects 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 5
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 208000017169 kidney disease Diseases 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 238000011552 rat model Methods 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- 206010019668 Hepatic fibrosis Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108700031297 Smad3 Proteins 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 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
- 239000006071 cream Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 125000005456 glyceride group Chemical group 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 3
- 239000004973 liquid crystal related substance Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- LPAPKMWNCWXGCP-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione Chemical compound CC1=CC=CC(C(=O)C(=O)C=2C=C3OCOC3=CC=2)=N1 LPAPKMWNCWXGCP-UHFFFAOYSA-N 0.000 description 2
- SGTRXCNZQBBJNN-UHFFFAOYSA-N 4-(3-oxopropyl)benzamide Chemical compound NC(=O)C1=CC=C(CCC=O)C=C1 SGTRXCNZQBBJNN-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 2
- 208000028006 Corneal injury Diseases 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 208000005777 Lupus Nephritis Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 description 2
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 101150052863 THY1 gene Proteins 0.000 description 2
- 108020004566 Transfer RNA Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 206010069351 acute lung injury Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000004658 aryl carbonyl amino group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000001434 glomerular Effects 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 230000002008 hemorrhagic effect Effects 0.000 description 2
- 208000027700 hepatic dysfunction Diseases 0.000 description 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 description 2
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 208000005987 polymyositis Diseases 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000011555 rabbit model Methods 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical group NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea group Chemical group NC(=S)N UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- GKTFLKJXZOYBRW-UHFFFAOYSA-N 2-ethylbenzamide Chemical compound CCC1=CC=CC=C1C(N)=O GKTFLKJXZOYBRW-UHFFFAOYSA-N 0.000 description 1
- PRRPUEWAMYRKPC-UHFFFAOYSA-N 2-hydroxyiminoacetaldehyde Chemical compound ON=CC=O PRRPUEWAMYRKPC-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- ADLIBSBJYAKITA-UHFFFAOYSA-N 3-(2-oxoethyl)benzonitrile Chemical compound O=CCC1=CC=CC(C#N)=C1 ADLIBSBJYAKITA-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
- BTDMXRCUNUVYDT-UHFFFAOYSA-N 4-(2-oxoethyl)benzonitrile Chemical compound O=CCC1=CC=C(C#N)C=C1 BTDMXRCUNUVYDT-UHFFFAOYSA-N 0.000 description 1
- KXQGRCMHTJUCJB-UHFFFAOYSA-N 4-(4-oxobutyl)benzonitrile Chemical compound O=CCCCC1=CC=C(C#N)C=C1 KXQGRCMHTJUCJB-UHFFFAOYSA-N 0.000 description 1
- WPDMOEYSPGGFNA-UHFFFAOYSA-N 4-[2-(1,3-dioxolan-2-yl)ethyl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1CCC1OCCO1 WPDMOEYSPGGFNA-UHFFFAOYSA-N 0.000 description 1
- WDWWIUCBOYJZGP-UHFFFAOYSA-N 4-[2-(1,3-dioxolan-2-yl)ethyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CCC1OCCO1 WDWWIUCBOYJZGP-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010058667 Oral toxicity Diseases 0.000 description 1
- 206010034650 Peritoneal adhesions Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
- 101100437153 Rattus norvegicus Acvr2b gene Proteins 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 102000007374 Smad Proteins Human genes 0.000 description 1
- 108010007945 Smad Proteins Proteins 0.000 description 1
- 102000057208 Smad2 Human genes 0.000 description 1
- 108700032504 Smad2 Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 description 1
- 102000004060 Transforming Growth Factor-beta Type II Receptor Human genes 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 201000008244 anti-basement membrane glomerulonephritis Diseases 0.000 description 1
- 239000010425 asbestos Substances 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
- 238000003556 assay Methods 0.000 description 1
- 230000003140 astrocytic effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 150000001602 bicycloalkyls Chemical group 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000005622 butynylene group Chemical group 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000004024 hepatic stellate cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical class OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000007422 luminescence assay Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 230000001338 necrotic effect Effects 0.000 description 1
- 238000013059 nephrectomy Methods 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 231100000418 oral toxicity Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic 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
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 206010035653 pneumoconiosis Diseases 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000026341 positive regulation of angiogenesis Effects 0.000 description 1
- 230000030795 positive regulation of cellular component movement Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 201000008171 proliferative glomerulonephritis Diseases 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical group CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 239000001944 prunus armeniaca kernel oil Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000037390 scarring Effects 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
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 210000005233 tubule cell Anatomy 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- 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
- A61P27/02—Ophthalmic 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Manufacturing & Machinery (AREA)
- Ceramic Engineering (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Materials Engineering (AREA)
- Structural Engineering (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
Abstract
Description
Claims (11)
- 다음 화학식 1로 표시되는 화합물 또는 이의 약제학적으로 허용 가능한 염 :[화학식 1]상기 화학식 1에서,R1은 치환 또는 비치환된 페닐기, 치환 또는 비치환된 나프틸기, 또는 치환 또는 비치환된 안트라세닐기이고, 상기 치환체는 할로겐원자, -O-C1-6알킬기, -S-C1-6알킬기, C1-6알킬기, C1-6할로알킬기, -O-(CH2)n-Ph, -S-(CH2)n-Ph, 시아노기, 페닐기, 및 CO2R (이때, R은 수소원자 또는 C1-6알킬기이고, n은 0 또는 1 내지 3 의 정수임)로 구성된 군으로부터 선택된 1종 이상일 수 있고; 또는 R1은 5 내지 7원의 방향족 또는 비방향족 싸이클릭 고리로 융합된 페닐기 또는 피리딜기이고, 이때 싸이클릭 고리는 N, O 및 S로부터 독립적으로 선택된 3종 이하의 헤테로원자를 함유할 수 있고, 상기 헤테로원자 N은 C1-6알킬기로 치환될 수 있으며, 또는 상기 싸이클릭 고리는 =O로 치환될 수 있고;R2는 수소원자, C1-6알킬기, C1-6알콕시기, 페닐기, C1-6할로알킬기, NH2, NH(CH2)n-Ph, NH-C1-6알킬기, 할로겐원자, 시아노기, 니트로기, CONHR, 또는 SO2NHR 이고 (이때,R은 수소원자 또는 C1-6알킬기이고, n은 0 또는 1내지 3 의 정수임);R3은 수소원자, C1-6알킬기, C3-7싸이클로알킬기, -(CH2) p-NO2, -(CH2)p-NR4R5, -(CH2)p-CHO, -(CH2)p-CONHOH, -(CH2)p -CN, -(CH2)p-CO2H, -(CH2)p-CO2 R4, -(CH2)p-CONR4R5, -(CH2)p-테트라졸, -(CH2)p -COR4, -(CH2)q-(OR6)2, -(CH2 )p-OR4, -(CH2)p-CH=CH-CN, -(CH2)p-CH=CH-CO2H, -(CH2)p-CH=CH-CO 2R4, -(CH2)p-CH=CH-CONR4R5, -(CH 2)p-NHCOR4, -(CH2)p-NHCO2R4, -(CH2) p-CONHSO2R4, -(CH2)p-NHSO2R 4, 또는 -(CH2)p-CH=CH-테트라졸이고;R4 및 R5는 각각 수소원자, 또는 C1-6알킬기이고;R6은 C1-6알킬기이고;p는 0 또는 1 내지 4의 정수이고;q는 1 내지 4의 정수이고;X는 C1-10알킬렌기, C2-10알케닐렌기, 또는 C2-10알키닐렌기이고;A1과 A2 둘 중의 하나는 N이고, 다른 하나는 NR7이고; 및R7은 수소원자, 하이드록시기, C1-6알킬기, 또는 C3-7싸이클로알킬기이다.
- 제 1 항에 있어서,상기 R1은 할로겐원자, C1-6알콕시기, C1-6알킬티오기, 및 페닐기 중에서 선택된 하나 또는 그 이상의 치환체로 치환 또는 비치환된 페닐기; 또는 R1은 5 내지 7원의 방향족 또는 비방향족 싸이클릭 고리로 융합된 페닐기이고, 이때 싸이클릭 고리는 N, O 및 S로부터 독립적으로 선택된 2종 이하의 헤테로원자를 함유할 수 있고, 상기 헤테로원자 N은 C1-6알킬기로 치환될 수 있으며, 또는 상기 싸이클릭 고리는 =O로 치환될 수 있고;R2는 수소원자 이외의 치환체로서, 상기 치환체는 피리딘 고리 질소의 오르쏘-위치에 치환되고;R3은 -(CH2)p-CONHOH, -(CH2)p-CN, -(CH2 )p-CO2H, -(CH2)p-CONR4R5, 또는 -(CH2)p-테트라졸기 이고;R4 및 R5는 각각 수소원자, 또는 C1-3알킬기 이고;p is 0, 1, 또는 2 이고;X is C1-6알킬렌기 이고; 및A1과 A2 둘 중의 하나는 N이고, 다른 하나는 NR7 (이때 R7은 수소원자)인 것임을 특징으로 하는 화합물.
- 제 1 항에 있어서, 상기 화학식 1로 표시되는 화합물이4-((4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)메틸)벤조니트릴;4-((4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;3-((4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)메틸)벤조니트릴;3-((4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;4-(2-(4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)에틸)벤조니트릴;4-(2-(4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;4-(3-(4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)프로필)벤조니트릴;4-(3-(4-(벤조[1,3]디옥솔-5-일)-5-(6-메틸피리딘-2-일)-1H-이미다졸-2-일)프로필)벤즈아마이드;4-((5-(6-메틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈 아마이드;4-((5-(6-에틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;4-((5-(6-n-프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;4-((5-(6-이소프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;4-((5-(6-n-부틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;3-((5-(6-메틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;3-((5-(6-에틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;3-((5-(6-n-프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;3-((5-(6-이소프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;3-((5-(6-n-부틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)메틸)벤즈아마이드;4-(2-(5-(6-메틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤 즈아마이드;4-(2-(5-(6-에틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;4-(2-(5-(6-n-프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;4-(2-(5-(6-이소프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;4-(2-(5-(6-n-부틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;3-(2-(5-(6-메틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;3-(2-(5-(6-에틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;3-(2-(5-(6-n-프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;3-(2-(5-(6-이소프로필피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드;3-(2-(5-(6-n-부틸피리딘-2-일)-4-(퀴녹사린-6-일)-1H-이미다졸-2-일)에틸)벤즈아마이드; 및이의 약제학적으로 허용 가능한 염 중에서 선택되는 것을 특징으로 하는 화 합물.
- 상기 청구항 1, 2 또는 3에서 정의된 화합물, 약제학적으로 허용 가능한 이의 염, 또는 이의 용매화물이 함유되어,신장 간극 섬유증, 약으로 인한 합병증에 의한 섬유증, 모든 병인에 의한 간 섬유증, 폐 섬유증, 감염성 있는 또는 독성 물질에 의한 특발성 폐 섬유증, 심근경색 후 심장 섬유증, 혈관 협착증, 재발협착증, 외상 또는 수술상 상처를 치료하는 동안에 발생하는 진피에 과도한 또는 비대성 상처 또는 케로이드의 형성, 피부경화증, 섬유경화증, 진행성 조직 경화증, 남성 발기 부전, 종양 전이 성장, 방사능에 의한 섬유증의 치료 및 예방에 유효한 약제조성물.
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
Priority Applications (18)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020040027591A KR100749566B1 (ko) | 2004-04-21 | 2004-04-21 | Alk5 및/또는 alk4 억제제로 유효한 2-피리딜이치환된 이미다졸 유도체 |
US10/983,227 US7407958B2 (en) | 2004-04-21 | 2004-11-08 | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
PCT/KR2004/002891 WO2005103028A1 (en) | 2004-04-21 | 2004-11-09 | 2-pyridyl substituted imidazoles as alk5 and/or alk4 inhibitors |
MXPA06012096A MXPA06012096A (es) | 2004-04-21 | 2004-11-09 | Imidazoles 2- piridil-sustituidos como inhibidores de alk5 y/o alk4. |
RU2006140989/04A RU2348626C2 (ru) | 2004-04-21 | 2004-11-09 | 2-пиридилзамещенные имидазолы как ингибиторы рецепторов alk5 и/или alk4 |
CA2564442A CA2564442C (en) | 2004-04-21 | 2004-11-09 | 2-pyridyl substituted imidazoles as alk5 and/or alk4 inhibitors |
CN2004800433657A CN1972921B (zh) | 2004-04-21 | 2004-11-09 | 作为alk5和/或alk4抑制剂的2-吡啶基取代的咪唑 |
BRPI0418765A BRPI0418765B8 (pt) | 2004-04-21 | 2004-11-09 | composto da fórmula (i) e composição farmacêutica |
AU2004318777A AU2004318777B2 (en) | 2004-04-21 | 2004-11-09 | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
EP04800071A EP1620426A1 (en) | 2004-04-21 | 2004-11-09 | 2-pyridyl substituted imidazoles as alk5 and/or alk4 inhibitors |
JP2007509388A JP4678540B2 (ja) | 2004-04-21 | 2004-11-09 | Alk5及び/又はalk4の抑制剤としての2−ピリジル置換イミダゾール類 |
IL178757A IL178757A (en) | 2004-04-21 | 2006-10-19 | Imidazoles are converted to 2-pyridyl as 5ALK and / or 4ALK inhibitors |
NO20064771A NO20064771L (no) | 2004-04-21 | 2006-10-19 | 2-pyridyl substituerte imidazoler som ALK5 og/eller ALK4 inhibitorer |
ZA200609626A ZA200609626B (en) | 2004-04-21 | 2006-11-20 | 2-pyridyl substituted Imidazoles as ALK5 and/or ALK4 Inhibitors |
US12/155,984 US20080319012A1 (en) | 2004-04-21 | 2008-06-12 | 2-Pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
US12/155,989 US8420685B2 (en) | 2004-04-21 | 2008-06-12 | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
US12/457,479 US8410146B2 (en) | 2004-04-21 | 2009-06-11 | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
US13/067,737 US20130245066A1 (en) | 2004-04-21 | 2011-06-22 | 2-Pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020040027591A KR100749566B1 (ko) | 2004-04-21 | 2004-04-21 | Alk5 및/또는 alk4 억제제로 유효한 2-피리딜이치환된 이미다졸 유도체 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20050102752A KR20050102752A (ko) | 2005-10-27 |
KR100749566B1 true KR100749566B1 (ko) | 2007-08-16 |
Family
ID=35196912
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020040027591A KR100749566B1 (ko) | 2004-04-21 | 2004-04-21 | Alk5 및/또는 alk4 억제제로 유효한 2-피리딜이치환된 이미다졸 유도체 |
Country Status (14)
Country | Link |
---|---|
US (1) | US7407958B2 (ko) |
EP (1) | EP1620426A1 (ko) |
JP (1) | JP4678540B2 (ko) |
KR (1) | KR100749566B1 (ko) |
CN (1) | CN1972921B (ko) |
AU (1) | AU2004318777B2 (ko) |
BR (1) | BRPI0418765B8 (ko) |
CA (1) | CA2564442C (ko) |
IL (1) | IL178757A (ko) |
MX (1) | MXPA06012096A (ko) |
NO (1) | NO20064771L (ko) |
RU (1) | RU2348626C2 (ko) |
WO (1) | WO2005103028A1 (ko) |
ZA (1) | ZA200609626B (ko) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20110022662A (ko) * | 2008-06-12 | 2011-03-07 | 에스케이케미칼주식회사 | Alk5 및/또는 alk4 저해제로서의 2-피리딜이 치환된 이미다졸 화합물 |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8420685B2 (en) * | 2004-04-21 | 2013-04-16 | Sk Chemicals Co., Ltd. | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
US8410146B2 (en) * | 2004-04-21 | 2013-04-02 | Sk Chemicals Co., Ltd. | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors |
BRPI0607639B1 (pt) | 2005-02-08 | 2022-04-05 | Genzyme Corporation | Moléculas de anticorpo humano ou fragmento de ligação a antígeno das mesmas que se ligam e neutralizam tgf-beta1, 2 e 3, uso das mesmas e composição farmacêutica |
JP5384611B2 (ja) * | 2008-03-21 | 2014-01-08 | ノバルティス アーゲー | 新規ヘテロ環式化合物およびそれらの使用 |
US8865732B2 (en) | 2008-03-21 | 2014-10-21 | Novartis Ag | Heterocyclic compounds and uses thereof |
EP2299812B1 (en) * | 2008-05-27 | 2017-07-12 | Yale University | Targeting tgf-beta as a therapy for alzheimer's disease |
EP2285380A4 (en) * | 2008-05-30 | 2012-03-14 | Summa Health Systems Llc | METHODS OF USING TGF-B RECEPTOR INHIBITORS OR ACTIVE KINASE (ALK) A-83-01 AND SB-431542 INHIBITORS TO TREAT EYE DISEASE AND INJURY HEALING |
US8513222B2 (en) | 2010-06-29 | 2013-08-20 | EWHA University—Industry Collaboration Foundation | Methods of treating fibrosis, cancer and vascular injuries |
USRE47141E1 (en) | 2010-06-29 | 2018-11-27 | EWHA University—Industry Collaboration Foundation | Methods of treating fibrosis, cancer and vascular injuries |
US8080568B1 (en) | 2010-06-29 | 2011-12-20 | Ewha University - Industry Collaboration Foundation | 2-pyridyl substituted imidazoles as therapeutic ALK5 and/or ALK4 inhibitors |
US9782452B2 (en) | 2011-11-22 | 2017-10-10 | Cornell University | Methods for stimulating hematopoietic recovery by inhibiting TGFβ signaling |
RU2475243C1 (ru) * | 2012-02-16 | 2013-02-20 | Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | Средство, обладающее антигипертензивной активностью |
US9242969B2 (en) | 2013-03-14 | 2016-01-26 | Novartis Ag | Biaryl amide compounds as kinase inhibitors |
UY36294A (es) | 2014-09-12 | 2016-04-29 | Novartis Ag | Compuestos y composiciones como inhibidores de quinasa |
KR102434226B1 (ko) | 2016-06-30 | 2022-08-19 | 한미약품 주식회사 | Alk5 억제제로서의 신규 피라졸 유도체 및 이의 용도 |
MX2019003095A (es) | 2016-09-19 | 2019-07-04 | Novartis Ag | Combinaciones terapeuticas que comprenden un inhibidor de raf y un inhibidor de erk. |
JP7309614B2 (ja) | 2017-05-02 | 2023-07-18 | ノバルティス アーゲー | 組み合わせ療法 |
CN110066277B (zh) * | 2018-01-24 | 2021-07-23 | 上海璎黎药业有限公司 | 芳香杂环取代烯烃化合物、其制备方法、药物组合物和应用 |
EP4087657A1 (en) | 2020-01-08 | 2022-11-16 | Synthis Therapeutics, Inc. | Alk5 inhibitor conjugates and uses thereof |
CN112266378B (zh) * | 2020-11-09 | 2021-10-12 | 延边大学 | 含吲唑结构的咪唑类衍生物及其制备方法和应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000061576A1 (en) * | 1999-04-09 | 2000-10-19 | Smithkline Beecham Corporation | Triarylimidazoles |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5656644A (en) * | 1994-07-20 | 1997-08-12 | Smithkline Beecham Corporation | Pyridyl imidazoles |
CO5271680A1 (es) * | 2000-02-21 | 2003-04-30 | Smithkline Beecham Corp | Compuestos |
GB0007405D0 (en) * | 2000-03-27 | 2000-05-17 | Smithkline Beecham Corp | Compounds |
WO2002096875A1 (en) | 2001-05-25 | 2002-12-05 | Mochida Pharmaceutical Co., Ltd. | 4-hydroxpiperidine derivative with analgetic activity |
JP2003040888A (ja) * | 2001-07-30 | 2003-02-13 | Sankyo Co Ltd | イミダゾール誘導体 |
GB0218079D0 (en) * | 2002-08-03 | 2002-09-11 | Boatman Peter J | A pipe and pipe assembly |
AU2003263404A1 (en) * | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Novel imidazole compounds as transforming growth factor (tgf) inhibitors |
WO2005063716A1 (en) * | 2003-12-22 | 2005-07-14 | Janssen Pharmaceutica, N.V. | Imidazoles and their use cck-1 receptor modulators |
-
2004
- 2004-04-21 KR KR1020040027591A patent/KR100749566B1/ko active IP Right Grant
- 2004-11-08 US US10/983,227 patent/US7407958B2/en active Active - Reinstated
- 2004-11-09 WO PCT/KR2004/002891 patent/WO2005103028A1/en active Application Filing
- 2004-11-09 RU RU2006140989/04A patent/RU2348626C2/ru active
- 2004-11-09 CN CN2004800433657A patent/CN1972921B/zh active Active
- 2004-11-09 AU AU2004318777A patent/AU2004318777B2/en not_active Ceased
- 2004-11-09 MX MXPA06012096A patent/MXPA06012096A/es active IP Right Grant
- 2004-11-09 JP JP2007509388A patent/JP4678540B2/ja not_active Expired - Fee Related
- 2004-11-09 BR BRPI0418765A patent/BRPI0418765B8/pt not_active IP Right Cessation
- 2004-11-09 EP EP04800071A patent/EP1620426A1/en not_active Withdrawn
- 2004-11-09 CA CA2564442A patent/CA2564442C/en active Active
-
2006
- 2006-10-19 NO NO20064771A patent/NO20064771L/no not_active Application Discontinuation
- 2006-10-19 IL IL178757A patent/IL178757A/en active IP Right Grant
- 2006-11-20 ZA ZA200609626A patent/ZA200609626B/xx unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000061576A1 (en) * | 1999-04-09 | 2000-10-19 | Smithkline Beecham Corporation | Triarylimidazoles |
Non-Patent Citations (1)
Title |
---|
국제공개특허공보 제00/61576호 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20110022662A (ko) * | 2008-06-12 | 2011-03-07 | 에스케이케미칼주식회사 | Alk5 및/또는 alk4 저해제로서의 2-피리딜이 치환된 이미다졸 화합물 |
KR101654859B1 (ko) | 2008-06-12 | 2016-09-07 | 에스케이케미칼주식회사 | Alk5 및/또는 alk4 저해제로서의 2-피리딜이 치환된 이미다졸 화합물 |
Also Published As
Publication number | Publication date |
---|---|
CA2564442A1 (en) | 2005-11-03 |
CA2564442C (en) | 2011-06-14 |
AU2004318777A1 (en) | 2005-11-03 |
CN1972921A (zh) | 2007-05-30 |
EP1620426A1 (en) | 2006-02-01 |
IL178757A (en) | 2011-08-31 |
US20050261299A1 (en) | 2005-11-24 |
RU2006140989A (ru) | 2008-05-27 |
IL178757A0 (en) | 2007-02-11 |
ZA200609626B (en) | 2008-08-27 |
BRPI0418765B8 (pt) | 2021-05-25 |
CN1972921B (zh) | 2012-01-04 |
JP4678540B2 (ja) | 2011-04-27 |
AU2004318777B2 (en) | 2008-10-16 |
WO2005103028A1 (en) | 2005-11-03 |
MXPA06012096A (es) | 2007-11-20 |
NO20064771L (no) | 2007-01-19 |
RU2348626C2 (ru) | 2009-03-10 |
BRPI0418765A (pt) | 2007-10-09 |
US7407958B2 (en) | 2008-08-05 |
KR20050102752A (ko) | 2005-10-27 |
BRPI0418765B1 (pt) | 2019-06-04 |
JP2007533734A (ja) | 2007-11-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100749566B1 (ko) | Alk5 및/또는 alk4 억제제로 유효한 2-피리딜이치환된 이미다졸 유도체 | |
RU2612958C2 (ru) | 2-пиридилзамещенные имидазолы в качестве ингибиторов alk5 и/или alk4 | |
KR101654859B1 (ko) | Alk5 및/또는 alk4 저해제로서의 2-피리딜이 치환된 이미다졸 화합물 | |
US8410146B2 (en) | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors | |
US8420685B2 (en) | 2-pyridyl substituted imidazoles as ALK5 and/or ALK4 inhibitors | |
KR20040094462A (ko) | 피리디닐[1,2,4]트리아졸 유도체 | |
KR20040094461A (ko) | 피리디닐[1,2,3]트리아졸 유도체 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E90F | Notification of reason for final refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
G170 | Re-publication after modification of scope of protection [patent] | ||
FPAY | Annual fee payment |
Payment date: 20120720 Year of fee payment: 6 |
|
FPAY | Annual fee payment |
Payment date: 20130719 Year of fee payment: 7 |
|
FPAY | Annual fee payment |
Payment date: 20140721 Year of fee payment: 8 |
|
FPAY | Annual fee payment |
Payment date: 20150721 Year of fee payment: 9 |
|
FPAY | Annual fee payment |
Payment date: 20160722 Year of fee payment: 10 |
|
FPAY | Annual fee payment |
Payment date: 20170809 Year of fee payment: 11 |
|
FPAY | Annual fee payment |
Payment date: 20190701 Year of fee payment: 13 |