KR20040111491A - 자가면역 질환 치료용（3－（2－에틸페닐）－5－메톡시페닐）－1ｈ－［1，2，4］－트리아졸의 용도 - Google Patents
자가면역 질환 치료용（3－（2－에틸페닐）－5－메톡시페닐）－1ｈ－［1，2，4］－트리아졸의 용도 Download PDFInfo
- Publication number
- KR20040111491A KR20040111491A KR10-2004-7015884A KR20047015884A KR20040111491A KR 20040111491 A KR20040111491 A KR 20040111491A KR 20047015884 A KR20047015884 A KR 20047015884A KR 20040111491 A KR20040111491 A KR 20040111491A
- Authority
- KR
- South Korea
- Prior art keywords
- cells
- ethylphenyl
- methoxyphenyl
- triazole
- cell
- 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.)
- Ceased
Links
- 208000023275 Autoimmune disease Diseases 0.000 title claims abstract description 7
- NAUNDFHXCIMBKS-UHFFFAOYSA-N 1-[3-(2-ethylphenyl)-5-methoxyphenyl]-1,2,4-triazole Chemical compound CCC1=CC=CC=C1C1=CC(OC)=CC(N2N=CN=C2)=C1 NAUNDFHXCIMBKS-UHFFFAOYSA-N 0.000 title claims description 16
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 62
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 28
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 5
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract description 3
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 3
- 206010046851 Uveitis Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 24
- 238000000034 method Methods 0.000 abstract description 11
- -1 3- (2-ethylphenyl) -5-methoxyphenyl Chemical group 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 52
- NUHSROFQTUXZQQ-UHFFFAOYSA-N isopentenyl diphosphate Chemical compound CC(=C)CCO[P@](O)(=O)OP(O)(O)=O NUHSROFQTUXZQQ-UHFFFAOYSA-N 0.000 description 20
- 102000004127 Cytokines Human genes 0.000 description 18
- 108090000695 Cytokines Proteins 0.000 description 18
- 230000005764 inhibitory process Effects 0.000 description 16
- 239000000427 antigen Substances 0.000 description 15
- 102000036639 antigens Human genes 0.000 description 15
- 108091007433 antigens Proteins 0.000 description 15
- 108091008874 T cell receptors Proteins 0.000 description 12
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 12
- 241000700159 Rattus Species 0.000 description 10
- 230000004044 response Effects 0.000 description 9
- 239000000839 emulsion Substances 0.000 description 8
- 101100181107 Homo sapiens KLRB1 gene Proteins 0.000 description 7
- 108010074328 Interferon-gamma Proteins 0.000 description 7
- 102100023678 Killer cell lectin-like receptor subfamily B member 1 Human genes 0.000 description 7
- 101150033443 Klrb1a gene Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000033289 adaptive immune response Effects 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 102100037850 Interferon gamma Human genes 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 230000015788 innate immune response Effects 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 239000008159 sesame oil Substances 0.000 description 6
- 235000011803 sesame oil Nutrition 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 201000002491 encephalomyelitis Diseases 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102000006386 Myelin Proteins Human genes 0.000 description 4
- 108010083674 Myelin Proteins Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 230000003915 cell function Effects 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 206010014599 encephalitis Diseases 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 210000005012 myelin Anatomy 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 3
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000002254 contraceptive effect Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- 102000047918 Myelin Basic Human genes 0.000 description 2
- 101710107068 Myelin basic protein Proteins 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 201000004982 autoimmune uveitis Diseases 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000010595 endothelial cell migration Effects 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000011694 lewis rat Methods 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 231100000065 noncytotoxic Toxicity 0.000 description 2
- 230000002020 noncytotoxic effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 238000010186 staining 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
- 230000002588 toxic effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 208000008822 Ankylosis Diseases 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108700012434 CCL3 Proteins 0.000 description 1
- 102000000013 Chemokine CCL3 Human genes 0.000 description 1
- 102000001326 Chemokine CCL4 Human genes 0.000 description 1
- 108010055165 Chemokine CCL4 Proteins 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 241000589601 Francisella Species 0.000 description 1
- 108700029228 Immunoglobulin Heavy Chain Genes Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 206010023198 Joint ankylosis 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
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000006470 autoimmune attack Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 1
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 238000012926 crystallographic analysis Methods 0.000 description 1
- 238000012866 crystallographic experiment Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical group [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 238000012137 double-staining Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000001048 lympholytic effect Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000006764 neuronal dysfunction Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 108010089193 pattern recognition receptors Proteins 0.000 description 1
- 102000007863 pattern recognition receptors Human genes 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- PBJCQAMKPSRWKL-UHFFFAOYSA-N phosphono pyren-1-yl hydrogen phosphate Chemical class C1=C2C(OP(O)(=O)OP(O)(=O)O)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 PBJCQAMKPSRWKL-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 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 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000013334 tissue model Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
Classifications
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/137,699 US6797722B2 (en) | 2002-05-03 | 2002-05-03 | Use of 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole for the treatment of autoimmune diseases |
| US10/137,699 | 2002-05-03 | ||
| PCT/IT2003/000237 WO2003092681A1 (en) | 2002-05-03 | 2003-04-15 | Use of (3-(2-ethylphenyl)-5-methoxyphenyl)-1h-[1,2,4]-triazole for the treatment of autoimmune diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20040111491A true KR20040111491A (ko) | 2004-12-31 |
Family
ID=29269138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2004-7015884A Ceased KR20040111491A (ko) | 2002-05-03 | 2003-04-15 | 자가면역 질환 치료용（3－（2－에틸페닐）－5－메톡시페닐）－1ｈ－［1，2，4］－트리아졸의 용도 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US6797722B2 (https=) |
| EP (1) | EP1501505B1 (https=) |
| JP (1) | JP2005529904A (https=) |
| KR (1) | KR20040111491A (https=) |
| AT (1) | ATE315935T1 (https=) |
| AU (1) | AU2003224453A1 (https=) |
| CA (1) | CA2483904A1 (https=) |
| DE (1) | DE60303296T2 (https=) |
| DK (1) | DK1501505T3 (https=) |
| ES (1) | ES2257666T3 (https=) |
| MX (1) | MXPA04010785A (https=) |
| PL (1) | PL374252A1 (https=) |
| PT (1) | PT1501505E (https=) |
| TW (1) | TWI284532B (https=) |
| WO (1) | WO2003092681A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY142651A (en) * | 2003-03-18 | 2010-12-15 | Merck Sharp & Dohme | Biaryl substituted triazoles as sodium channel blockers |
| WO2005077411A2 (en) * | 2004-02-10 | 2005-08-25 | Innate Pharma | Composition and method for the treatment of carcinoma |
| EP1921073A1 (en) | 2006-11-10 | 2008-05-14 | Laboratorios del Dr. Esteve S.A. | 1,2,4-Triazole derivatives as sigma receptor inhibitors |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4379155A (en) * | 1979-06-11 | 1983-04-05 | Gruppo Lepetit S.P.A. | 3,5-Disubstituted-1H-1,2,4-triazole derivatives |
| JPS58126810A (ja) * | 1981-12-24 | 1983-07-28 | Kaken Pharmaceut Co Ltd | 抗炎症眼科用液剤およびその製法 |
| DE3808283A1 (de) * | 1988-03-12 | 1989-09-21 | Boehringer Ingelheim Kg | Neue 3,4,5-substituierte 4h-1,2,4-triazole, ihre herstellung und verwendung |
| US4895872A (en) * | 1989-03-15 | 1990-01-23 | Cetus Corporation | Immunosupressive analogues and derivatives of succinylacetone |
| US5273979A (en) * | 1991-08-01 | 1993-12-28 | Merck & Co., Inc. | C-31 desmethyl FR-900520 cyclic hemiketal immunosuppressant agent |
| US5189042A (en) * | 1991-08-22 | 1993-02-23 | Merck & Co. Inc. | Fluoromacrolides having immunosuppressive activity |
| US5484788A (en) * | 1993-03-26 | 1996-01-16 | Beth Israel Hospital Association | Buspirone as a systemic immunosuppressant |
| DE4320801A1 (de) * | 1993-06-23 | 1995-01-05 | Fahlberg List Pharma Gmbh | 2-Hydroxyphenylsubstituierte 1,2,4-Triazole und 1,2,4-Oxadiazole, ihre Verwendung als pharmazeutische Wirkstoffe und sie enthaltende Arzneimittel |
| AU4385696A (en) * | 1996-01-18 | 1997-08-11 | Christian Gronhoj Larsen | Synthetic il-10 analogues |
| ATE298740T1 (de) * | 1997-04-04 | 2005-07-15 | Mitsubishi Pharma Corp | 2-aminopropan-1,3-diol-verbindungen, ihre medizinische anwendung und zwischenprodukte zu ihrer synthese |
| IT1292092B1 (it) * | 1997-06-05 | 1999-01-25 | Geange Ltd | Impiego di derivati eterociclici aromatici azotati nel trattamento topico di affezioni di tessuti epiteliali |
| EP1099695A1 (en) * | 1999-11-09 | 2001-05-16 | Laboratoire Theramex S.A. | 5-aryl-1H-1,2,4-triazole compounds as inhibitors of cyclooxygenase-2 and pharmaceutical compositions containing them |
-
2002
- 2002-05-03 US US10/137,699 patent/US6797722B2/en not_active Expired - Fee Related
-
2003
- 2003-04-15 PT PT03720879T patent/PT1501505E/pt unknown
- 2003-04-15 JP JP2004500865A patent/JP2005529904A/ja active Pending
- 2003-04-15 PL PL03374252A patent/PL374252A1/xx not_active Application Discontinuation
- 2003-04-15 KR KR10-2004-7015884A patent/KR20040111491A/ko not_active Ceased
- 2003-04-15 WO PCT/IT2003/000237 patent/WO2003092681A1/en not_active Ceased
- 2003-04-15 AT AT03720879T patent/ATE315935T1/de not_active IP Right Cessation
- 2003-04-15 EP EP03720879A patent/EP1501505B1/en not_active Expired - Lifetime
- 2003-04-15 AU AU2003224453A patent/AU2003224453A1/en not_active Abandoned
- 2003-04-15 ES ES03720879T patent/ES2257666T3/es not_active Expired - Lifetime
- 2003-04-15 DK DK03720879T patent/DK1501505T3/da active
- 2003-04-15 CA CA002483904A patent/CA2483904A1/en not_active Abandoned
- 2003-04-15 MX MXPA04010785A patent/MXPA04010785A/es active IP Right Grant
- 2003-04-15 DE DE60303296T patent/DE60303296T2/de not_active Expired - Fee Related
- 2003-04-22 TW TW092109389A patent/TWI284532B/zh not_active IP Right Cessation
-
2004
- 2004-03-30 US US10/812,308 patent/US20050026980A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE60303296T2 (de) | 2006-08-17 |
| PL374252A1 (en) | 2005-10-03 |
| EP1501505B1 (en) | 2006-01-18 |
| EP1501505A1 (en) | 2005-02-02 |
| JP2005529904A (ja) | 2005-10-06 |
| CA2483904A1 (en) | 2003-11-13 |
| ES2257666T3 (es) | 2006-08-01 |
| PT1501505E (pt) | 2006-05-31 |
| US20050026980A1 (en) | 2005-02-03 |
| MXPA04010785A (es) | 2005-03-07 |
| DK1501505T3 (da) | 2006-05-22 |
| US6797722B2 (en) | 2004-09-28 |
| AU2003224453A1 (en) | 2003-11-17 |
| ATE315935T1 (de) | 2006-02-15 |
| TW200418464A (en) | 2004-10-01 |
| DE60303296D1 (de) | 2006-04-06 |
| WO2003092681A1 (en) | 2003-11-13 |
| TWI284532B (en) | 2007-08-01 |
| US20030207931A1 (en) | 2003-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sato et al. | CC chemokine receptor (CCR) 2 is required for Langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells: absence of CCR2 shifts the Leishmania major–resistant phenotype to a susceptible state dominated by Th2 cytokines, B cell outgrowth, and sustained neutrophilic inflammation | |
| Abbas et al. | Functional diversity of helper T lymphocytes | |
| Fukuyama et al. | Topically administered Janus-kinase inhibitors tofacitinib and oclacitinib display impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitis | |
| Bansal et al. | Experimental autoimmune uveitis and other animal models of uveitis: An update | |
| Romagnani | Human TH1 and TH2 subsets: regulation of differentiation and role in protection and immunopathology | |
| Moller et al. | Inhibition of IL-12 production by thalidomide | |
| Wilson et al. | Janus-like role of regulatory iNKT cells in autoimmune disease and tumour immunity | |
| Beeton et al. | Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation | |
| De Jong et al. | Chronic murine colitis is dependent on the CD154/CD40 pathway and can be attenuated by anti-CD154 administration | |
| Barbour et al. | IL‐33 attenuates the development of experimental autoimmune uveitis | |
| Cumberbatch et al. | Differential regulation of epidermal Langerhans cell migration by interleukins (IL)-1α and IL-1β during irritant-and allergen-induced cutaneous immune responses | |
| Barış et al. | Immunomodulation as a neuroprotective strategy for glaucoma treatment | |
| Suzuki et al. | Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis | |
| Ghadially et al. | NK p46 regulates allergic responses | |
| Yamada et al. | Mice with Th2-biased immune systems accept orthotopic corneal allografts placed in “high risk” eyes | |
| Almeida et al. | The capsular polysaccharides of Cryptococcus neoformans activate normal CD4+ T cells in a dominant Th2 pattern | |
| Kudchodkar et al. | Hyperbaric oxygen treatment attenuates the pro-inflammatory and immune responses in apolipoprotein E knockout mice | |
| Gurung et al. | Chronic ethanol induces inhibition of antigen-specific CD8+ but not CD4+ immunodominant T cell responses following Listeria monocytogenes inoculation | |
| Siegmund et al. | Suppression of tumor necrosis factor-α production by interleukin-10 is enhanced by cAMP-elevating agents | |
| Mbanefo et al. | STAT3-Specific single domain nanobody inhibits expansion of pathogenic Th17 responses and suppresses uveitis in mice | |
| Wang et al. | Interleukin-17 receptor E and CC motif chemokine receptor 10 identify heterogeneous T helper 17 subsets in a mouse dry eye disease model | |
| Li et al. | Matairesinol ameliorates experimental autoimmune uveitis by suppression of IRBP-specific Th17 cells | |
| KR20040111491A (ko) | 자가면역 질환 치료용（3－（2－에틸페닐）－5－메톡시페닐）－1ｈ－［1，2，4］－트리아졸의 용도 | |
| LAUNOIS et al. | Setting in motion the immune mechanisms underlying genetically determined resistance and susceptibility to infection with Leishmania major | |
| Zhou et al. | Up-regulation of IL-10 expression in dendritic cells is involved in Trichosanthin-induced immunosuppression |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20041005 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20080221 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20091201 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20100412 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20091201 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |