TWI403506B - 用於治療急性和慢性發炎疾病之５－（４－甲磺醯基－苯基）－噻唑衍生物類 - Google Patents
用於治療急性和慢性發炎疾病之５－（４－甲磺醯基－苯基）－噻唑衍生物類 Download PDFInfo
- Publication number
- TWI403506B TWI403506B TW098118927A TW98118927A TWI403506B TW I403506 B TWI403506 B TW I403506B TW 098118927 A TW098118927 A TW 098118927A TW 98118927 A TW98118927 A TW 98118927A TW I403506 B TWI403506 B TW I403506B
- Authority
- TW
- Taiwan
- Prior art keywords
- compound
- tnf
- unsubstituted
- disease
- substituted
- Prior art date
Links
- 230000001154 acute effect Effects 0.000 title claims abstract description 24
- 208000037976 chronic inflammation Diseases 0.000 title claims abstract description 19
- 208000037893 chronic inflammatory disorder Diseases 0.000 title claims abstract description 19
- 208000030090 Acute Disease Diseases 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title claims abstract description 13
- ZSYQCVZWUMOZJW-UHFFFAOYSA-N 5-(4-methylsulfonylphenyl)-1,3-thiazole Chemical class C1=CC(S(=O)(=O)C)=CC=C1C1=CN=CS1 ZSYQCVZWUMOZJW-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 116
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims abstract description 84
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims abstract description 78
- 238000004519 manufacturing process Methods 0.000 claims abstract description 57
- 108010074328 Interferon-gamma Proteins 0.000 claims abstract description 38
- 102100037850 Interferon gamma Human genes 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 108090001007 Interleukin-8 Proteins 0.000 claims abstract description 32
- 239000003814 drug Substances 0.000 claims abstract description 21
- 102000003814 Interleukin-10 Human genes 0.000 claims abstract description 19
- 108090000174 Interleukin-10 Proteins 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 230000001105 regulatory effect Effects 0.000 claims abstract description 15
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 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 claims abstract 5
- 102000004890 Interleukin-8 Human genes 0.000 claims description 31
- 108020004999 messenger RNA Proteins 0.000 claims description 30
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 29
- 102000015696 Interleukins Human genes 0.000 claims description 27
- 108010063738 Interleukins Proteins 0.000 claims description 27
- 230000002757 inflammatory effect Effects 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 230000014509 gene expression Effects 0.000 claims description 17
- 210000000056 organ Anatomy 0.000 claims description 17
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 229940047122 interleukins Drugs 0.000 claims description 12
- 230000001575 pathological effect Effects 0.000 claims description 12
- 230000002519 immonomodulatory effect Effects 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 230000001684 chronic effect Effects 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 206010036030 Polyarthritis Diseases 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 206010014599 encephalitis Diseases 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 230000001413 cellular effect Effects 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000036303 septic shock Effects 0.000 claims description 6
- 238000002054 transplantation Methods 0.000 claims description 6
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 206010046851 Uveitis Diseases 0.000 claims description 5
- 230000006907 apoptotic process Effects 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 4
- 206010006895 Cachexia Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000027932 Collagen disease Diseases 0.000 claims description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
- 208000034486 Multi-organ failure Diseases 0.000 claims description 4
- 208000010718 Multiple Organ Failure Diseases 0.000 claims description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 4
- 206010037779 Radiculopathy Diseases 0.000 claims description 4
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 208000006045 Spondylarthropathies Diseases 0.000 claims description 4
- 208000024780 Urticaria Diseases 0.000 claims description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 4
- 206010000496 acne Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- 206010002022 amyloidosis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 230000010261 cell growth Effects 0.000 claims description 4
- 201000003146 cystitis Diseases 0.000 claims description 4
- 230000007850 degeneration Effects 0.000 claims description 4
- 230000001419 dependent effect Effects 0.000 claims description 4
- 201000001981 dermatomyositis Diseases 0.000 claims description 4
- 208000024908 graft versus host disease Diseases 0.000 claims description 4
- 201000006334 interstitial nephritis Diseases 0.000 claims description 4
- 208000023589 ischemic disease Diseases 0.000 claims description 4
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 206010028417 myasthenia gravis Diseases 0.000 claims description 4
- 230000017074 necrotic cell death Effects 0.000 claims description 4
- 230000003076 paracrine Effects 0.000 claims description 4
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 4
- 208000030428 polyarticular arthritis Diseases 0.000 claims description 4
- 201000005671 spondyloarthropathy Diseases 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 206010043778 thyroiditis Diseases 0.000 claims description 4
- 208000016192 Demyelinating disease Diseases 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000009525 Myocarditis Diseases 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
- 241000220317 Rosa Species 0.000 claims description 3
- 208000018359 Systemic autoimmune disease Diseases 0.000 claims description 3
- 206010047115 Vasculitis Diseases 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000003305 autocrine Effects 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 230000007882 cirrhosis Effects 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 201000006370 kidney failure Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 208000008494 pericarditis Diseases 0.000 claims description 3
- 201000007094 prostatitis Diseases 0.000 claims description 3
- 210000002418 meninge Anatomy 0.000 claims description 2
- 201000011475 meningoencephalitis Diseases 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 3
- 206010048302 Tubulointerstitial nephritis Diseases 0.000 claims 1
- 230000016396 cytokine production Effects 0.000 claims 1
- 201000008383 nephritis Diseases 0.000 claims 1
- 239000012453 solvate Substances 0.000 abstract description 25
- 239000000651 prodrug Substances 0.000 abstract description 21
- 229940002612 prodrug Drugs 0.000 abstract description 21
- 230000000770 proinflammatory effect Effects 0.000 abstract description 9
- 238000002360 preparation method Methods 0.000 abstract description 5
- 102000004127 Cytokines Human genes 0.000 abstract description 4
- 108090000695 Cytokines Proteins 0.000 abstract description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 104
- 210000004027 cell Anatomy 0.000 description 84
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 62
- 229940125797 compound 12 Drugs 0.000 description 62
- 239000002158 endotoxin Substances 0.000 description 59
- 229920006008 lipopolysaccharide Polymers 0.000 description 59
- 210000001616 monocyte Anatomy 0.000 description 45
- 230000028327 secretion Effects 0.000 description 39
- 230000000694 effects Effects 0.000 description 38
- 229940096397 interleukin-8 Drugs 0.000 description 29
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 29
- 238000000034 method Methods 0.000 description 28
- 238000012360 testing method Methods 0.000 description 25
- 239000002609 medium Substances 0.000 description 22
- 230000002269 spontaneous effect Effects 0.000 description 22
- 230000000638 stimulation Effects 0.000 description 21
- 241000282414 Homo sapiens Species 0.000 description 19
- 108090000623 proteins and genes Proteins 0.000 description 17
- 229940076144 interleukin-10 Drugs 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000011161 development Methods 0.000 description 13
- 230000018109 developmental process Effects 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 11
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 11
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 11
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 11
- 230000009696 proliferative response Effects 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- 108010004729 Phycoerythrin Proteins 0.000 description 10
- 230000028993 immune response Effects 0.000 description 10
- 208000027866 inflammatory disease Diseases 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 238000003753 real-time PCR Methods 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000012228 culture supernatant Substances 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 239000000090 biomarker Substances 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000009826 distribution Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000003018 immunosuppressive agent Substances 0.000 description 7
- 230000021995 interleukin-8 production Effects 0.000 description 7
- 210000005087 mononuclear cell Anatomy 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000009885 systemic effect Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- 102000019034 Chemokines Human genes 0.000 description 6
- 108010012236 Chemokines Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 6
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 6
- 102100033467 L-selectin Human genes 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- -1 binding efficiency Proteins 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 229940125721 immunosuppressive agent Drugs 0.000 description 6
- 238000010839 reverse transcription Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
- 201000009906 Meningitis Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940126142 compound 16 Drugs 0.000 description 5
- 229940125898 compound 5 Drugs 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 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 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 230000001506 immunosuppresive effect Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000031261 interleukin-10 production Effects 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 239000004005 microsphere Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 206010018364 Glomerulonephritis Diseases 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000006052 T cell proliferation Effects 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000000139 costimulatory effect Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 102000057041 human TNF Human genes 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 230000004968 inflammatory condition Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000003226 mitogen Substances 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- 239000002777 nucleoside Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 210000001541 thymus gland Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 208000009386 Experimental Arthritis Diseases 0.000 description 3
- 229920001917 Ficoll Polymers 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 206010028851 Necrosis Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000002456 anti-arthritic effect Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 230000008076 immune mechanism Effects 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 238000010841 mRNA extraction Methods 0.000 description 3
- 230000005291 magnetic effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002493 microarray Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 210000005239 tubule Anatomy 0.000 description 3
- 230000006433 tumor necrosis factor production Effects 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 206010004053 Bacterial toxaemia Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 235000000177 Indigofera tinctoria Nutrition 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 108020000411 Toll-like receptor Proteins 0.000 description 2
- 102000002689 Toll-like receptor Human genes 0.000 description 2
- 208000013222 Toxemia Diseases 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 230000009266 disease activity Effects 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000002134 immunopathologic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229940097275 indigo Drugs 0.000 description 2
- COHYTHOBJLSHDF-UHFFFAOYSA-N indigo powder Natural products N1C2=CC=CC=C2C(=O)C1=C1C(=O)C2=CC=CC=C2N1 COHYTHOBJLSHDF-UHFFFAOYSA-N 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000012022 methylating agents Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 125000003835 nucleoside group Chemical group 0.000 description 2
- 229940029358 orthoclone okt3 Drugs 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 229920002223 polystyrene 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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229940104230 thymidine Drugs 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
- 238000013519 translation Methods 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- YYVPXGDTHRHXLM-UHFFFAOYSA-N (4-methylphenyl)sulfanylmethyl acetate Chemical compound CC(=O)OCSC1=CC=C(C)C=C1 YYVPXGDTHRHXLM-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 1
- XCRDQVBOVYWDPH-UHFFFAOYSA-N 2-(4-methylphenyl)sulfanylacetic acid Chemical compound CC1=CC=C(SCC(O)=O)C=C1 XCRDQVBOVYWDPH-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
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- YVNVWIGXULADLD-UHFFFAOYSA-N 2-methyl-5-(4-methylsulfonylphenyl)-1,3-thiazol-4-ol Chemical compound S1C(C)=NC(O)=C1C1=CC=C(S(C)(=O)=O)C=C1 YVNVWIGXULADLD-UHFFFAOYSA-N 0.000 description 1
- CZWWCTHQXBMHDA-UHFFFAOYSA-N 3h-1,3-thiazol-2-one Chemical compound OC1=NC=CS1 CZWWCTHQXBMHDA-UHFFFAOYSA-N 0.000 description 1
- DCPLSZRONTVIIH-UHFFFAOYSA-N 4-cyclopentyloxy-2-methyl-5-(4-methylsulfonylphenyl)-1,3-thiazole Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1SC(C)=NC=1OC1CCCC1 DCPLSZRONTVIIH-UHFFFAOYSA-N 0.000 description 1
- 108091007505 ADAM17 Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010062269 Adrenalitis Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 101100398412 Arabidopsis thaliana ASK1 gene Proteins 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 101150085479 CHS2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000025985 Central nervous system inflammatory disease Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 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
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 101150103171 DARS1 gene Proteins 0.000 description 1
- 238000011763 DBA/1J (JAX™ mouse strain) Methods 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000012153 HLA-B27 Antigen Human genes 0.000 description 1
- 108010061486 HLA-B27 Antigen Proteins 0.000 description 1
- 101000811217 Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) 30S ribosomal protein S19e Proteins 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 108700027089 Hirudo medicinalis macrolin Proteins 0.000 description 1
- 101100215371 Homo sapiens ACTB gene Proteins 0.000 description 1
- 101000756632 Homo sapiens Actin, cytoplasmic 1 Proteins 0.000 description 1
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 description 1
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 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
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102100026236 Interleukin-8 Human genes 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 102000005482 Lipopolysaccharide Receptors Human genes 0.000 description 1
- 108010031801 Lipopolysaccharide Receptors Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 101100046526 Mus musculus Tnf gene Proteins 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 208000020663 Nasal mucosal disease Diseases 0.000 description 1
- 208000011623 Obstructive Lung disease Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010047620 Phytohemagglutinins Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000220221 Rosales Species 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 229920004482 WACKER® Polymers 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 229960001931 ampicillin sodium Drugs 0.000 description 1
- KLOHDWPABZXLGI-YWUHCJSESA-M ampicillin sodium Chemical compound [Na+].C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)=CC=CC=C1 KLOHDWPABZXLGI-YWUHCJSESA-M 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
- 230000001042 autoregulative effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 210000000133 brain stem 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
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 238000006352 cycloaddition reaction Methods 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
- KDUIUFJBNGTBMD-VXMYFEMYSA-N cyclooctatetraene Chemical compound C1=C\C=C/C=C\C=C1 KDUIUFJBNGTBMD-VXMYFEMYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- BABWHSBPEIVBBZ-UHFFFAOYSA-N diazete Chemical class C1=CN=N1 BABWHSBPEIVBBZ-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000002503 granulosa cell Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 102000052620 human IL10 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 230000001329 hyperkeratotic effect Effects 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- HCMUPMCWKYOOBZ-UHFFFAOYSA-N methyl 2-(4-methylsulfonylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(S(C)(=O)=O)C=C1 HCMUPMCWKYOOBZ-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000003909 pattern recognition Methods 0.000 description 1
- 230000032390 pattern recognition receptor signaling pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 230000001885 phytohemagglutinin Effects 0.000 description 1
- 108010086662 phytohemagglutinin-M Proteins 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000021625 positive regulation of cell division Effects 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent 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
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002947 procoagulating effect Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 230000019254 respiratory burst Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- ALNUHUMOGUVHIO-XXJNWDAFSA-M sodium;7-[(1r,2s)-2-hexyl-5-hydroxycyclopentyl]heptanoate Chemical compound [Na+].CCCCCC[C@H]1CCC(O)[C@@H]1CCCCCCC([O-])=O ALNUHUMOGUVHIO-XXJNWDAFSA-M 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 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
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000005382 thermal cycling Methods 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000019432 tissue death Effects 0.000 description 1
- 230000008354 tissue degradation Effects 0.000 description 1
- 230000000287 tissue oxygenation Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000007794 visualization technique Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss 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
- A61K31/425—Thiazoles
-
- 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
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Otolaryngology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/139,661 US7781594B2 (en) | 2008-06-16 | 2008-06-16 | 5-(4-methanesulfonyl-phenyl)-thiazole derivatives for the treatment of acute and chronic inflammatory diseases |
| EP08380177A EP2135864A1 (en) | 2008-06-16 | 2008-06-16 | 5-(4-methanesulfonyl-phenyl)-thiazole derivatives for the treatment of acute and chronic inflammatory diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201010988A TW201010988A (en) | 2010-03-16 |
| TWI403506B true TWI403506B (zh) | 2013-08-01 |
Family
ID=43414178
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW098118927A TWI403506B (zh) | 2008-06-16 | 2009-06-06 | 用於治療急性和慢性發炎疾病之５－（４－甲磺醯基－苯基）－噻唑衍生物類 |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP2313382A1 (enExample) |
| JP (1) | JP2011524352A (enExample) |
| KR (1) | KR20110022679A (enExample) |
| CN (1) | CN102083806A (enExample) |
| AR (1) | AR072113A1 (enExample) |
| AU (1) | AU2009259451B2 (enExample) |
| BR (1) | BRPI0915325A2 (enExample) |
| CA (1) | CA2728139A1 (enExample) |
| CO (1) | CO6331429A2 (enExample) |
| IL (1) | IL209801A0 (enExample) |
| MA (1) | MA32473B1 (enExample) |
| MX (1) | MX2010013978A (enExample) |
| NZ (1) | NZ589894A (enExample) |
| RU (1) | RU2495031C2 (enExample) |
| SA (1) | SA109300384B1 (enExample) |
| TW (1) | TWI403506B (enExample) |
| UY (1) | UY31896A (enExample) |
| WO (1) | WO2009153226A1 (enExample) |
| ZA (1) | ZA201008877B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2961695B1 (fr) * | 2010-06-29 | 2012-07-06 | Galderma Res & Dev | Utilisation de composes dans le traitement ou la prevention de troubles cutanes |
| RU2502513C2 (ru) * | 2012-01-11 | 2013-12-27 | Государственное бюджетное учреждение здравоохранения Свердловской области "Свердловский областной клинический психоневрологический госпиталь для ветеранов войн" (ГБУЗ СО "СОКП Госпиталь для ветеранов войн") | Способ лечения больных с полиорганной патологией озонотерапией |
| CN111343975A (zh) * | 2017-11-23 | 2020-06-26 | 埃慕尼克股份公司 | 用于预防或治疗慢性炎性疾病和/或自身免疫疾病的维多地莫的剂量方案 |
| KR102076936B1 (ko) * | 2019-08-12 | 2020-02-13 | 연세대학교 산학협력단 | 티아졸 또는 이의 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염 예방 또는 치료용 조성물 |
| IT202000008125A1 (it) * | 2020-04-16 | 2021-10-16 | Minerva Srl | Acidi carbossilici 3-aza-biciclo[3.2.1]ottani e loro derivati per l’uso nel trattamento di infiammazioni |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5124342A (en) * | 1989-02-08 | 1992-06-23 | Abbott Laboratories | 4-hydroxythiazoles as 5-lipoxygenase inhibitors |
| US20050026902A1 (en) * | 2003-01-31 | 2005-02-03 | Timothy Maziasz | Methods and compositions for the treatment or prevention of human immunodeficiency virus and related conditions using cyclooxygenase-2 selective inhibitors and antiviral agents |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU3201095A (en) * | 1994-07-27 | 1996-02-22 | G.D. Searle & Co. | Substituted thiazoles for the treatment of inflammation |
| JPH11507670A (ja) * | 1995-06-12 | 1999-07-06 | ジー．ディー．サール アンド カンパニー | シクロオキシゲナーゼ−２インヒビターと５−リポキシゲナーゼインヒビターの組合せによる炎症と炎症関連疾患の治療 |
| AU7559200A (en) * | 1999-10-12 | 2001-04-23 | Japan Tobacco Inc. | Hypertriglyceridemia remedies and antiobestics |
| HRP20040098B1 (en) * | 2001-08-13 | 2012-08-31 | Janssen Pharmaceutica N.V. | 2,4,5-TRlSUBSTITUTED THIAZOLYL DERIVATIVES AND THEIR ANTIINFLAMMATORY ACTIVITY |
-
2009
- 2009-06-06 TW TW098118927A patent/TWI403506B/zh not_active IP Right Cessation
- 2009-06-12 AR ARP090102121A patent/AR072113A1/es unknown
- 2009-06-12 UY UY0001031896A patent/UY31896A/es not_active Application Discontinuation
- 2009-06-15 JP JP2011513001A patent/JP2011524352A/ja active Pending
- 2009-06-15 NZ NZ589894A patent/NZ589894A/en not_active IP Right Cessation
- 2009-06-15 KR KR1020117001228A patent/KR20110022679A/ko not_active Ceased
- 2009-06-15 SA SA109300384A patent/SA109300384B1/ar unknown
- 2009-06-15 MX MX2010013978A patent/MX2010013978A/es active IP Right Grant
- 2009-06-15 CN CN2009801226820A patent/CN102083806A/zh active Pending
- 2009-06-15 EP EP09765806A patent/EP2313382A1/en not_active Withdrawn
- 2009-06-15 AU AU2009259451A patent/AU2009259451B2/en not_active Ceased
- 2009-06-15 WO PCT/EP2009/057324 patent/WO2009153226A1/en not_active Ceased
- 2009-06-15 CA CA2728139A patent/CA2728139A1/en not_active Abandoned
- 2009-06-15 RU RU2011101439/04A patent/RU2495031C2/ru not_active IP Right Cessation
- 2009-06-15 BR BRPI0915325A patent/BRPI0915325A2/pt not_active IP Right Cessation
-
2010
- 2010-12-06 IL IL209801A patent/IL209801A0/en unknown
- 2010-12-09 ZA ZA2010/08877A patent/ZA201008877B/en unknown
-
2011
- 2011-01-13 MA MA33516A patent/MA32473B1/fr unknown
- 2011-01-14 CO CO11003796A patent/CO6331429A2/es active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5124342A (en) * | 1989-02-08 | 1992-06-23 | Abbott Laboratories | 4-hydroxythiazoles as 5-lipoxygenase inhibitors |
| US20050026902A1 (en) * | 2003-01-31 | 2005-02-03 | Timothy Maziasz | Methods and compositions for the treatment or prevention of human immunodeficiency virus and related conditions using cyclooxygenase-2 selective inhibitors and antiviral agents |
Non-Patent Citations (1)
| Title |
|---|
| Gauthier JY, et al. "Synthesis and biological evaluation of 2,3-diarylthiophenes as selective COX-2 inhibitors. Part II: replacing the heterocycle" Bioorganic and Medicinal Chemistry Letters 1996;6(1):87-92 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AR072113A1 (es) | 2010-08-04 |
| JP2011524352A (ja) | 2011-09-01 |
| NZ589894A (en) | 2011-08-26 |
| MX2010013978A (es) | 2011-03-29 |
| UY31896A (es) | 2010-01-29 |
| KR20110022679A (ko) | 2011-03-07 |
| IL209801A0 (en) | 2011-02-28 |
| CN102083806A (zh) | 2011-06-01 |
| CA2728139A1 (en) | 2009-12-23 |
| TW201010988A (en) | 2010-03-16 |
| EP2313382A1 (en) | 2011-04-27 |
| RU2495031C2 (ru) | 2013-10-10 |
| RU2011101439A (ru) | 2012-07-27 |
| ZA201008877B (en) | 2012-02-29 |
| SA109300384B1 (ar) | 2013-04-20 |
| BRPI0915325A2 (pt) | 2015-10-27 |
| CO6331429A2 (es) | 2011-10-20 |
| WO2009153226A1 (en) | 2009-12-23 |
| AU2009259451B2 (en) | 2013-03-14 |
| MA32473B1 (fr) | 2011-07-03 |
| AU2009259451A1 (en) | 2009-12-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100516204C (zh) | 干细胞及其分离方法 | |
| JP6778747B2 (ja) | 胃腸炎症性腸疾患の処置のための、ｊａｋ阻害剤化合物のプロドラッグ | |
| Fiocchi et al. | Human intestinal mucosal mononuclear cells exhibit lymphokine-activated killer cell activity | |
| JP6499165B2 (ja) | 二重選択的ｐｉ３デルタ及びガンマキナーゼ阻害剤 | |
| TWI403506B (zh) | 用於治療急性和慢性發炎疾病之５－（４－甲磺醯基－苯基）－噻唑衍生物類 | |
| US20210347811A1 (en) | Steroid compounds as treg modulators and uses thereof | |
| AU2019293163B2 (en) | Natural killer cells | |
| US20240376082A1 (en) | Pyridinyl substituted oxoisoindoline compounds | |
| KR102338568B1 (ko) | 퀴나졸린 유도체 | |
| WO2022133056A1 (en) | Expanded and stimulated natural killer cells | |
| JP2022549923A (ja) | Ｎヘテロ五員環含有カプシドタンパク質集合阻害剤の結晶形及びその使用 | |
| WO2020130120A1 (ja) | 癌転移抑制剤 | |
| US8492411B2 (en) | 5-(4-methanesulfonyl-phenyl)-thiazole derivatives for the treatment of acute and chronic inflammatory diseases | |
| EP2135864A1 (en) | 5-(4-methanesulfonyl-phenyl)-thiazole derivatives for the treatment of acute and chronic inflammatory diseases | |
| JP2004509167A (ja) | 安息香酸誘導体及びその使用方法 | |
| CN102203099A (zh) | 一种具有手性螺环碳架结构的新化合物及其制备方法以及包含该化合物的药物组合物 | |
| HK1157325A (en) | 5-(4-methanesulfonyl-phenyl)-thiazole derivatives for the treatment of acute and chronic inflammatory diseases | |
| US20220370586A1 (en) | Method of generating activated t cells for cancer therapy | |
| CN120693400A (zh) | 自然杀伤细胞 | |
| EP4511371A1 (en) | Substituted phenyl oxazolone compounds | |
| KR101739659B1 (ko) | 면역질환 치료 효능을 갖는 Ｇｒｉｍ１９이 과발현된 중간엽줄기세포 및 이의 용도 | |
| WO2020140960A1 (zh) | 吲哚甲酰胺类衍生物的晶型及其制备方法 | |
| JP2006089399A (ja) | ２型糖尿病治療剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |