BG107013A - Il-8 рецепторни антагонисти - Google Patents
Il-8 рецепторни антагонисти Download PDFInfo
- Publication number
- BG107013A BG107013A BG107013A BG10701302A BG107013A BG 107013 A BG107013 A BG 107013A BG 107013 A BG107013 A BG 107013A BG 10701302 A BG10701302 A BG 10701302A BG 107013 A BG107013 A BG 107013A
- Authority
- BG
- Bulgaria
- Prior art keywords
- alkyl
- chloro
- hydroxy
- optionally substituted
- heterocyclyl
- Prior art date
Links
- 102000010681 interleukin-8 receptors Human genes 0.000 title description 7
- 108010038415 interleukin-8 receptors Proteins 0.000 title description 6
- 239000002464 receptor antagonist Substances 0.000 title description 2
- 229940044551 receptor antagonist Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 102000019034 Chemokines Human genes 0.000 claims abstract description 26
- 108010012236 Chemokines Proteins 0.000 claims abstract description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 230000001404 mediated effect Effects 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 116
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- -1 hydroxy, hydroxy Chemical group 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 208000014674 injury Diseases 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 239000004202 carbamide Substances 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 210000003169 central nervous system Anatomy 0.000 claims description 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 238000001356 surgical procedure Methods 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- CMRLUFNYQJTEFJ-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-(2-methylcyclopropyl)urea Chemical compound CC1CC1NC(=O)NC1=CC=C(Cl)C(S(N)(=O)=O)=C1O CMRLUFNYQJTEFJ-UHFFFAOYSA-N 0.000 claims description 4
- ZTLMJQZASJPGLX-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-(3-methoxycyclohexyl)urea Chemical compound C1C(OC)CCCC1NC(=O)NC1=CC=C(Cl)C(S(N)(=O)=O)=C1O ZTLMJQZASJPGLX-UHFFFAOYSA-N 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 206010006451 bronchitis Diseases 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 230000008733 trauma Effects 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- GTPLUYMCQIYGHI-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-(oxolan-3-yl)urea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)NC2COCC2)=C1O GTPLUYMCQIYGHI-UHFFFAOYSA-N 0.000 claims description 2
- AVCKTWYHWOPPIM-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-cyclobutylurea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)NC2CCC2)=C1O AVCKTWYHWOPPIM-UHFFFAOYSA-N 0.000 claims description 2
- QSKCFJGYXIKQPE-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-cyclopropylurea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)NC2CC2)=C1O QSKCFJGYXIKQPE-UHFFFAOYSA-N 0.000 claims description 2
- 206010033646 Acute and chronic pancreatitis Diseases 0.000 claims description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
- 206010006448 Bronchiolitis Diseases 0.000 claims description 2
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010009137 Chronic sinusitis Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 206010013975 Dyspnoeas Diseases 0.000 claims description 2
- 206010014561 Emphysema Diseases 0.000 claims description 2
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
- 206010058490 Hyperoxia Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 2
- 206010051606 Necrotising colitis Diseases 0.000 claims description 2
- 206010067472 Organising pneumonia Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 206010063837 Reperfusion injury Diseases 0.000 claims description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
- 206010040047 Sepsis Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 2
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 206010047115 Vasculitis Diseases 0.000 claims description 2
- 241000700605 Viruses Species 0.000 claims description 2
- 206010047924 Wheezing Diseases 0.000 claims description 2
- 208000002353 alcoholic hepatitis Diseases 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 208000026935 allergic disease Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 201000009267 bronchiectasis Diseases 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 208000007451 chronic bronchitis Diseases 0.000 claims description 2
- 208000027157 chronic rhinosinusitis Diseases 0.000 claims description 2
- 201000009805 cryptogenic organizing pneumonia Diseases 0.000 claims description 2
- 125000006843 cycloalkyl-C1-5-alkyl Chemical group 0.000 claims description 2
- 206010014599 encephalitis Diseases 0.000 claims description 2
- 208000007565 gingivitis Diseases 0.000 claims description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 2
- 208000006454 hepatitis Diseases 0.000 claims description 2
- 231100000283 hepatitis Toxicity 0.000 claims description 2
- 230000000222 hyperoxic effect Effects 0.000 claims description 2
- 230000009610 hypersensitivity Effects 0.000 claims description 2
- 208000018875 hypoxemia Diseases 0.000 claims description 2
- 230000007954 hypoxia Effects 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 201000004792 malaria Diseases 0.000 claims description 2
- 208000004995 necrotizing enterocolitis Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- OGDOBXMNVNGETJ-UHFFFAOYSA-N oxan-2-ylurea Chemical compound NC(=O)NC1CCCCO1 OGDOBXMNVNGETJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000010412 perfusion Effects 0.000 claims description 2
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 201000000306 sarcoidosis Diseases 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 230000009529 traumatic brain injury Effects 0.000 claims description 2
- 241001529453 unidentified herpesvirus Species 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 8
- WUESWDIHTKHGQA-UHFFFAOYSA-N cyclohexylurea Chemical compound NC(=O)NC1CCCCC1 WUESWDIHTKHGQA-UHFFFAOYSA-N 0.000 claims 2
- VMTSVXQUFQOMNP-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-piperazin-1-ylsulfonylphenyl)-3-cyclopentylurea Chemical compound C1=CC(Cl)=C(S(=O)(=O)N2CCNCC2)C(O)=C1NC(=O)NC1CCCC1 VMTSVXQUFQOMNP-UHFFFAOYSA-N 0.000 claims 1
- VDFURVFRSNIHPU-RDJZCZTQSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-[(1s,2s)-2-phenylmethoxycyclohexyl]urea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)N[C@@H]2[C@H](CCCC2)OCC=2C=CC=CC=2)=C1O VDFURVFRSNIHPU-RDJZCZTQSA-N 0.000 claims 1
- 208000000884 Airway Obstruction Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 208000034656 Contusions Diseases 0.000 claims 1
- 206010014824 Endotoxic shock Diseases 0.000 claims 1
- 208000005232 Glossitis Diseases 0.000 claims 1
- 208000032843 Hemorrhage Diseases 0.000 claims 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 claims 1
- 208000029523 Interstitial Lung disease Diseases 0.000 claims 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 206010046851 Uveitis Diseases 0.000 claims 1
- 230000036428 airway hyperreactivity Effects 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 230000009519 contusion Effects 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 230000036303 septic shock Effects 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 230000002861 ventricular Effects 0.000 claims 1
- 102000004890 Interleukin-8 Human genes 0.000 abstract description 60
- 108090001007 Interleukin-8 Proteins 0.000 abstract description 60
- 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 abstract description 59
- 229940096397 interleukin-8 Drugs 0.000 abstract description 59
- 239000000203 mixture Substances 0.000 abstract description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 26
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 101000973997 Homo sapiens Nucleosome assembly protein 1-like 4 Proteins 0.000 description 21
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 description 21
- 102100036154 Platelet basic protein Human genes 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- 230000006378 damage Effects 0.000 description 15
- 210000000440 neutrophil Anatomy 0.000 description 15
- 150000002431 hydrogen Chemical class 0.000 description 14
- UALHUJCTSBPMRB-UHFFFAOYSA-N 3-amino-6-chloro-2-hydroxybenzenesulfonamide Chemical compound NC1=CC=C(Cl)C(S(N)(=O)=O)=C1O UALHUJCTSBPMRB-UHFFFAOYSA-N 0.000 description 13
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 13
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 13
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 13
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 208000027418 Wounds and injury Diseases 0.000 description 12
- 108020004999 messenger RNA Proteins 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 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 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- 210000004556 brain Anatomy 0.000 description 11
- 235000013877 carbamide Nutrition 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 8
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 102000000589 Interleukin-1 Human genes 0.000 description 7
- 108010002352 Interleukin-1 Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 230000035605 chemotaxis Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 5
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 102000016387 Pancreatic elastase Human genes 0.000 description 5
- 108010067372 Pancreatic elastase Proteins 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 208000029028 brain injury Diseases 0.000 description 5
- 229940126214 compound 3 Drugs 0.000 description 5
- 230000009514 concussion Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229940100601 interleukin-6 Drugs 0.000 description 5
- 230000001936 parietal effect Effects 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 229940124530 sulfonamide Drugs 0.000 description 5
- 150000003456 sulfonamides Chemical group 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 4
- 230000003511 endothelial effect Effects 0.000 description 4
- 210000001508 eye Anatomy 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 150000003460 sulfonic acids Chemical class 0.000 description 4
- IAVUPMFITXYVAF-HTRCEHHLSA-N (4r,6r)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4h-thieno[2,3-b]thiopyran-2-sulfonamide Chemical compound CCN[C@@H]1C[C@@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-HTRCEHHLSA-N 0.000 description 3
- VFASNYJXNREXAE-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-(4-methylcyclohexyl)urea Chemical compound C1CC(C)CCC1NC(=O)NC1=CC=C(Cl)C(S(N)(=O)=O)=C1O VFASNYJXNREXAE-UHFFFAOYSA-N 0.000 description 3
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 210000003651 basophil Anatomy 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- 230000003399 chemotactic effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000011242 neutrophil chemotaxis Effects 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 150000003461 sulfonyl halides Chemical class 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000000472 traumatic effect Effects 0.000 description 3
- CNRSGBJHIHSXCY-UHFFFAOYSA-N (3-chloro-6-nitro-2-sulfamoylphenyl) acetate Chemical compound CC(=O)OC1=C([N+]([O-])=O)C=CC(Cl)=C1S(N)(=O)=O CNRSGBJHIHSXCY-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- GKPBKEGYKTZZSE-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-(2,2,3,3-tetramethylcyclopropyl)urea Chemical compound CC1(C)C(C)(C)C1NC(=O)NC1=CC=C(Cl)C(S(N)(=O)=O)=C1O GKPBKEGYKTZZSE-UHFFFAOYSA-N 0.000 description 2
- BJRTUULSRWFVBT-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-piperidin-4-ylurea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)NC2CCNCC2)=C1O BJRTUULSRWFVBT-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- QQUJUEWKTUDYKI-UHFFFAOYSA-N 2,6-dichloro-3-nitrobenzenesulfonamide Chemical compound NS(=O)(=O)C1=C(Cl)C=CC([N+]([O-])=O)=C1Cl QQUJUEWKTUDYKI-UHFFFAOYSA-N 0.000 description 2
- RAJHEZQFXIHNNL-UHFFFAOYSA-N 2,6-dichlorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=C(Cl)C=CC=C1Cl RAJHEZQFXIHNNL-UHFFFAOYSA-N 0.000 description 2
- WGGKQIKICKLWGN-UHFFFAOYSA-N 2,6-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=CC(Cl)=C1S(Cl)(=O)=O WGGKQIKICKLWGN-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 2
- ZGMZHBQXGORABP-UHFFFAOYSA-N 6-chloro-2-hydroxy-3-nitrobenzenesulfonamide Chemical compound NS(=O)(=O)C1=C(O)C([N+]([O-])=O)=CC=C1Cl ZGMZHBQXGORABP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000018652 Closed Head injury Diseases 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101500025785 Homo sapiens IL-8(6-77) Proteins 0.000 description 2
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 2
- 102400001232 IL-8(6-77) Human genes 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- 102000013967 Monokines Human genes 0.000 description 2
- 108010050619 Monokines Proteins 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- CZALJDQHONFVFU-UHFFFAOYSA-N isocyanatocyclopentane Chemical compound O=C=NC1CCCC1 CZALJDQHONFVFU-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000000865 liniment Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- CMEUDEVBFFPSEI-NFHWZJRKSA-N methyl 4-[[(2s)-1-[[(2s)-1-[(2s)-2-[[(2s)-3-methyl-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)NC1=CC=C(C(C)=CC(=O)O2)C2=C1 CMEUDEVBFFPSEI-NFHWZJRKSA-N 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 230000000802 nitrating effect Effects 0.000 description 2
- 210000001331 nose Anatomy 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- WRLGYAWRGXKSKG-UHFFFAOYSA-M phenobarbital sodium Chemical compound [Na+].C=1C=CC=CC=1C1(CC)C(=O)NC([O-])=NC1=O WRLGYAWRGXKSKG-UHFFFAOYSA-M 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- 230000019254 respiratory burst Effects 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- VAJDPANPZHGXTF-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-(oxan-2-yl)urea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)NC2OCCCC2)=C1O VAJDPANPZHGXTF-UHFFFAOYSA-N 0.000 description 1
- UMAPTBCRLNGFQA-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-cyclopentylurea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)NC2CCCC2)=C1O UMAPTBCRLNGFQA-UHFFFAOYSA-N 0.000 description 1
- QYYHPAUOLCHORH-UHFFFAOYSA-N 1-adamantylurea Chemical compound C1C(C2)CC3CC2CC1(NC(=O)N)C3 QYYHPAUOLCHORH-UHFFFAOYSA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
- VBHCPGFCIQDXGZ-UHFFFAOYSA-N 1-isocyanatoadamantane Chemical compound C1C(C2)CC3CC2CC1(N=C=O)C3 VBHCPGFCIQDXGZ-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- SFHVXKNMCGSLAR-UHFFFAOYSA-N 2,2,3,3-tetramethylcyclopropanecarboxylic acid Chemical compound CC1(C)C(C(O)=O)C1(C)C SFHVXKNMCGSLAR-UHFFFAOYSA-N 0.000 description 1
- QIULLHZMZMGGFH-UHFFFAOYSA-N 2,5-dichlorobenzenethiol Chemical compound SC1=CC(Cl)=CC=C1Cl QIULLHZMZMGGFH-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
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- VXVWIRKAABQIGS-UHFFFAOYSA-N 2-isocyanatooxane Chemical compound O=C=NC1CCCCO1 VXVWIRKAABQIGS-UHFFFAOYSA-N 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- AYEGPMGNMOIHDL-UHFFFAOYSA-N 2-methylcyclopropane-1-carboxylic acid Chemical compound CC1CC1C(O)=O AYEGPMGNMOIHDL-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- KAWNRNMMEKTYGM-UHFFFAOYSA-N 3-methoxycyclohexane-1-carboxylic acid Chemical compound COC1CCCC(C(O)=O)C1 KAWNRNMMEKTYGM-UHFFFAOYSA-N 0.000 description 1
- QTDXSEZXAPHVBI-UHFFFAOYSA-N 4-methylcyclohexane-1-carboxylic acid Chemical compound CC1CCC(C(O)=O)CC1 QTDXSEZXAPHVBI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000040717 Alpha family Human genes 0.000 description 1
- 108091071248 Alpha family Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 239000007989 BIS-Tris Propane buffer Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- PHTWJYKTJHIGSI-UHFFFAOYSA-N ClC1=C(C(=C(C=C1)N(C(=O)N)C1COCC1)O)S(N)(=O)=O Chemical compound ClC1=C(C(=C(C=C1)N(C(=O)N)C1COCC1)O)S(N)(=O)=O PHTWJYKTJHIGSI-UHFFFAOYSA-N 0.000 description 1
- JIXHELUJMDZLEA-UHFFFAOYSA-N ClN(Cl)S(=O)=O Chemical compound ClN(Cl)S(=O)=O JIXHELUJMDZLEA-UHFFFAOYSA-N 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 101100289989 Drosophila melanogaster alpha-Man-Ia gene Proteins 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101000818522 Homo sapiens fMet-Leu-Phe receptor Proteins 0.000 description 1
- 206010020591 Hypercapnia Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 101150021286 MAS1 gene Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- DKAGYWMRLDKJMI-UHFFFAOYSA-N NS(=O)(=O)C=1C(=C(C=CC1Cl)N(C(=O)N)C1CC1)O Chemical compound NS(=O)(=O)C=1C(=C(C=CC1Cl)N(C(=O)N)C1CC1)O DKAGYWMRLDKJMI-UHFFFAOYSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 208000028361 Penetrating Head injury Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Chemical class 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 208000000924 Right ventricular hypertrophy Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage 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
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- VYWQTJWGWLKBQA-UHFFFAOYSA-N [amino(hydroxy)methylidene]azanium;chloride Chemical compound Cl.NC(N)=O VYWQTJWGWLKBQA-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 210000001056 activated astrocyte Anatomy 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 230000009692 acute damage Effects 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000005667 attractant Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- HHKZCCWKTZRCCL-UHFFFAOYSA-N bis-tris propane Chemical compound OCC(CO)(CO)NCCCNC(CO)(CO)CO HHKZCCWKTZRCCL-UHFFFAOYSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000036978 cell physiology Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000031902 chemoattractant activity Effects 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960002152 chlorhexidine acetate Drugs 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 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
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- UQHKFADEQIVWID-UHFFFAOYSA-N cytokinin Natural products C1=NC=2C(NCC=C(CO)C)=NC=NC=2N1C1CC(O)C(CO)O1 UQHKFADEQIVWID-UHFFFAOYSA-N 0.000 description 1
- 239000004062 cytokinin Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- BPXYEYJNCXITEY-UHFFFAOYSA-N diazonio(trifluoromethoxy)azanide Chemical compound FC(F)(F)ON=[N+]=[N-] BPXYEYJNCXITEY-UHFFFAOYSA-N 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 210000003622 mature neutrocyte Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- JEDHEXUPBRMUMB-UHFFFAOYSA-N n,n-dimethylpyridin-3-amine Chemical compound CN(C)C1=CC=CN=C1 JEDHEXUPBRMUMB-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 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
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000000025 natural resin Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- UJJUJHTVDYXQON-UHFFFAOYSA-N nitro benzenesulfonate Chemical compound [O-][N+](=O)OS(=O)(=O)C1=CC=CC=C1 UJJUJHTVDYXQON-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- BOTREHHXSQGWTR-UHFFFAOYSA-N oxolane-3-carboxylic acid Chemical compound OC(=O)C1CCOC1 BOTREHHXSQGWTR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 235000021400 peanut butter Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- IIKFXOLJMNWWCH-UHFFFAOYSA-N piperidine-1,4-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)CC1 IIKFXOLJMNWWCH-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000009719 regenerative response Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- BSWOVOPHAZMAHS-UHFFFAOYSA-N tert-butyl 5-chloro-2-oxo-4-sulfamoyl-1,3-benzoxazole-3-carboxylate Chemical compound NS(=O)(=O)C1=C(C=CC2=C1N(C(O2)=O)C(=O)OC(C)(C)C)Cl BSWOVOPHAZMAHS-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/47—Y being a hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no 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
- C07D307/22—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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
- C07D309/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biotechnology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Toxicology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18984800P | 2000-03-16 | 2000-03-16 | |
| PCT/US2001/008672 WO2001068084A1 (en) | 2000-03-16 | 2001-03-16 | Il-8 receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BG107013A true BG107013A (bg) | 2003-05-30 |
Family
ID=22699008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG107013A BG107013A (bg) | 2000-03-16 | 2002-08-20 | Il-8 рецепторни антагонисти |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP1263427A4 (enExample) |
| JP (1) | JP2003526664A (enExample) |
| KR (1) | KR20020091130A (enExample) |
| CN (1) | CN1424910A (enExample) |
| AP (1) | AP2002002606A0 (enExample) |
| AR (1) | AR031098A1 (enExample) |
| AU (1) | AU2001250873A1 (enExample) |
| BG (1) | BG107013A (enExample) |
| BR (1) | BR0108749A (enExample) |
| CA (1) | CA2403062A1 (enExample) |
| CO (1) | CO5280089A1 (enExample) |
| CZ (1) | CZ20023075A3 (enExample) |
| DZ (1) | DZ3317A1 (enExample) |
| EA (1) | EA200200981A1 (enExample) |
| HU (1) | HUP0300470A3 (enExample) |
| MA (1) | MA25659A1 (enExample) |
| MX (1) | MXPA02009094A (enExample) |
| NO (1) | NO20024367L (enExample) |
| OA (1) | OA12231A (enExample) |
| PL (1) | PL366034A1 (enExample) |
| SK (1) | SK13282002A3 (enExample) |
| WO (1) | WO2001068084A1 (enExample) |
| ZA (1) | ZA200207325B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR030689A1 (es) * | 2000-03-14 | 2003-09-03 | Smithkline Beecham Corp | Compuestos de 3-aminosulfonil-2-hidroxifenil urea, composiciones farmaceuticas que los comprenden, y uso de dichos compuestos en la manufactura de medicamentos para tratar enfermedades mediadas por quimioquinas |
| CN1984899B (zh) | 2004-05-12 | 2011-07-27 | 先灵公司 | Cxcr1和cxcr2趋化因子拮抗剂 |
| CA2650007A1 (en) * | 2006-04-21 | 2007-11-01 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
| MX2008013600A (es) * | 2006-04-21 | 2008-10-31 | Smithkline Beechman Corp | Antagonistas del receptor de interleuquina-8. |
| CR20160557A (es) | 2014-05-29 | 2017-01-20 | Glaxosmithkline Ip Dev Ltd | Compuestos derivados de 1-(ciclopent-2-en-1-il)-3-(2-hidroxi-3-(arilsulfonil)fenil)urea como inhibidores cxcr2 |
| KR20170036753A (ko) * | 2014-07-31 | 2017-04-03 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 화학요법 유도된 말초 신경병증 (cipn)의 예방 및/또는 치료를 위한 cxcr2 길항제의 용도 |
| CN111727184B (zh) | 2018-01-11 | 2022-06-28 | 深圳嘉科生物科技有限公司 | Cxcr2拮抗剂 |
| WO2021004531A1 (zh) * | 2019-07-11 | 2021-01-14 | 南京明德新药研发有限公司 | 一种cxcr2拮抗剂的晶型及其应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11503110A (ja) * | 1995-02-17 | 1999-03-23 | スミスクライン・ビーチャム・コーポレイション | Ｉｌ−８受容体拮抗剤 |
| CZ425598A3 (cs) * | 1996-06-27 | 1999-08-11 | Smithkline Beecham Corporation | Antagonista IL-8 receptoru |
| WO1998007418A1 (en) * | 1996-08-21 | 1998-02-26 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
| DK1115701T3 (da) * | 1998-09-23 | 2003-06-23 | Tularik Inc | Arylsulfonanilidurinstoffer |
| UY25842A1 (es) * | 1998-12-16 | 2001-04-30 | Smithkline Beecham Corp | Antagonistas de receptores de il-8 |
-
2001
- 2001-03-14 CO CO01020681A patent/CO5280089A1/es not_active Application Discontinuation
- 2001-03-14 AR ARP010101183A patent/AR031098A1/es unknown
- 2001-03-16 EA EA200200981A patent/EA200200981A1/ru unknown
- 2001-03-16 BR BR0108749-5A patent/BR0108749A/pt not_active Application Discontinuation
- 2001-03-16 DZ DZ013317A patent/DZ3317A1/fr active
- 2001-03-16 AP APAP/P/2002/002606A patent/AP2002002606A0/en unknown
- 2001-03-16 PL PL01366034A patent/PL366034A1/xx not_active Application Discontinuation
- 2001-03-16 OA OA1200200289A patent/OA12231A/en unknown
- 2001-03-16 SK SK1328-2002A patent/SK13282002A3/sk unknown
- 2001-03-16 CZ CZ20023075A patent/CZ20023075A3/cs unknown
- 2001-03-16 WO PCT/US2001/008672 patent/WO2001068084A1/en not_active Ceased
- 2001-03-16 CN CN01806605A patent/CN1424910A/zh active Pending
- 2001-03-16 MX MXPA02009094A patent/MXPA02009094A/es active IP Right Grant
- 2001-03-16 CA CA002403062A patent/CA2403062A1/en not_active Abandoned
- 2001-03-16 EP EP01924195A patent/EP1263427A4/en not_active Withdrawn
- 2001-03-16 HU HU0300470A patent/HUP0300470A3/hu unknown
- 2001-03-16 JP JP2001566648A patent/JP2003526664A/ja not_active Withdrawn
- 2001-03-16 KR KR1020027012102A patent/KR20020091130A/ko not_active Withdrawn
- 2001-03-16 AU AU2001250873A patent/AU2001250873A1/en not_active Abandoned
-
2002
- 2002-08-20 BG BG107013A patent/BG107013A/bg unknown
- 2002-09-12 MA MA26815A patent/MA25659A1/fr unknown
- 2002-09-12 NO NO20024367A patent/NO20024367L/no unknown
- 2002-09-12 ZA ZA200207325A patent/ZA200207325B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AP2002002606A0 (en) | 2002-09-30 |
| WO2001068084A1 (en) | 2001-09-20 |
| MXPA02009094A (es) | 2003-03-12 |
| HUP0300470A3 (en) | 2005-05-30 |
| PL366034A1 (en) | 2005-01-24 |
| CO5280089A1 (es) | 2003-05-30 |
| EP1263427A4 (en) | 2005-08-24 |
| AR031098A1 (es) | 2003-09-10 |
| OA12231A (en) | 2003-11-07 |
| NO20024367D0 (no) | 2002-09-12 |
| KR20020091130A (ko) | 2002-12-05 |
| CN1424910A (zh) | 2003-06-18 |
| EA200200981A1 (ru) | 2003-02-27 |
| CZ20023075A3 (cs) | 2003-05-14 |
| EP1263427A1 (en) | 2002-12-11 |
| SK13282002A3 (sk) | 2003-02-04 |
| HUP0300470A2 (hu) | 2003-06-28 |
| CA2403062A1 (en) | 2001-09-20 |
| ZA200207325B (en) | 2003-10-17 |
| BR0108749A (pt) | 2004-06-29 |
| AU2001250873A1 (en) | 2001-09-24 |
| NO20024367L (no) | 2002-10-22 |
| MA25659A1 (fr) | 2002-12-31 |
| DZ3317A1 (enExample) | 2001-09-20 |
| JP2003526664A (ja) | 2003-09-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20030109527A1 (en) | Hydroxy diphenyl urea sulfonamides as IL-8 receptor antagonists | |
| US20040132694A1 (en) | Il-8 receptor antagonists | |
| US7709485B2 (en) | IL-8 receptor antagonists | |
| BG107014A (bg) | Il - 8 рецепторни антагонисти | |
| JP2008517054A (ja) | Ｉｌ−８受容体アンタゴニスト | |
| US6680317B2 (en) | IL-8 receptor antagonists | |
| EP1274415A2 (en) | Il-8 receptor antagonists | |
| US6653310B2 (en) | IL-8 receptor antagonists | |
| US6767922B2 (en) | IL-8 receptor antagonists | |
| SK13282002A3 (sk) | Sulfónamidové substituované difenylmočovinové zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie | |
| US6664259B2 (en) | Il-8 receptor antagonists | |
| US20030050298A1 (en) | Il-8 receptor antagonists | |
| US20030065170A1 (en) | Il-8 receptor antagonists | |
| EP1265603B1 (en) | Il-8 receptor antagonists |