CZ20023075A3 - Antagonisté IL-8 receptoru - Google Patents
Antagonisté IL-8 receptoru Download PDFInfo
- Publication number
- CZ20023075A3 CZ20023075A3 CZ20023075A CZ20023075A CZ20023075A3 CZ 20023075 A3 CZ20023075 A3 CZ 20023075A3 CZ 20023075 A CZ20023075 A CZ 20023075A CZ 20023075 A CZ20023075 A CZ 20023075A CZ 20023075 A3 CZ20023075 A3 CZ 20023075A3
- Authority
- CZ
- Czechia
- Prior art keywords
- carbon atoms
- group
- alkyl
- chloro
- optionally substituted
- Prior art date
Links
- 102000010681 interleukin-8 receptors Human genes 0.000 title description 9
- 108010038415 interleukin-8 receptors Proteins 0.000 title description 7
- 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 83
- 201000010099 disease Diseases 0.000 claims abstract description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 230000001404 mediated effect Effects 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 154
- 125000000217 alkyl group Chemical group 0.000 claims description 81
- -1 OR a Chemical group 0.000 claims description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000003342 alkenyl group Chemical group 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 208000014674 injury Diseases 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 25
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 18
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims description 9
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 230000009529 traumatic brain injury Effects 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 7
- 206010040070 Septic Shock Diseases 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 230000008733 trauma Effects 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 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
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 108010018976 Interleukin-8A Receptors Proteins 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 230000000241 respiratory effect Effects 0.000 claims description 4
- 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 3
- FXCSFWFPSKYJDE-UHFFFAOYSA-N 1-(4-chloro-2-hydroxy-3-sulfamoylphenyl)-3-cyclohexylurea Chemical compound NS(=O)(=O)C1=C(Cl)C=CC(NC(=O)NC2CCCCC2)=C1O FXCSFWFPSKYJDE-UHFFFAOYSA-N 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 230000002685 pulmonary effect Effects 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 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 description 2
- 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
- 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 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
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
- 208000000884 Airway Obstruction Diseases 0.000 claims description 2
- 208000024827 Alzheimer disease 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
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000034656 Contusions Diseases 0.000 claims description 2
- 206010011224 Cough Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 208000000059 Dyspnea Diseases 0.000 claims description 2
- 206010013975 Dyspnoeas Diseases 0.000 claims description 2
- 206010014561 Emphysema Diseases 0.000 claims description 2
- 206010014824 Endotoxic shock Diseases 0.000 claims description 2
- 206010020591 Hypercapnia Diseases 0.000 claims description 2
- 206010058490 Hyperoxia 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
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 201000009906 Meningitis Diseases 0.000 claims description 2
- 206010050031 Muscle strain Diseases 0.000 claims description 2
- 206010029888 Obliterative bronchiolitis Diseases 0.000 claims description 2
- 206010030216 Oesophagitis Diseases 0.000 claims description 2
- 208000006399 Premature Obstetric Labor Diseases 0.000 claims description 2
- 206010036600 Premature labour Diseases 0.000 claims description 2
- 208000003251 Pruritus Diseases 0.000 claims description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
- 208000036824 Psoriatic arthropathy 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
- 208000037656 Respiratory Sounds Diseases 0.000 claims description 2
- 208000000924 Right ventricular hypertrophy Diseases 0.000 claims description 2
- 206010040047 Sepsis Diseases 0.000 claims description 2
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 2
- 208000032851 Subarachnoid Hemorrhage 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
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 206010047115 Vasculitis Diseases 0.000 claims description 2
- 206010047924 Wheezing Diseases 0.000 claims description 2
- 206010000496 acne Diseases 0.000 claims description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- 201000003848 bronchiolitis obliterans Diseases 0.000 claims description 2
- 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 208000010353 central nervous system vasculitis Diseases 0.000 claims description 2
- 208000027157 chronic rhinosinusitis Diseases 0.000 claims description 2
- 208000000718 duodenal ulcer Diseases 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 206010014599 encephalitis Diseases 0.000 claims description 2
- 208000006881 esophagitis Diseases 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 208000006454 hepatitis Diseases 0.000 claims description 2
- 231100000283 hepatitis Toxicity 0.000 claims description 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 2
- 230000000222 hyperoxic effect Effects 0.000 claims description 2
- 208000018875 hypoxemia Diseases 0.000 claims description 2
- 230000007954 hypoxia Effects 0.000 claims description 2
- 230000007803 itching Effects 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 230000036407 pain Effects 0.000 claims description 2
- 208000005987 polymyositis Diseases 0.000 claims description 2
- 208000026440 premature labor Diseases 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 208000023504 respiratory system disease Diseases 0.000 claims description 2
- 201000000306 sarcoidosis Diseases 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 241001529453 unidentified herpesvirus Species 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims 3
- 206010033646 Acute and chronic pancreatitis Diseases 0.000 claims 1
- 206010006448 Bronchiolitis Diseases 0.000 claims 1
- 206010006458 Bronchitis chronic Diseases 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 claims 1
- 206010024453 Ligament sprain Diseases 0.000 claims 1
- 206010051606 Necrotising colitis Diseases 0.000 claims 1
- 208000002353 alcoholic hepatitis Diseases 0.000 claims 1
- 125000005324 aryloxy alkyloxy group Chemical group 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 208000025997 central nervous system neoplasm Diseases 0.000 claims 1
- 208000007451 chronic bronchitis Diseases 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 208000007565 gingivitis Diseases 0.000 claims 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 claims 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 claims 1
- 159000000001 potassium salts Chemical class 0.000 claims 1
- 208000013220 shortness of breath Diseases 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 35
- 238000011282 treatment Methods 0.000 abstract description 16
- 108090001007 Interleukin-8 Proteins 0.000 abstract description 5
- 102000004890 Interleukin-8 Human genes 0.000 abstract description 4
- 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 2
- 229940096397 interleukin-8 Drugs 0.000 abstract 2
- 102000019034 Chemokines Human genes 0.000 abstract 1
- 108010012236 Chemokines Proteins 0.000 abstract 1
- 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 39
- 239000000243 solution Substances 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 22
- 108010014419 Chemokine CXCL1 Proteins 0.000 description 22
- 101000973997 Homo sapiens Nucleosome assembly protein 1-like 4 Proteins 0.000 description 22
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 description 22
- 102100036154 Platelet basic protein Human genes 0.000 description 22
- 208000027418 Wounds and injury Diseases 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 230000006378 damage Effects 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 210000000440 neutrophil Anatomy 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
- 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 15
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 15
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 12
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 108020004999 messenger RNA Proteins 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 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 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 239000004062 cytokinin Substances 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 229940124530 sulfonamide Drugs 0.000 description 8
- 150000003456 sulfonamides Chemical class 0.000 description 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000035605 chemotaxis Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 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
- 230000004913 activation Effects 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 208000029028 brain injury Diseases 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 102000016387 Pancreatic elastase Human genes 0.000 description 5
- 108010067372 Pancreatic elastase Proteins 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 210000002889 endothelial cell Anatomy 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000010791 quenching Methods 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
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-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
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 4
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 210000003651 basophil Anatomy 0.000 description 4
- 239000004202 carbamide 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
- 229940079593 drug Drugs 0.000 description 4
- 238000002451 electron ionisation mass spectrometry Methods 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
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 230000001936 parietal effect Effects 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
- 239000013641 positive control Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 150000003460 sulfonic acids Chemical class 0.000 description 4
- 150000003461 sulfonyl halides Chemical class 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-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
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 235000019483 Peanut oil Nutrition 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- 150000001412 amines Chemical class 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- 230000003399 chemotactic effect Effects 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 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
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 210000001519 tissue Anatomy 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
- 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
- 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 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
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000018652 Closed Head injury Diseases 0.000 description 2
- 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 206010019196 Head injury Diseases 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
- 208000032382 Ischaemic stroke Diseases 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
- 206010028980 Neoplasm Diseases 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
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 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
- 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 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
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000008611 intercellular interaction Effects 0.000 description 2
- 230000021995 interleukin-8 production Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000000302 ischemic effect Effects 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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 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
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 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
- 238000002156 mixing Methods 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 230000011242 neutrophil chemotaxis Effects 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 210000001331 nose Anatomy 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
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 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
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- 230000009719 regenerative response Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000010079 rubber tapping Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GWEHVDNNLFDJLR-UHFFFAOYSA-N 1,3-diphenylurea Chemical class C=1C=CC=CC=1NC(=O)NC1=CC=CC=C1 GWEHVDNNLFDJLR-UHFFFAOYSA-N 0.000 description 1
- WPRAXAOJIODQJR-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(C)C(C)=C1 WPRAXAOJIODQJR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 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
- 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 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
- 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 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- LNAANGYWIDUDRG-UHFFFAOYSA-N 1-butoxycarbonylpiperidine-4-carboxylic acid Chemical compound CCCCOC(=O)N1CCC(C(O)=O)CC1 LNAANGYWIDUDRG-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
- 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
- 125000004974 2-butenyl group Chemical group C(C=CC)* 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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 101001069913 Bos taurus Growth-regulated protein homolog beta Proteins 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
- 102100036189 C-X-C motif chemokine 3 Human genes 0.000 description 1
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
- 101100504320 Caenorhabditis elegans mcp-1 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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 class ClN(Cl)S(=O)=O JIXHELUJMDZLEA-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 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
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000947193 Homo sapiens C-X-C motif chemokine 3 Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101000818522 Homo sapiens fMet-Leu-Phe receptor Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 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
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- 102100026236 Interleukin-8 Human genes 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 208000032984 Intraoperative Complications Diseases 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
- 239000004166 Lanolin Substances 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028851 Necrosis Diseases 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
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Chemical class 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 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
- 229910021626 Tin(II) chloride Inorganic materials 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
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010052428 Wound Diseases 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
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 210000001056 activated astrocyte Anatomy 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000026816 acute arthritis Diseases 0.000 description 1
- 230000009692 acute damage Effects 0.000 description 1
- 238000007259 addition reaction Methods 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
- 230000010085 airway hyperresponsiveness Effects 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
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 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
- 238000013459 approach Methods 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000003143 atherosclerotic effect Effects 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
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid 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
- 230000036770 blood supply Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 208000034526 bruise Diseases 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- WOBLPDAWNVAVAS-UHFFFAOYSA-N butyl carboxy carbonate Chemical compound CCCCOC(=O)OC(O)=O WOBLPDAWNVAVAS-UHFFFAOYSA-N 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
- 239000003093 cationic surfactant Substances 0.000 description 1
- 230000036978 cell physiology Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000031902 chemoattractant activity Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229960002152 chlorhexidine acetate Drugs 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 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
- 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
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 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
- 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
- 208000010227 enterocolitis Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- RYNBQQWODYCGRR-UHFFFAOYSA-N ethyl 5-(4-chlorophenyl)-2-methyl-1-phenylpyrrole-3-carboxylate Chemical compound C=1C=CC=CC=1N1C(C)=C(C(=O)OCC)C=C1C1=CC=C(Cl)C=C1 RYNBQQWODYCGRR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 description 1
- 238000010265 fast atom bombardment Methods 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
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 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
- 239000003292 glue Substances 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 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
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 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
- NONOKGVFTBWRLD-UHFFFAOYSA-N isocyanatosulfanylimino(oxo)methane Chemical compound O=C=NSN=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000012669 liquid formulation Substances 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
- 230000002132 lysosomal effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 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
- ZKTLKYRAZWGBDB-UHFFFAOYSA-N n-methyl-n-propan-2-ylformamide Chemical compound CC(C)N(C)C=O ZKTLKYRAZWGBDB-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000030505 negative regulation of chemotaxis Effects 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
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- BOTREHHXSQGWTR-UHFFFAOYSA-N oxolane-3-carboxylic acid Chemical compound OC(=O)C1CCOC1 BOTREHHXSQGWTR-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 238000009527 percussion Methods 0.000 description 1
- 150000002978 peroxides Chemical class 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
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 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
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000009666 routine test Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 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
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000003375 sulfoxide group Chemical group 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
- 239000003826 tablet Substances 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 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
- 238000002560 therapeutic procedure Methods 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
- 150000003585 thioureas Chemical class 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 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
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (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)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Transplantation (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US18984800P | 2000-03-16 | 2000-03-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
CZ20023075A3 true CZ20023075A3 (cs) | 2003-05-14 |
Family
ID=22699008
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CZ20023075A CZ20023075A3 (cs) | 2000-03-16 | 2001-03-16 | Antagonisté IL-8 receptoru |
Country Status (23)
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 |
US7326729B2 (en) | 2004-05-12 | 2008-02-05 | Schering Corporation | CXCR1 and CXCR2 chemokine antagonists |
AU2007240364A1 (en) * | 2006-04-21 | 2007-11-01 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
BRPI0710232B8 (pt) * | 2006-04-21 | 2021-05-25 | Glaxosmithkline Llc | composto antagonista do receptor de il-8, composição farmacêutica que compreende o dito composto e uso do mesmo para o tratamento de uma doença mediada por quimiocina |
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 |
BR112017002060A2 (pt) * | 2014-07-31 | 2017-12-26 | Glaxosmithkline Ip Dev Ltd | novo uso |
JP7223764B2 (ja) * | 2018-01-11 | 2023-02-16 | シェンチェン オプティマム バイオロジカル テクノロジー カンパニー,リミティド | Cxcr2アンタゴニスト |
CN114286819B (zh) * | 2019-07-11 | 2024-03-05 | 深圳嘉科生物科技有限公司 | 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 |
CA2258850A1 (en) * | 1996-06-27 | 1997-12-31 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
WO1998007418A1 (en) * | 1996-08-21 | 1998-02-26 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
PT1115701E (pt) * | 1998-09-23 | 2003-09-30 | Tularik Inc | Ureias de arilsulfonanilida |
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 WO PCT/US2001/008672 patent/WO2001068084A1/en not_active Application Discontinuation
- 2001-03-16 AU AU2001250873A patent/AU2001250873A1/en not_active Abandoned
- 2001-03-16 OA OA1200200289A patent/OA12231A/en unknown
- 2001-03-16 HU HU0300470A patent/HUP0300470A3/hu unknown
- 2001-03-16 KR KR1020027012102A patent/KR20020091130A/ko not_active Withdrawn
- 2001-03-16 MX MXPA02009094A patent/MXPA02009094A/es active IP Right Grant
- 2001-03-16 EA EA200200981A patent/EA200200981A1/ru unknown
- 2001-03-16 DZ DZ013317A patent/DZ3317A1/fr active
- 2001-03-16 BR BR0108749-5A patent/BR0108749A/pt not_active Application Discontinuation
- 2001-03-16 EP EP01924195A patent/EP1263427A4/en not_active Withdrawn
- 2001-03-16 CA CA002403062A patent/CA2403062A1/en not_active Abandoned
- 2001-03-16 CN CN01806605A patent/CN1424910A/zh active Pending
- 2001-03-16 SK SK1328-2002A patent/SK13282002A3/sk unknown
- 2001-03-16 AP APAP/P/2002/002606A patent/AP2002002606A0/en unknown
- 2001-03-16 JP JP2001566648A patent/JP2003526664A/ja not_active Withdrawn
- 2001-03-16 CZ CZ20023075A patent/CZ20023075A3/cs unknown
- 2001-03-16 PL PL01366034A patent/PL366034A1/xx not_active Application Discontinuation
-
2002
- 2002-08-20 BG BG107013A patent/BG107013A/bg unknown
- 2002-09-12 MA MA26815A patent/MA25659A1/fr unknown
- 2002-09-12 ZA ZA200207325A patent/ZA200207325B/en unknown
- 2002-09-12 NO NO20024367A patent/NO20024367L/no unknown
Also Published As
Publication number | Publication date |
---|---|
DZ3317A1 (enrdf_load_stackoverflow) | 2001-09-20 |
OA12231A (en) | 2003-11-07 |
MXPA02009094A (es) | 2003-03-12 |
EP1263427A1 (en) | 2002-12-11 |
NO20024367L (no) | 2002-10-22 |
KR20020091130A (ko) | 2002-12-05 |
WO2001068084A1 (en) | 2001-09-20 |
BG107013A (bg) | 2003-05-30 |
NO20024367D0 (no) | 2002-09-12 |
AP2002002606A0 (en) | 2002-09-30 |
CA2403062A1 (en) | 2001-09-20 |
PL366034A1 (en) | 2005-01-24 |
AR031098A1 (es) | 2003-09-10 |
HUP0300470A3 (en) | 2005-05-30 |
JP2003526664A (ja) | 2003-09-09 |
CN1424910A (zh) | 2003-06-18 |
BR0108749A (pt) | 2004-06-29 |
EP1263427A4 (en) | 2005-08-24 |
SK13282002A3 (sk) | 2003-02-04 |
ZA200207325B (en) | 2003-10-17 |
MA25659A1 (fr) | 2002-12-31 |
HUP0300470A2 (hu) | 2003-06-28 |
AU2001250873A1 (en) | 2001-09-24 |
EA200200981A1 (ru) | 2003-02-27 |
CO5280089A1 (es) | 2003-05-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6271261B1 (en) | IL-8 receptor antagonists | |
US6218539B1 (en) | IL-8 receptor antagonists | |
US6133319A (en) | IL-8 receptor antagonists | |
US6204294B1 (en) | IL-8 receptor antagonists | |
CZ20023915A3 (cs) | Antagonisté IL-8 receptoru | |
CZ20012150A3 (cs) | Sulfonamid hydroxydifenylmočoviny jako antagonista IL-8 receptoru | |
JP2001511130A (ja) | Il−8受容体アンタゴニスト | |
CZ20023007A3 (cs) | Antagonisté IL-8 receptoru | |
ZA200206988B (en) | IL-8 receptor antagonists. | |
US20090093492A1 (en) | Il-8 receptor antagonists | |
US6166055A (en) | Benzoisothiazole compounds useful as IL-8 receptor antagonists | |
CZ20023192A3 (cs) | Antagonisté IL-8 receptoru | |
CZ20014472A3 (cs) | Antagoniské IL-8 receptoru | |
JP2003527360A (ja) | Il−8受容体アンタゴニスト | |
CZ20023075A3 (cs) | Antagonisté IL-8 receptoru | |
US6653310B2 (en) | IL-8 receptor antagonists | |
US6767922B2 (en) | IL-8 receptor antagonists | |
US6221889B1 (en) | IL-8 receptor antagonists | |
US6664259B2 (en) | Il-8 receptor antagonists | |
US20030050298A1 (en) | Il-8 receptor antagonists | |
US20030065170A1 (en) | Il-8 receptor antagonists | |
CZ20023076A3 (cs) | Antagonisté IL-8 receptoru | |
CZ20014490A3 (cs) | Antagonisté IL-8 receptoru | |
JP2003513919A (ja) | Il−8受容体アンタゴニスト |