NO316625B1 - Nye substituerte imidazol-forbindelser - Google Patents

Info

Publication number

NO316625B1

NO316625B1 NO19983181A NO983181A NO316625B1 NO 316625 B1 NO316625 B1 NO 316625B1 NO 19983181 A NO19983181 A NO 19983181A NO 983181 A NO983181 A NO 983181A NO 316625 B1 NO316625 B1 NO 316625B1

Authority

NO

Norway

Prior art keywords

formula

compound

fluorophenyl

imidazole

pyrimidinyl

Prior art date

1996-01-11

Links

• Espacenet
• Global Dossier
• Discuss

• 150000002460 imidazoles Chemical class 0.000 title claims description 18
• -1 5-substituted imidazole compounds Chemical class 0.000 claims abstract description 47
• 150000001875 compounds Chemical class 0.000 claims description 182
• 238000000034 method Methods 0.000 claims description 62
• 238000006243 chemical reaction Methods 0.000 claims description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 50
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 50
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 40
• 201000010099 disease Diseases 0.000 claims description 40
• 238000002360 preparation method Methods 0.000 claims description 36
• 239000002904 solvent Substances 0.000 claims description 35
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
• 150000003839 salts Chemical class 0.000 claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• 150000002466 imines Chemical class 0.000 claims description 18
• 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 claims description 15
• 230000015572 biosynthetic process Effects 0.000 claims description 14
• 230000001404 mediated effect Effects 0.000 claims description 14
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 13
• 108010084680 Heterogeneous-Nuclear Ribonucleoprotein K Proteins 0.000 claims description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
• 239000002243 precursor Substances 0.000 claims description 9
• 206010061218 Inflammation Diseases 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 8
• 238000011065 in-situ storage Methods 0.000 claims description 8
• 230000004054 inflammatory process Effects 0.000 claims description 8
• 150000003141 primary amines Chemical class 0.000 claims description 8
• PDTYLGXVBIWRIM-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-methoxypyrimidine Chemical compound COC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCNCC2)=N1 PDTYLGXVBIWRIM-UHFFFAOYSA-N 0.000 claims description 7
• 239000003153 chemical reaction reagent Substances 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 125000000217 alkyl group Chemical group 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 5
• 150000002367 halogens Chemical class 0.000 claims description 5
• XFXPMWWXUTWYJX-UHFFFAOYSA-N isonitrile group Chemical group N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 5
• 229910052744 lithium Inorganic materials 0.000 claims description 5
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
• 230000008569 process Effects 0.000 claims description 5
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 4
• MNHRKQKSNCFFOW-UHFFFAOYSA-N 2-ethoxy-4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]pyrimidine Chemical compound CCOC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCNCC2)=N1 MNHRKQKSNCFFOW-UHFFFAOYSA-N 0.000 claims description 3
• AIXRGYVBRPTJPB-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-methoxypyridine Chemical compound C1=NC(OC)=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCNCC2)=C1 AIXRGYVBRPTJPB-UHFFFAOYSA-N 0.000 claims description 3
• FIZLSLKOKJYBBO-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-propan-2-yloxypyrimidine Chemical compound CC(C)OC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCNCC2)=N1 FIZLSLKOKJYBBO-UHFFFAOYSA-N 0.000 claims description 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
• 150000004678 hydrides Chemical class 0.000 claims description 3
• 102000004127 Cytokines Human genes 0.000 abstract description 41
• 108090000695 Cytokines Proteins 0.000 abstract description 41
• 239000000203 mixture Substances 0.000 abstract description 19
• 239000003112 inhibitor Substances 0.000 abstract description 7
• 238000002560 therapeutic procedure Methods 0.000 abstract description 4
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 57
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 56
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
• 239000000047 product Substances 0.000 description 41
• 102000000589 Interleukin-1 Human genes 0.000 description 40
• 108010002352 Interleukin-1 Proteins 0.000 description 40
• 210000004027 cell Anatomy 0.000 description 40
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• 102000004890 Interleukin-8 Human genes 0.000 description 33
• 108090001007 Interleukin-8 Proteins 0.000 description 33
• 239000002585 base Substances 0.000 description 32
• XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 31
• 229940096397 interleukin-8 Drugs 0.000 description 31
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 23
• 235000019439 ethyl acetate Nutrition 0.000 description 23
• 239000007787 solid Substances 0.000 description 23
• 238000011282 treatment Methods 0.000 description 23
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
• 230000014509 gene expression Effects 0.000 description 20
• 230000005764 inhibitory process Effects 0.000 description 19
• 238000004519 manufacturing process Methods 0.000 description 19
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 18
• 108090001005 Interleukin-6 Proteins 0.000 description 18
• 102000004889 Interleukin-6 Human genes 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• 229940100601 interleukin-6 Drugs 0.000 description 18
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
• 241000700605 Viruses Species 0.000 description 17
• 230000000694 effects Effects 0.000 description 17
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 239000011734 sodium Substances 0.000 description 15
• 239000000243 solution Substances 0.000 description 15
• 210000001616 monocyte Anatomy 0.000 description 14
• 239000003054 catalyst Substances 0.000 description 13
• 125000001072 heteroaryl group Chemical group 0.000 description 13
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
• 108020004999 messenger RNA Proteins 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• 241000725303 Human immunodeficiency virus Species 0.000 description 12
• 210000001744 T-lymphocyte Anatomy 0.000 description 12
• 230000000875 corresponding effect Effects 0.000 description 12
• 239000002158 endotoxin Substances 0.000 description 12
• 230000002401 inhibitory effect Effects 0.000 description 12
• 208000014674 injury Diseases 0.000 description 12
• 238000003786 synthesis reaction Methods 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 11
• 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 11
• 208000027418 Wounds and injury Diseases 0.000 description 11
• 125000003118 aryl group Chemical group 0.000 description 11
• 230000006378 damage Effects 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
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• 206010040070 Septic Shock Diseases 0.000 description 10
• 238000005859 coupling reaction Methods 0.000 description 10
• 230000002757 inflammatory effect Effects 0.000 description 10
• 229920006008 lipopolysaccharide Polymers 0.000 description 10
• 210000002540 macrophage Anatomy 0.000 description 10
• 210000000440 neutrophil Anatomy 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 238000005481 NMR spectroscopy Methods 0.000 description 9
• 150000001299 aldehydes Chemical class 0.000 description 9
• 150000001408 amides Chemical class 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• 241001465754 Metazoa Species 0.000 description 8
• 210000004556 brain Anatomy 0.000 description 8
• 238000010168 coupling process Methods 0.000 description 8
• 238000002474 experimental method Methods 0.000 description 8
• 238000010438 heat treatment Methods 0.000 description 8
• 150000002527 isonitriles Chemical class 0.000 description 8
• 230000006433 tumor necrosis factor production Effects 0.000 description 8
• DILXLMRYFWFBGR-UHFFFAOYSA-N 2-formylbenzene-1,4-disulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(S(O)(=O)=O)C(C=O)=C1 DILXLMRYFWFBGR-UHFFFAOYSA-N 0.000 description 7
• 208000030507 AIDS Diseases 0.000 description 7
• 206010006895 Cachexia Diseases 0.000 description 7
• 241000124008 Mammalia Species 0.000 description 7
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 150000001450 anions Chemical class 0.000 description 7
• 206010003246 arthritis Diseases 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 230000021995 interleukin-8 production Effects 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 239000002953 phosphate buffered saline Substances 0.000 description 7
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 6
• 102000014914 Carrier Proteins Human genes 0.000 description 6
• 241000713800 Feline immunodeficiency virus Species 0.000 description 6
• 208000031886 HIV Infections Diseases 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 6
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• 208000030886 Traumatic Brain injury Diseases 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 239000003377 acid catalyst Substances 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 108091008324 binding proteins Proteins 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• UQSQSQZYBQSBJZ-UHFFFAOYSA-M fluorosulfonate Chemical compound [O-]S(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-M 0.000 description 6
• 229910052739 hydrogen Inorganic materials 0.000 description 6
• 239000001257 hydrogen Substances 0.000 description 6
• 239000012442 inert solvent Substances 0.000 description 6
• 208000015181 infectious disease Diseases 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
• 230000000770 proinflammatory effect Effects 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 description 6
• 210000003491 skin Anatomy 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• 230000009529 traumatic brain injury Effects 0.000 description 6
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 208000002193 Pain Diseases 0.000 description 5
• 208000036142 Viral infection Diseases 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 230000008878 coupling Effects 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 230000016396 cytokine production Effects 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 230000018276 interleukin-1 production Effects 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 230000036407 pain Effects 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 150000003180 prostaglandins Chemical class 0.000 description 5
• 230000010076 replication Effects 0.000 description 5
• 230000009385 viral infection Effects 0.000 description 5
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• 206010001513 AIDS related complex Diseases 0.000 description 4
• 241000701022 Cytomegalovirus Species 0.000 description 4
• 206010014824 Endotoxic shock Diseases 0.000 description 4
• 201000005569 Gout Diseases 0.000 description 4
• 102000013967 Monokines Human genes 0.000 description 4
• 108010050619 Monokines Proteins 0.000 description 4
• 206010028289 Muscle atrophy Diseases 0.000 description 4
• 241000283973 Oryctolagus cuniculus Species 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 206010063837 Reperfusion injury Diseases 0.000 description 4
• 206010040047 Sepsis Diseases 0.000 description 4
• 230000006044 T cell activation Effects 0.000 description 4
• 206010044248 Toxic shock syndrome Diseases 0.000 description 4
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 4
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
• 150000001409 amidines Chemical class 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 208000029028 brain injury Diseases 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
• 230000005595 deprotonation Effects 0.000 description 4
• 238000010537 deprotonation reaction Methods 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• 210000002889 endothelial cell Anatomy 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 239000012530 fluid Substances 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 239000000499 gel Substances 0.000 description 4
• 210000001320 hippocampus Anatomy 0.000 description 4
• 238000007912 intraperitoneal administration Methods 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• 239000006210 lotion Substances 0.000 description 4
• 238000004949 mass spectrometry Methods 0.000 description 4
• 239000012074 organic phase Substances 0.000 description 4
• 201000008482 osteoarthritis Diseases 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 230000001936 parietal effect Effects 0.000 description 4
• 229920000136 polysorbate Polymers 0.000 description 4
• 238000011321 prophylaxis Methods 0.000 description 4
• 238000000159 protein binding assay Methods 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 150000003335 secondary amines Chemical class 0.000 description 4
• 238000010561 standard procedure Methods 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• 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 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
• 241000713704 Bovine immunodeficiency virus Species 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 3
• 238000012286 ELISA Assay Methods 0.000 description 3
• 241000713730 Equine infectious anemia virus Species 0.000 description 3
• 208000037357 HIV infectious disease Diseases 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
• 241000713340 Human immunodeficiency virus 2 Species 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 206010061598 Immunodeficiency Diseases 0.000 description 3
• 208000029462 Immunodeficiency disease Diseases 0.000 description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
• 102000004083 Lymphotoxin-alpha Human genes 0.000 description 3
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 3
• 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 3
• 201000004681 Psoriasis Diseases 0.000 description 3
• 206010037660 Pyrexia Diseases 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 3
• 206010038997 Retroviral infections Diseases 0.000 description 3
• 208000005074 Retroviridae Infections Diseases 0.000 description 3
• 208000006011 Stroke Diseases 0.000 description 3
• 241000713325 Visna/maedi virus Species 0.000 description 3
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 235000011054 acetic acid Nutrition 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 230000000844 anti-bacterial effect Effects 0.000 description 3
• 239000003899 bactericide agent Substances 0.000 description 3
• 210000003651 basophil Anatomy 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 150000001642 boronic acid derivatives Chemical class 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
• 238000001816 cooling Methods 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 239000012228 culture supernatant Substances 0.000 description 3
• 239000012024 dehydrating agents‎ Substances 0.000 description 3
• 230000018044 dehydration Effects 0.000 description 3
• 238000006297 dehydration reaction Methods 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 230000003828 downregulation Effects 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
• 150000002431 hydrogen Chemical class 0.000 description 3
• 230000007813 immunodeficiency Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000008595 infiltration Effects 0.000 description 3
• 238000001764 infiltration Methods 0.000 description 3
• 206010022000 influenza Diseases 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 3
• 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 208000021601 lentivirus infection Diseases 0.000 description 3
• 238000012423 maintenance Methods 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• 125000002734 organomagnesium group Chemical group 0.000 description 3
• 125000002524 organometallic group Chemical group 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 3
• 210000005259 peripheral blood Anatomy 0.000 description 3
• 239000011886 peripheral blood Substances 0.000 description 3
• 239000000825 pharmaceutical preparation Substances 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 239000013641 positive control Substances 0.000 description 3
• 235000015320 potassium carbonate Nutrition 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 230000035939 shock Effects 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 239000004094 surface-active agent Substances 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 230000029812 viral genome replication Effects 0.000 description 3
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• GACUCTNCAUTQPH-UHFFFAOYSA-N 2-methylpyrimidine-4-carbothialdehyde Chemical compound CC1=NC=CC(C=S)=N1 GACUCTNCAUTQPH-UHFFFAOYSA-N 0.000 description 2
• WVIBCGOMZSLTLD-UHFFFAOYSA-N 4-[5-(2-fluorophenyl)-3-(1-methylpiperidin-4-yl)imidazol-4-yl]-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(C=2N(C=NC=2C=2C(=CC=CC=2)F)C2CCN(C)CC2)=N1 WVIBCGOMZSLTLD-UHFFFAOYSA-N 0.000 description 2
• UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 2
• MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical compound C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 description 2
• PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• 206010002091 Anaesthesia Diseases 0.000 description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• 108010002493 Arachin Proteins 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 206010063094 Cerebral malaria Diseases 0.000 description 2
• 206010009900 Colitis ulcerative Diseases 0.000 description 2
• 206010010741 Conjunctivitis Diseases 0.000 description 2
• 206010011224 Cough Diseases 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• 102000001301 EGF receptor Human genes 0.000 description 2
• 108060006698 EGF receptor Proteins 0.000 description 2
• 208000037487 Endotoxemia Diseases 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• 206010018634 Gouty Arthritis Diseases 0.000 description 2
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
• 206010020164 HIV infection CDC Group III 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
• 102400001232 IL-8(6-77) Human genes 0.000 description 2
• 238000012404 In vitro experiment Methods 0.000 description 2
• 108010002350 Interleukin-2 Proteins 0.000 description 2
• 102000000588 Interleukin-2 Human genes 0.000 description 2
• 108010074338 Lymphokines Proteins 0.000 description 2
• 102000008072 Lymphokines Human genes 0.000 description 2
• AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 208000000112 Myalgia Diseases 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• 108010025020 Nerve Growth Factor Proteins 0.000 description 2
• 238000000636 Northern blotting Methods 0.000 description 2
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
• 208000033464 Reiter syndrome Diseases 0.000 description 2
• 201000010001 Silicosis Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• 206010042496 Sunburn Diseases 0.000 description 2
• 208000007536 Thrombosis Diseases 0.000 description 2
• 206010048873 Traumatic arthritis Diseases 0.000 description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• GELXFVQAWNTGPQ-UHFFFAOYSA-N [N].C1=CNC=N1 Chemical compound [N].C1=CNC=N1 GELXFVQAWNTGPQ-UHFFFAOYSA-N 0.000 description 2
• 150000001241 acetals Chemical class 0.000 description 2
• 238000007171 acid catalysis Methods 0.000 description 2
• 150000001266 acyl halides Chemical class 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 230000037005 anaesthesia Effects 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 229940114079 arachidonic acid Drugs 0.000 description 2
• 235000021342 arachidonic acid Nutrition 0.000 description 2
• 230000002917 arthritic effect Effects 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 230000027455 binding Effects 0.000 description 2
• 238000004166 bioassay Methods 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• 208000019664 bone resorption disease Diseases 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000001273 butane Substances 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 230000000747 cardiac effect Effects 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
• 150000001768 cations Chemical class 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• WNPXRNJEBMRJGV-UHFFFAOYSA-N chembl1399590 Chemical compound COC1=CC=CC(C=2N=C3C=CC=CC3=C(N3C(CCCC3)C)N=2)=C1O WNPXRNJEBMRJGV-UHFFFAOYSA-N 0.000 description 2
• 230000035605 chemotaxis Effects 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 230000020176 deacylation Effects 0.000 description 2
• 238000005947 deacylation reaction Methods 0.000 description 2
• 239000003814 drug Substances 0.000 description 2
• 210000002950 fibroblast Anatomy 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 239000012737 fresh medium Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000000417 fungicide Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 150000003278 haem Chemical class 0.000 description 2
• 238000009396 hybridization Methods 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 238000010952 in-situ formation Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• 125000002346 iodo group Chemical group I* 0.000 description 2
• 208000011379 keloid formation Diseases 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 210000000265 leukocyte Anatomy 0.000 description 2
• 239000000865 liniment Substances 0.000 description 2
• 150000002641 lithium Chemical class 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 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
• 230000036210 malignancy Effects 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 210000005087 mononuclear cell Anatomy 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 229940053128 nerve growth factor Drugs 0.000 description 2
• 230000011242 neutrophil chemotaxis Effects 0.000 description 2
• 230000003448 neutrophilic effect Effects 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• HCZKYJDFEPMADG-UHFFFAOYSA-N nordihydroguaiaretic acid Chemical compound C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 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
• 239000002674 ointment Substances 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 235000008390 olive oil Nutrition 0.000 description 2
• 238000005580 one pot reaction Methods 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 2
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
• 239000006072 paste Substances 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
• 229960001412 pentobarbital Drugs 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 230000002685 pulmonary effect Effects 0.000 description 2
• 201000003651 pulmonary sarcoidosis Diseases 0.000 description 2
• 230000035484 reaction time Effects 0.000 description 2
• 208000002574 reactive arthritis Diseases 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 201000005404 rubella Diseases 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 231100000241 scar Toxicity 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 238000012453 sprague-dawley rat model Methods 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 239000012258 stirred mixture Substances 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 230000035882 stress Effects 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 201000004595 synovitis Diseases 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
• LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 2
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
• 230000009772 tissue formation Effects 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000000699 topical effect Effects 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
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• 150000008648 triflates Chemical class 0.000 description 2
• 238000001665 trituration Methods 0.000 description 2
• 201000008827 tuberculosis Diseases 0.000 description 2
• PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 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
• AVGQTJUPLKNPQP-UHFFFAOYSA-N 1,1,1-trichloropropane Chemical compound CCC(Cl)(Cl)Cl AVGQTJUPLKNPQP-UHFFFAOYSA-N 0.000 description 1
• SZXUTTGMFUSMCE-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)pyridine Chemical class C1=CNC(C=2N=CC=CC=2)=N1 SZXUTTGMFUSMCE-UHFFFAOYSA-N 0.000 description 1
• AGSOOCUNMTYPSE-UHFFFAOYSA-N 2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-1,2-oxazol-4-yl]propanoic acid Chemical compound CC(C)(C)C=1ON=C(OCP(O)(O)=O)C=1CC(N)C(O)=O AGSOOCUNMTYPSE-UHFFFAOYSA-N 0.000 description 1
• VLUWLNIMIAFOSY-UHFFFAOYSA-N 2-methylbenzenesulfinic acid Chemical compound CC1=CC=CC=C1S(O)=O VLUWLNIMIAFOSY-UHFFFAOYSA-N 0.000 description 1
• SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• FVKFHMNJTHKMRX-UHFFFAOYSA-N 3,4,6,7,8,9-hexahydro-2H-pyrimido[1,2-a]pyrimidine Chemical compound C1CCN2CCCNC2=N1 FVKFHMNJTHKMRX-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
• JAOINXWEFKZYIL-UHFFFAOYSA-N 4-(1-methyl-2-oxoquinolin-4-yl)oxy-n-(4-methylpyridin-2-yl)butanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CC=NC(NC(=O)CCCOC=2C3=CC=CC=C3N(C)C(=O)C=2)=C1 JAOINXWEFKZYIL-UHFFFAOYSA-N 0.000 description 1
• HRNNNYZRMMSALR-UHFFFAOYSA-N 4-(sulfanylmethyl)benzaldehyde Chemical compound SCC1=CC=C(C=O)C=C1 HRNNNYZRMMSALR-UHFFFAOYSA-N 0.000 description 1
• SBBOUGYYUQJJQX-UHFFFAOYSA-N 4-[3-tert-butyl-5-(4-fluorophenyl)imidazol-4-yl]-2-methylsulfinylpyrimidine Chemical compound CS(=O)C1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C(C)(C)C)=N1 SBBOUGYYUQJJQX-UHFFFAOYSA-N 0.000 description 1
• FGQOBCJFMXLOSX-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-methoxypyrimidine 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-propan-2-yloxypyrimidine Chemical compound N1CCC(CC1)N1C=NC(=C1C1=NC(=NC=C1)OC)C1=CC=C(C=C1)F.N1CCC(CC1)N1C=NC(=C1C1=NC(=NC=C1)OC(C)C)C1=CC=C(C=C1)F FGQOBCJFMXLOSX-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 1
• GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 1
• RTLUPHDWSUGAOS-UHFFFAOYSA-N 4-iodopyridine Chemical compound IC1=CC=NC=C1 RTLUPHDWSUGAOS-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 1
• FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 1
• YOELZIQOLWZLQC-UHFFFAOYSA-N 6-(4-fluorophenyl)-5-pyridin-4-yl-2,3-dihydroimidazo[2,1-b]thiazole Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N2CCSC2=N1 YOELZIQOLWZLQC-UHFFFAOYSA-N 0.000 description 1
• USXRQLHRXISPLK-UHFFFAOYSA-N 6-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-1h-pyrimidin-2-one Chemical compound OC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCNCC2)=N1 USXRQLHRXISPLK-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 102100021870 ATP synthase subunit O, mitochondrial Human genes 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
• 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 244000144725 Amygdalus communis Species 0.000 description 1
• 235000011437 Amygdalus communis Nutrition 0.000 description 1
• 206010003645 Atopy Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 208000006386 Bone Resorption Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• 241000283074 Equus asinus Species 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• OUHGTOMCWYHIPN-UHFFFAOYSA-N FC(F)(F)S(=O)(=O)[IH]Br Chemical compound FC(F)(F)S(=O)(=O)[IH]Br OUHGTOMCWYHIPN-UHFFFAOYSA-N 0.000 description 1
• 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
• 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
• 229920001917 Ficoll Polymers 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 102100030385 Granzyme B Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 208000009889 Herpes Simplex Diseases 0.000 description 1
• 208000007514 Herpes zoster Diseases 0.000 description 1
• 101000970995 Homo sapiens ATP synthase subunit O, mitochondrial Proteins 0.000 description 1
• 101001009603 Homo sapiens Granzyme B 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
• 101000976900 Homo sapiens Mitogen-activated protein kinase 14 Proteins 0.000 description 1
• 101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-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
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• 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
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• 102000003820 Lipoxygenases Human genes 0.000 description 1
• 108090000128 Lipoxygenases Proteins 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 102100037611 Lysophospholipase Human genes 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
• 229920000715 Mucilage Polymers 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 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
• 208000001388 Opportunistic Infections Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 229910002666 PdCl2 Inorganic materials 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 101150093295 Pla2g4a gene Proteins 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 229920003171 Poly (ethylene oxide) Chemical class 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000001253 Protein Kinase Human genes 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
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• CDMGBJANTYXAIV-UHFFFAOYSA-N SB 203580 Chemical compound C1=CC(S(=O)C)=CC=C1C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N1 CDMGBJANTYXAIV-UHFFFAOYSA-N 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
• 229930006000 Sucrose Natural products 0.000 description 1
• 230000024932 T cell mediated immunity Effects 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
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 102100040247 Tumor necrosis factor Human genes 0.000 description 1
• 108010067390 Viral Proteins Proteins 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
• 210000001056 activated astrocyte Anatomy 0.000 description 1
• 150000001263 acyl chlorides Chemical class 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• 239000000853 adhesive Substances 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
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 150000005215 alkyl ethers Chemical class 0.000 description 1
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• 235000020224 almond Nutrition 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
• 125000003277 amino group Chemical group 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
• 238000010533 azeotropic distillation Methods 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 230000001580 bacterial effect Effects 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
• 229960004365 benzoic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-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
• 125000001743 benzylic group Chemical group 0.000 description 1
• 230000008512 biological response Effects 0.000 description 1
• XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
• 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
• 230000024279 bone resorption Effects 0.000 description 1
• 230000006931 brain damage Effects 0.000 description 1
• 231100000874 brain damage Toxicity 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 244000309464 bull Species 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
• 239000006227 byproduct Substances 0.000 description 1
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 125000002091 cationic group Chemical group 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
• 238000005119 centrifugation Methods 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000007810 chemical reaction solvent Substances 0.000 description 1
• 230000001889 chemoattractive effect Effects 0.000 description 1
• 239000005482 chemotactic factor Substances 0.000 description 1
• 229960002152 chlorhexidine acetate Drugs 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000009514 concussion Effects 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 238000005520 cutting process Methods 0.000 description 1
• 238000006352 cycloaddition reaction Methods 0.000 description 1
• 230000001120 cytoprotective effect Effects 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 229960003964 deoxycholic acid Drugs 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 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
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002168 ethanoic acid esters Chemical class 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• GQQQULCEHJQUJT-UHFFFAOYSA-N ethyl 4-aminopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(N)CC1 GQQQULCEHJQUJT-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000005713 exacerbation Effects 0.000 description 1
• 230000003090 exacerbative effect Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 239000004744 fabric Substances 0.000 description 1
• 238000010265 fast atom bombardment Methods 0.000 description 1
• 235000013861 fat-free Nutrition 0.000 description 1
• 235000019197 fats Nutrition 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
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 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
• 102000037865 fusion proteins Human genes 0.000 description 1
• 108020001507 fusion proteins Proteins 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
• 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 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 150000008282 halocarbons Chemical class 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 210000002443 helper t lymphocyte Anatomy 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 229960001340 histamine Drugs 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
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 230000007365 immunoregulation Effects 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 239000011147 inorganic material Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000017306 interleukin-6 production Effects 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 150000004694 iodide salts Chemical class 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 239000002555 ionophore Substances 0.000 description 1
• 230000000236 ionophoric effect Effects 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 210000002510 keratinocyte Anatomy 0.000 description 1
• 238000002372 labelling Methods 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
• 238000011031 large-scale manufacturing process Methods 0.000 description 1
• 150000002617 leukotrienes Chemical class 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
• 238000012417 linear regression Methods 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 108010019677 lymphotactin Proteins 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 230000002132 lysosomal effect Effects 0.000 description 1
• 235000019359 magnesium stearate Nutrition 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
• 229940099690 malic acid Drugs 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
• 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229940071648 metered dose inhaler Drugs 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
• OFXSXYCSPVKZPF-UHFFFAOYSA-N methoxyperoxymethane Chemical compound COOOC OFXSXYCSPVKZPF-UHFFFAOYSA-N 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 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
• IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
• 229920001206 natural gum Polymers 0.000 description 1
• 210000000822 natural killer cell Anatomy 0.000 description 1
• 230000030991 negative regulation of bone resorption Effects 0.000 description 1
• 230000007302 negative regulation of cytokine production Effects 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 230000002232 neuromuscular Effects 0.000 description 1
• PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• ZAQDQFFQEKUULQ-UHFFFAOYSA-N nitrooxy(phenyl)mercury;phenylmercury;hydrate Chemical compound O.[Hg]C1=CC=CC=C1.[O-][N+](=O)O[Hg]C1=CC=CC=C1 ZAQDQFFQEKUULQ-UHFFFAOYSA-N 0.000 description 1
• 210000000929 nociceptor Anatomy 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 229940116315 oxalic acid Drugs 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• WXHIJDCHNDBCNY-UHFFFAOYSA-N palladium dihydride Chemical compound [PdH2] WXHIJDCHNDBCNY-UHFFFAOYSA-N 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 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
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 229950000964 pepstatin Drugs 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 238000002823 phage display Methods 0.000 description 1
• 238000003408 phase transfer catalysis Methods 0.000 description 1
• 239000003444 phase transfer catalyst Substances 0.000 description 1
• CMCWWLVWPDLCRM-UHFFFAOYSA-N phenidone Chemical compound N1C(=O)CCN1C1=CC=CC=C1 CMCWWLVWPDLCRM-UHFFFAOYSA-N 0.000 description 1
• 229960003424 phenylacetic acid Drugs 0.000 description 1
• 239000003279 phenylacetic acid Substances 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 229940080469 phosphocellulose Drugs 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 229960005235 piperonyl butoxide Drugs 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
• 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
• 238000002731 protein assay Methods 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• CCOXWRVWKFVFDG-UHFFFAOYSA-N pyrimidine-2-carbaldehyde Chemical class O=CC1=NC=CC=N1 CCOXWRVWKFVFDG-UHFFFAOYSA-N 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000001172 regenerating effect Effects 0.000 description 1
• 230000009719 regenerative response Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000019254 respiratory burst Effects 0.000 description 1
• HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
• 229950005741 rolipram Drugs 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 239000000344 soap Substances 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• KFZUDNZQQCWGKF-UHFFFAOYSA-M sodium;4-methylbenzenesulfinate Chemical compound [Na+].CC1=CC=C(S([O-])=O)C=C1 KFZUDNZQQCWGKF-UHFFFAOYSA-M 0.000 description 1
• WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 239000011269 tar Substances 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 229960001367 tartaric acid Drugs 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000007669 thermal treatment Methods 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 238000006478 transmetalation reaction Methods 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
• AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical group CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical group CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
• 230000001562 ulcerogenic effect Effects 0.000 description 1
• 210000003954 umbilical cord Anatomy 0.000 description 1
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 238000006175 van Leusen reaction Methods 0.000 description 1
• LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000002699 waste material Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1