AP259A - Inhibitors for tumor necrosis factor (TNF) based 8-substituted xanthines. - Google Patents
Inhibitors for tumor necrosis factor (TNF) based 8-substituted xanthines. Download PDFInfo
- Publication number
- AP259A AP259A APAP/P/1991/000335A AP9100335A AP259A AP 259 A AP259 A AP 259A AP 9100335 A AP9100335 A AP 9100335A AP 259 A AP259 A AP 259A
- Authority
- AP
- ARIPO
- Prior art keywords
- tnf
- xanthine
- compound
- formula
- mammal
- Prior art date
Links
- 108060008682 Tumor Necrosis Factor Proteins 0.000 title claims description 138
- 102000003390 tumor necrosis factor Human genes 0.000 title claims 12
- -1 8-substituted xanthines Chemical class 0.000 title abstract description 7
- 239000003112 inhibitor Substances 0.000 title description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 50
- 201000010099 disease Diseases 0.000 claims abstract description 47
- 238000011282 treatment Methods 0.000 claims abstract description 38
- 238000004519 manufacturing process Methods 0.000 claims abstract description 29
- 230000006433 tumor necrosis factor production Effects 0.000 claims abstract description 26
- 230000001404 mediated effect Effects 0.000 claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims description 122
- 238000000034 method Methods 0.000 claims description 69
- 241000700605 Viruses Species 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 27
- 241000124008 Mammalia Species 0.000 claims description 24
- 208000015181 infectious disease Diseases 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 206010006895 Cachexia Diseases 0.000 claims description 12
- 206010040070 Septic Shock Diseases 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 206010001513 AIDS related complex Diseases 0.000 claims description 9
- 208000036142 Viral infection Diseases 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 230000009385 viral infection Effects 0.000 claims description 9
- 229940075420 xanthine Drugs 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 4
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- KSPYMJJKQMWWNB-UHFFFAOYSA-N cipamfylline Chemical compound O=C1N(CC2CC2)C(=O)C=2NC(N)=NC=2N1CC1CC1 KSPYMJJKQMWWNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 206010014824 Endotoxic shock Diseases 0.000 claims description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 230000002458 infectious effect Effects 0.000 claims description 3
- NODRXLCGHIPPNV-UHFFFAOYSA-N 1,3-dibutyl-8-chloro-7h-purine-2,6-dione Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1NC(Cl)=N2 NODRXLCGHIPPNV-UHFFFAOYSA-N 0.000 claims description 2
- LCPGQPIZMXWYDE-UHFFFAOYSA-N 8-amino-1,3-dibutyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1NC(N)=N2 LCPGQPIZMXWYDE-UHFFFAOYSA-N 0.000 claims description 2
- 208000006386 Bone Resorption Diseases 0.000 claims description 2
- 241000283073 Equus caballus Species 0.000 claims description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 claims description 2
- 241000713666 Lentivirus Species 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 241000713325 Visna/maedi virus Species 0.000 claims description 2
- 208000007502 anemia Diseases 0.000 claims description 2
- 230000024279 bone resorption Effects 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- FHHJDLUVUSSPDK-UHFFFAOYSA-N n-(1,3-dibutyl-2,6-dioxo-7h-purin-8-yl)acetamide Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1NC(NC(C)=O)=N2 FHHJDLUVUSSPDK-UHFFFAOYSA-N 0.000 claims description 2
- 230000007812 deficiency Effects 0.000 claims 2
- 206010053879 Sepsis syndrome Diseases 0.000 claims 1
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims 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 claims 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 124
- 210000004027 cell Anatomy 0.000 description 46
- 230000000694 effects Effects 0.000 description 37
- 210000001616 monocyte Anatomy 0.000 description 33
- 241000699670 Mus sp. Species 0.000 description 27
- 210000004072 lung Anatomy 0.000 description 20
- 102000000589 Interleukin-1 Human genes 0.000 description 18
- 108010002352 Interleukin-1 Proteins 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000002158 endotoxin Substances 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 241000725303 Human immunodeficiency virus Species 0.000 description 16
- 206010022000 influenza Diseases 0.000 description 16
- 229920006008 lipopolysaccharide Polymers 0.000 description 16
- 210000001744 T-lymphocyte Anatomy 0.000 description 15
- 239000006228 supernatant Substances 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 13
- 208000030507 AIDS Diseases 0.000 description 12
- 210000002540 macrophage Anatomy 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 238000003556 assay Methods 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000012530 fluid Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 230000002452 interceptive effect Effects 0.000 description 8
- 230000002685 pulmonary effect Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 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 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000003937 drug carrier Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000029812 viral genome replication Effects 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 6
- 102100034343 Integrase Human genes 0.000 description 6
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 6
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 238000011200 topical administration Methods 0.000 description 6
- 241000712461 unidentified influenza virus Species 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 208000031886 HIV Infections Diseases 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 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 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 230000001665 lethal effect Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 206010063094 Cerebral malaria Diseases 0.000 description 4
- 201000004624 Dermatitis Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000013967 Monokines Human genes 0.000 description 4
- 108010050619 Monokines Proteins 0.000 description 4
- 206010040047 Sepsis Diseases 0.000 description 4
- 230000006044 T cell activation Effects 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- 208000019664 bone resorption disease Diseases 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical class [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 102000057041 human TNF Human genes 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 229940100601 interleukin-6 Drugs 0.000 description 4
- 231100000518 lethal Toxicity 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 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 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 3
- LNDZXOWGUAIUBG-UHFFFAOYSA-N 6-aminouracil Chemical compound NC1=CC(=O)NC(=O)N1 LNDZXOWGUAIUBG-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 235000003911 Arachis Nutrition 0.000 description 3
- 244000105624 Arachis hypogaea Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 3
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 208000037357 HIV infectious disease Diseases 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 201000010001 Silicosis Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 238000004166 bioassay Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000007910 systemic administration Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-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
- PKUFNWPSFCOSLU-UHFFFAOYSA-N 6-chloro-1h-pyrimidine-2,4-dione Chemical compound ClC1=CC(=O)NC(=O)N1 PKUFNWPSFCOSLU-UHFFFAOYSA-N 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 206010018634 Gouty Arthritis Diseases 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 206010028289 Muscle atrophy Diseases 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 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 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- YVGVBKYNDBGWGY-UHFFFAOYSA-N [N].O=C1NC(=O)NC2=C1NC=N2 Chemical group [N].O=C1NC(=O)NC2=C1NC=N2 YVGVBKYNDBGWGY-UHFFFAOYSA-N 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000003090 exacerbative effect Effects 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- 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 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 208000011379 keloid formation Diseases 0.000 description 2
- 239000000865 liniment Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002941 microtiter virus yield reduction assay Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 230000000802 nitrating effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-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
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002947 procoagulating effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000009772 tissue formation Effects 0.000 description 2
- 229960001479 tosylchloramide sodium Drugs 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 2
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-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
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 102100025854 Acyl-coenzyme A thioesterase 1 Human genes 0.000 description 1
- 101710175445 Acyl-coenzyme A thioesterase 1 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
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241001517013 Calidris pugnax Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 206010010755 Conjunctivitis viral Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 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 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 241000197306 H1N1 subtype Species 0.000 description 1
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
- 206010020164 HIV infection CDC Group III 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
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons 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
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 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
- 208000002193 Pain Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Chemical class 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 206010062109 Reversible airways obstruction Diseases 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 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
- 206010042496 Sunburn Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 102100026966 Thrombomodulin Human genes 0.000 description 1
- 108010079274 Thrombomodulin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 208000005914 Viral Conjunctivitis Diseases 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 102100029477 Vitamin K-dependent protein C Human genes 0.000 description 1
- 101710193900 Vitamin K-dependent protein C Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- FROZIYRKKUFAOC-UHFFFAOYSA-N amobam Chemical compound N.N.SC(=S)NCCNC(S)=S FROZIYRKKUFAOC-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 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
- 230000008512 biological response Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 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
- 238000004364 calculation method Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 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
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229960002152 chlorhexidine acetate Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000005796 circulatory shock Effects 0.000 description 1
- 235000020415 coconut juice Nutrition 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000003182 dose-response assay Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 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
- 238000005538 encapsulation Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 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
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000009791 fibrotic reaction Effects 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000011521 glass Substances 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
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 238000003306 harvesting Methods 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
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical group [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000009390 immune abnormality Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 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
- 229940079322 interferon Drugs 0.000 description 1
- 230000018276 interleukin-1 production Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000001875 irritant dermatitis Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 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
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 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
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 1
- 229960002455 methoxyflurane Drugs 0.000 description 1
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 description 1
- 238000007392 microtiter assay Methods 0.000 description 1
- 201000002266 mite infestation Diseases 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000011242 neutrophil chemotaxis Effects 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000007170 pathology 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
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic 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
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000002976 reverse transcriptase assay Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 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
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- 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
- 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
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Agronomy & Crop Science (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61647990A | 1990-11-21 | 1990-11-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9100335A0 AP9100335A0 (en) | 1992-01-31 |
| AP259A true AP259A (en) | 1993-06-03 |
Family
ID=24469639
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1991/000335A AP259A (en) | 1990-11-21 | 1991-11-21 | Inhibitors for tumor necrosis factor (TNF) based 8-substituted xanthines. |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0558659A4 (OSRAM) |
| JP (1) | JP3204971B2 (OSRAM) |
| KR (1) | KR930702896A (OSRAM) |
| AP (1) | AP259A (OSRAM) |
| AU (1) | AU656938B2 (OSRAM) |
| CA (1) | CA2096623A1 (OSRAM) |
| HU (1) | HUT65838A (OSRAM) |
| IE (1) | IE914034A1 (OSRAM) |
| IL (1) | IL100088A (OSRAM) |
| MX (1) | MX9102173A (OSRAM) |
| NZ (1) | NZ240644A (OSRAM) |
| TW (1) | TW222001B (OSRAM) |
| WO (1) | WO1992009203A1 (OSRAM) |
| ZA (1) | ZA919178B (OSRAM) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1531492A (en) * | 1991-02-14 | 1992-09-15 | Rockefeller University, The | Method for controlling abnormal concentration tnf alpha in human tissues |
| AU7376394A (en) * | 1993-08-04 | 1995-02-28 | Andrulis Pharmaceuticals Corporation | Use of tumor necrosis factor inhibitors together with antiviral agents and therapeutic compositions thereof against hiv infection |
| US5504090A (en) * | 1994-03-30 | 1996-04-02 | Trustees Of The University Of Pennsylvania | Compositions and methods for the prevention and treatment of ischemia-reperfusion organ injury |
| US7608262B2 (en) * | 1996-02-16 | 2009-10-27 | The Kennedy Institute Of Rheumatology | Methods of preventing or treating thrombosis with tumor necrosis factor antagonists |
| GB9703044D0 (en) | 1997-02-14 | 1997-04-02 | Glaxo Group Ltd | Phenyl xanthine esters and amides |
| GB9817623D0 (en) | 1998-08-13 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
| AU2003289898A1 (en) * | 2002-11-27 | 2004-06-18 | Altana Pharma Ag | Pde4 and pde3/4 inhibitors for use in the treatment of cachexia |
| RU2395511C2 (ru) * | 2004-02-14 | 2010-07-27 | Смитклайн Бичам Корпорейшн | Новые соединения |
| PT1781657E (pt) | 2004-02-14 | 2013-05-23 | Glaxosmithkline Ip Dev Ltd | Medicamentos com actividade no receptor hm74a |
| WO2007017262A1 (en) | 2005-08-10 | 2007-02-15 | Smithkline Beecham Corporation | Xanthine derivatives as selective hm74a agonists |
| BR112017007194B1 (pt) | 2014-10-09 | 2023-11-07 | Guangdong Raynovent Biotech Co., Ltd | Compostos de hidroxil purina e uso dos mesmos |
| ES2784826T3 (es) | 2015-10-29 | 2020-10-01 | Guangdong Raynovent Biotech Co Ltd | Forma cristalina de un compuesto de 4H-pirazol[1,5-]benzimidazol, procedimiento de preparación de la misma e intermediario de la misma |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0389289A1 (en) * | 1989-03-23 | 1990-09-26 | Oy Tampella Ab | Apparatus for breaking a threaded connection |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US757328A (en) * | 1903-02-07 | 1904-04-12 | Boehringer & Soehne | Art of preparing xanthin derivatives. |
| US2517410A (en) * | 1947-08-15 | 1950-08-01 | Searle & Co | Hydroxy alkyl xanthines and the production thereof |
| US4120947A (en) * | 1976-03-31 | 1978-10-17 | Cooper Laboratories, Inc. | Xanthine compounds and method of treating bronchospastic and allergic diseases |
| CH654008A5 (fr) * | 1979-05-22 | 1986-01-31 | Nestle Sa | Procede de preparation de 1,3,7-trialkylxanthines. |
| DE2944568A1 (de) * | 1979-11-05 | 1981-05-14 | Institut für industrielle Pharmazie F + E GmbH, 8750 Aschaffenburg | Pharmazeutische zubereitung |
| IT1200944B (it) * | 1982-08-10 | 1989-01-27 | Malesci Sas | Derivati xantinici,procedimento per la loro preparazione,composizione farmaceutiche che il contengono e loro impiego terapeutico |
| US4593095A (en) * | 1983-02-18 | 1986-06-03 | The Johns Hopkins University | Xanthine derivatives |
| US4636507A (en) * | 1984-04-30 | 1987-01-13 | Hoechst-Roussel Pharmaceuticals Inc. | Host defense mechanism enhancement |
| GB8610136D0 (en) * | 1986-04-25 | 1986-05-29 | Wellcome Found | Compounds |
| IT1197516B (it) * | 1986-12-24 | 1988-11-30 | Abc Ist Biolog Chem Spa | Derivati teofillinmetilanici e teofillinmetilditianici procedimento per la loro preparazione e composizioni farmaceutiche che li comprendono |
| US4965271A (en) * | 1986-12-31 | 1990-10-23 | Hoechst Roussel Pharmaceuticals, Inc. | Method of inhibiting the activity of leukocyte derived cytokines |
| US5015647A (en) * | 1987-04-24 | 1991-05-14 | Burroughs Wellcome Co. | Method for treating viral infections |
| DE3817955A1 (de) * | 1988-05-27 | 1989-11-30 | Hoechst Ag | Tnf-inhibitor enthaltendes arzneimittel |
| GB8906792D0 (en) * | 1989-03-23 | 1989-05-10 | Beecham Wuelfing Gmbh & Co Kg | Treatment and compounds |
-
1991
- 1991-11-19 IL IL10008891A patent/IL100088A/en not_active IP Right Cessation
- 1991-11-19 NZ NZ240644A patent/NZ240644A/en unknown
- 1991-11-20 JP JP50198592A patent/JP3204971B2/ja not_active Expired - Lifetime
- 1991-11-20 WO PCT/US1991/008734 patent/WO1992009203A1/en not_active Ceased
- 1991-11-20 CA CA002096623A patent/CA2096623A1/en not_active Abandoned
- 1991-11-20 IE IE403491A patent/IE914034A1/en not_active Application Discontinuation
- 1991-11-20 HU HU9301509A patent/HUT65838A/hu unknown
- 1991-11-20 EP EP19920901819 patent/EP0558659A4/en not_active Withdrawn
- 1991-11-20 ZA ZA919178A patent/ZA919178B/xx unknown
- 1991-11-20 AU AU91159/91A patent/AU656938B2/en not_active Ceased
- 1991-11-21 MX MX9102173A patent/MX9102173A/es unknown
- 1991-11-21 AP APAP/P/1991/000335A patent/AP259A/en active
- 1991-12-30 TW TW080110250A patent/TW222001B/zh active
-
1993
- 1993-05-21 KR KR1019930701529A patent/KR930702896A/ko not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0389289A1 (en) * | 1989-03-23 | 1990-09-26 | Oy Tampella Ab | Apparatus for breaking a threaded connection |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0558659A4 (en) | 1993-10-20 |
| IL100088A (en) | 1995-07-31 |
| IE914034A1 (en) | 1992-06-03 |
| EP0558659A1 (en) | 1993-09-08 |
| ZA919178B (en) | 1992-10-28 |
| CA2096623A1 (en) | 1992-05-22 |
| AP9100335A0 (en) | 1992-01-31 |
| HU9301509D0 (en) | 1993-11-29 |
| NZ240644A (en) | 1994-08-26 |
| HUT65838A (en) | 1994-07-28 |
| AU656938B2 (en) | 1995-02-23 |
| JPH06506192A (ja) | 1994-07-14 |
| AU9115991A (en) | 1992-06-25 |
| IL100088A0 (en) | 1992-08-18 |
| WO1992009203A1 (en) | 1992-06-11 |
| KR930702896A (ko) | 1993-11-29 |
| TW222001B (OSRAM) | 1994-04-01 |
| MX9102173A (es) | 1992-06-01 |
| JP3204971B2 (ja) | 2001-09-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0542795B1 (en) | Tnf inhibitors | |
| AP259A (en) | Inhibitors for tumor necrosis factor (TNF) based 8-substituted xanthines. | |
| HUP0001358A2 (hu) | QT diszperzió és szívverés változékonyság javítása CRF antagonista hatású heterociklusos vegyületek alkalmazásával hirtelen halál megelőzése céljából | |
| HUP0204079A2 (hu) | Szedatív hatástól mentes antihisztaminok és leukotrién hatást befolyásoló anyagok új kombinációja orrnyálkahártya-gyulladás, vagy kötőhártya-gyulladás kezelésére | |
| HU202108B (en) | Process for producing pharmaceutical compositions containing serotonine antqgonistic derivatives of indol-carboxylic acid or imidazolyl-methyl-carbazol | |
| KR102372194B1 (ko) | Lsd1 억제제를 이용한 다발성 경화증의 치료방법 | |
| EP0572537B1 (en) | Cytokine inhibitors | |
| US20060083714A1 (en) | Combination of a pde iv inhibitor and a tnf-alpha antagonist | |
| JP2023528722A (ja) | サイトカインストーム症候群及び関連疾患を治療する方法 | |
| US5547979A (en) | TNF inhibition | |
| JP5148478B2 (ja) | マラリア治療用のフェロキンとアーテミシニン誘導体との組合せ | |
| CN1260784A (zh) | 作为pdeiv和tnf抑制剂的喹啉衍生物 | |
| WO1993016699A1 (en) | Tnf inhibitors | |
| WO2021194991A1 (en) | Use of losmapimod for treatment of covid-19 | |
| WO2009026584A1 (en) | Methods of treating inflammatory conditions with adrenergic antagonists | |
| US20120190751A1 (en) | Compounds for treatments of inflammation | |
| EA007952B1 (ru) | Применение ирбесартана для изготовления лекарств, которые пригодны для предупреждения или лечения лёгочной артериальной гипертензии | |
| WO2004054616A1 (ja) | ケモカイン受容体の強結合部位に結合するアンタゴニストおよびアゴニスト | |
| EP1054669B1 (en) | Use of thiadiazolo[4,3-a]pyridine derivatives | |
| PT100429B (pt) | Uso de derivados da xantina na preparacao de um medicamento para inibicao da producao de factor de necrose tumoral | |
| KR20000035861A (ko) | Ａｉｄｓ 치료용 약제를 제조하기 위한 ｐｋｃ 억제제의 사용 방법 | |
| JPH10503178A (ja) | Ｈｉｖ感染のための組合わせ療法 | |
| US7858612B2 (en) | Therapeutic agent for inflammatory bowel diseases | |
| JPH08502044A (ja) | ヒトウイルス感染の治療 | |
| CN116437960A (zh) | 用于治疗病毒感染的化合物 |