DE60306546T2 - Entzündungshemmende 3-arylthio-3-thiazolylalkylamine - Google Patents
Entzündungshemmende 3-arylthio-3-thiazolylalkylamine Download PDFInfo
- Publication number
- DE60306546T2 DE60306546T2 DE60306546T DE60306546T DE60306546T2 DE 60306546 T2 DE60306546 T2 DE 60306546T2 DE 60306546 T DE60306546 T DE 60306546T DE 60306546 T DE60306546 T DE 60306546T DE 60306546 T2 DE60306546 T2 DE 60306546T2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compound
- pharmaceutically acceptable
- compounds
- thiazolyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000002757 inflammatory effect Effects 0.000 title claims description 6
- 150000003973 alkyl amines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 96
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 27
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 24
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 24
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
- 230000008569 process Effects 0.000 claims abstract description 10
- 238000011321 prophylaxis Methods 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 229940111134 coxibs Drugs 0.000 claims description 6
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- HIMGQYNKYSNTGS-WCQYABFASA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-4-chlorobenzonitrile Chemical compound S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=CC(Cl)=CC=C1C#N HIMGQYNKYSNTGS-WCQYABFASA-N 0.000 claims description 2
- KLEJNUKHFIABHF-WCQYABFASA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-5-chlorobenzonitrile Chemical compound S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=CC=C(Cl)C=C1C#N KLEJNUKHFIABHF-WCQYABFASA-N 0.000 claims description 2
- HTKSSNUQYKTPJO-WDEREUQCSA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-5-chloropyridine-3-carbonitrile Chemical compound S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=NC=C(Cl)C=C1C#N HTKSSNUQYKTPJO-WDEREUQCSA-N 0.000 claims description 2
- DIIWCKNRKGUDEN-VHSXEESVSA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-6-(trifluoromethyl)pyridine-3-carbonitrile Chemical compound S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=NC(C(F)(F)F)=CC=C1C#N DIIWCKNRKGUDEN-VHSXEESVSA-N 0.000 claims description 2
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 claims 1
- 208000028774 intestinal disease Diseases 0.000 claims 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract description 15
- 239000003112 inhibitor Substances 0.000 abstract description 11
- 239000000203 mixture Substances 0.000 abstract description 11
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- 206010065390 Inflammatory pain Diseases 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
- -1 n -propyl Chemical group 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 6
- 108010029485 Protein Isoforms Proteins 0.000 description 6
- 102000001708 Protein Isoforms Human genes 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 5
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 5
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 5
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 5
- 206010040070 Septic Shock Diseases 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 229960002173 citrulline Drugs 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
- 229930064664 L-arginine Natural products 0.000 description 4
- 235000014852 L-arginine Nutrition 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 235000009697 arginine Nutrition 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 3
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 3
- 239000011768 flavin mononucleotide Substances 0.000 description 3
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 3
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 230000036303 septic shock Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- DTYVSVIVLHYCCX-VZCPBZATSA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-4-chlorobenzonitrile;dihydrochloride Chemical compound Cl.Cl.S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=CC(Cl)=CC=C1C#N DTYVSVIVLHYCCX-VZCPBZATSA-N 0.000 description 2
- WCSGVMNFTPJQER-VZCPBZATSA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-5-chlorobenzonitrile;dihydrochloride Chemical compound Cl.Cl.S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=CC=C(Cl)C=C1C#N WCSGVMNFTPJQER-VZCPBZATSA-N 0.000 description 2
- NPHODNGPXRIMIJ-VZXYPILPSA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-5-chloropyridine-3-carbonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=NC=C(Cl)C=C1C#N NPHODNGPXRIMIJ-VZXYPILPSA-N 0.000 description 2
- VIYUCQVZNOONGM-JXGSBULDSA-N 2-[(1r,3s)-3-amino-4-hydroxy-1-(1,3-thiazol-5-yl)butyl]sulfanyl-6-(trifluoromethyl)pyridine-3-carbonitrile;dihydrochloride Chemical compound Cl.Cl.S([C@H](C[C@@H](CO)N)C=1SC=NC=1)C1=NC(C(F)(F)F)=CC=C1C#N VIYUCQVZNOONGM-JXGSBULDSA-N 0.000 description 2
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- 208000018737 Parkinson disease Diseases 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000013477 citrulline Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 206010013663 drug dependence Diseases 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 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
- 150000003003 phosphines Chemical class 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 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
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RCIVUMDLBQZEHP-UHFFFAOYSA-N (2-methylpropan-2-yl)oxycarbamic acid Chemical class CC(C)(C)ONC(O)=O RCIVUMDLBQZEHP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KAVIOGXCVVZYEM-SMDDNHRTSA-N (4s)-4-[(2r)-2-[2-chloro-5-(trifluoromethyl)phenyl]sulfanyl-2-(1,3-thiazol-5-yl)ethyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylic acid Chemical compound OC(=O)N1C(C)(C)OC[C@@H]1C[C@H](C=1SC=NC=1)SC1=CC(C(F)(F)F)=CC=C1Cl KAVIOGXCVVZYEM-SMDDNHRTSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- HKBWIKAFHCGRTH-UHFFFAOYSA-N 1-chloro-2-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC(C(F)(F)F)=CC=C1Cl HKBWIKAFHCGRTH-UHFFFAOYSA-N 0.000 description 1
- CZKCARRNABGWOH-UHFFFAOYSA-N 2,5-dichloropyridine-3-carbonitrile Chemical compound ClC1=CN=C(Cl)C(C#N)=C1 CZKCARRNABGWOH-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- CDSFASYGONAHHN-UHFFFAOYSA-N 2-chloro-6-(trifluoromethyl)pyridine-3-carbonitrile Chemical compound FC(F)(F)C1=CC=C(C#N)C(Cl)=N1 CDSFASYGONAHHN-UHFFFAOYSA-N 0.000 description 1
- KLEYVGWAORGTIT-UHFFFAOYSA-N 2-chlorothiazole Chemical compound ClC1=NC=CS1 KLEYVGWAORGTIT-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- JRDMGVGCATYZPW-UHFFFAOYSA-N 4-chloro-2-fluorobenzonitrile Chemical compound FC1=CC(Cl)=CC=C1C#N JRDMGVGCATYZPW-UHFFFAOYSA-N 0.000 description 1
- GJNJDELEHIGPKJ-UHFFFAOYSA-N 5-chloro-2-fluorobenzonitrile Chemical compound FC1=CC=C(Cl)C=C1C#N GJNJDELEHIGPKJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 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
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 229940124638 COX inhibitor Drugs 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010052804 Drug tolerance 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
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 208000001456 Jet Lag Syndrome Diseases 0.000 description 1
- 208000006264 Korsakoff syndrome Diseases 0.000 description 1
- MRAUNPAHJZDYCK-BYPYZUCNSA-N L-nitroarginine Chemical compound OC(=O)[C@@H](N)CCCNC(=N)N[N+]([O-])=O MRAUNPAHJZDYCK-BYPYZUCNSA-N 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
- 208000019693 Lung disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 101100080274 Mus musculus Nos3 gene Proteins 0.000 description 1
- NULAJYZBOLVQPQ-UHFFFAOYSA-N N-(1-naphthyl)ethylenediamine Chemical compound C1=CC=C2C(NCCN)=CC=CC2=C1 NULAJYZBOLVQPQ-UHFFFAOYSA-N 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 206010036618 Premenstrual syndrome Diseases 0.000 description 1
- 206010036631 Presenile dementia Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 208000001407 Vascular Headaches Diseases 0.000 description 1
- 201000008485 Wernicke-Korsakoff syndrome Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 208000002399 aphthous stomatitis Diseases 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- UIJGNTRUPZPVNG-UHFFFAOYSA-N benzenecarbothioic s-acid Chemical compound SC(=O)C1=CC=CC=C1 UIJGNTRUPZPVNG-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 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
- 206010006451 bronchitis Diseases 0.000 description 1
- LMSNZLCSZWZZGU-UHFFFAOYSA-N butan-1-ol;hydrochloride Chemical compound Cl.CCCCO LMSNZLCSZWZZGU-UHFFFAOYSA-N 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 150000004908 diazepines Chemical class 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 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
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 1
- 229940013640 flavin mononucleotide Drugs 0.000 description 1
- 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010448 genetic screening Methods 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 1
- 208000018937 joint inflammation Diseases 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
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000004203 pancreatic function Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000013102 re-test Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 1
- 229960004617 sapropterin Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 208000012233 scrotal disease Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- LGHPZUHWLZXZBO-VHSXEESVSA-N tert-butyl (4s)-4-[(2r)-2-(2-chloro-1,3-thiazol-5-yl)-2-hydroxyethyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate Chemical compound C1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1C[C@@H](O)C1=CN=C(Cl)S1 LGHPZUHWLZXZBO-VHSXEESVSA-N 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/28—Radicals substituted by nitrogen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0203304 | 2002-11-07 | ||
| SE0203304A SE0203304D0 (sv) | 2002-11-07 | 2002-11-07 | Novel Coumpounds |
| PCT/SE2003/001712 WO2004041794A1 (en) | 2002-11-07 | 2003-11-06 | Antiinflammatory 3-arylthio-3-thiazolyl-alkylamines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60306546D1 DE60306546D1 (de) | 2006-08-10 |
| DE60306546T2 true DE60306546T2 (de) | 2007-07-05 |
Family
ID=20289508
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60306546T Expired - Fee Related DE60306546T2 (de) | 2002-11-07 | 2003-11-06 | Entzündungshemmende 3-arylthio-3-thiazolylalkylamine |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20060040992A1 (https=) |
| EP (1) | EP1562920B1 (https=) |
| JP (1) | JP2006506414A (https=) |
| AT (1) | ATE331711T1 (https=) |
| AU (1) | AU2003278667A1 (https=) |
| DE (1) | DE60306546T2 (https=) |
| ES (1) | ES2268441T3 (https=) |
| SE (1) | SE0203304D0 (https=) |
| WO (1) | WO2004041794A1 (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
| AU2008313660B2 (en) | 2007-10-19 | 2013-11-07 | Boehringer Ingelheim International Gmbh | Substituted piperidino-dihydrothienopyrimidines |
| HUE025547T2 (en) | 2008-12-19 | 2016-02-29 | Boehringer Ingelheim Int | Cyclic pyrimidine-4-carboxamides as CCR2 receptor antagonists for the treatment of inflammation, asthma and COPD |
| ES2674275T3 (es) | 2009-12-17 | 2018-06-28 | Centrexion Therapeutics Corporation | Antagonistas del receptor CCR2 y usos de los mismos |
| US20130143905A1 (en) | 2009-12-17 | 2013-06-06 | Boehringer Ingelheim International Gmbh | Novel antagonists for ccr2 and uses thereof |
| NZ600857A (en) | 2010-01-29 | 2014-06-27 | Boehringer Ingelheim Int | Substituted naphthyridines and their use as syk kinase inhibitors |
| EP2569298B1 (en) | 2010-05-12 | 2015-11-25 | Boehringer Ingelheim International GmbH | Novel ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| WO2011141477A1 (en) | 2010-05-12 | 2011-11-17 | Boehringer Ingelheim International Gmbh | New ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| WO2011144501A1 (en) | 2010-05-17 | 2011-11-24 | Boehringer Ingelheim International Gmbh | Ccr2 antagonists and uses thereof |
| EP2576542B1 (en) | 2010-05-25 | 2015-04-22 | Boehringer Ingelheim International GmbH | Cyclic amide derivatives of pyridazine-3-carboxylic acids and their use in the treatment of pulmonary, pain, immune related and cardiovascular diseases |
| EP2576538B1 (en) | 2010-06-01 | 2015-10-28 | Boehringer Ingelheim International GmbH | New CCR2 antagonists |
| JP5959537B2 (ja) | 2011-01-28 | 2016-08-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換ピリジニル−ピリミジン及び医薬としてのその使用 |
| JP5786257B2 (ja) | 2011-06-16 | 2015-09-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規の選択的ｃｃｒ２拮抗薬 |
| EP2731941B1 (en) | 2011-07-15 | 2019-05-08 | Boehringer Ingelheim International GmbH | Novel and selective ccr2 antagonists |
| CN103827090B (zh) | 2011-07-26 | 2016-04-20 | 勃林格殷格翰国际有限公司 | 取代的喹啉及其作为药物的用途 |
| US20130059866A1 (en) | 2011-08-24 | 2013-03-07 | Boehringer Ingelheim International Gmbh | Novel piperidino-dihydrothienopyrimidine sulfoxides and their use for treating copd and asthma |
| US9096579B2 (en) | 2012-04-20 | 2015-08-04 | Boehringer Ingelheim International Gmbh | Amino-indolyl-substituted imidazolyl-pyrimidines and their use as medicaments |
| CN106255689B (zh) | 2014-03-19 | 2019-09-17 | 勃林格殷格翰国际有限公司 | 杂芳基syk抑制剂 |
| GB201512635D0 (en) | 2015-07-17 | 2015-08-26 | Ucl Business Plc | Uses of therapeutic compounds |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2688638A (en) * | 1951-07-17 | 1954-09-07 | Givaudan Corp | Nu-(beta-phenoxyethyl) haloethylamines |
| US4314081A (en) * | 1974-01-10 | 1982-02-02 | Eli Lilly And Company | Arloxyphenylpropylamines |
| FR2432500A1 (fr) * | 1978-02-24 | 1980-02-29 | Roussel Uclaf | Nouveaux derives de la benzene propanamine et leurs sels, procede de preparation et application a titre de medicaments |
| US4325953A (en) * | 1979-09-14 | 1982-04-20 | John Wyeth And Brother Limited | 4-Aryl-4-aryloxypiperidines |
| DE3138550A1 (de) * | 1981-09-28 | 1983-04-07 | Boehringer Ingelheim KG, 6507 Ingelheim | Substituierte 2-phenyl-2-(pyridyloxy)-ethylamine und isostere verbindungen, verfahren zu ihrer herstellung und verwendung |
| DE3328348A1 (de) * | 1983-08-05 | 1985-02-14 | Degussa Ag, 6000 Frankfurt | Verfahren zur duennschichtchromatographischen trennung von enantiomeren |
| US4902710A (en) * | 1988-12-14 | 1990-02-20 | Eli Lilly And Company | Serotonin and norepinephrine uptake inhibitors |
| GB0004153D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004152D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| GB0004151D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004149D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
| SE0102640D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102641D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| CN100469784C (zh) * | 2001-11-21 | 2009-03-18 | 奥尔胡斯大学 | 甘油一酯和甘油二酯糖苷作为抗炎药物的用途 |
-
2002
- 2002-11-07 SE SE0203304A patent/SE0203304D0/xx unknown
-
2003
- 2003-11-06 EP EP03770201A patent/EP1562920B1/en not_active Expired - Lifetime
- 2003-11-06 ES ES03770201T patent/ES2268441T3/es not_active Expired - Lifetime
- 2003-11-06 WO PCT/SE2003/001712 patent/WO2004041794A1/en not_active Ceased
- 2003-11-06 JP JP2004549780A patent/JP2006506414A/ja not_active Withdrawn
- 2003-11-06 DE DE60306546T patent/DE60306546T2/de not_active Expired - Fee Related
- 2003-11-06 AT AT03770201T patent/ATE331711T1/de not_active IP Right Cessation
- 2003-11-06 AU AU2003278667A patent/AU2003278667A1/en not_active Abandoned
- 2003-11-06 US US10/534,191 patent/US20060040992A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004041794A1 (en) | 2004-05-21 |
| WO2004041794A8 (en) | 2005-03-10 |
| EP1562920B1 (en) | 2006-06-28 |
| JP2006506414A (ja) | 2006-02-23 |
| EP1562920A1 (en) | 2005-08-17 |
| AU2003278667A1 (en) | 2004-06-07 |
| DE60306546D1 (de) | 2006-08-10 |
| ES2268441T3 (es) | 2007-03-16 |
| SE0203304D0 (sv) | 2002-11-07 |
| US20060040992A1 (en) | 2006-02-23 |
| ATE331711T1 (de) | 2006-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60306546T2 (de) | Entzündungshemmende 3-arylthio-3-thiazolylalkylamine | |
| DE60107820T2 (de) | Neue verwendung von phenylheteroalkylamin-derivaten | |
| DE69404044T2 (de) | Isoxazolinverbindungen als entzündungshemmende mittel | |
| DE69725293T2 (de) | N-(2 oxoacetyl oder sulphonyl)-pyrrolidine/piperidine-2-carbonsäurederivate mit verbesserter multi-drug resistenz aktivität | |
| DE60225316T2 (de) | Cyanoalkylamino-derivate als protease-hemmer | |
| EP1119557B1 (de) | Indeno-, naphtho- und benzocyclohepta-dihydrothiazol derivate, deren herstellung und deren verwendung als anorektische arzneimittel | |
| DE69721134T2 (de) | Verfahren zur Herstellung von 4-(2-(2-Pyridyl)Ethoxy)Benzaldehyd-Derivate | |
| DE60210784T2 (de) | Orale antidiabetische wirkstoffe | |
| WO2002100825A2 (de) | Anthranilsäureamide mit heteroarylsulfonyl-seitenkette und ihre verwendung als antiarrhythmische wirkstoffe | |
| DE69015322T2 (de) | Substituierte Zyklobutendion-Verbindungen. | |
| DE4126662A1 (de) | Neue 3,5-di-tert.butyl-4-hydroxyphenyl-derivate, verfahren zu ihrer herstellung und arzneimittel | |
| EP1259498A1 (de) | 8,8a-dihydro-indeno [1,2-d]thiazol-derivate, die in 8a-stellung substituiert sind, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel z.b. als anorektika | |
| DE69222459T2 (de) | Thiazolidindionderivate, ihre Herstellung und Anwendung | |
| DE69006872T2 (de) | 1H,3H,7-Pyrrolo [1,2-c]thiazolcarbonsäureamid-Derivate, ihre Herstellung und diese enthaltende pharmazeutische Zubereitungen. | |
| JP2024540318A (ja) | Ｃｄ３８阻害剤としてのｎ－（４－アミノシクロヘキシル）ピリミジン－４－カルボキサミド誘導体 | |
| DE60209806T2 (de) | 2-amino-thiazolinderivate und ihre verwendung als hemmstoffe der induzierbaren no-synthase | |
| DE60103033T2 (de) | Neue phenylheteroalkylamin-derivate | |
| DE60207104T2 (de) | 2-amino-4-heteroarylethyl-thiazolinderivate und ihre verwendung als hemmstoffe der induzierbaren no-synthase | |
| DE60103034T2 (de) | Neue phenylheteroalkylamin-derivate | |
| DE3613573A1 (de) | Cyclopentylether und ihre herstellung sowie pharmazeutische formulierung | |
| EP0552462A1 (de) | Thiadiazincarbonsäureamidderivate, Verfahren zu ihrer Herstellung und Arzneimittel | |
| DE60210981T2 (de) | Heteroarylheteroalkylamin derivate und deren verwendung als inhibitoren der stickoxidsynthase | |
| DE60103035T2 (de) | Neue verwendung von phenylheteroalkylamin-derivaten | |
| DE69014930T2 (de) | Aralkylamin-Verbindungen. | |
| EP0409048A2 (de) | Aminoalkylsubstituierte 2-Aminothiazole und diese enthaltende therapeutische Mittel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |