DE4244539A1 - - Google Patents
Info
- Publication number
- DE4244539A1 DE4244539A1 DE4244539A DE4244539A DE4244539A1 DE 4244539 A1 DE4244539 A1 DE 4244539A1 DE 4244539 A DE4244539 A DE 4244539A DE 4244539 A DE4244539 A DE 4244539A DE 4244539 A1 DE4244539 A1 DE 4244539A1
- Authority
- DE
- Germany
- Prior art keywords
- compound
- compounds
- precursor
- formula
- acid
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 89
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 20
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 20
- 229960000905 indomethacin Drugs 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000002243 precursor Substances 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims description 11
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims description 11
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 10
- 229960004889 salicylic acid Drugs 0.000 claims description 10
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 claims description 10
- 229960000894 sulindac Drugs 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 8
- 229940126062 Compound A Drugs 0.000 claims description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 7
- 229960001680 ibuprofen Drugs 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 229960003464 mefenamic acid Drugs 0.000 claims description 5
- -1 amino, methylamino, ethylamino, hydrazino, methyl Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000637 arginyl group Chemical class N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 1
- MRAUNPAHJZDYCK-BYPYZUCNSA-N L-nitroarginine Chemical group OC(=O)[C@@H](N)CCCNC(=N)N[N+]([O-])=O MRAUNPAHJZDYCK-BYPYZUCNSA-N 0.000 description 23
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 23
- 239000002158 endotoxin Substances 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 229920006008 lipopolysaccharide Polymers 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 12
- KCWZGJVSDFYRIX-YFKPBYRVSA-N N(gamma)-nitro-L-arginine methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N[N+]([O-])=O KCWZGJVSDFYRIX-YFKPBYRVSA-N 0.000 description 12
- 229960001138 acetylsalicylic acid Drugs 0.000 description 12
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 11
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 10
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 210000002540 macrophage Anatomy 0.000 description 8
- 206010061216 Infarction Diseases 0.000 description 7
- NTNWOCRCBQPEKQ-YFKPBYRVSA-N N(omega)-methyl-L-arginine Chemical group CN=C(N)NCCC[C@H](N)C(O)=O NTNWOCRCBQPEKQ-YFKPBYRVSA-N 0.000 description 7
- 230000007574 infarction Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 159000000000 sodium salts Chemical class 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 5
- 201000006474 Brain Ischemia Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 210000000709 aorta Anatomy 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 210000001772 blood platelet Anatomy 0.000 description 4
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 4
- 229960004484 carbachol Drugs 0.000 description 4
- 206010008118 cerebral infarction Diseases 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000003038 endothelium Anatomy 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 3
- WJAJPNHVVFWKKL-UHFFFAOYSA-N Methoxamine Chemical compound COC1=CC=C(OC)C(C(O)C(C)N)=C1 WJAJPNHVVFWKKL-UHFFFAOYSA-N 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 3
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 210000002376 aorta thoracic Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 231100000225 lethality Toxicity 0.000 description 3
- 229940013798 meclofenamate Drugs 0.000 description 3
- 229960005192 methoxamine Drugs 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 238000013222 sprague-dawley male rat Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- RDSUFEJPLMOUOL-UHFFFAOYSA-N 1-(2-methylpropyl)-3,7-dihydropurine-2,6-dione Chemical compound O=C1N(CC(C)C)C(=O)NC2=C1NC=N2 RDSUFEJPLMOUOL-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- 229930064664 L-arginine Natural products 0.000 description 2
- 235000014852 L-arginine Nutrition 0.000 description 2
- 125000002059 L-arginyl group Chemical class O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- QBNXAGZYLSRPJK-JEDNCBNOSA-N N(gamma)-nitro-L-arginine methyl ester hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CCCNC(=N)N[N+]([O-])=O QBNXAGZYLSRPJK-JEDNCBNOSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000011067 equilibration Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- KFGOFTHODYBSGM-IJCBKZNRSA-N 6-Keto-prostaglandin F1a Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC(=O)CCCCC(O)=O KFGOFTHODYBSGM-IJCBKZNRSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000007204 Brain death Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- MLTRLIITQPXHBJ-BQBZGAKWSA-N Leu-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC(N)=O MLTRLIITQPXHBJ-BQBZGAKWSA-N 0.000 description 1
- 101001044384 Mus musculus Interferon gamma Proteins 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- NTWVQPHTOUKMDI-YFKPBYRVSA-N N-Methyl-arginine Chemical compound CN[C@H](C(O)=O)CCCN=C(N)N NTWVQPHTOUKMDI-YFKPBYRVSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N Nitrogen oxide(NO) Natural products O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 238000011795 OF1 mouse Methods 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 206010035039 Piloerection Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 206010049771 Shock haemorrhagic Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 1
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- ZVARSKBWVMXPQO-UHFFFAOYSA-N [2-(chloromethyl)phenyl] acetate Chemical compound CC(=O)OC1=CC=CC=C1CCl ZVARSKBWVMXPQO-UHFFFAOYSA-N 0.000 description 1
- RAUARFJXOYWAHD-JEDNCBNOSA-N acetic acid;(2s)-5-(diaminomethylideneamino)-2-(methylamino)pentanoic acid Chemical compound CC(O)=O.CN[C@H](C(O)=O)CCCNC(N)=N RAUARFJXOYWAHD-JEDNCBNOSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- QZNJPJDUBTYMRS-UHFFFAOYSA-M amfenac sodium hydrate Chemical compound O.[Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=CC=C1 QZNJPJDUBTYMRS-UHFFFAOYSA-M 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940069078 citric acid / sodium citrate Drugs 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000009989 contractile response Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- NHNBFGGVMKEFGY-OUBTZVSYSA-N dioxido(oxo)azanium Chemical class [O-][15N+]([O-])=O NHNBFGGVMKEFGY-OUBTZVSYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000001490 effect on brain Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 231100000284 endotoxic Toxicity 0.000 description 1
- 230000002346 endotoxic effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 210000003024 peritoneal macrophage Anatomy 0.000 description 1
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000005371 pilomotor reflex Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000005599 propionic acid derivatives Chemical class 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 108010003641 statine renin inhibitory peptide Proteins 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000003600 vasopressic effect Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/03—Monoamines
- C07C211/04—Mono-, di- or tri-methylamine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
- C07C65/05—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring o-Hydroxy carboxylic acids
- C07C65/10—Salicylic acid
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
- C07C229/58—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/30—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to nitro or nitroso groups
- C07C279/32—N-nitroguanidines
- C07C279/36—Substituted N-nitroguanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/14—Acetic acid esters of monohydroxylic compounds
- C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
- C07C69/157—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
- C07D209/28—1-(4-Chlorobenzoyl)-2-methyl-indolyl-3-acetic acid, substituted in position 5 by an oxygen or nitrogen atom; Esters thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9200114 | 1992-01-04 | ||
| GB929200114A GB9200114D0 (en) | 1992-01-04 | 1992-01-04 | Dual inhibitors of no synthase and cyclooxygenase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE4244539A1 true DE4244539A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-07-08 |
| DE4244539B4 DE4244539B4 (de) | 2006-10-26 |
Family
ID=10708115
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE4244539A Expired - Fee Related DE4244539B4 (de) | 1992-01-04 | 1992-12-30 | Duale Inhibitoren der No-Synthese und Cyclooxygenase, Verfahren zu ihrer Herstellung und therapeutische Präparate, die sie enthalten |
Country Status (34)
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2162462C2 (ru) * | 1994-11-23 | 2001-01-27 | Фармация Энд Апджон Компани | Аминогуанидинкарбоксилаты |
| US6274580B1 (en) | 1996-05-21 | 2001-08-14 | Pharmacia & Upjohn Company | Aminoguanidine carboxylate lactams for the treatment of non-insulin-dependent diabetes mellitus |
| EP1255544A4 (en) * | 2000-01-31 | 2005-02-02 | Genaera Corp | MUCIN SYNTHESIS INHIBITORS |
| US7345051B2 (en) | 2000-01-31 | 2008-03-18 | Genaera Corporation | Mucin synthesis inhibitors |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2188680A1 (en) * | 1994-05-07 | 1996-01-25 | James Edwin Macdonald | Bicyclic amidine derivatives as inhibitors of nitric oxide synthetase |
| WO1995031195A1 (en) * | 1994-05-11 | 1995-11-23 | Jes Olesen | Use of no scavengers, inhibitors or antagonists in the treatment of migraine |
| CA2132690A1 (en) * | 1994-09-22 | 1996-03-23 | Dean Willis | Control and modulation of inflammatory response in humans in need of such control and modulation |
| US6066333A (en) * | 1994-09-22 | 2000-05-23 | William Harvey Research Limited | Pharmaceutical control of inflammation |
| FR2727111B1 (fr) * | 1994-11-21 | 1997-01-17 | Hoechst Lab | Nouveaux analogues soufres d'aminoacides, leur procede de preparation et leurs applications comme medicaments |
| JPH08333258A (ja) | 1994-12-14 | 1996-12-17 | Japan Tobacco Inc | チアジン又はチアゼピン誘導体及びそれら化合物を含有してなる一酸化窒素合成酵素阻害剤 |
| ES2096524B1 (es) * | 1994-12-22 | 1997-11-16 | Sanchez Manuel Guerra | Uso de la ng-monometil-l-arginina, para aumentar la capacidad de hacer ejercicio fisico. |
| FR2730930B1 (fr) | 1995-02-27 | 1997-04-04 | Oreal | Utilisation d'inhibiteurs de no-synthase pour diminuer l'effet irritant cutane de produits utilises dans le domaine cosmetique ou pharmaceutique |
| GB9504350D0 (en) * | 1995-03-04 | 1995-04-26 | Sod Conseils Rech Applic | Arginine derivatives |
| US5703073A (en) * | 1995-04-19 | 1997-12-30 | Nitromed, Inc. | Compositions and methods to prevent toxicity induced by nonsteroidal antiinflammatory drugs |
| GB9514518D0 (en) * | 1995-07-15 | 1995-09-13 | Sod Conseils Rech Applic | Guanidine salt inhibitors of NO synthase and cyclooxygenase |
| BR9707953A (pt) * | 1996-03-05 | 2000-10-24 | Childrens Hosp Medical Center | Derivados de mercapto como inibidores de ciclooxigenases |
| US8022095B2 (en) * | 1996-08-16 | 2011-09-20 | Pozen, Inc. | Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs |
| US5872145A (en) * | 1996-08-16 | 1999-02-16 | Pozen, Inc. | Formulation of 5-HT agonist and NSAID for treatment of migraine |
| US6586458B1 (en) | 1996-08-16 | 2003-07-01 | Pozen Inc. | Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs |
| US5789395A (en) * | 1996-08-30 | 1998-08-04 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds for inhibition of endogenous nitric oxide production |
| IT1288123B1 (it) * | 1996-09-04 | 1998-09-10 | Nicox Sa | Uso di nitroderivati per l'incontinenza urinaria |
| US6066092A (en) * | 1997-11-06 | 2000-05-23 | Cady; Roger K. | Preemptive prophylaxis of migraine device and method |
| IT1301966B1 (it) | 1998-07-30 | 2000-07-20 | Zambon Spa | Composizioni farmaceutiche ad attivita' analgesica |
| US6207700B1 (en) * | 1999-01-07 | 2001-03-27 | Vanderbilt University | Amide derivatives for antiangiogenic and/or antitumorigenic use |
| JP2005539089A (ja) * | 2002-07-03 | 2005-12-22 | ニトロメッド インコーポレーティッド | ニトロソ化非ステロイド性抗炎症化合物、組成物および使用方法 |
| AU2003261281A1 (en) * | 2002-07-29 | 2004-02-16 | Nicox S.A. | Cyclooxygenase- 2 selective inhibitors, compositions and methods of use |
| JP4616009B2 (ja) * | 2002-12-26 | 2011-01-19 | ポーゼン インコーポレイテッド | ＮＳＡＩＤｓおよびトリプタンを含有する多層剤型 |
| US20070184109A1 (en) * | 2003-06-06 | 2007-08-09 | Floyd Alison G | Compositions comprising triptans and nsaids |
| AU2004249775A1 (en) * | 2003-06-19 | 2004-12-29 | Genaera Corporation | Mucin synthesis inhibitors |
| AU2004253159A1 (en) * | 2003-06-25 | 2005-01-06 | Vanderbilt University | COX-2-targeted imaging agents |
| EP1744747A4 (en) * | 2004-04-26 | 2009-12-02 | Univ Vanderbilt | INDIC ACID AND INDULECTIC ACID DERIVATIVES AS THERAPEUTIC ACTIVITIES WITH REDUCED GASTROINTESTINAL TOXICITY |
| JP2008526185A (ja) * | 2005-01-04 | 2008-07-24 | ノバルティス アクチエンゲゼルシャフト | ヒトｆｐｐｓのｘ線構造およびｆｐｐｓ結合化合物を選択するための使用 |
| CN101528222A (zh) | 2006-06-19 | 2009-09-09 | 范德比尔特大学 | 用于诊断性和治疗性靶向cox-2的方法和组合物 |
| EP3078374B1 (en) | 2011-10-17 | 2019-06-19 | Vanderbilt University | Indomethacin analogs for the treatment of castrate-resistant prostate cancer |
| TWM469254U (zh) | 2013-08-29 | 2014-01-01 | J D Components Co Ltd | 自行車之三件式豎管 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR6838M (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1967-12-08 | 1969-03-31 | ||
| ES423794A1 (es) * | 1974-03-01 | 1976-05-01 | Medicinales S A Promesa Prod | Procediemiento de obtencion de una nueva sal soluble de acido acetilsalicilico. |
| FR2320759A1 (fr) * | 1975-08-11 | 1977-03-11 | Union Pharma Scient Appl | Solution d'acide acetylsalicylique extemporanee injectable |
| IT1127274B (it) * | 1979-12-04 | 1986-05-21 | Selvi & C Spa | Sali dell'acido 5-fluoro-2-metil-1-(p-(metilsulfinil)-benzilidene)-indene-3-acetico |
| JPS5781409A (en) * | 1980-11-10 | 1982-05-21 | Toko Yakuhin Kogyo Kk | External plaster |
| CA1213888A (en) * | 1983-09-28 | 1986-11-12 | Warner-Lambert Company | L-arginine isoxicamate |
| US5081184A (en) * | 1985-08-02 | 1992-01-14 | General Electric Company | Solvent-resistant, compatible blends of polyphenylene ethers and linear polyesters |
| JPS6393718A (ja) * | 1986-10-07 | 1988-04-25 | Green Cross Corp:The | 注射剤 |
| US5028627A (en) * | 1989-09-13 | 1991-07-02 | Cornell Research Foundation, Inc. | Method of using arginine derivatives to inhibit systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor |
| US5059712A (en) * | 1989-09-13 | 1991-10-22 | Cornell Research Foundation, Inc. | Isolating aminoarginine and use to block nitric oxide formation in body |
| DE69022678T2 (de) * | 1989-10-17 | 1996-03-21 | Merck & Co Inc | S(+)-Ibuprofen-L-Aminosäure und S(+)-Ibuprofen-D-Aminosäure als Analgetika mit grösserem pharmakologischem Potential. |
| GB8929076D0 (en) * | 1989-12-22 | 1990-02-28 | Scras | Treatment of shock by blocking agents of edrf effect or formation |
| US5468476A (en) * | 1994-03-16 | 1995-11-21 | Ahluwalia; Gurpreet S. | Reduction of hair growth |
-
1992
- 1992-01-04 GB GB929200114A patent/GB9200114D0/en active Pending
- 1992-12-14 NO NO924835A patent/NO302943B1/no unknown
- 1992-12-16 CA CA002085555A patent/CA2085555C/en not_active Expired - Fee Related
- 1992-12-17 NZ NZ245499A patent/NZ245499A/en unknown
- 1992-12-18 SE SE9203825A patent/SE511568C2/sv not_active IP Right Cessation
- 1992-12-18 GR GR920100563A patent/GR1001443B/el not_active IP Right Cessation
- 1992-12-18 CH CH3890/92A patent/CH685629A5/fr not_active IP Right Cessation
- 1992-12-18 MY MYPI92002343A patent/MY109846A/en unknown
- 1992-12-18 TW TW081110175A patent/TW267152B/zh active
- 1992-12-22 BE BE9201127A patent/BE1006227A3/fr not_active IP Right Cessation
- 1992-12-22 FR FR9215447A patent/FR2685869B1/fr not_active Expired - Fee Related
- 1992-12-22 FR FR9215448A patent/FR2685916B1/fr not_active Expired - Fee Related
- 1992-12-23 AT AT0256092A patent/AT401054B/de not_active IP Right Cessation
- 1992-12-23 IT ITMI922953A patent/IT1256761B/it active IP Right Grant
- 1992-12-23 US US07/995,792 patent/US5480999A/en not_active Expired - Lifetime
- 1992-12-24 GB GB9227026A patent/GB2263111B/en not_active Expired - Lifetime
- 1992-12-25 MA MA23045A patent/MA22753A1/fr unknown
- 1992-12-28 FI FI925883A patent/FI925883L/fi not_active Application Discontinuation
- 1992-12-29 LU LU88208A patent/LU88208A1/fr unknown
- 1992-12-29 ES ES09202635A patent/ES2052452B1/es not_active Expired - Fee Related
- 1992-12-29 DZ DZ920171A patent/DZ1657A1/fr active
- 1992-12-29 ZA ZA9210080A patent/ZA9210080B/xx unknown
- 1992-12-30 PL PL92297247A patent/PL169432B1/pl not_active IP Right Cessation
- 1992-12-30 PT PT101165A patent/PT101165B/pt not_active IP Right Cessation
- 1992-12-30 DE DE4244539A patent/DE4244539B4/de not_active Expired - Fee Related
- 1992-12-30 HU HU9204173A patent/HU220218B/hu not_active IP Right Cessation
- 1992-12-30 KR KR1019920026433A patent/KR100287539B1/ko not_active Expired - Fee Related
- 1992-12-30 DK DK157592A patent/DK157592A/da not_active Application Discontinuation
- 1992-12-31 IE IE922954A patent/IE71675B1/en not_active IP Right Cessation
- 1992-12-31 AU AU30498/92A patent/AU664399B2/en not_active Ceased
- 1992-12-31 OA OA60325A patent/OA10050A/fr unknown
- 1992-12-31 RU RU92016217A patent/RU2104999C1/ru not_active IP Right Cessation
-
1993
- 1993-01-04 JP JP5000091A patent/JP2984498B2/ja not_active Expired - Fee Related
- 1993-01-04 NL NL9300001A patent/NL194889C/nl not_active IP Right Cessation
- 1993-01-04 TN TNTNSN93001A patent/TNSN93001A1/fr unknown
- 1993-09-29 US US08/128,908 patent/US5360925A/en not_active Expired - Lifetime
-
1996
- 1996-02-08 HK HK22296A patent/HK22296A/xx not_active IP Right Cessation
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2162462C2 (ru) * | 1994-11-23 | 2001-01-27 | Фармация Энд Апджон Компани | Аминогуанидинкарбоксилаты |
| US6329545B1 (en) | 1994-11-23 | 2001-12-11 | Scott D. Larsen | Aminoguanidine carboxylates for the treatment of non-insulin-dependent diabetes mellitus |
| US6274580B1 (en) | 1996-05-21 | 2001-08-14 | Pharmacia & Upjohn Company | Aminoguanidine carboxylate lactams for the treatment of non-insulin-dependent diabetes mellitus |
| EP1255544A4 (en) * | 2000-01-31 | 2005-02-02 | Genaera Corp | MUCIN SYNTHESIS INHIBITORS |
| US7345051B2 (en) | 2000-01-31 | 2008-03-18 | Genaera Corporation | Mucin synthesis inhibitors |
| US7504409B2 (en) | 2000-01-31 | 2009-03-17 | Genaera Corporation | Mucin synthesis inhibitors |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE4244539B4 (de) | Duale Inhibitoren der No-Synthese und Cyclooxygenase, Verfahren zu ihrer Herstellung und therapeutische Präparate, die sie enthalten | |
| DE69528359T2 (de) | Guanylhydrazon zur behandlung von entzündungen | |
| DE2857415C2 (de) | Amidinderivate von Glycerin und diese enthaltende Arzneimittel | |
| DE69632193T2 (de) | Cyclooxygenaseinhibitor und salze von amidinderivaten, verfahren zu deren herstellung, deren verwendung als arzneiwirkstoffe sowie diese salze enthaltende arzneimittel | |
| EP0013376A2 (de) | Ein Isoxazolderivat, Verfahren zu seiner Herstellung und diese Verbindung enthaltende Mittel | |
| DE2634288A1 (de) | Benzylidenderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel | |
| DE4321444A1 (de) | Pharmazeutische Zubereitung | |
| DE69512929T2 (de) | Salze von aminoalkoholen und diese enthaltende pharmazeutische zusammensetzungen | |
| DE69031913T2 (de) | Antivirale mittel | |
| DE3005580C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| DE2519394A1 (de) | Mittel zur behandlung von virusinfektionen | |
| AT391688B (de) | Verfahren zur herstellung des neuen n-methyl-dglucamin-salzes von (+)-2-(2-fluor-4-biphenylyl)- propionsaeure | |
| DE69415570T2 (de) | Esculetin Derivate und pharmazeutische Zusammenstellung | |
| DE69626514T2 (de) | Mono-und disulfosubstituierte anthrachinone und deren verwendung zur behandlung von knochenmatrixerkrankungen | |
| DE2318784A1 (de) | N-(2,4-dihydroxybenzoyl)-4-aminosalizylsaeure | |
| DE69506702T2 (de) | Verwendung einer naphtolsulfonsäure zur hemmung der retroviraler infektionen | |
| DE69509621T2 (de) | Diarylheptanoidderivat und diese enthaltende pharmazeutische Zusammensetzung | |
| DE2329745A1 (de) | Therapeutisches mittel und verwendung desselben | |
| DE69715637T2 (de) | Mit wasser mischbare monoglyceridester mit antimikrobieller aktivität | |
| DE68914392T2 (de) | Verwendung von oxydierten Polyamiden, speziell NN'-Bis-(3-propionaldehyd)-1-4-diaminobutan als Immunsuppressiva. | |
| DE2537294B2 (de) | S-Inosyl-L-cystein und Verfahren zu seiner Herstellung | |
| WO1993000326A1 (de) | Omega-3 mehrfach ungesättigte fettsäurederivate, ihre herstellung und verwendung | |
| AT165069B (de) | Verfahren zur Herstellung neuer Phenoxyacetamidine | |
| DE69313535T2 (de) | N-Benzoylaminosäurederivate, diese enthaltende pharmazeutische Zusammensetzungen und Verfahren zur deren Herstellung | |
| DE2827452A1 (de) | Anionisch substituierte benzoltetrayltetrakis(carbonylimino-tetraisophthalsaeuresalze |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8110 | Request for examination paragraph 44 | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |