DE2926472A1 - Neue benzoylderivate, deren herstellung und deren verwendung als arzneimittel - Google Patents
Neue benzoylderivate, deren herstellung und deren verwendung als arzneimittelInfo
- Publication number
- DE2926472A1 DE2926472A1 DE19792926472 DE2926472A DE2926472A1 DE 2926472 A1 DE2926472 A1 DE 2926472A1 DE 19792926472 DE19792926472 DE 19792926472 DE 2926472 A DE2926472 A DE 2926472A DE 2926472 A1 DE2926472 A1 DE 2926472A1
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- amino
- deep
- ethyl
- group
- 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.)
- Withdrawn
Links
- 238000004519 manufacturing process Methods 0.000 title description 11
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical class C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 title 1
- 229940126601 medicinal product Drugs 0.000 title 1
- -1 pyrrolidino, piperidino, hexamethyleneimino, morpholino Chemical group 0.000 claims abstract description 370
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 72
- 239000000460 chlorine Chemical group 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- 239000002253 acid Substances 0.000 claims abstract description 20
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 19
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 16
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000011737 fluorine Chemical group 0.000 claims abstract description 11
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 150000003462 sulfoxides Chemical class 0.000 claims abstract description 10
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 8
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 7
- 125000005042 acyloxymethyl group Chemical group 0.000 claims abstract description 6
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000001741 anti-phlogistic effect Effects 0.000 claims abstract description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 125000002993 cycloalkylene group Chemical group 0.000 claims abstract description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 4
- 125000004970 halomethyl group Chemical group 0.000 claims abstract description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 4
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 97
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 claims description 65
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 14
- 150000007522 mineralic acids Chemical class 0.000 claims description 13
- 150000007524 organic acids Chemical class 0.000 claims description 13
- 239000004305 biphenyl Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 235000005985 organic acids Nutrition 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 11
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- 125000004434 sulfur atom Chemical group 0.000 claims description 9
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
- 239000012312 sodium hydride Substances 0.000 claims description 7
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 7
- 150000008064 anhydrides Chemical class 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 230000010933 acylation Effects 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 4
- 150000001447 alkali salts Chemical class 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 239000012024 dehydrating agents Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 150000007530 organic bases Chemical group 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
- SKHQTRTWACSLAU-UHFFFAOYSA-N 5-[2-[2-(2,6-dichloroanilino)phenyl]acetyl]oxypentyl 4-amino-3-bromo-5-[[cyclohexyl(ethyl)amino]methyl]benzoate Chemical compound C1CCCCC1N(CC)CC(C(=C(Br)C=1)N)=CC=1C(=O)OCCCCCOC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl SKHQTRTWACSLAU-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000003983 crown ethers Chemical class 0.000 claims description 2
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 2
- 125000000466 oxiranyl group Chemical group 0.000 claims description 2
- 239000003444 phase transfer catalyst Substances 0.000 claims description 2
- 125000006308 propyl amino group Chemical group 0.000 claims description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- 125000003375 sulfoxide group Chemical group 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
- 125000001424 substituent group Chemical group 0.000 abstract 3
- 125000002252 acyl group Chemical group 0.000 abstract 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract 1
- 229910052794 bromium Chemical group 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 239000011593 sulfur Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 207
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 180
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 124
- 238000002844 melting Methods 0.000 description 76
- 230000008018 melting Effects 0.000 description 76
- 238000002329 infrared spectrum Methods 0.000 description 56
- 238000002211 ultraviolet spectrum Methods 0.000 description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 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 description 48
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 23
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 19
- 229960000583 acetic acid Drugs 0.000 description 17
- 239000000843 powder Substances 0.000 description 17
- 239000000126 substance Substances 0.000 description 16
- KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 15
- KHRMSHGCBBTELF-UHFFFAOYSA-N 4-amino-3-bromo-5-[[cyclohexyl(ethyl)amino]methyl]benzoyl chloride Chemical compound C1CCCCC1N(CC)CC1=CC(C(Cl)=O)=CC(Br)=C1N KHRMSHGCBBTELF-UHFFFAOYSA-N 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- LJSQFQKUNVCTIA-UHFFFAOYSA-N Diethyl sulfide Natural products CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 229920002261 Corn starch Polymers 0.000 description 7
- 239000008120 corn starch Substances 0.000 description 7
- 229940093915 gynecological organic acid Drugs 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 239000003279 phenylacetic acid Substances 0.000 description 7
- 229960003424 phenylacetic acid Drugs 0.000 description 7
- 239000000829 suppository Substances 0.000 description 7
- VCVWWGAKIXAYTN-UHFFFAOYSA-N 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl chloride Chemical compound CC1=C(CC(Cl)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 VCVWWGAKIXAYTN-UHFFFAOYSA-N 0.000 description 6
- BVSFHZBQKVQTIS-UHFFFAOYSA-N 2-hydroxyethyl 4-amino-3-bromo-5-[[cyclohexyl(ethyl)amino]methyl]benzoate Chemical compound C1CCCCC1N(CC)CC1=CC(C(=O)OCCO)=CC(Br)=C1N BVSFHZBQKVQTIS-UHFFFAOYSA-N 0.000 description 6
- ZQHLMASNRJKCKD-UHFFFAOYSA-N 5-[2-[2-(2,6-dichloroanilino)phenyl]acetyl]oxypentyl 4-amino-3-bromo-5-[[cyclohexyl(ethyl)amino]methyl]benzoate;hydrochloride Chemical compound Cl.C1CCCCC1N(CC)CC(C(=C(Br)C=1)N)=CC=1C(=O)OCCCCCOC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl ZQHLMASNRJKCKD-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- CIQFXTRZSGSGAU-UHFFFAOYSA-N 4-amino-3-bromo-5-[[cyclohexyl(ethyl)amino]methyl]benzoyl chloride;hydrochloride Chemical compound Cl.C1CCCCC1N(CC)CC1=CC(C(Cl)=O)=CC(Br)=C1N CIQFXTRZSGSGAU-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- NARWYSCMDPLCIQ-UHFFFAOYSA-N ethane;hydrochloride Chemical compound Cl.CC NARWYSCMDPLCIQ-UHFFFAOYSA-N 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- KCDQHLJEPWTFJR-UHFFFAOYSA-N 2-[2-hydroxyethyl(propan-2-yl)amino]ethyl 4-amino-3-bromo-5-[[cyclohexyl(ethyl)amino]methyl]benzoate Chemical compound C1CCCCC1N(CC)CC1=CC(C(=O)OCCN(CCO)C(C)C)=CC(Br)=C1N KCDQHLJEPWTFJR-UHFFFAOYSA-N 0.000 description 4
- HNSKVRBABRMWQA-UHFFFAOYSA-N 2-[2-hydroxyethyl(propyl)amino]ethyl 4-amino-3-bromo-5-[[cyclohexyl(ethyl)amino]methyl]benzoate Chemical compound CCCN(CCO)CCOC(=O)C1=CC(Br)=C(N)C(CN(CC)C2CCCCC2)=C1 HNSKVRBABRMWQA-UHFFFAOYSA-N 0.000 description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
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- 239000011780 sodium chloride Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- 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]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms 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 the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Priority Applications (18)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792926472 DE2926472A1 (de) | 1979-06-30 | 1979-06-30 | Neue benzoylderivate, deren herstellung und deren verwendung als arzneimittel |
| GR62113A GR68757B (enExample) | 1979-06-30 | 1980-06-03 | |
| AT80103099T ATE3415T1 (de) | 1979-06-30 | 1980-06-04 | Neue benzoylderivate, deren herstellung und deren verwendung als arzneimittel. |
| EP80103099A EP0024282B1 (de) | 1979-06-30 | 1980-06-04 | Neue Benzoylderivate, deren Herstellung und deren Verwendung als Arzneimittel |
| DE8080103099T DE3063290D1 (en) | 1979-06-30 | 1980-06-04 | Benzoyl derivatives, their preparation and their use as medicines |
| JP7828180A JPS5610155A (en) | 1979-06-30 | 1980-06-10 | Novel benzoyl derivative |
| US06/158,587 US4362738A (en) | 1979-06-30 | 1980-06-11 | Esters and amides containing the 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetyl moiety |
| PT71453A PT71453B (de) | 1979-06-30 | 1980-06-25 | Neue benzoylderivate deren herstellung und deren verwendung als arzneimittel |
| ES492845A ES8201128A1 (es) | 1979-06-30 | 1980-06-27 | Procedimiento para la preparacion de nuevos derivados ben- zoilicos |
| NO801931A NO801931L (no) | 1979-06-30 | 1980-06-27 | Analogifremgangsmaate for fremstilling av farmakologisk aktive benzoylderivater |
| FI802049A FI802049A7 (fi) | 1979-06-30 | 1980-06-27 | Uusia bentsoyylijohdoksia, niiden valmistaminen ja niiden käyttö lääkeaineina. |
| NZ194172A NZ194172A (en) | 1979-06-30 | 1980-06-27 | Benzoyl derivatives preparation and antiinflammatory compositions |
| IL60418A IL60418A (en) | 1979-06-30 | 1980-06-27 | Benzoyl derivatives,their preparation and pharmaceutical compositions containing them |
| AU59735/80A AU538776B2 (en) | 1979-06-30 | 1980-06-27 | Chemical compounds |
| DK279480A DK279480A (da) | 1979-06-30 | 1980-06-27 | Fremgangsmaade til fremstilling af benzoylderivater |
| ZA00803907A ZA803907B (en) | 1979-06-30 | 1980-06-30 | Benzoyl derivatives,processes for their preparation,pharmaceutical compositions containing these,and use thereof |
| CA000355151A CA1140564A (en) | 1979-06-30 | 1980-06-30 | Benzoyl derivatives, their preparation and their use as pharmaceutical compositions |
| PH24211A PH16813A (en) | 1979-06-30 | 1980-06-30 | Esters and amides containing the 1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1h-indole-3-acetyl moiety |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792926472 DE2926472A1 (de) | 1979-06-30 | 1979-06-30 | Neue benzoylderivate, deren herstellung und deren verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2926472A1 true DE2926472A1 (de) | 1981-01-15 |
Family
ID=6074591
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19792926472 Withdrawn DE2926472A1 (de) | 1979-06-30 | 1979-06-30 | Neue benzoylderivate, deren herstellung und deren verwendung als arzneimittel |
| DE8080103099T Expired DE3063290D1 (en) | 1979-06-30 | 1980-06-04 | Benzoyl derivatives, their preparation and their use as medicines |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8080103099T Expired DE3063290D1 (en) | 1979-06-30 | 1980-06-04 | Benzoyl derivatives, their preparation and their use as medicines |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4362738A (enExample) |
| EP (1) | EP0024282B1 (enExample) |
| JP (1) | JPS5610155A (enExample) |
| AT (1) | ATE3415T1 (enExample) |
| AU (1) | AU538776B2 (enExample) |
| CA (1) | CA1140564A (enExample) |
| DE (2) | DE2926472A1 (enExample) |
| DK (1) | DK279480A (enExample) |
| ES (1) | ES8201128A1 (enExample) |
| FI (1) | FI802049A7 (enExample) |
| GR (1) | GR68757B (enExample) |
| IL (1) | IL60418A (enExample) |
| NO (1) | NO801931L (enExample) |
| NZ (1) | NZ194172A (enExample) |
| PH (1) | PH16813A (enExample) |
| PT (1) | PT71453B (enExample) |
| ZA (1) | ZA803907B (enExample) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6207700B1 (en) | 1999-01-07 | 2001-03-27 | Vanderbilt University | Amide derivatives for antiangiogenic and/or antitumorigenic use |
| US6306890B1 (en) | 1999-08-30 | 2001-10-23 | Vanderbilt University | Esters derived from indolealkanols and novel amides derived from indolealkylamides that are selective COX-2 inhibitors |
| US6762182B1 (en) | 1999-01-07 | 2004-07-13 | Vanderbilt University | Converting cox inhibition compounds that are not COX-2 selective inhibitors to derivatives that are COX-2 selective inhibitors |
| USRE41151E1 (en) | 2000-06-23 | 2010-02-23 | Medinox, Inc. | Protected forms of pharmacologically active agents and uses thereof |
| US7736624B2 (en) | 2006-06-19 | 2010-06-15 | Univ Vanderbilt | Methods and compositions for diagnostic and therapeutic targeting of COX-2 |
| US8168656B2 (en) | 2004-04-26 | 2012-05-01 | Vanderbilt University | Indoleacetic acid and indenacetic acid derivatives as therapeutic agents with reduced gastrointestinal toxicity |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57194563U (enExample) * | 1982-04-13 | 1982-12-09 | ||
| US4748184A (en) * | 1982-07-26 | 1988-05-31 | E. I. Du Pont De Nemours And Company | Aryl substituted aminomethyl benzene derivatives having antiarrhythmic utility |
| US4562201A (en) * | 1982-07-26 | 1985-12-31 | American Hospital Supply Corporation | Aminomethyl benzanilides |
| US4755527A (en) * | 1982-07-26 | 1988-07-05 | E. I. Du Pont De Nemours And Company | Aryl substituted aminomethyl benzene derivatives |
| JPS6011483A (ja) * | 1983-06-29 | 1985-01-21 | Taiho Yakuhin Kogyo Kk | ピペラジン化合物 |
| GB8410899D0 (en) * | 1984-04-27 | 1984-06-06 | Ici Plc | Phenol derivatives |
| ES8605220A1 (es) * | 1985-10-25 | 1986-03-16 | Espanola Prod Quimicos | Procedimiento de preparacion de esteres del dietilenglicol |
| US5569659A (en) * | 1991-09-11 | 1996-10-29 | Mcneilab, Inc. | 4-arylpiperazines and 4-arylpiperidines |
| NZ240863A (en) * | 1991-09-11 | 1995-04-27 | Mcneilab Inc | Substituted 4-aryl piperidine and 4-aryl piperazine derivatives, preparation and pharmaceutical compositions thereof |
| BR9510360A (pt) * | 1994-12-23 | 1997-12-23 | Thomae Gmbh Dr K | Derivados de piperazina medicamentos contendo esses compostos sua aplicação e processo para sua preparação |
| DE69632338T2 (de) * | 1995-03-07 | 2005-05-12 | Santen Pharmaceutical Co., Ltd | Neue aminosäurederivate, die eine n, n-dialkylaminophenylgruppe haben |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3564009A (en) * | 1966-01-13 | 1971-02-16 | Sumitomo Chemical Co | Process for producing 1-acylindole derivatives |
| AT332375B (de) * | 1973-04-13 | 1976-09-27 | Thomae Gmbh Dr K | Verfahren zur herstellung von neuen aminobenzylaminen sowie deren saureadditionssalzen |
| IT1043937B (it) * | 1974-08-12 | 1980-02-29 | Rotta Research Lab | Defivati della n benzoil n' n' di ,n, propil, dl, isoglutamina ad attivita antiartrosioa ed antiin fiammatoria |
-
1979
- 1979-06-30 DE DE19792926472 patent/DE2926472A1/de not_active Withdrawn
-
1980
- 1980-06-03 GR GR62113A patent/GR68757B/el unknown
- 1980-06-04 DE DE8080103099T patent/DE3063290D1/de not_active Expired
- 1980-06-04 EP EP80103099A patent/EP0024282B1/de not_active Expired
- 1980-06-04 AT AT80103099T patent/ATE3415T1/de not_active IP Right Cessation
- 1980-06-10 JP JP7828180A patent/JPS5610155A/ja active Pending
- 1980-06-11 US US06/158,587 patent/US4362738A/en not_active Expired - Lifetime
- 1980-06-25 PT PT71453A patent/PT71453B/pt unknown
- 1980-06-27 AU AU59735/80A patent/AU538776B2/en not_active Withdrawn - After Issue
- 1980-06-27 IL IL60418A patent/IL60418A/xx unknown
- 1980-06-27 NO NO801931A patent/NO801931L/no unknown
- 1980-06-27 FI FI802049A patent/FI802049A7/fi not_active Application Discontinuation
- 1980-06-27 ES ES492845A patent/ES8201128A1/es not_active Expired
- 1980-06-27 DK DK279480A patent/DK279480A/da not_active Application Discontinuation
- 1980-06-27 NZ NZ194172A patent/NZ194172A/xx unknown
- 1980-06-30 CA CA000355151A patent/CA1140564A/en not_active Expired
- 1980-06-30 PH PH24211A patent/PH16813A/en unknown
- 1980-06-30 ZA ZA00803907A patent/ZA803907B/xx unknown
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6207700B1 (en) | 1999-01-07 | 2001-03-27 | Vanderbilt University | Amide derivatives for antiangiogenic and/or antitumorigenic use |
| US6399647B2 (en) | 1999-01-07 | 2002-06-04 | Vanderbilt University | Amide derivatives for antiangiogenic and/or antitumorigenic use |
| US6762182B1 (en) | 1999-01-07 | 2004-07-13 | Vanderbilt University | Converting cox inhibition compounds that are not COX-2 selective inhibitors to derivatives that are COX-2 selective inhibitors |
| US6306890B1 (en) | 1999-08-30 | 2001-10-23 | Vanderbilt University | Esters derived from indolealkanols and novel amides derived from indolealkylamides that are selective COX-2 inhibitors |
| USRE41151E1 (en) | 2000-06-23 | 2010-02-23 | Medinox, Inc. | Protected forms of pharmacologically active agents and uses thereof |
| US8168656B2 (en) | 2004-04-26 | 2012-05-01 | Vanderbilt University | Indoleacetic acid and indenacetic acid derivatives as therapeutic agents with reduced gastrointestinal toxicity |
| US7736624B2 (en) | 2006-06-19 | 2010-06-15 | Univ Vanderbilt | Methods and compositions for diagnostic and therapeutic targeting of COX-2 |
Also Published As
| Publication number | Publication date |
|---|---|
| FI802049A7 (fi) | 1981-01-01 |
| ES492845A0 (es) | 1981-11-01 |
| JPS5610155A (en) | 1981-02-02 |
| ATE3415T1 (de) | 1983-06-15 |
| EP0024282A1 (de) | 1981-03-04 |
| GR68757B (enExample) | 1982-02-17 |
| PT71453A (de) | 1980-07-01 |
| ES8201128A1 (es) | 1981-11-01 |
| PT71453B (de) | 1981-10-23 |
| IL60418A0 (en) | 1980-09-16 |
| EP0024282B1 (de) | 1983-05-18 |
| AU5973580A (en) | 1981-02-05 |
| PH16813A (en) | 1984-03-06 |
| DK279480A (da) | 1980-12-31 |
| NZ194172A (en) | 1982-08-17 |
| NO801931L (no) | 1981-01-02 |
| IL60418A (en) | 1984-02-29 |
| DE3063290D1 (en) | 1983-07-07 |
| CA1140564A (en) | 1983-02-01 |
| AU538776B2 (en) | 1984-08-30 |
| US4362738A (en) | 1982-12-07 |
| ZA803907B (en) | 1982-02-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |