HUT63624A - Process for producing benzimidazole derivatives and pharmaceutical compositions comprising such compounds - Google Patents
Process for producing benzimidazole derivatives and pharmaceutical compositions comprising such compounds Download PDFInfo
- Publication number
- HUT63624A HUT63624A HU9300385A HU9300385A HUT63624A HU T63624 A HUT63624 A HU T63624A HU 9300385 A HU9300385 A HU 9300385A HU 9300385 A HU9300385 A HU 9300385A HU T63624 A HUT63624 A HU T63624A
- Authority
- HU
- Hungary
- Prior art keywords
- amino
- substituted
- ethyl
- group
- carbonyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 115
- 238000000034 method Methods 0.000 title claims description 41
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
- -1 perhydroazepin-1-yl Chemical group 0.000 claims description 323
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 53
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 239000000460 chlorine Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 238000006722 reduction reaction Methods 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Chemical group 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- ZPXOABCKCVLHDO-UHFFFAOYSA-N 4-amino-n-[3-(3h-benzimidazol-5-yl)-1-(4-methylpiperidin-1-yl)-1-oxopropan-2-yl]-3,5-dichlorobenzenesulfonamide Chemical compound C1CC(C)CCN1C(=O)C(NS(=O)(=O)C=1C=C(Cl)C(N)=C(Cl)C=1)CC1=CC=C(NC=N2)C2=C1 ZPXOABCKCVLHDO-UHFFFAOYSA-N 0.000 claims description 5
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 150000001556 benzimidazoles Chemical class 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 4
- 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 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 claims description 3
- SNKOJZRETNUCKY-UHFFFAOYSA-N 4-amino-n-[3-(3h-benzimidazol-5-yl)-1-(4-ethylpiperidin-1-yl)-1-oxopropan-2-yl]-3,5-dichlorobenzenesulfonamide Chemical compound C1CC(CC)CCN1C(=O)C(NS(=O)(=O)C=1C=C(Cl)C(N)=C(Cl)C=1)CC1=CC=C(NC=N2)C2=C1 SNKOJZRETNUCKY-UHFFFAOYSA-N 0.000 claims description 3
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- PKDSOHYUBDLWOR-UHFFFAOYSA-N n-[3-(3h-benzimidazol-5-yl)-1-(4-ethylpiperidin-1-yl)-1-oxopropan-2-yl]-3,5-dichloro-4-(ethylamino)benzenesulfonamide Chemical compound C1=C(Cl)C(NCC)=C(Cl)C=C1S(=O)(=O)NC(C(=O)N1CCC(CC)CC1)CC1=CC=C(NC=N2)C2=C1 PKDSOHYUBDLWOR-UHFFFAOYSA-N 0.000 claims description 3
- RYEOAUHQDBWHII-UHFFFAOYSA-N n-[3-(3h-benzimidazol-5-yl)-1-(4-methylpiperidin-1-yl)-1-oxopropan-2-yl]-1,2,3,4-tetrahydroquinoline-8-sulfonamide Chemical compound C1CC(C)CCN1C(=O)C(NS(=O)(=O)C=1C=2NCCCC=2C=CC=1)CC1=CC=C(NC=N2)C2=C1 RYEOAUHQDBWHII-UHFFFAOYSA-N 0.000 claims description 3
- HEJDCCYABIWHDM-UHFFFAOYSA-N n-[3-(3h-benzimidazol-5-yl)-1-(4-methylpiperidin-1-yl)-1-oxopropan-2-yl]-9-ethylcarbazole-3-sulfonamide Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1S(=O)(=O)NC(CC=1C=C2N=CNC2=CC=1)C(=O)N1CCC(C)CC1 HEJDCCYABIWHDM-UHFFFAOYSA-N 0.000 claims description 3
- 238000005932 reductive alkylation reaction Methods 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- ITIOHKBVHNWDPQ-UHFFFAOYSA-N 4-amino-n-[3-(3h-benzimidazol-5-yl)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]-3,5-dichlorobenzenesulfonamide Chemical compound C1CN(C)CCN1C(=O)C(NS(=O)(=O)C=1C=C(Cl)C(N)=C(Cl)C=1)CC1=CC=C(NC=N2)C2=C1 ITIOHKBVHNWDPQ-UHFFFAOYSA-N 0.000 claims description 2
- DGJNAXVLPKTRED-UHFFFAOYSA-N 5,6,7,8-tetrahydro-[1,3]thiazolo[3,4]thieno[1,3-a]pyridin-2-amine Chemical compound C1CNCC2=C1SC1=C2SC(N)=N1 DGJNAXVLPKTRED-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 108010022999 Serine Proteases Proteins 0.000 claims description 2
- 102000012479 Serine Proteases Human genes 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 230000002785 anti-thrombosis Effects 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 206010029897 Obsessive thoughts Diseases 0.000 claims 3
- 239000003085 diluting agent Substances 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000269 nucleophilic effect Effects 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
- 239000002904 solvent Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 15
- 238000000354 decomposition reaction Methods 0.000 description 15
- 235000019253 formic acid Nutrition 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 11
- VFPSSPUSLSACRX-UHFFFAOYSA-N 2-amino-3-(3h-benzimidazol-5-yl)-1-(4-methylpiperidin-1-yl)propan-1-one Chemical compound C1CC(C)CCN1C(=O)C(N)CC1=CC=C(NC=N2)C2=C1 VFPSSPUSLSACRX-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000155 melt Substances 0.000 description 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 108090000190 Thrombin Proteins 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 229960004072 thrombin Drugs 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- QHRNEDXPRFMWSK-UHFFFAOYSA-N 3-(4-nitrophenyl)-2-[(2,2,2-trifluoroacetyl)amino]propanoic acid Chemical compound FC(F)(F)C(=O)NC(C(=O)O)CC1=CC=C([N+]([O-])=O)C=C1 QHRNEDXPRFMWSK-UHFFFAOYSA-N 0.000 description 2
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- OCERHFVIXWVCFP-UHFFFAOYSA-N n-ethyl-n-piperidin-4-ylacetamide Chemical compound CCN(C(C)=O)C1CCNCC1 OCERHFVIXWVCFP-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N n-hexadecyl alcohol Natural products CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- LECBBGYIXBZWIA-UHFFFAOYSA-N n-methyl-n-piperidin-4-ylpropanamide Chemical compound CCC(=O)N(C)C1CCNCC1 LECBBGYIXBZWIA-UHFFFAOYSA-N 0.000 description 1
- IAQHGKOMQZMEPL-UHFFFAOYSA-N n-piperidin-4-yl-n-propylacetamide Chemical compound CCCN(C(C)=O)C1CCNCC1 IAQHGKOMQZMEPL-UHFFFAOYSA-N 0.000 description 1
- DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical compound C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005583 trifluoroacetylation reaction Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (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)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4204270A DE4204270A1 (de) | 1992-02-13 | 1992-02-13 | Benzimidazolylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HU9300385D0 HU9300385D0 (en) | 1993-04-28 |
| HUT63624A true HUT63624A (en) | 1993-09-28 |
Family
ID=6451613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9300385A HUT63624A (en) | 1992-02-13 | 1993-02-12 | Process for producing benzimidazole derivatives and pharmaceutical compositions comprising such compounds |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5391556A (show.php) |
| EP (1) | EP0555824A1 (show.php) |
| JP (1) | JPH0616648A (show.php) |
| KR (1) | KR930017900A (show.php) |
| AU (1) | AU663556B2 (show.php) |
| CA (1) | CA2089466A1 (show.php) |
| CZ (1) | CZ18593A3 (show.php) |
| DE (1) | DE4204270A1 (show.php) |
| FI (1) | FI930620A7 (show.php) |
| HU (1) | HUT63624A (show.php) |
| IL (1) | IL104703A (show.php) |
| MX (1) | MX9300735A (show.php) |
| NO (1) | NO930517L (show.php) |
| NZ (1) | NZ245886A (show.php) |
| PH (1) | PH31294A (show.php) |
| PL (1) | PL297716A1 (show.php) |
| TW (1) | TW222271B (show.php) |
| ZA (1) | ZA93975B (show.php) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4129603A1 (de) * | 1991-09-06 | 1993-03-11 | Thomae Gmbh Dr K | Kondensierte 5-gliedrige heterocyclen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE4430755A1 (de) * | 1994-08-30 | 1996-03-07 | Boehringer Mannheim Gmbh | Neue Phosphanoxide, Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel |
| IL115420A0 (en) | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
| GB9505538D0 (en) * | 1995-03-18 | 1995-05-03 | Ciba Geigy Ag | New compounds |
| GB9602166D0 (en) * | 1996-02-02 | 1996-04-03 | Zeneca Ltd | Aminoheterocyclic derivatives |
| US6313127B1 (en) | 1996-02-02 | 2001-11-06 | Zeneca Limited | Heterocyclic compounds useful as pharmaceutical agents |
| GB9602294D0 (en) * | 1996-02-05 | 1996-04-03 | Zeneca Ltd | Heterocyclic compounds |
| GB9611461D0 (en) * | 1996-06-01 | 1996-08-07 | Ciba Geigy Ag | New compounds |
| WO1998006705A1 (en) * | 1996-08-14 | 1998-02-19 | Zeneca Limited | Substituted pyrimidine derivatives and their pharmaceutical use |
| KR20000068415A (ko) * | 1996-09-04 | 2000-11-25 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | 매트릭스 메탈로프로테이나제 억제용 화합물 및 방법 |
| US6011155A (en) * | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| UA56197C2 (uk) | 1996-11-08 | 2003-05-15 | Зенека Лімітед | Гетероциклічні похідні |
| JP2001511799A (ja) | 1997-02-13 | 2001-08-14 | ゼネカ・リミテッド | オキシド−スクアレンシクラーゼ阻害剤として有用なヘテロ環式化合物 |
| WO1998035956A1 (en) | 1997-02-13 | 1998-08-20 | Zeneca Limited | Heterocyclic compounds useful as oxido-squalene cyclase inhibitors |
| KR100361827B1 (ko) * | 1997-04-07 | 2003-01-24 | 주식회사 엘지생명과학 | 트롬빈 억제제로서 유용한 헤테로사이클릭알라닌 유도체 |
| IL123986A (en) | 1997-04-24 | 2011-10-31 | Organon Nv | Medicinal compounds |
| GB9715895D0 (en) | 1997-07-29 | 1997-10-01 | Zeneca Ltd | Heterocyclic compounds |
| US6350885B1 (en) | 1998-07-30 | 2002-02-26 | Warner-Lambert Company | Tricyclic heteroaromatics and their derivatives as inhibitors of matrix metalloproteinases |
| OA11589A (en) | 1998-07-30 | 2004-07-30 | Warner Lambert Co | Tricyclic sulfonamides and their derivatives as inhibitors of matrix metalloproteinases. |
| CO5150173A1 (es) * | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
| GB9902989D0 (en) | 1999-02-11 | 1999-03-31 | Zeneca Ltd | Heterocyclic derivatives |
| US6713473B1 (en) | 1999-04-20 | 2004-03-30 | Meiji Seika Kaisha, Ltd. | Tricyclic compounds |
| US6172081B1 (en) | 1999-06-24 | 2001-01-09 | Novartis Ag | Tetrahydroisoquinoline 3-carboxamide derivatives |
| US6110949A (en) * | 1999-06-24 | 2000-08-29 | Novartis Ag | N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| US6617340B1 (en) | 1999-07-29 | 2003-09-09 | Novartis Ag | N-(substituted glycyl)-pyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| EP1283199A4 (en) * | 2000-05-16 | 2003-12-17 | Takeda Chemical Industries Ltd | MELANINE CONCENTRATING HORMONE ANTAGONISTS |
| TWI341835B (en) * | 2003-11-12 | 2011-05-11 | Lg Life Sciences Ltd | Melanocortin receptor agonists |
| MX2007011453A (es) * | 2005-04-22 | 2008-02-12 | Alantos Pharmaceuticals Holding Inc | Inhibidores de la dipeptidil peptidasa-iv. |
| CN104193761B (zh) | 2009-12-04 | 2017-10-17 | 桑诺维恩药品公司 | 多环化合物及其使用方法 |
| BR112019001407A2 (pt) | 2016-07-29 | 2019-07-09 | Sunovion Pharmaceuticals Inc. | compostos e composições e usos dos mesmos |
| SG10202100724UA (en) | 2016-07-29 | 2021-03-30 | Sunovion Pharmaceuticals Inc | Compounds and compositions and uses thereof |
| WO2018118838A1 (en) * | 2016-12-20 | 2018-06-28 | Biomarin Pharmaceutical Inc. | Ceramide galactosyltransferase inhibitors for the treatment of disease |
| EP3582815A1 (en) | 2017-02-16 | 2019-12-25 | Sunovion Pharmaceuticals Inc. | Methods of treating schizophrenia |
| MX2020000523A (es) | 2017-08-02 | 2020-08-20 | Sunovion Pharmaceuticals Inc | Compuestos de isocromano y usos de los mismos. |
| SG11202007823PA (en) | 2018-02-16 | 2020-09-29 | Sunovion Pharmaceuticals Inc | Salts, crystal forms, and production methods thereof |
| JP7703449B2 (ja) | 2019-03-14 | 2025-07-07 | スミトモ・ファーマ・アメリカ・インコーポレイテッド | イソクロマニル化合物の塩およびその結晶体、ならびにそれらの製造方法、治療用途および医薬組成物 |
| KR20230003503A (ko) | 2020-04-14 | 2023-01-06 | 선오비온 파마슈티컬스 인코포레이티드 | 신경학적 및 정신의학적 장애의 치료를 위한 (S)-(4,5-디히드로-7H-티에노[2,3-c]피란-7-일)-N-메틸메탄아민 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD142804A3 (de) * | 1977-11-07 | 1980-07-16 | Wagner Guenter | Verfahren zur herstellung von na-alkyl-bzw.na-aryl-sulfonylierten omega-amidinophenyl-alpha-aminoalkylcarbonsaeureamiden |
| SE8203887D0 (sv) * | 1982-06-23 | 1982-06-23 | Kabivitrum Ab | Nya trombininhiberande foreningar |
| KR920703558A (ko) * | 1990-11-15 | 1992-12-18 | 원본미기재 | 메타-치환 페닐알라닌 유도체 |
-
1992
- 1992-01-12 PH PH45722A patent/PH31294A/en unknown
- 1992-02-13 DE DE4204270A patent/DE4204270A1/de not_active Withdrawn
-
1993
- 1993-01-20 TW TW082100359A patent/TW222271B/zh active
- 1993-02-08 US US08/014,598 patent/US5391556A/en not_active Expired - Fee Related
- 1993-02-10 EP EP93102052A patent/EP0555824A1/de not_active Ceased
- 1993-02-11 AU AU32968/93A patent/AU663556B2/en not_active Ceased
- 1993-02-11 NZ NZ245886A patent/NZ245886A/en unknown
- 1993-02-11 KR KR1019930001831A patent/KR930017900A/ko not_active Ceased
- 1993-02-11 MX MX9300735A patent/MX9300735A/es not_active IP Right Cessation
- 1993-02-12 HU HU9300385A patent/HUT63624A/hu unknown
- 1993-02-12 ZA ZA93975A patent/ZA93975B/xx unknown
- 1993-02-12 CA CA002089466A patent/CA2089466A1/en not_active Abandoned
- 1993-02-12 FI FI930620A patent/FI930620A7/fi unknown
- 1993-02-12 PL PL29771693A patent/PL297716A1/xx unknown
- 1993-02-12 IL IL104703A patent/IL104703A/xx not_active IP Right Cessation
- 1993-02-12 JP JP5024205A patent/JPH0616648A/ja active Pending
- 1993-02-12 NO NO93930517A patent/NO930517L/no unknown
- 1993-02-12 CZ CZ93185A patent/CZ18593A3/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL104703A (en) | 1997-07-13 |
| PL297716A1 (en) | 1994-01-24 |
| PH31294A (en) | 1998-07-06 |
| JPH0616648A (ja) | 1994-01-25 |
| CA2089466A1 (en) | 1993-08-14 |
| CZ18593A3 (en) | 1993-12-15 |
| EP0555824A1 (de) | 1993-08-18 |
| TW222271B (show.php) | 1994-04-11 |
| AU663556B2 (en) | 1995-10-12 |
| NO930517D0 (no) | 1993-02-12 |
| NZ245886A (en) | 1995-12-21 |
| MX9300735A (es) | 1993-08-01 |
| NO930517L (no) | 1993-08-16 |
| KR930017900A (ko) | 1993-09-20 |
| FI930620A0 (fi) | 1993-02-12 |
| US5391556A (en) | 1995-02-21 |
| HU9300385D0 (en) | 1993-04-28 |
| AU3296893A (en) | 1993-08-19 |
| FI930620A7 (fi) | 1993-08-14 |
| DE4204270A1 (de) | 1993-11-04 |
| IL104703A0 (en) | 1993-06-10 |
| ZA93975B (en) | 1994-08-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DFA9 | Temporary protection cancelled due to abandonment |