NO874194L - Fremgangsmaate ved fremstilling av dihydro-pyridinderivater - Google Patents
Fremgangsmaate ved fremstilling av dihydro-pyridinderivaterInfo
- Publication number
- NO874194L NO874194L NO874194A NO874194A NO874194L NO 874194 L NO874194 L NO 874194L NO 874194 A NO874194 A NO 874194A NO 874194 A NO874194 A NO 874194A NO 874194 L NO874194 L NO 874194L
- Authority
- NO
- Norway
- Prior art keywords
- methylbenzimidazol
- methyl
- chlorophenyl
- alkyl
- dihydropyridine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 24
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 4
- 229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 54
- -1 2-methylbenzimidazol-1-yl Chemical group 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- CGJGMHQUYSLYDT-WAYWQWQTSA-N (z)-3-amino-n-tert-butylbut-2-enamide Chemical compound C\C(N)=C\C(=O)NC(C)(C)C CGJGMHQUYSLYDT-WAYWQWQTSA-N 0.000 claims description 6
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- FYPDSGOTUAZIDV-UHFFFAOYSA-N ethyl 4-[2-(2-methylbenzimidazol-1-yl)ethoxy]-3-oxobutanoate Chemical compound C1=CC=C2N(CCOCC(=O)CC(=O)OCC)C(C)=NC2=C1 FYPDSGOTUAZIDV-UHFFFAOYSA-N 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 3
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 2
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 claims 2
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 125000004965 chloroalkyl group Chemical group 0.000 claims 1
- ILZFBCUIXFVPBE-UHFFFAOYSA-N ethyl 4-(2-chlorophenyl)-6-methyl-2-[3-(1-methylbenzimidazol-2-yl)propoxymethyl]-5-(pyridin-2-ylcarbamoyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(COCCCC=2N(C3=CC=CC=C3N=2)C)NC(C)=C(C(=O)NC=2N=CC=CC=2)C1C1=CC=CC=C1Cl ILZFBCUIXFVPBE-UHFFFAOYSA-N 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 30
- 108010003541 Platelet Activating Factor Proteins 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
- 239000000047 product Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000000172 allergic effect Effects 0.000 description 6
- 208000010668 atopic eczema Diseases 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- GUKKGBSNKJVHDK-IHWYPQMZSA-N (z)-2-aminobut-2-enamide Chemical compound C\C=C(/N)C(N)=O GUKKGBSNKJVHDK-IHWYPQMZSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 230000004044 response Effects 0.000 description 3
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- 229910002027 silica gel Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VHKJEOWXOOZAKP-UHFFFAOYSA-N 2-(2-aminoanilino)-2-methylpropan-1-ol Chemical compound OCC(C)(C)NC1=CC=CC=C1N VHKJEOWXOOZAKP-UHFFFAOYSA-N 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
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- MZFGOCRYTYIQQL-UHFFFAOYSA-N ethyl 4-[3-(1-methylbenzimidazol-2-yl)propoxy]-3-oxobutanoate Chemical compound C1=CC=C2N(C)C(CCCOCC(=O)CC(=O)OCC)=NC2=C1 MZFGOCRYTYIQQL-UHFFFAOYSA-N 0.000 description 2
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- CPNQDDVQHYYFLC-UHFFFAOYSA-N ethyl 5-(tert-butylcarbamoyl)-4-(2-chlorophenyl)-6-methyl-2-[2-(2-methylbenzimidazol-1-yl)ethoxymethyl]-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(COCCN2C3=CC=CC=C3N=C2C)NC(C)=C(C(=O)NC(C)(C)C)C1C1=CC=CC=C1Cl CPNQDDVQHYYFLC-UHFFFAOYSA-N 0.000 description 2
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- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 1
- KTUYMKVNPBJODA-UHFFFAOYSA-N benzyl 4-[2-(2-methylbenzimidazol-1-yl)ethoxy]-3-oxobutaneperoxoate Chemical compound CC1=NC2=CC=CC=C2N1CCOCC(=O)CC(=O)OOCC1=CC=CC=C1 KTUYMKVNPBJODA-UHFFFAOYSA-N 0.000 description 1
- IGEHLZHNJCGKPC-UHFFFAOYSA-N benzyl 5-(tert-butylcarbamoyl)-4-(2-chlorophenyl)-6-methyl-2-[2-(2-methylbenzimidazol-1-yl)ethoxymethyl]-1,4-dihydropyridine-3-carboxylate Chemical compound CC1=NC2=CC=CC=C2N1CCOCC(NC(C)=C1C(=O)NC(C)(C)C)=C(C(=O)OCC=2C=CC=CC=2)C1C1=CC=CC=C1Cl IGEHLZHNJCGKPC-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 229930188620 butyrolactone Natural products 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940089960 chloroacetate Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000005796 circulatory shock Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- NMEPGHYMFYJIEO-UHFFFAOYSA-N ethyl 2-(2,5,6-trimethylbenzimidazol-1-yl)acetate Chemical compound CC1=C(C)C=C2N(CC(=O)OCC)C(C)=NC2=C1 NMEPGHYMFYJIEO-UHFFFAOYSA-N 0.000 description 1
- WEOAVDYRSABQIV-UHFFFAOYSA-N ethyl 4-(2-chlorophenyl)-6-methyl-2-[2-(2-methylbenzimidazol-1-yl)ethoxymethyl]-5-(pyridin-2-ylcarbamoyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(COCCN2C3=CC=CC=C3N=C2C)NC(C)=C(C(=O)NC=2N=CC=CC=2)C1C1=CC=CC=C1Cl WEOAVDYRSABQIV-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- DKEONVNYXODZRQ-UHFFFAOYSA-N hydron;2-n-methylbenzene-1,2-diamine;dichloride Chemical compound Cl.Cl.CNC1=CC=CC=C1N DKEONVNYXODZRQ-UHFFFAOYSA-N 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 150000004797 ketoamides Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- CGGJVHBWBNSMLY-UHFFFAOYSA-N n-tert-butyl-3-oxobutanamide Chemical compound CC(=O)CC(=O)NC(C)(C)C CGGJVHBWBNSMLY-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- ADWLHOJXRMFAIU-UHFFFAOYSA-N propan-2-yl 5-(tert-butylcarbamoyl)-4-(2-chlorophenyl)-6-methyl-2-[3-(1-methylbenzimidazol-2-yl)propoxymethyl]-1,4-dihydropyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(COCCCC=2N(C3=CC=CC=C3N=2)C)NC(C)=C(C(=O)NC(C)(C)C)C1C1=CC=CC=C1Cl ADWLHOJXRMFAIU-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB868626698A GB8626698D0 (en) | 1986-11-07 | 1986-11-07 | Therapeutic agents |
| GB878709842A GB8709842D0 (en) | 1987-04-25 | 1987-04-25 | Therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO874194D0 NO874194D0 (no) | 1987-10-06 |
| NO874194L true NO874194L (no) | 1988-05-09 |
Family
ID=26291518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO874194A NO874194L (no) | 1986-11-07 | 1987-10-06 | Fremgangsmaate ved fremstilling av dihydro-pyridinderivater |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4801598A (ko) |
| EP (1) | EP0266989B1 (ko) |
| JP (1) | JPH064624B2 (ko) |
| KR (1) | KR880006196A (ko) |
| CN (1) | CN87107723A (ko) |
| AU (1) | AU8089687A (ko) |
| DE (1) | DE3763573D1 (ko) |
| DK (1) | DK582787A (ko) |
| ES (1) | ES2036214T3 (ko) |
| FI (1) | FI874866A (ko) |
| GR (2) | GR880300183T1 (ko) |
| HU (1) | HUT45990A (ko) |
| IL (1) | IL84380A0 (ko) |
| NO (1) | NO874194L (ko) |
| PL (1) | PL268618A1 (ko) |
| PT (1) | PT86082B (ko) |
| YU (1) | YU201987A (ko) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8712747D0 (en) * | 1987-05-30 | 1987-07-01 | Pfizer Ltd | Therapeutic agents |
| GB8716971D0 (en) * | 1987-07-17 | 1987-08-26 | Pfizer Ltd | Therapeutic agents |
| MY104933A (en) | 1987-09-30 | 1994-07-30 | Pfizer Ltd | Platelet activating factor antagonists |
| GB8804439D0 (en) * | 1988-02-25 | 1988-03-23 | Pfizer Ltd | Dihydropyridines |
| GB8906324D0 (en) * | 1989-03-20 | 1989-05-04 | Pfizer Ltd | 1,4-dihydropyridines |
| DE4237617A1 (de) * | 1992-11-06 | 1994-05-11 | Bayer Ag | Verwendung von substituierten Benzimidazolen |
| US5496855A (en) * | 1995-01-27 | 1996-03-05 | Smithkline Beecham Corp. | Anti-inflammatory compounds |
| CA2450073C (en) | 2001-07-25 | 2017-08-29 | Biomarin Pharmaceutical Inc. | Compositions and methods for modulating blood-brain barrier transport |
| US6566359B1 (en) | 2002-05-20 | 2003-05-20 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | 2,4,6-trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid esters as neuroprotective drugs |
| PT1889198E (pt) | 2005-04-28 | 2015-03-06 | Proteus Digital Health Inc | Sistema fármaco-informático |
| US8795627B2 (en) | 2007-03-21 | 2014-08-05 | Raptor Pharmaceuticals Inc. | Treatment of liver disorders by administration of RAP conjugates |
| WO2010095940A2 (en) | 2009-02-20 | 2010-08-26 | To-Bbb Holding B.V. | Glutathione-based drug delivery system |
| NZ596876A (en) | 2009-05-06 | 2014-01-31 | Lab Skin Care Inc | Dermal delivery compositions comprising active agent-calcium phosphate particle complexes and methods of using the same |
| US20120077778A1 (en) | 2010-09-29 | 2012-03-29 | Andrea Bourdelais | Ladder-Frame Polyether Conjugates |
| JP7148192B1 (ja) | 2022-05-09 | 2022-10-05 | 有限会社Amplus | 表示制御装置および方法並びにプログラム |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3363743D1 (en) * | 1982-07-22 | 1986-07-03 | Pfizer Ltd | Dihydropyridine anti-ischaemic and antihypertensive agents |
| NL8503262A (nl) * | 1984-12-10 | 1986-07-01 | Sandoz Ag | 1,4-dihydropyridinederivaten, werkwijze voor het bereiden van deze derivaten en farmaceutische preparaten die ze bevatten. |
| AU593278B2 (en) * | 1985-08-06 | 1990-02-08 | Boehringer Mannheim Italia S.P.A. | Pharmaceutically active 2-thiomethyl-substituted-1,4- dihydropyridines |
| EP0225175A3 (en) * | 1985-11-28 | 1988-12-28 | FISONS plc | Dihydropyridine derivatives, processes for their preparation and pharmaceutical compositions thereof |
-
1987
- 1987-10-06 NO NO874194A patent/NO874194L/no unknown
- 1987-10-30 US US07/115,213 patent/US4801598A/en not_active Expired - Fee Related
- 1987-11-02 ES ES198787309674T patent/ES2036214T3/es not_active Expired - Lifetime
- 1987-11-02 DE DE8787309674T patent/DE3763573D1/de not_active Expired - Lifetime
- 1987-11-02 EP EP87309674A patent/EP0266989B1/en not_active Expired - Lifetime
- 1987-11-04 FI FI874866A patent/FI874866A/fi not_active IP Right Cessation
- 1987-11-05 PT PT86082A patent/PT86082B/pt not_active IP Right Cessation
- 1987-11-05 PL PL26861887A patent/PL268618A1/xx unknown
- 1987-11-05 KR KR870012409A patent/KR880006196A/ko not_active Application Discontinuation
- 1987-11-05 IL IL84380A patent/IL84380A0/xx unknown
- 1987-11-06 DK DK582787A patent/DK582787A/da not_active Application Discontinuation
- 1987-11-06 HU HU874984A patent/HUT45990A/hu unknown
- 1987-11-06 YU YU02019/87A patent/YU201987A/xx unknown
- 1987-11-06 JP JP62280832A patent/JPH064624B2/ja not_active Expired - Lifetime
- 1987-11-06 AU AU80896/87A patent/AU8089687A/en not_active Abandoned
- 1987-11-07 CN CN198787107723A patent/CN87107723A/zh active Pending
-
1989
- 1989-06-22 GR GR88300183T patent/GR880300183T1/el unknown
-
1990
- 1990-07-18 GR GR90400486T patent/GR3000820T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GR3000820T3 (en) | 1991-11-15 |
| EP0266989A3 (en) | 1988-09-28 |
| FI874866A0 (fi) | 1987-11-04 |
| NO874194D0 (no) | 1987-10-06 |
| EP0266989A2 (en) | 1988-05-11 |
| DK582787A (da) | 1988-05-08 |
| EP0266989B1 (en) | 1990-07-04 |
| JPS63139167A (ja) | 1988-06-10 |
| GR880300183T1 (en) | 1989-06-22 |
| HUT45990A (en) | 1988-09-28 |
| FI874866A (fi) | 1988-05-08 |
| KR880006196A (ko) | 1988-07-22 |
| YU201987A (en) | 1988-12-31 |
| DE3763573D1 (de) | 1990-08-09 |
| DK582787D0 (da) | 1987-11-06 |
| PT86082A (en) | 1987-12-01 |
| IL84380A0 (en) | 1988-04-29 |
| CN87107723A (zh) | 1988-05-18 |
| ES2036214T3 (es) | 1993-05-16 |
| JPH064624B2 (ja) | 1994-01-19 |
| AU8089687A (en) | 1988-05-12 |
| PL268618A1 (en) | 1988-09-01 |
| US4801598A (en) | 1989-01-31 |
| PT86082B (pt) | 1990-11-20 |
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