NL8500909A - Pyridinederivaten en werkwijze voor de bereiding ervan. - Google Patents
Pyridinederivaten en werkwijze voor de bereiding ervan. Download PDFInfo
- Publication number
- NL8500909A NL8500909A NL8500909A NL8500909A NL8500909A NL 8500909 A NL8500909 A NL 8500909A NL 8500909 A NL8500909 A NL 8500909A NL 8500909 A NL8500909 A NL 8500909A NL 8500909 A NL8500909 A NL 8500909A
- Authority
- NL
- Netherlands
- Prior art keywords
- formula
- methyl
- oxo
- hydrogen
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 36
- 238000002360 preparation method Methods 0.000 title claims description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- MBELGTLJWJJGLF-UHFFFAOYSA-N 1,4-dihydropyridine-3-carboxylic acid Chemical class OC(=O)C1=CNC=CC1 MBELGTLJWJJGLF-UHFFFAOYSA-N 0.000 claims abstract description 6
- -1 tetrahydrofurfuryl Chemical group 0.000 claims description 154
- 150000001875 compounds Chemical class 0.000 claims description 83
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 150000001540 azides Chemical class 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 239000000460 chlorine Chemical group 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 150000003863 ammonium salts Chemical class 0.000 claims description 5
- 229930195733 hydrocarbon Natural products 0.000 claims description 5
- 150000002430 hydrocarbons Chemical class 0.000 claims description 5
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical class 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000004076 pyridyl group Chemical class 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 230000018044 dehydration Effects 0.000 claims description 3
- 238000006297 dehydration reaction Methods 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 6
- 229910052801 chlorine Chemical group 0.000 claims 6
- HVZWVEKIQMJYIK-UHFFFAOYSA-N nitryl chloride Chemical compound [O-][N+](Cl)=O HVZWVEKIQMJYIK-UHFFFAOYSA-N 0.000 claims 6
- 229910021529 ammonia Inorganic materials 0.000 claims 4
- 125000003282 alkyl amino group Chemical group 0.000 claims 3
- 125000006009 dihaloalkoxy group Chemical group 0.000 claims 3
- 125000004953 trihalomethyl group Chemical group 0.000 claims 3
- 150000003935 benzaldehydes Chemical class 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 101100368081 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) sym-1 gene Proteins 0.000 claims 1
- 230000001077 hypotensive effect Effects 0.000 abstract description 17
- 230000000304 vasodilatating effect Effects 0.000 abstract description 12
- 208000001953 Hypotension Diseases 0.000 abstract description 6
- 208000021822 hypotensive Diseases 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 238000000921 elemental analysis Methods 0.000 description 69
- 238000002844 melting Methods 0.000 description 66
- 230000008018 melting Effects 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000843 powder Substances 0.000 description 11
- 239000007858 starting material Substances 0.000 description 10
- 239000000969 carrier Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000036772 blood pressure Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 5
- 229960004166 diltiazem Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000001099 ammonium carbonate Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229960001597 nifedipine Drugs 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- CUFUMXQZMOXRGC-UHFFFAOYSA-N 1-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)propan-2-one Chemical compound CC(=O)CP1(=O)OCCCO1 CUFUMXQZMOXRGC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 235000012501 ammonium carbonate Nutrition 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 2
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 2
- MEJLJMKRBSNAKK-UHFFFAOYSA-N 4-(3-nitrophenyl)-3-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)but-3-en-2-one Chemical compound O1CCCOP1(=O)C(C(=O)C)=CC1=CC=CC([N+]([O-])=O)=C1 MEJLJMKRBSNAKK-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 2
- NVUCZSRFPOQCGJ-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCO2)C1C1=CC=CC([N+]([O-])=O)=C1 NVUCZSRFPOQCGJ-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-M nicotinate Chemical compound [O-]C(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-M 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- OXPBZLSMCNWKAW-UHFFFAOYSA-N (1-benzylpiperidin-4-yl) 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OC2CCN(CC=3C=CC=CC=3)CC2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCCCO1 OXPBZLSMCNWKAW-UHFFFAOYSA-N 0.000 description 1
- NXNCOTYCVOUIPE-UHFFFAOYSA-N (2-methyl-1,3-dioxolan-2-yl)methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCC2(C)OCCO2)C(C=2C(=CC=CC=2)[N+]([O-])=O)C=1P1(=O)OCCCO1 NXNCOTYCVOUIPE-UHFFFAOYSA-N 0.000 description 1
- ISLWZBTUAHMAND-UHFFFAOYSA-N 1,3,2-dioxaphosphinan-2-ium 2-oxide Chemical compound O=[P+]1OCCCO1 ISLWZBTUAHMAND-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000006037 1-ethyl-2-propenyl group Chemical group 0.000 description 1
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- DLCPXHXXKZCBPM-WAYWQWQTSA-N 2-(methylamino)ethyl (z)-3-aminobut-2-enoate Chemical compound CNCCOC(=O)\C=C(\C)N DLCPXHXXKZCBPM-WAYWQWQTSA-N 0.000 description 1
- FEDJGPQLLNQAIY-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-3-yl)oxy]acetic acid Chemical compound OC(=O)COC=1C=CC(=O)NN=1 FEDJGPQLLNQAIY-UHFFFAOYSA-N 0.000 description 1
- WCERTLKEZVCKQE-UHFFFAOYSA-N 2-[benzyl(methyl)amino]ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-5-propan-2-yl-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound O1CC(C(C)C)COP1(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 WCERTLKEZVCKQE-UHFFFAOYSA-N 0.000 description 1
- CMEYPZMBSQFWLM-UHFFFAOYSA-N 2-[benzyl(methyl)amino]ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(3-oxo-2,4-dioxa-3$l^{5}-phosphaspiro[5.5]undecan-3-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound C=1C=CC=CC=1CN(C)CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCC3(CCCCC3)CO2)C1C1=CC=CC([N+]([O-])=O)=C1 CMEYPZMBSQFWLM-UHFFFAOYSA-N 0.000 description 1
- QWJVNCIBNFUUQA-UHFFFAOYSA-N 2-[benzyl(methyl)amino]ethyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(7-oxo-6,8-dioxa-7$l^{5}-phosphaspiro[3.5]nonan-7-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound C=1C=CC=CC=1CN(C)CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCC3(CCC3)CO2)C1C1=CC=CC([N+]([O-])=O)=C1 QWJVNCIBNFUUQA-UHFFFAOYSA-N 0.000 description 1
- DZJHKTVKXBITPD-UHFFFAOYSA-N 2-[benzyl(methyl)amino]ethyl 4-[2-(difluoromethoxy)phenyl]-5-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate Chemical compound C=1C=CC=CC=1CN(C)CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(C)(C)CO2)C1C1=CC=CC=C1OC(F)F DZJHKTVKXBITPD-UHFFFAOYSA-N 0.000 description 1
- DMENNRCFBTYJTE-UHFFFAOYSA-N 2-[benzyl(methyl)amino]ethyl 5-(5,5-diethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound O1CC(CC)(CC)COP1(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 DMENNRCFBTYJTE-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- RIGDZGXRNDHBHK-UHFFFAOYSA-N 2-oxopropyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC(=O)COC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCO2)C1C1=CC=CC=C1[N+]([O-])=O RIGDZGXRNDHBHK-UHFFFAOYSA-N 0.000 description 1
- LFSBCCZBGVUBOA-UHFFFAOYSA-N 2-oxopropyl 2,6-dimethyl-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound CC(=O)COC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCO2)C1C1=CC=CC=C1C(F)(F)F LFSBCCZBGVUBOA-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- NZVQBWNDIUWAKA-UHFFFAOYSA-N 2-phenylmethoxyethyl 5-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCOCC=2C=CC=CC=2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCC(C)(C)CO1 NZVQBWNDIUWAKA-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- NEGSUYMFWPSBMV-UHFFFAOYSA-N 2-propoxyethyl 5-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCCOCCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(C)(C)CO2)C1C1=CC=CC([N+]([O-])=O)=C1 NEGSUYMFWPSBMV-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- CVUWEQPPJPRAGT-UHFFFAOYSA-N 3-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-4-[2-(trifluoromethyl)phenyl]but-3-en-2-one Chemical compound O1CCCOP1(=O)C(C(=O)C)=CC1=CC=CC=C1C(F)(F)F CVUWEQPPJPRAGT-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- MVKRYQSHFZQQQD-UHFFFAOYSA-N 4-(2-nitrophenyl)-3-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)but-3-en-2-one Chemical compound O1CCCOP1(=O)C(C(=O)C)=CC1=CC=CC=C1[N+]([O-])=O MVKRYQSHFZQQQD-UHFFFAOYSA-N 0.000 description 1
- LSWRZFVTNJOYJB-UHFFFAOYSA-N 4-[2-(difluoromethoxy)phenyl]-3-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)but-3-en-2-one Chemical compound O1CCCOP1(=O)C(C(=O)C)=CC1=CC=CC=C1OC(F)F LSWRZFVTNJOYJB-UHFFFAOYSA-N 0.000 description 1
- RJBSTXIIQYFNPX-UHFFFAOYSA-N 4-methoxy-6-phenyl-1,3,5-triazin-2-amine Chemical compound COC1=NC(N)=NC(C=2C=CC=CC=2)=N1 RJBSTXIIQYFNPX-UHFFFAOYSA-N 0.000 description 1
- VZMRZFQPBREGLM-UHFFFAOYSA-N 4-nitro-3-(2-oxo-1,3,2lambda5-dioxaphosphinan-2-yl)-4-phenylbut-3-en-2-one Chemical compound [N+](=O)([O-])C(C1=CC=CC=C1)=C(C(=O)C)P1(OCCCO1)=O VZMRZFQPBREGLM-UHFFFAOYSA-N 0.000 description 1
- VYUABXDZPPOHDT-UHFFFAOYSA-N 5-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound CC=1NC(C)=C(C(O)=O)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCC(C)(C)CO1 VYUABXDZPPOHDT-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010065929 Cardiovascular insufficiency Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
- UULYVBBLIYLRCU-UHFFFAOYSA-N Palmitinsaeure-n-tetradecylester Natural products CCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC UULYVBBLIYLRCU-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- OZUCABDHYYWHBW-UHFFFAOYSA-N cyclopentyl 2,6-dimethyl-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OC2CCCC2)C(C=2C(=CC=CC=2)C(F)(F)F)C=1P1(=O)OCCCO1 OZUCABDHYYWHBW-UHFFFAOYSA-N 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- PPDLMTPEDNAJDO-UHFFFAOYSA-N cyclopropylmethyl 2,6-dimethyl-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCC2CC2)C(C=2C(=CC=CC=2)C(F)(F)F)C=1P1(=O)OCCCO1 PPDLMTPEDNAJDO-UHFFFAOYSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- NAEDLKCHTPCUDO-UHFFFAOYSA-N diethyl 2-[5-[2-[benzyl(methyl)amino]ethoxycarbonyl]-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridin-3-yl]-2-oxo-1,3,2$l^{5}-dioxaphosphinane-5,5-dicarboxylate Chemical compound O1CC(C(=O)OCC)(C(=O)OCC)COP1(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 NAEDLKCHTPCUDO-UHFFFAOYSA-N 0.000 description 1
- PORWTRBBYVCCRV-UHFFFAOYSA-N diethyl 2-[5-methoxycarbonyl-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridin-3-yl]-2-oxo-1,3,2$l^{5}-dioxaphosphinane-5,5-dicarboxylate Chemical compound O1CC(C(=O)OCC)(C(=O)OCC)COP1(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O PORWTRBBYVCCRV-UHFFFAOYSA-N 0.000 description 1
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 1
- 229960005316 diltiazem hydrochloride Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- MXXIFPWMWQCZFO-UHFFFAOYSA-N ethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCO2)C1C1=CC=CC=C1[N+]([O-])=O MXXIFPWMWQCZFO-UHFFFAOYSA-N 0.000 description 1
- SVYNAYCNYRXGDK-UHFFFAOYSA-N ethyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-propan-2-yl-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CO2)C(C)C)C1C1=CC=CC=C1[N+]([O-])=O SVYNAYCNYRXGDK-UHFFFAOYSA-N 0.000 description 1
- DKWCATBAIOMQAG-UHFFFAOYSA-N ethyl 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCO2)C1C1=CC=CC=C1OC(F)F DKWCATBAIOMQAG-UHFFFAOYSA-N 0.000 description 1
- QWZPUTIGSFLIRE-UHFFFAOYSA-N ethyl 5-(4,6-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OC(C)CC(C)O2)C1C1=CC=CC=C1[N+]([O-])=O QWZPUTIGSFLIRE-UHFFFAOYSA-N 0.000 description 1
- LEGPWSZNRUOMJE-UHFFFAOYSA-N ethyl 5-(5,5-diethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CC)(CC)CO2)C1C1=CC=CC([N+]([O-])=O)=C1 LEGPWSZNRUOMJE-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- YRWBBOWFFYXEOL-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphepan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCCO2)C1C1=CC=CC=C1[N+]([O-])=O YRWBBOWFFYXEOL-UHFFFAOYSA-N 0.000 description 1
- XPZQVXCEVOPMHB-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-4,7-dihydro-1,3,2$l^{5}-dioxaphosphepin-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC=CCO2)C1C1=CC=CC=C1[N+]([O-])=O XPZQVXCEVOPMHB-UHFFFAOYSA-N 0.000 description 1
- AZPUDPRRNXODDX-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-phenoxy-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CO2)OC=2C=CC=CC=2)C1C1=CC=CC=C1[N+]([O-])=O AZPUDPRRNXODDX-UHFFFAOYSA-N 0.000 description 1
- LXSQTADPZZNDRU-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-phenyl-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CO2)C=2C=CC=CC=2)C1C1=CC=CC=C1[N+]([O-])=O LXSQTADPZZNDRU-UHFFFAOYSA-N 0.000 description 1
- PHDMRYINEWXVIN-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-phenylmethoxy-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CO2)OCC=2C=CC=CC=2)C1C1=CC=CC=C1[N+]([O-])=O PHDMRYINEWXVIN-UHFFFAOYSA-N 0.000 description 1
- OFSAMVXZLVNKGS-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-5-propan-2-yl-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CO2)C(C)C)C1C1=CC=CC=C1[N+]([O-])=O OFSAMVXZLVNKGS-UHFFFAOYSA-N 0.000 description 1
- ONFYRAZSXIUFBY-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(3-oxo-2,4-dioxa-3$l^{5}-phosphaspiro[5.5]undecan-3-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC3(CCCCC3)CO2)C1C1=CC=CC=C1[N+]([O-])=O ONFYRAZSXIUFBY-UHFFFAOYSA-N 0.000 description 1
- UDZSCYPBCVVYJU-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(2-oxo-5-propan-2-yl-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CO2)C(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 UDZSCYPBCVVYJU-UHFFFAOYSA-N 0.000 description 1
- XKSRBTSKUKXIRS-UHFFFAOYSA-N methyl 2,6-dimethyl-4-(3-nitrophenyl)-5-(3-oxo-2,4-dioxa-3$l^{5}-phosphaspiro[5.5]undecan-3-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC3(CCCCC3)CO2)C1C1=CC=CC([N+]([O-])=O)=C1 XKSRBTSKUKXIRS-UHFFFAOYSA-N 0.000 description 1
- BECHYRSAKIFPSF-UHFFFAOYSA-N methyl 2,6-dimethyl-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCO2)C1C1=CC=CC=C1C(F)(F)F BECHYRSAKIFPSF-UHFFFAOYSA-N 0.000 description 1
- HTCKKZBKRMOUIZ-UHFFFAOYSA-N methyl 2,6-dimethyl-5-(5-methyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(C)CO2)C1C1=CC=CC([N+]([O-])=O)=C1 HTCKKZBKRMOUIZ-UHFFFAOYSA-N 0.000 description 1
- UMQCWMCWTAFVQC-UHFFFAOYSA-N methyl 2,6-dimethyl-5-[5-(2-methylpropyl)-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl]-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(CC(C)C)CO2)C1C1=CC=CC=C1[N+]([O-])=O UMQCWMCWTAFVQC-UHFFFAOYSA-N 0.000 description 1
- LYUBYLJQOZIBQB-UHFFFAOYSA-N methyl 2-[(3-nitrophenyl)methylidene]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)=CC1=CC=CC([N+]([O-])=O)=C1 LYUBYLJQOZIBQB-UHFFFAOYSA-N 0.000 description 1
- ZCVSJRYGKBFGMJ-UHFFFAOYSA-N methyl 5-(5,5-diethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound O1CC(CC)(CC)COP1(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O ZCVSJRYGKBFGMJ-UHFFFAOYSA-N 0.000 description 1
- RYWXNSOKKYJKLL-UHFFFAOYSA-N methyl 5-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(C)(C)CO2)C1C1=CC=CC=C1[N+]([O-])=O RYWXNSOKKYJKLL-UHFFFAOYSA-N 0.000 description 1
- CNVVMRHJPCLNCY-UHFFFAOYSA-N methyl 5-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(C)(C)CO2)C1C1=CC=CC([N+]([O-])=O)=C1 CNVVMRHJPCLNCY-UHFFFAOYSA-N 0.000 description 1
- JYUQHRKZASWOCN-UHFFFAOYSA-N methyl 5-(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(P2(=O)OCC(C)(C)CO2)C1C1=CC=CC=C1C(F)(F)F JYUQHRKZASWOCN-UHFFFAOYSA-N 0.000 description 1
- NVHCMJYUPCYYRL-UHFFFAOYSA-N methyl 5-(5-ethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound O1CC(CC)COP1(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O NVHCMJYUPCYYRL-UHFFFAOYSA-N 0.000 description 1
- CDZFWMYSWXJEEQ-UHFFFAOYSA-N methyl 5-(5-methoxy-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound O1CC(OC)COP1(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O CDZFWMYSWXJEEQ-UHFFFAOYSA-N 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000002071 phenylalkoxy group Chemical group 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- VXTFGYMINLXJPW-UHFFFAOYSA-N phosphinane Chemical compound C1CCPCC1 VXTFGYMINLXJPW-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DOTRDHBBMLRINK-UHFFFAOYSA-N propan-2-yl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(C)NC(C)=C(P2(=O)OCCCO2)C1C1=CC=CC=C1[N+]([O-])=O DOTRDHBBMLRINK-UHFFFAOYSA-N 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 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
- 239000007901 soft capsule Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000004873 systolic arterial blood pressure Effects 0.000 description 1
- POPKNUTXYHFBQH-UHFFFAOYSA-N tert-butyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OC(C)(C)C)C(C=2C(=CC=CC=2)[N+]([O-])=O)C=1P1(=O)OCCCO1 POPKNUTXYHFBQH-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
- C07F9/657181—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/6574—Esters of oxyacids of phosphorus
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7956084 | 1984-04-19 | ||
| JP59079560A JPS60248693A (ja) | 1984-04-19 | 1984-04-19 | ピリジン誘導体及び製法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8500909A true NL8500909A (nl) | 1985-11-18 |
Family
ID=13693390
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8500909A NL8500909A (nl) | 1984-04-19 | 1985-03-28 | Pyridinederivaten en werkwijze voor de bereiding ervan. |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5036059A (de) |
| EP (1) | EP0159040B1 (de) |
| JP (1) | JPS60248693A (de) |
| KR (1) | KR850007603A (de) |
| AT (1) | ATE83237T1 (de) |
| AU (1) | AU570552B2 (de) |
| BE (1) | BE902210A (de) |
| DE (1) | DE3586879D1 (de) |
| ES (1) | ES8606276A1 (de) |
| FR (1) | FR2563222B1 (de) |
| GB (1) | GB2157695A (de) |
| IT (1) | IT1209945B (de) |
| NL (1) | NL8500909A (de) |
| SE (1) | SE464028B (de) |
| ZA (1) | ZA852591B (de) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6163688A (ja) * | 1984-08-03 | 1986-04-01 | Nissan Chem Ind Ltd | ジヒドロピリジン−５−ホスホン酸環状エステル類 |
| CN1016063B (zh) | 1986-01-22 | 1992-04-01 | 日产化学工业株式会社 | 二氢吡啶-5-膦酸环亚丙基酯的制备 |
| US4885284A (en) * | 1986-01-22 | 1989-12-05 | Nissan Chemical Industries Ltd. | Dihydropyridine-5-phosphonic acid cyclic propylene ester |
| UA5590A1 (uk) * | 1986-01-23 | 1994-12-28 | Ніссан Кемікал Індастріз Лтд | Спосіб одержання пропіленглікового ефіру заміщеної 1,4-дігідропіріділ-5-фосфорної кислоти, або його фармацевтично прийнятной солі або сольвата |
| JPS63115890A (ja) * | 1986-10-31 | 1988-05-20 | Nippon Shinyaku Co Ltd | ２位置換１，４−ジヒドロピリジン誘導体 |
| JPH01275591A (ja) * | 1988-04-27 | 1989-11-06 | Nissan Chem Ind Ltd | ジヒドロピリジン−５−ホスホン酸誘導体 |
| JP2850376B2 (ja) * | 1988-08-02 | 1999-01-27 | 日産化学工業株式会社 | 抗癌剤薬効増強剤 |
| ATE128623T1 (de) * | 1988-08-02 | 1995-10-15 | Nissan Chemical Ind Ltd | Mittel zur verbesserung von arzneimitteleffekten für antitumormittel. |
| US20020119201A1 (en) * | 2000-09-08 | 2002-08-29 | Novozymes A/S | Lubricated granules |
| AU2004226547B2 (en) | 2003-03-28 | 2008-10-23 | Nissan Chemical Industries,Ltd. | T-Type calcium channel blockers |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2094678A5 (de) * | 1970-06-30 | 1972-02-04 | Pepro | |
| DE2508181A1 (de) * | 1975-02-26 | 1976-09-09 | Bayer Ag | 1,4-dihydropyridincarbonsaeurearal- kylester, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| JPS59161392A (ja) * | 1983-03-04 | 1984-09-12 | Nippon Shinyaku Co Ltd | ジヒドロピリジン誘導体及びその製法 |
| EP0141222B1 (de) * | 1983-09-26 | 1989-04-12 | Nissan Chemical Industries Ltd. | Zyklische Dihydropyridin-5-Phosphonsäure-Ester |
-
1984
- 1984-04-19 JP JP59079560A patent/JPS60248693A/ja active Granted
-
1985
- 1985-03-25 IT IT8547862A patent/IT1209945B/it active
- 1985-03-26 GB GB08507897A patent/GB2157695A/en not_active Withdrawn
- 1985-03-27 KR KR1019850002009A patent/KR850007603A/ko not_active Application Discontinuation
- 1985-03-28 NL NL8500909A patent/NL8500909A/nl not_active Application Discontinuation
- 1985-04-04 ZA ZA852591A patent/ZA852591B/xx unknown
- 1985-04-04 FR FR8505174A patent/FR2563222B1/fr not_active Expired
- 1985-04-17 US US06/724,019 patent/US5036059A/en not_active Expired - Fee Related
- 1985-04-17 SE SE8501882A patent/SE464028B/sv not_active IP Right Cessation
- 1985-04-17 BE BE0/214853A patent/BE902210A/fr not_active IP Right Cessation
- 1985-04-18 DE DE8585104723T patent/DE3586879D1/de not_active Expired - Lifetime
- 1985-04-18 AU AU41405/85A patent/AU570552B2/en not_active Ceased
- 1985-04-18 EP EP85104723A patent/EP0159040B1/de not_active Expired - Lifetime
- 1985-04-18 AT AT85104723T patent/ATE83237T1/de not_active IP Right Cessation
- 1985-04-18 ES ES542378A patent/ES8606276A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB8507897D0 (en) | 1985-05-01 |
| DE3586879D1 (de) | 1993-01-21 |
| SE8501882L (sv) | 1985-10-20 |
| ES8606276A1 (es) | 1986-04-01 |
| ZA852591B (en) | 1986-01-29 |
| AU4140585A (en) | 1985-10-24 |
| FR2563222A1 (fr) | 1985-10-25 |
| JPS60248693A (ja) | 1985-12-09 |
| IT8547862A0 (it) | 1985-03-25 |
| FR2563222B1 (fr) | 1989-06-09 |
| BE902210A (fr) | 1985-10-17 |
| KR850007603A (ko) | 1985-12-07 |
| EP0159040A3 (en) | 1988-08-17 |
| JPH0259835B2 (de) | 1990-12-13 |
| IT1209945B (it) | 1989-08-30 |
| ATE83237T1 (de) | 1992-12-15 |
| AU570552B2 (en) | 1988-03-17 |
| SE8501882D0 (sv) | 1985-04-17 |
| EP0159040A2 (de) | 1985-10-23 |
| EP0159040B1 (de) | 1992-12-09 |
| ES542378A0 (es) | 1986-04-01 |
| SE464028B (sv) | 1991-02-25 |
| US5036059A (en) | 1991-07-30 |
| GB2157695A (en) | 1985-10-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5021433A (en) | Novel pharmacological compounds | |
| NZ194805A (en) | 1,4-dihydropyridine derivatives and pharmaceutical compositions | |
| EP0116769B1 (de) | Dihydropyridine | |
| NL8301640A (nl) | Bicyclische verbindingen, werkwijze voor de bereiding ervan alsmede geneesmiddelen die deze verbindingen bevatten. | |
| NL8500909A (nl) | Pyridinederivaten en werkwijze voor de bereiding ervan. | |
| EP0121117B1 (de) | Dihydropyridin-Derivate und deren Herstellung | |
| US4994461A (en) | 1,4-dihydropyridine enantiomers | |
| MORITA et al. | Synthesis and antihypertensive activities of 1, 4-dihydropyridine-5-phosphonate derivatives. II | |
| US5512564A (en) | Tricyclic thiazole and oxazole derivatives and pharmaceutical agents containing them | |
| JPH0363274A (ja) | ６，１１―ジヒドロ―５Ｈ―ピリド［２，３―ｂ］［１，５］ベンゾジアゼピン―５―オン及び―チオン並びに該化合物のＡＩＤＳの予防又は治療における使用法 | |
| FI96312C (fi) | Menetelmä valmistaa terapeuttisesti aktiivisia tienopyraaneja | |
| EP0063359B1 (de) | 1,4-Dihydropyridin-Derivate und Verfahren zu ihrer Herstellung | |
| US4876255A (en) | Substituted 1,4-dihydropyridines for control of circulation and thromboses | |
| MORITA et al. | Synthesis and antihypertensive activities of 1, 4-dihydropyridine-5-phosphonate derivatives. I | |
| US4857515A (en) | Certain antihypertensive 1,4-dihydro-6-methyl-5-phosphonic acid-4-aryl-3-carboxylic acid-2-cyano diesters | |
| EP0286041A1 (de) | Imidazothiadiazin-Derivate, ein Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel | |
| JP2640245B2 (ja) | １，４−ジヒドロピリジン誘導体 | |
| KR950006546B1 (ko) | 카르복사마이드 화합물, 이를 함유하는 약제학적 조성물 및 제조방법 | |
| FI85491B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara fosfonsyraderivat. | |
| US4623647A (en) | [1,3]oxazino[4,3-a]-isoquinoline derivatives and pharmaceutical compositions containing them | |
| KR860000583B1 (ko) | 광학적 활성 1,4-디하이드로피리딘 화합물의 제조방법 | |
| HU193763B (en) | Process for preparing 1,4-dihydro-2,6-dimethyl-3-(alkoxycarbonyl or alkoxy-alkoxycarbonyl)-4-(substituted phenyl)-5-pyridinecarboxylic acid esters and pharmaceutics comprising the same | |
| JPS6163689A (ja) | ピリジン誘導体 | |
| JPH0455438B2 (de) | ||
| DK152285B (da) | Analogifremgangsmaade til fremstilling af 1,4-dihydropyridinderivater |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BT | A notification was added to the application dossier and made available to the public | ||
| BA | A request for search or an international-type search has been filed | ||
| BB | A search report has been drawn up | ||
| BV | The patent application has lapsed |