NO884671L - Nye flourmetoksyfenyldihydropyridiner, fremgangsmaate til deres fremstilling og deres anvendelse i legemidler. - Google Patents

Nye flourmetoksyfenyldihydropyridiner, fremgangsmaate til deres fremstilling og deres anvendelse i legemidler.

Info

Publication number: NO884671L
Authority: NO; Norway
Prior art keywords: carbon atoms; formula; general formula; ester; dimethyl
Prior art date: 1987-11-04

Application number

NO88884671A

Other languages

English (en)

Norwegian (no)

Other versions

NO884671D0 (no

Inventor

Gerhard Franckowiak

Juergen Stoltefuss

Martin Bechem

Reiner Gross

Michael Kayser

Siegbert Habisch

Matthias Schramm

Original Assignee

Bayer Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1987-11-04

Filing date

1988-10-20

Publication date

1989-05-05

1988-10-20 Application filed by Bayer Ag filed Critical Bayer Ag

1988-10-20 Publication of NO884671D0 publication Critical patent/NO884671D0/no

1989-05-05 Publication of NO884671L publication Critical patent/NO884671L/no

Links

238000000034 method Methods 0.000 title claims abstract description 34
239000003814 drug Substances 0.000 title claims abstract description 8
238000002360 preparation method Methods 0.000 title claims abstract description 8
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 42
229910052731 fluorine Chemical group 0.000 claims abstract description 10
239000011737 fluorine Chemical group 0.000 claims abstract description 10
125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
239000001257 hydrogen Substances 0.000 claims abstract description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
239000001301 oxygen Substances 0.000 claims abstract description 6
125000004434 sulfur atom Chemical group 0.000 claims abstract description 6
229940079593 drug Drugs 0.000 claims abstract description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract 5
-1 hydroxy, cyano, phenyl Chemical group 0.000 claims description 31
150000001875 compounds Chemical class 0.000 claims description 27
150000001298 alcohols Chemical class 0.000 claims description 11
239000000203 mixture Substances 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 10
125000003277 amino group Chemical group 0.000 claims description 10
150000002148 esters Chemical group 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 8
125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
QCDJOJKIHZQJGX-UHFFFAOYSA-N 1-nitropropan-2-one Chemical compound CC(=O)C[N+]([O-])=O QCDJOJKIHZQJGX-UHFFFAOYSA-N 0.000 claims description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
239000000969 carrier Substances 0.000 claims description 5
230000032050 esterification Effects 0.000 claims description 5
238000005886 esterification reaction Methods 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000005936 piperidyl group Chemical group 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
238000006000 Knoevenagel condensation reaction Methods 0.000 claims description 4
150000001735 carboxylic acids Chemical class 0.000 claims description 4
239000007859 condensation product Substances 0.000 claims description 4
238000009826 distribution Methods 0.000 claims description 4
150000002168 ethanoic acid esters Chemical class 0.000 claims description 4
239000012442 inert solvent Substances 0.000 claims description 4
230000009090 positive inotropic effect Effects 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 3
125000004423 acyloxy group Chemical group 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
238000004587 chromatography analysis Methods 0.000 claims description 3
238000002425 crystallisation Methods 0.000 claims description 3
230000008025 crystallization Effects 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
PAWSVPVNIXFKOS-IHWYPQMZSA-N (Z)-2-aminobutenoic acid Chemical class C\C=C(/N)C(O)=O PAWSVPVNIXFKOS-IHWYPQMZSA-N 0.000 claims description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 2
239000005695 Ammonium acetate Substances 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
229940043376 ammonium acetate Drugs 0.000 claims description 2
235000019257 ammonium acetate Nutrition 0.000 claims description 2
150000003863 ammonium salts Chemical class 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
239000000460 chlorine Chemical group 0.000 claims description 2
229910052801 chlorine Chemical group 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
229940126601 medicinal product Drugs 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
235000019441 ethanol Nutrition 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
229960000583 acetic acid Drugs 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 11
VXXUZRAIRUAGSM-UHFFFAOYSA-N 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylic acid Chemical compound [O-][N+](=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1OC(F)F VXXUZRAIRUAGSM-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
239000013078 crystal Substances 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
230000010412 perfusion Effects 0.000 description 7
239000011347 resin Substances 0.000 description 7
229920005989 resin Polymers 0.000 description 7
239000002904 solvent Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
235000019439 ethyl acetate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
230000008602 contraction Effects 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
239000013543 active substance Substances 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
230000007017 scission Effects 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000037396 body weight Effects 0.000 description 3
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
239000000052 vinegar Substances 0.000 description 3
235000021419 vinegar Nutrition 0.000 description 3
ANPBZISJWIAHSH-UHFFFAOYSA-N 2-phenylethyl 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylate Chemical compound C1(=CC=CC=C1)CCOC(=O)C=1C(C(=C(NC=1C)C)[N+](=O)[O-])C1=C(C=CC=C1)OC(F)F ANPBZISJWIAHSH-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
XPPCTPBPJPZCBU-UHFFFAOYSA-N 4-[2-(difluoromethoxy)phenyl]-3-nitrobut-3-en-2-one Chemical compound CC(=O)C([N+]([O-])=O)=CC1=CC=CC=C1OC(F)F XPPCTPBPJPZCBU-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
241000700198 Cavia Species 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
239000000654 additive Substances 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
210000000038 chest Anatomy 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
235000013312 flour Nutrition 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
150000003903 lactic acid esters Chemical class 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
229960002510 mandelic acid Drugs 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
210000004165 myocardium Anatomy 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
AOHMPUFCLHOLQS-UHFFFAOYSA-N octyl 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylate Chemical compound CCCCCCCCOC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)C1C1=CC=CC=C1OC(F)F AOHMPUFCLHOLQS-UHFFFAOYSA-N 0.000 description 2
239000000047 product Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
210000002460 smooth muscle Anatomy 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
LRIBRELXSZLLOX-UHFFFAOYSA-N (1-ethoxy-1-oxopropan-2-yl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylate Chemical compound CCOC(=O)C(C)OC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)C1C1=CC=CC=C1OC(F)F LRIBRELXSZLLOX-UHFFFAOYSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
VEYVOOQGLVMPFQ-UHFFFAOYSA-N (4-methoxy-4-oxobutyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)CCCOC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)C1C1=CC=CC=C1OC(F)F VEYVOOQGLVMPFQ-UHFFFAOYSA-N 0.000 description 1
WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 1
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
YRWNWKUUJANORD-UHFFFAOYSA-N 2,6-dimethyl-5-nitro-4-[2-(trifluoromethoxy)phenyl]-1,4-dihydropyridine-3-carboxylic acid Chemical compound [O-][N+](=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1OC(F)(F)F YRWNWKUUJANORD-UHFFFAOYSA-N 0.000 description 1
JXAMZXRILQQEDF-UHFFFAOYSA-N 2-(4-methoxyphenoxy)ethyl 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylate Chemical compound C1=CC(OC)=CC=C1OCCOC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)C1C1=CC=CC=C1OC(F)F JXAMZXRILQQEDF-UHFFFAOYSA-N 0.000 description 1
QPBNHDFPMRENBC-UHFFFAOYSA-N 2-(difluoromethoxy)benzaldehyde Chemical compound FC(F)OC1=CC=CC=C1C=O QPBNHDFPMRENBC-UHFFFAOYSA-N 0.000 description 1
CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical compound FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 description 1
ZMOSGXRSLGVFEN-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]propyl 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylate Chemical compound C(C)(C)(C)OC(=O)NC(COC(=O)C=1C(C(=C(NC=1C)C)[N+](=O)[O-])C1=C(C=CC=C1)OC(F)F)C ZMOSGXRSLGVFEN-UHFFFAOYSA-N 0.000 description 1
AXKUWISZDRPQBV-UHFFFAOYSA-N 2-acetyloxyethyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethoxy)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound CC(=O)OCCOC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)C1C1=CC=CC=C1OC(F)(F)F AXKUWISZDRPQBV-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
SHVDZRSNKKRGET-UHFFFAOYSA-N 2-cyanoethyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethoxy)phenyl]-1,4-dihydropyridine-3-carboxylate Chemical compound [O-][N+](=O)C1=C(C)NC(C)=C(C(=O)OCCC#N)C1C1=CC=CC=C1OC(F)(F)F SHVDZRSNKKRGET-UHFFFAOYSA-N 0.000 description 1
ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
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BDPLDEUXEBFDRZ-UHFFFAOYSA-N propan-2-yl 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-5-nitro-1,4-dihydropyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)C1C1=CC=CC=C1OC(F)F BDPLDEUXEBFDRZ-UHFFFAOYSA-N 0.000 description 1
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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
- C07D211/84—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 hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- 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
- C07D211/84—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 hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Heart & Thoracic Surgery (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)

NO88884671A 1987-11-04 1988-10-20 Nye flourmetoksyfenyldihydropyridiner, fremgangsmaate til deres fremstilling og deres anvendelse i legemidler. NO884671L (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19873737340 DE3737340A1 (de)	1987-11-04	1987-11-04	Neue fluormethoxyphenyl-dihydropyridine, verfahren zur herstellung und ihre verwendung in arzneimitteln

Publications (2)

Publication Number	Publication Date
NO884671D0 NO884671D0 (no)	1988-10-20
NO884671L true NO884671L (no)	1989-05-05

Family

ID=6339713

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO88884671A NO884671L (no)	1987-11-04	1988-10-20	Nye flourmetoksyfenyldihydropyridiner, fremgangsmaate til deres fremstilling og deres anvendelse i legemidler.

Country Status (15)

Country	Link
US (1)	US5008279A (pt)
EP (1)	EP0315018A3 (pt)
JP (1)	JPH01151555A (pt)
KR (1)	KR890008097A (pt)
CN (1)	CN1040192A (pt)
AU (1)	AU613101B2 (pt)
DD (1)	DD283380A5 (pt)
DE (1)	DE3737340A1 (pt)
DK (1)	DK614088A (pt)
FI (1)	FI885056A (pt)
HU (1)	HU201526B (pt)
IL (1)	IL88237A0 (pt)
NO (1)	NO884671L (pt)
PT (1)	PT88920B (pt)
ZA (1)	ZA888234B (pt)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5137889A (en) *	1983-12-02	1992-08-11	Otsuka Pharmaceutical Co., Ltd.	Dihydropyridine derivatives and process for preparing the same
US6515009B1 (en)	1991-09-27	2003-02-04	Neorx Corporation	Therapeutic inhibitor of vascular smooth muscle cells
US5811447A (en)	1993-01-28	1998-09-22	Neorx Corporation	Therapeutic inhibitor of vascular smooth muscle cells
US6251920B1 (en)	1993-05-13	2001-06-26	Neorx Corporation	Prevention and treatment of cardiovascular pathologies
US5770609A (en) *	1993-01-28	1998-06-23	Neorx Corporation	Prevention and treatment of cardiovascular pathologies
US6491938B2 (en)	1993-05-13	2002-12-10	Neorx Corporation	Therapeutic inhibitor of vascular smooth muscle cells
CA2223595C (en)	1995-06-07	2008-08-05	Neorx Corporation	Prevention and treatment of cardiovascular pathologies with tamoxifen analogues
US6117911A (en)	1997-04-11	2000-09-12	Neorx Corporation	Compounds and therapies for the prevention of vascular and non-vascular pathologies
EP0985667A4 (en)	1997-04-25	2000-03-22	Ajinomoto Kk	NEW DIHYDROPYRIDINE DERIVATIVE

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2752820A1 (de) *	1977-11-26	1979-05-31	Bayer Ag	Neue nitrosubstituierte 1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
US4285955A (en) *	1978-10-31	1981-08-25	Bayer Aktiengesellschaft	1,4-Dihydropyridinecarboxylic acids
DE3447169A1 (de) *	1984-12-22	1986-07-03	Bayer Ag, 5090 Leverkusen	Optisch aktive nitrodihydropyridine, verfahren zur herstellung und ihre verwendung in arzneimitteln
US4868181A (en) *	1986-08-04	1989-09-19	E. I. Du Pont De Nemours And Company	1,4-dihydropyridine derivatives with calcium agonist and alpha1 -antagonist activity
US4920225A (en) *	1986-12-22	1990-04-24	Laboratoires Syntex S.A.	Resolution of 1,4-dihydropyridine derivatives
DE3737341A1 (de) *	1987-11-04	1989-05-18	Bayer Ag	Neue fluormethoxyphenyl-dihydropyridine, verfahren zur herstellung und ihre verwendung in arzneimitteln
DE3821334A1 (de) *	1988-06-24	1989-12-28	Bayer Ag	1,4-dihydropyridin-threonin-derivate, verfahren zu ihrer herstellung, zwischenprodukte und ihre verwendung als arzneimittel

1987
- 1987-11-04 DE DE19873737340 patent/DE3737340A1/de not_active Withdrawn
1988
- 1988-10-20 NO NO88884671A patent/NO884671L/no unknown
- 1988-10-25 EP EP88117702A patent/EP0315018A3/de not_active Withdrawn
- 1988-10-27 US US07/263,671 patent/US5008279A/en not_active Expired - Fee Related
- 1988-10-31 IL IL88237A patent/IL88237A0/xx unknown
- 1988-11-01 DD DD88321316A patent/DD283380A5/de not_active IP Right Cessation
- 1988-11-01 AU AU24576/88A patent/AU613101B2/en not_active Ceased
- 1988-11-02 PT PT88920A patent/PT88920B/pt not_active IP Right Cessation
- 1988-11-02 FI FI885056A patent/FI885056A/fi not_active Application Discontinuation
- 1988-11-03 CN CN88107639A patent/CN1040192A/zh active Pending
- 1988-11-03 KR KR1019880014437A patent/KR890008097A/ko not_active Application Discontinuation
- 1988-11-03 ZA ZA888234A patent/ZA888234B/xx unknown
- 1988-11-03 DK DK614088A patent/DK614088A/da not_active Application Discontinuation
- 1988-11-04 JP JP63279182A patent/JPH01151555A/ja active Pending
- 1988-11-04 HU HU885711A patent/HU201526B/hu not_active IP Right Cessation

Also Published As

Publication number	Publication date
NO884671D0 (no)	1988-10-20
PT88920A (pt)	1988-12-01
JPH01151555A (ja)	1989-06-14
US5008279A (en)	1991-04-16
HU201526B (en)	1990-11-28
DE3737340A1 (de)	1989-05-24
CN1040192A (zh)	1990-03-07
EP0315018A3 (de)	1990-07-18
ZA888234B (en)	1989-07-26
PT88920B (pt)	1993-01-29
AU2457688A (en)	1989-05-04
FI885056A0 (fi)	1988-11-02
IL88237A0 (en)	1989-06-30
FI885056A (fi)	1989-05-05
KR890008097A (ko)	1989-11-26
EP0315018A2 (de)	1989-05-10
AU613101B2 (en)	1991-07-25
DK614088A (da)	1989-05-05
DD283380A5 (de)	1990-10-10
HUT48591A (en)	1989-06-28
DK614088D0 (da)	1988-11-03

Publication	Publication Date	Title
US5104890A (en)	1992-04-14	Benzopyran derivatives and processes for preparation thereof
NO159928B (no)	1988-11-14	Fremgangsmaate til fremstilling av optisk aktive 1-,4-dihydropyridinkarboksylsyreestere.
US4559351A (en)	1985-12-17	Dihydropyridine derivatives of 1,4:3,6-dianhydrohexitols
EP0185964B1 (de)	1990-02-28	Dihydropyridin-carbonsäureamide, Verfahren zu ihrer Herstellung und ihre Verwendung in Arzneimitteln
AU640217B2 (en)	1993-08-19	New 4-quinolyl-dihydropyridines, processes for their preparation and their use in medicaments
US4772612A (en)	1988-09-20	Circulation-active 1,4-dihydropyridines
NO884671L (no)	1989-05-05	Nye flourmetoksyfenyldihydropyridiner, fremgangsmaate til deres fremstilling og deres anvendelse i legemidler.
US5380851A (en)	1995-01-10	2-amino-5-cyano-1,4-dihydropyridines, processes for their preparation
US4889866A (en)	1989-12-26	Arylsulfonyl dihydropyridine derivatives
HUT70488A (en)	1995-10-30	Condensed quinolyl-dihydropyridine derivatives, pharmaceutical compositions containing them and process for producing the compounds and the pharmaceutical compositions
EP0186028B1 (de)	1990-08-01	Optisch aktive Nitrodihydropyridine, Verfahren zur Herstellung und ihre Verwendung in Arzneimitteln
CZ99994A3 (en)	1994-11-16	3-quinolyl substituted dihydropyridines, process of their preparation, medicaments in which they are comprised, process of their preparation and the use of said compounds
US4876255A (en)	1989-10-24	Substituted 1,4-dihydropyridines for control of circulation and thromboses
EP0106276B1 (en)	1988-10-26	1,4-dihydropyridine derivatives
AU664406B2 (en)	1995-11-16	New 4-cinnolinyl- and 4-naphthyridinyl-dihydropyridines, processes for their use in medicaments
KR920003626B1 (ko)	1992-05-04	디히드로피리딘-3,5-디카르복실산 에스테르 유도체의 제조방법
NO884672L (no)	1989-05-05	Nye fluormetoksyfenyl-dihydropyridiner, fremgangsmaate tilderes fremstilling og deres anvendelse i legemidler.
US4645775A (en)	1987-02-24	Positive inotropic 3-nitro-5-substituted ester and thioester-1,4-dihydropyridines
CZ99694A3 (en)	1994-11-16	Quinolyl-dihydropyridine esters, process of their preparation, medicaments in which they are comprised, process of their preparation and the use of said compounds
CZ99594A3 (en)	1994-11-16	2-amino-4-heteroaryl-1,4-dihydropyridine, process of their preparation, medicament in which they are comprised, process of their preparation, and the use of said compounds
NZ264769A (en)	1995-08-28	Substituted pyridine intermediates