CS273172B2 - Method of dihydropyridine derivatives production - Google Patents

Method of dihydropyridine derivatives production Download PDF

Info

Publication number: CS273172B2
Authority: CS; Czechoslovakia
Prior art keywords: methyl; group; phenylene; phenyl; carbon atoms
Prior art date: 1985-02-11

Application number

CS91186A

Other languages

Czech (cs)

English (en)

Other versions

CS91186A2 (en

Inventor

Rodney B Hargreaves

Bernard J Mcloughlin

Stuart D Mills

Original Assignee

Ici Plc

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.)

1985-02-11

Filing date

1986-02-10

Publication date

1991-03-12

1986-02-10 Application filed by Ici Plc filed Critical Ici Plc

1987-05-11 Priority to CS334987A priority Critical patent/CS273180B2/cs

1990-07-12 Publication of CS91186A2 publication Critical patent/CS91186A2/cs

1991-03-12 Publication of CS273172B2 publication Critical patent/CS273172B2/cs

Links

238000000034 method Methods 0.000 title claims abstract description 28
229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 title claims description 14
238000004519 manufacturing process Methods 0.000 title abstract 2
125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 title description 6
-1 imino, substituted imino, phenylene, substituted phenylene Chemical group 0.000 claims abstract description 91
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 34
150000001875 compounds Chemical class 0.000 claims abstract description 31
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
150000003839 salts Chemical class 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims abstract description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
125000001424 substituent group Chemical group 0.000 claims abstract description 10
125000002947 alkylene group Chemical group 0.000 claims abstract description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
239000001301 oxygen Substances 0.000 claims abstract description 7
125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
125000005843 halogen group Chemical group 0.000 claims abstract description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 58
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 19
239000002253 acid Substances 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 8
239000007858 starting material Substances 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 4
125000003302 alkenyloxy group Chemical group 0.000 claims description 4
125000001841 imino group Chemical group [H]N=* 0.000 claims description 4
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
150000002118 epoxides Chemical class 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
125000005336 allyloxy group Chemical group 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
125000005605 benzo group Chemical group 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
125000001589 carboacyl group Chemical group 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
230000000903 blocking effect Effects 0.000 abstract description 7
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 abstract description 5
229910001424 calcium ion Inorganic materials 0.000 abstract description 5
229920006395 saturated elastomer Polymers 0.000 abstract description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 4
206010020772 Hypertension Diseases 0.000 abstract description 3
239000008194 pharmaceutical composition Substances 0.000 abstract description 3
229910052757 nitrogen Inorganic materials 0.000 abstract description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 2
239000005864 Sulphur Chemical group 0.000 abstract 2
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 abstract 1
125000002373 5 membered heterocyclic group Chemical group 0.000 abstract 1
125000004070 6 membered heterocyclic group Chemical group 0.000 abstract 1
125000004450 alkenylene group Chemical group 0.000 abstract 1
125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
125000003368 amide group Chemical group 0.000 abstract 1
125000002993 cycloalkylene group Chemical group 0.000 abstract 1
125000005842 heteroatom Chemical group 0.000 abstract 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 abstract 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 abstract 1
125000001624 naphthyl group Chemical group 0.000 abstract 1
125000005551 pyridylene group Chemical group 0.000 abstract 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 abstract 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 21
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
241000700159 Rattus Species 0.000 description 18
238000002844 melting Methods 0.000 description 15
230000008018 melting Effects 0.000 description 15
239000000203 mixture Substances 0.000 description 13
239000000243 solution Substances 0.000 description 12
230000003276 anti-hypertensive effect Effects 0.000 description 11
238000011699 spontaneously hypertensive rat Methods 0.000 description 11
125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 description 10
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
210000000278 spinal cord Anatomy 0.000 description 10
239000000126 substance Substances 0.000 description 10
241001465754 Metazoa Species 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
229960001317 isoprenaline Drugs 0.000 description 8
239000000047 product Substances 0.000 description 7
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 6
102000012740 beta Adrenergic Receptors Human genes 0.000 description 6
108010079452 beta Adrenergic Receptors Proteins 0.000 description 6
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 6
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
150000001299 aldehydes Chemical class 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 description 4
IHFRMUGEILMHNU-UHFFFAOYSA-N 2-hydroxy-5-nitrobenzaldehyde Chemical compound OC1=CC=C([N+]([O-])=O)C=C1C=O IHFRMUGEILMHNU-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
239000005695 Ammonium acetate Substances 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000001800 adrenalinergic effect Effects 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
235000019257 ammonium acetate Nutrition 0.000 description 3
235000019445 benzyl alcohol Nutrition 0.000 description 3
230000037396 body weight Effects 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000007787 solid Substances 0.000 description 3
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
VFVHWCKUHAEDMY-UHFFFAOYSA-N 2-chloro-5-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=O)=C1 VFVHWCKUHAEDMY-UHFFFAOYSA-N 0.000 description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
206010002383 Angina Pectoris Diseases 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-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
FQYUMYWMJTYZTK-UHFFFAOYSA-N Phenyl glycidyl ether Chemical compound C1OC1COC1=CC=CC=C1 FQYUMYWMJTYZTK-UHFFFAOYSA-N 0.000 description 2
LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229940030600 antihypertensive agent Drugs 0.000 description 2
239000002220 antihypertensive agent Substances 0.000 description 2
206010003119 arrhythmia Diseases 0.000 description 2
JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
210000001715 carotid artery Anatomy 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
229960003132 halothane Drugs 0.000 description 2
208000019622 heart disease Diseases 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000007791 liquid phase Substances 0.000 description 2
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
238000004949 mass spectrometry Methods 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
229920001223 polyethylene glycol Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
229940125723 sedative agent Drugs 0.000 description 2
239000000932 sedative agent Substances 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
239000002904 solvent Substances 0.000 description 2
238000004611 spectroscopical analysis Methods 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
238000005303 weighing Methods 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
OPCJOXGBLDJWRM-UHFFFAOYSA-N 1,2-diamino-2-methylpropane Chemical compound CC(C)(N)CN OPCJOXGBLDJWRM-UHFFFAOYSA-N 0.000 description 1
YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
125000005978 1-naphthyloxy group Chemical group 0.000 description 1
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
WQFXJSOUBPGBGW-UHFFFAOYSA-N 2,6-dimethylpyridine-3,5-dicarboxylic acid Chemical compound CC1=NC(C)=C(C(O)=O)C=C1C(O)=O WQFXJSOUBPGBGW-UHFFFAOYSA-N 0.000 description 1
UXFWTIGUWHJKDD-UHFFFAOYSA-N 2-(4-bromobutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCBr)C(=O)C2=C1 UXFWTIGUWHJKDD-UHFFFAOYSA-N 0.000 description 1
GOPZIBJWDYBGHL-UHFFFAOYSA-N 2-[2-[2-(bromomethyl)phenyl]ethyl]isoindole-1,3-dione Chemical compound BrCC1=CC=CC=C1CCN1C(=O)C2=CC=CC=C2C1=O GOPZIBJWDYBGHL-UHFFFAOYSA-N 0.000 description 1
JFMGJNJFIZIVSB-UHFFFAOYSA-N 2-[2-[3-(bromomethyl)phenoxy]ethyl]isoindole-1,3-dione Chemical compound BrCC1=CC=CC(OCCN2C(C3=CC=CC=C3C2=O)=O)=C1 JFMGJNJFIZIVSB-UHFFFAOYSA-N 0.000 description 1
MKZRHSJGVHNSLD-UHFFFAOYSA-N 2-[2-[3-(bromomethyl)phenyl]ethyl]isoindole-1,3-dione Chemical compound BrCC1=CC=CC(CCN2C(C3=CC=CC=C3C2=O)=O)=C1 MKZRHSJGVHNSLD-UHFFFAOYSA-N 0.000 description 1
MCSRCSAYYHJUMC-UHFFFAOYSA-N 2-[2-[4-(bromomethyl)phenyl]ethyl]isoindole-1,3-dione Chemical compound C1=CC(CBr)=CC=C1CCN1C(=O)C2=CC=CC=C2C1=O MCSRCSAYYHJUMC-UHFFFAOYSA-N 0.000 description 1
OCGNRULUMISBAD-UHFFFAOYSA-N 2-[2-[4-(chloromethyl)phenoxy]ethyl]isoindole-1,3-dione Chemical compound C1=CC(CCl)=CC=C1OCCN1C(=O)C2=CC=CC=C2C1=O OCGNRULUMISBAD-UHFFFAOYSA-N 0.000 description 1
PHWNKGQVWPYLJT-UHFFFAOYSA-N 2-[3-(1,3-dioxoisoindol-2-yl)propylsulfanyl]-5-nitrobenzaldehyde Chemical compound O=CC1=CC([N+](=O)[O-])=CC=C1SCCCN1C(=O)C2=CC=CC=C2C1=O PHWNKGQVWPYLJT-UHFFFAOYSA-N 0.000 description 1
LLHDFGLDPWLUOT-UHFFFAOYSA-N 2-[4-(1,3-dioxoisoindol-2-yl)butoxy]-5-nitrobenzaldehyde Chemical compound O=CC1=CC([N+](=O)[O-])=CC=C1OCCCCN1C(=O)C2=CC=CC=C2C1=O LLHDFGLDPWLUOT-UHFFFAOYSA-N 0.000 description 1
JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
PHRHXTTZZWUGNN-UHFFFAOYSA-N 3-amino-3-methylbutan-1-ol Chemical compound CC(C)(N)CCO PHRHXTTZZWUGNN-UHFFFAOYSA-N 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
CZOKEWNUUNAFEU-UHFFFAOYSA-N BrCCCC=1C(=C2C(C(=O)NC2=O)=CC1)CCC Chemical compound BrCCCC=1C(=C2C(C(=O)NC2=O)=CC1)CCC CZOKEWNUUNAFEU-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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- 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
- A61P9/06—Antiarrhythmics
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/44—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by —CHO groups
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Obesity (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Diabetes (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Pyridine Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CS91186A 1985-02-11 1986-02-10 Method of dihydropyridine derivatives production CS273172B2 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CS334987A CS273180B2 (en)	1985-02-11	1987-05-11	Method of dihydropyridine derivatives production

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB858503425A GB8503425D0 (en)	1985-02-11	1985-02-11	Alkanolamine derivatives

Publications (2)

Publication Number	Publication Date
CS91186A2 CS91186A2 (en)	1990-07-12
CS273172B2 true CS273172B2 (en)	1991-03-12

Family

ID=10574270

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS91186A CS273172B2 (en)	1985-02-11	1986-02-10	Method of dihydropyridine derivatives production

Country Status (21)

Country	Link
US (1)	US4873254A (de)
EP (1)	EP0194751B1 (de)
JP (1)	JPH0819100B2 (de)
KR (1)	KR860006443A (de)
AU (1)	AU5339486A (de)
CS (1)	CS273172B2 (de)
DD (1)	DD250533A5 (de)
DE (1)	DE3684803D1 (de)
DK (1)	DK66186A (de)
ES (2)	ES8802139A1 (de)
FI (1)	FI860621A7 (de)
GB (2)	GB8503425D0 (de)
GR (1)	GR860369B (de)
HU (1)	HU196179B (de)
NO (1)	NO860465L (de)
NZ (1)	NZ215083A (de)
PH (1)	PH22683A (de)
PL (2)	PL153857B1 (de)
PT (1)	PT82008B (de)
SU (1)	SU1590041A3 (de)
ZA (1)	ZA86967B (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6112662A (ja) *	1984-06-28	1986-01-21	Yamanouchi Pharmaceut Co Ltd	ジヒドロピリジン誘導体及びその製法
EP0276552A1 (de) *	1986-12-08	1988-08-03	Yamanouchi Pharmaceutical Co. Ltd.	1,4-Dihydropyridin-Derivate und ihre Herstellung
GB9102031D0 (en) *	1991-01-30	1991-03-13	Fujisawa Pharmaceutical Co	Dihydropyridine compounds,and process for their preparation
WO2000005209A1 (fr) *	1998-07-23	2000-02-03	Lin, Tong-Ho	GUAIACOXYPROPANOLAMINES A ACTIVITE α/β-ADRENOLYTIQUE
MY156662A (en) *	2007-11-01	2016-03-15	Acucela Inc	Amine derivative compounds for treating ophthalmic diseases and disorders

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2228363A1 (de) *	1972-06-10	1974-01-03	Bayer Ag	1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
GB1409865A (en) *	1973-02-13	1975-10-15	Science Union & Cie	Dihydropyridines derivatives their preparation and pharmaceu tical compositions containing them
US4500527A (en) *	1983-06-22	1985-02-19	Usv Pharmaceutical Corporation	Antihypertensive 4[(3-alkylamino-2-hydroxypropyl)-oxyiminomethyl phenyl]-1,4-dihydropyridines
JPS6112662A (ja) *	1984-06-28	1986-01-21	Yamanouchi Pharmaceut Co Ltd	ジヒドロピリジン誘導体及びその製法

1985
- 1985-02-11 GB GB858503425A patent/GB8503425D0/en active Pending
1986
- 1986-02-04 GB GB868602704A patent/GB8602704D0/en active Pending
- 1986-02-07 GR GR860369A patent/GR860369B/el unknown
- 1986-02-10 SU SU864027023A patent/SU1590041A3/ru active
- 1986-02-10 DE DE8686300884T patent/DE3684803D1/de not_active Expired - Lifetime
- 1986-02-10 NZ NZ215083A patent/NZ215083A/xx unknown
- 1986-02-10 PT PT82008A patent/PT82008B/pt not_active IP Right Cessation
- 1986-02-10 CS CS91186A patent/CS273172B2/cs unknown
- 1986-02-10 HU HU86535A patent/HU196179B/hu not_active IP Right Cessation
- 1986-02-10 EP EP86300884A patent/EP0194751B1/de not_active Expired - Lifetime
- 1986-02-10 ZA ZA86967A patent/ZA86967B/xx unknown
- 1986-02-10 DD DD86286947A patent/DD250533A5/de unknown
- 1986-02-10 NO NO860465A patent/NO860465L/no unknown
- 1986-02-11 DK DK66186A patent/DK66186A/da not_active Application Discontinuation
- 1986-02-11 PL PL1986265252A patent/PL153857B1/pl unknown
- 1986-02-11 FI FI860621A patent/FI860621A7/fi not_active Application Discontinuation
- 1986-02-11 PH PH33404A patent/PH22683A/en unknown
- 1986-02-11 KR KR1019860000921A patent/KR860006443A/ko not_active Ceased
- 1986-02-11 US US07/828,363 patent/US4873254A/en not_active Expired - Lifetime
- 1986-02-11 PL PL1986257902A patent/PL149828B1/pl unknown
- 1986-02-11 ES ES551844A patent/ES8802139A1/es not_active Expired
- 1986-02-11 AU AU53394/86A patent/AU5339486A/en not_active Abandoned
- 1986-02-12 JP JP61028760A patent/JPH0819100B2/ja not_active Expired - Lifetime
1987
- 1987-07-16 ES ES557630A patent/ES8802496A1/es not_active Expired

Also Published As

Publication number	Publication date
SU1590041A3 (ru)	1990-08-30
PL153857B1 (en)	1991-06-28
FI860621A0 (fi)	1986-02-11
DK66186D0 (da)	1986-02-11
ES557630A0 (es)	1988-07-01
ES8802139A1 (es)	1988-04-01
JPH0819100B2 (ja)	1996-02-28
US4873254A (en)	1989-10-10
ES8802496A1 (es)	1988-07-01
NZ215083A (en)	1989-10-27
GR860369B (en)	1986-06-02
HUT40415A (en)	1986-12-28
PL257902A1 (en)	1988-03-03
PL265252A1 (en)	1988-06-09
FI860621A7 (fi)	1986-08-12
GB8602704D0 (en)	1986-03-12
HU196179B (en)	1988-10-28
PH22683A (en)	1988-11-14
ZA86967B (en)	1986-11-26
DK66186A (da)	1986-08-12
EP0194751B1 (de)	1992-04-15
AU5339486A (en)	1986-08-14
ES551844A0 (es)	1988-04-01
KR860006443A (ko)	1986-09-11
CS91186A2 (en)	1990-07-12
PT82008B (pt)	1988-07-01
NO860465L (no)	1986-08-12
GB8503425D0 (en)	1985-03-13
DD250533A5 (de)	1987-10-14
PT82008A (en)	1986-03-01
EP0194751A1 (de)	1986-09-17
JPS61233669A (ja)	1986-10-17
PL149828B1 (en)	1990-03-31
DE3684803D1 (de)	1992-05-21

Publication	Publication Date	Title
EP0094159B1 (de)	1990-03-14	Dihydropyridinderivate, deren Herstellung und Verwendung
US4656181A (en)	1987-04-07	Esters of 1,4-dihydropyridines, processes for the preparation of the new esters, and medicaments containing the same
EP0126449B1 (de)	1987-12-23	Cardioselektive Aryloxy- und Arylthio-hydroxypropyl-piperazinyl-acetanilide, die das Eindringen von Calcium beeinflussen
KR880000180B1 (ko)	1988-03-12	디하이드로 피리딘의 제조방법
RU2091379C1 (ru)	1997-09-27	Дифенилметилпиперазиновые производные или их фармацевтически приемлемая соль
US4472411A (en)	1984-09-18	1,4-Dihydropyridine derivatives and use as vasodilators
FR2562892A1 (fr)	1985-10-18	Nouveaux dihydropyridinyldicarboxylates amides et esters, utilisation de ces composes comme medicament, compositions pharmaceutiques comprenant de tels composes et procede pour la preparation de tels composes
WO1986004581A1 (en)	1986-08-14	Dihydropyridine alkanolamines
KR960009427B1 (ko)	1996-07-19	1,4-디히드로피리딘 유도체, 그의 약학적 조성물 및 그 제조방법
CS273172B2 (en)	1991-03-12	Method of dihydropyridine derivatives production
JPS6256474A (ja)	1987-03-12	ジヒドロピリジン−２−ヒドロキシアミン類
US8063093B2 (en)	2011-11-22	Potassium channel blockers and uses thereof
EP0207674A2 (de)	1987-01-07	1,4-Dihydropyridinderivate, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung
CS273180B2 (en)	1991-03-12	Method of dihydropyridine derivatives production
JPS62226960A (ja)	1987-10-05	単環式エステル、その製法及びこのエステルを含有する、高血圧、冠状心臓病、末梢及び脳循環障害及び／又は高められた水−又はナトリウム貯留に帰因する疾患を治療及び予防するための医薬
EP0194752A1 (de)	1986-09-17	Dihydropyridin-Alkanolamine, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
JPS5916876A (ja)	1984-01-28	カルシウムに拮抗する塩基性エステル、その製造法およびそれを有効成分とする医薬
NO860464L (no)	1986-08-12	Fremgangsmaate for fremstilling av farmasoeytisk aktive dihydropyridinderivater.
FR2502619A1 (fr)	1982-10-01	Derives de la 1(2h)-isoquinolone et leurs utilisations therapeutiques notamment dans le traitement des ulceres
JPH07215965A (ja)	1995-08-15	インドールスルホンアミド−置換ジヒドロピリジン類
JP3514784B2 (ja)	2004-03-31	アリールアミド誘導体
EP0194047A1 (de)	1986-09-10	Dihydropyridin-Alkanolamine, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
JPH0535150B2 (de)	1993-05-25
JPS61137861A (ja)	1986-06-25	１，４−ジヒドロピリジン−ヒドロキシアミン類
JPH02138257A (ja)	1990-05-28	１，４―ジヒドロピリジン化合物