CA1080223A - Derives de la 1,4-dihydropyridine; leur preparation et les produits pharmaceutiques qui en derivent - Google Patents

Derives de la 1,4-dihydropyridine; leur preparation et les produits pharmaceutiques qui en derivent

Info

Publication number: CA1080223A
Authority: CA; Canada
Prior art keywords: alkyl; formula; methyl; compound; alkoxycarbonyl
Prior art date: 1975-07-02
Legal status (The legal status 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 status listed.): Expired

Application number

CA256,210A

Other languages

English (en)

Inventor

Yoshinari Sato

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Fujisawa Pharmaceutical Co Ltd

Original Assignee

Fujisawa Pharmaceutical Co Ltd

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.)

1975-07-02

Filing date

1976-07-02

Publication date

1980-06-24

1975-07-02 Priority claimed from GB27945/75A external-priority patent/GB1552911A/en

1976-07-02 Application filed by Fujisawa Pharmaceutical Co Ltd filed Critical Fujisawa Pharmaceutical Co Ltd

1976-12-17 Priority claimed from GB52720/76A external-priority patent/GB1591089A/en

1980-06-24 Application granted granted Critical

1980-06-24 Publication of CA1080223A publication Critical patent/CA1080223A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 201
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title claims abstract description 133
238000002360 preparation method Methods 0.000 title claims abstract description 25
239000008194 pharmaceutical composition Substances 0.000 title description 7
-1 cyano, hydroxy Chemical group 0.000 claims abstract description 415
125000000217 alkyl group Chemical group 0.000 claims abstract description 385
150000001875 compounds Chemical class 0.000 claims abstract description 165
239000001257 hydrogen Substances 0.000 claims abstract description 119
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 119
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 68
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 53
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 52
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 46
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 35
125000005277 alkyl imino group Chemical group 0.000 claims abstract description 26
125000001424 substituent group Chemical group 0.000 claims abstract description 24
125000004423 acyloxy group Chemical group 0.000 claims abstract description 21
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 16
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims abstract description 13
125000000676 alkoxyimino group Chemical group 0.000 claims abstract description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 61
239000000203 mixture Substances 0.000 claims description 244
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 140
239000000126 substance Substances 0.000 claims description 110
238000006243 chemical reaction Methods 0.000 claims description 64
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 53
125000003545 alkoxy group Chemical group 0.000 claims description 50
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 50
125000001589 carboacyl group Chemical group 0.000 claims description 46
239000002253 acid Substances 0.000 claims description 37
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 30
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 23
125000005843 halogen group Chemical group 0.000 claims description 20
230000007062 hydrolysis Effects 0.000 claims description 20
238000006460 hydrolysis reaction Methods 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
239000003795 chemical substances by application Substances 0.000 claims description 17
125000005530 alkylenedioxy group Chemical group 0.000 claims description 16
238000010438 heat treatment Methods 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 12
150000003863 ammonium salts Chemical class 0.000 claims description 11
125000002541 furyl group Chemical group 0.000 claims description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 10
239000012024 dehydrating agents‎ Substances 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
125000001544 thienyl group Chemical group 0.000 claims description 10
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 9
150000002148 esters Chemical class 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
229910052708 sodium Inorganic materials 0.000 claims description 9
239000011734 sodium Substances 0.000 claims description 9
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000002252 acyl group Chemical group 0.000 claims description 7
125000003302 alkenyloxy group Chemical group 0.000 claims description 7
150000001412 amines Chemical class 0.000 claims description 7
230000003301 hydrolyzing effect Effects 0.000 claims description 7
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 6
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
238000006467 substitution reaction Methods 0.000 claims description 6
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 5
150000003973 alkyl amines Chemical class 0.000 claims description 5
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
229910021529 ammonia Inorganic materials 0.000 claims description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
230000002140 halogenating effect Effects 0.000 claims description 5
238000005658 halogenation reaction Methods 0.000 claims description 5
229910052751 metal Chemical group 0.000 claims description 5
239000002184 metal Chemical group 0.000 claims description 5
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 4
230000026030 halogenation Effects 0.000 claims description 4
230000001590 oxidative effect Effects 0.000 claims description 4
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 38
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 13
238000004519 manufacturing process Methods 0.000 claims 7
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 6
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 6
125000005059 halophenyl group Chemical group 0.000 claims 6
125000006501 nitrophenyl group Chemical group 0.000 claims 6
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 5
125000005037 alkyl phenyl group Chemical group 0.000 claims 5
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 4
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 4
125000005036 alkoxyphenyl group Chemical group 0.000 claims 3
230000002301 combined effect Effects 0.000 claims 2
125000004193 piperazinyl group Chemical group 0.000 claims 2
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 1
125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 25
125000006239 protecting group Chemical group 0.000 abstract description 20
229920006395 saturated elastomer Polymers 0.000 abstract description 19
206010020772 Hypertension Diseases 0.000 abstract description 7
230000001225 therapeutic effect Effects 0.000 abstract description 6
208000024172 Cardiovascular disease Diseases 0.000 abstract description 5
230000003276 anti-hypertensive effect Effects 0.000 abstract description 4
230000000304 vasodilatating effect Effects 0.000 abstract description 4
241000282414 Homo sapiens Species 0.000 abstract description 3
125000000623 heterocyclic group Chemical group 0.000 abstract description 2
125000005638 hydrazono group Chemical group 0.000 abstract description 2
125000003118 aryl group Chemical group 0.000 abstract 1
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 352
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 315
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 234
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 224
239000003921 oil Substances 0.000 description 170
235000019198 oils Nutrition 0.000 description 170
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 170
239000000243 solution Substances 0.000 description 151
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 149
239000013078 crystal Substances 0.000 description 135
229940093499 ethyl acetate Drugs 0.000 description 117
235000019439 ethyl acetate Nutrition 0.000 description 117
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 113
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 102
239000002904 solvent Substances 0.000 description 100
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 88
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 77
239000000284 extract Substances 0.000 description 70
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 68
241000786363 Rhampholeon spectrum Species 0.000 description 64
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 60
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 47
239000011369 resultant mixture Substances 0.000 description 47
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 46
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
239000000843 powder Substances 0.000 description 42
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
239000003480 eluent Substances 0.000 description 41
229960000443 hydrochloric acid Drugs 0.000 description 41
239000000047 product Substances 0.000 description 41
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 39
239000000741 silica gel Substances 0.000 description 39
229910002027 silica gel Inorganic materials 0.000 description 39
229960001866 silicon dioxide Drugs 0.000 description 39
235000011054 acetic acid Nutrition 0.000 description 38
229960003390 magnesium sulfate Drugs 0.000 description 38
229910052943 magnesium sulfate Inorganic materials 0.000 description 38
235000019341 magnesium sulphate Nutrition 0.000 description 38
238000001816 cooling Methods 0.000 description 37
238000001914 filtration Methods 0.000 description 37
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 36
238000003756 stirring Methods 0.000 description 36
238000004440 column chromatography Methods 0.000 description 35
235000002639 sodium chloride Nutrition 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
239000011541 reaction mixture Substances 0.000 description 31
239000007864 aqueous solution Substances 0.000 description 30
235000011167 hydrochloric acid Nutrition 0.000 description 30
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 30
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 28
125000004356 hydroxy functional group Chemical group O* 0.000 description 23
239000011780 sodium chloride Substances 0.000 description 23
229960002668 sodium chloride Drugs 0.000 description 23
230000018044 dehydration Effects 0.000 description 22
238000006297 dehydration reaction Methods 0.000 description 22
235000017557 sodium bicarbonate Nutrition 0.000 description 21
229960001407 sodium bicarbonate Drugs 0.000 description 21
229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
239000007858 starting material Substances 0.000 description 21
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 20
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
239000008187 granular material Substances 0.000 description 18
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
239000000706 filtrate Substances 0.000 description 15
125000004043 oxo group Chemical group O=* 0.000 description 15
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 15
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 14
229940073584 methylene chloride Drugs 0.000 description 14
238000010992 reflux Methods 0.000 description 14
239000001632 sodium acetate Substances 0.000 description 14
235000017281 sodium acetate Nutrition 0.000 description 14
239000012279 sodium borohydride Substances 0.000 description 14
229910000033 sodium borohydride Inorganic materials 0.000 description 14
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 13
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000010410 layer Substances 0.000 description 12
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 10
YGFPTOGFJZRWJR-FPLPWBNLSA-N ethyl (z)-3-amino-4,4-diethoxybut-2-enoate Chemical compound CCOC(OCC)C(\N)=C\C(=O)OCC YGFPTOGFJZRWJR-FPLPWBNLSA-N 0.000 description 10
YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 10
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 9
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
230000003197 catalytic effect Effects 0.000 description 9
230000000875 corresponding effect Effects 0.000 description 9
HYVRRAANXHHPGH-UHFFFAOYSA-N ethyl 4,4-diethoxy-3-oxobutanoate Chemical compound CCOC(OCC)C(=O)CC(=O)OCC HYVRRAANXHHPGH-UHFFFAOYSA-N 0.000 description 9
235000019253 formic acid Nutrition 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
239000007787 solid Substances 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
238000009833 condensation Methods 0.000 description 8
230000005494 condensation Effects 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
229910000029 sodium carbonate Inorganic materials 0.000 description 8
235000017550 sodium carbonate Nutrition 0.000 description 8
CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 7
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
235000019502 Orange oil Nutrition 0.000 description 7
239000007853 buffer solution Substances 0.000 description 7
DXVKUDLSCITGFT-UHFFFAOYSA-N diethyl 2-formyl-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C=O)=C(C(=O)OCC)C1C1=CC=CC=C1[N+]([O-])=O DXVKUDLSCITGFT-UHFFFAOYSA-N 0.000 description 7
239000007788 liquid Substances 0.000 description 7
239000010502 orange oil Substances 0.000 description 7
125000004742 propyloxycarbonyl group Chemical group 0.000 description 7
238000006722 reduction reaction Methods 0.000 description 7
238000010792 warming Methods 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229940022663 acetate Drugs 0.000 description 6
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 6
150000007522 mineralic acids Chemical class 0.000 description 6
150000007524 organic acids Chemical class 0.000 description 6
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 6
238000007363 ring formation reaction Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 5
FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 5
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
239000012346 acetyl chloride Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
QUJMAJRCHXBYPY-UHFFFAOYSA-N diethyl 4-(2-chlorophenyl)-2-(hydroxymethyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(CO)=C(C(=O)OCC)C1C1=CC=CC=C1Cl QUJMAJRCHXBYPY-UHFFFAOYSA-N 0.000 description 5
125000001841 imino group Chemical group [H]N=* 0.000 description 5
PVNIIMVLHYAWGP-UHFFFAOYSA-M nicotinate Chemical compound [O-]C(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-M 0.000 description 5
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QDQJFXGCPQMOJK-UHFFFAOYSA-N diethyl 4-(2-chlorophenyl)-2,6-bis(diethoxymethyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C(OCC)OCC)NC(C(OCC)OCC)=C(C(=O)OCC)C1C1=CC=CC=C1Cl QDQJFXGCPQMOJK-UHFFFAOYSA-N 0.000 description 1
KAZXFCZSQMHUMC-UHFFFAOYSA-N diethyl 4-(2-chlorophenyl)-2-(diethoxymethyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C(OCC)OCC)=C(C(=O)OCC)C1C1=CC=CC=C1Cl KAZXFCZSQMHUMC-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
SIFUNSZWFWTQKM-UHFFFAOYSA-N dimethyl 2-acetyl-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C(C)=O)=C(C(=O)OC)C1C1=CC=CC=C1Cl SIFUNSZWFWTQKM-UHFFFAOYSA-N 0.000 description 1
IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
MPFLRYZEEAQMLQ-UHFFFAOYSA-N dinicotinic acid Chemical compound OC(=O)C1=CN=CC(C(O)=O)=C1 MPFLRYZEEAQMLQ-UHFFFAOYSA-N 0.000 description 1
150000004662 dithiols Chemical class 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
230000000694 effects Effects 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
KPSOXFYZXAGMPT-UHFFFAOYSA-N ethyl 2-[(2-chloro-5-nitrophenyl)methylidene]-4,4-diethoxy-3-oxobutanoate Chemical compound CCOC(OCC)C(=O)C(C(=O)OCC)=CC1=CC([N+]([O-])=O)=CC=C1Cl KPSOXFYZXAGMPT-UHFFFAOYSA-N 0.000 description 1
MBOKFGZIDJQEBT-UHFFFAOYSA-N ethyl 2-methyl-4-(2-nitrophenyl)-5-oxo-4,7-dihydro-1h-furo[3,4-b]pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(COC2=O)=C2C1C1=CC=CC=C1[N+]([O-])=O MBOKFGZIDJQEBT-UHFFFAOYSA-N 0.000 description 1
KTVKUIDGFVUWET-UHFFFAOYSA-N ethyl 4,4-diethoxy-3-oxo-2-(thiophen-2-ylmethylidene)butanoate Chemical compound CCOC(OCC)C(=O)C(C(=O)OCC)=CC1=CC=CS1 KTVKUIDGFVUWET-UHFFFAOYSA-N 0.000 description 1
OZSLMVAWLCQORW-UHFFFAOYSA-N ethyl 4,4-diethoxy-3-oxo-2-[[2-(trifluoromethyl)phenyl]methylidene]butanoate Chemical compound CCOC(OCC)C(=O)C(C(=O)OCC)=CC1=CC=CC=C1C(F)(F)F OZSLMVAWLCQORW-UHFFFAOYSA-N 0.000 description 1
NERZGJMDVRLFHL-UHFFFAOYSA-N ethyl 4-(2-chlorophenyl)-2-methyl-5-oxo-4,7-dihydro-1h-furo[3,4-b]pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(COC2=O)=C2C1C1=CC=CC=C1Cl NERZGJMDVRLFHL-UHFFFAOYSA-N 0.000 description 1
SMIOKMXUCRPQPW-UHFFFAOYSA-N ethyl 4-(2-methoxyphenyl)-2-methyl-5-oxo-4,7-dihydro-1h-furo[3,4-b]pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(COC2=O)=C2C1C1=CC=CC=C1OC SMIOKMXUCRPQPW-UHFFFAOYSA-N 0.000 description 1
VEOZBFFLKPBVIY-UHFFFAOYSA-N ethyl 6-chloro-6-oxohexanoate Chemical compound CCOC(=O)CCCCC(Cl)=O VEOZBFFLKPBVIY-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical compound CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
235000013905 glycine and its sodium salt Nutrition 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
150000002366 halogen compounds Chemical class 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-O hydron;1,2-oxazole Chemical compound C=1C=[NH+]OC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-O 0.000 description 1
XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 description 1
239000000463 material Substances 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical group Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 1
WVMNFKZDPIPANH-UHFFFAOYSA-N methyl 2-[(2-chlorophenyl)methylidene]-4,4-dimethoxy-3-oxopentanoate Chemical compound COC(C)(OC)C(=O)C(C(=O)OC)=CC1=CC=CC=C1Cl WVMNFKZDPIPANH-UHFFFAOYSA-N 0.000 description 1
ZQFJOBUKEHFXKY-UHFFFAOYSA-N methyl 4,4-dimethoxy-3-oxopentanoate Chemical compound COC(=O)CC(=O)C(C)(OC)OC ZQFJOBUKEHFXKY-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
ODWNMLQSQNQLNP-UHFFFAOYSA-N n',n'-bis(methylamino)propane-1,3-diamine Chemical compound CNN(NC)CCCN ODWNMLQSQNQLNP-UHFFFAOYSA-N 0.000 description 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
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 1
229960001597 nifedipine Drugs 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
HLYVNXRHROOICH-UHFFFAOYSA-N o-propan-2-ylhydroxylamine Chemical compound CC(C)ON HLYVNXRHROOICH-UHFFFAOYSA-N 0.000 description 1
ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 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
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical group O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
229920000166 polytrimethylene carbonate Polymers 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
150000003138 primary alcohols Chemical group 0.000 description 1
ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
230000002000 scavenging effect Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
239000008279 sol Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
229940014800 succinic anhydride Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003459 sulfonic acid esters Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
125000005425 toluyl group Chemical group 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
229940005605 valeric acid Drugs 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)

CA256,210A 1975-07-02 1976-07-02 Derives de la 1,4-dihydropyridine; leur preparation et les produits pharmaceutiques qui en derivent Expired CA1080223A (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GB27945/75A GB1552911A (en)	1975-07-02	1975-07-02	1,4 dihydropyridine derivatives and the preparation thereof
GB3985475		1975-09-29
GB5152475		1975-12-16
GB1376176		1976-04-05
GB52720/76A GB1591089A (en)	1976-12-17	1976-12-17	1,4-dihydropyridine derivatives and process for preparation thereof

Publications (1)

Publication Number	Publication Date
CA1080223A true CA1080223A (fr)	1980-06-24

Family

ID=27516131

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA256,210A Expired CA1080223A (fr)	1975-07-02	1976-07-02	Derives de la 1,4-dihydropyridine; leur preparation et les produits pharmaceutiques qui en derivent

Country Status (1)

Country	Link
CA (1)	CA1080223A (fr)

1976
- 1976-07-02 CA CA256,210A patent/CA1080223A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1997-06-24	MKEX	Expiry

Publication	Publication Date	Title
US4145432A (en)	1979-03-20	6-acyloryalkyl-1,4-dihydropyridine derivatives and a method of effecting vasodilation therewith
US4338322A (en)	1982-07-06	1,4-Dihydropyridine derivatives, pharmaceutical compositions containing same and methods of effecting vasodilation using same
US4284634A (en)	1981-08-18	1,4-Dihydropyridine derivatives, and pharmaceutical method of the same
EP0088903A2 (fr)	1983-09-21	Dérivés d'esters de 1,4-dihydropyridine-3,5-diacides carboxyliques
IE921544A1 (en)	1992-11-18	New thiopyranopyrrole derivatives and their preparation
IE921543A1 (en)	1992-11-18	New thiopyranopyrrole derivatives, their preparation and¹pharmaceutical compositions containing them
HU184821B (en)	1984-10-29	Process for preparing new optically active derivatives of 1,4-dihydro-pyridine
CA2026386A1 (fr)	1991-04-03	Derives de 2-hydroxythiopene et -furan fusionne avec un anneau contenant de l'azote, procede de preparation et leur application en therapie
US4559351A (en)	1985-12-17	Dihydropyridine derivatives of 1,4:3,6-dianhydrohexitols
GB1591089A (en)	1981-06-10	1,4-dihydropyridine derivatives and process for preparation thereof
US4370334A (en)	1983-01-25	1,4-Dihydro-pyridine derivatives and methods of using same
PL173645B1 (pl)	1998-04-30	Sposób wytwarzania monobenzenosulfonianu (+) 2-[(2-aminoetoksy)metylo]-4-(2-chlorofenylo)-1,4-dihydro-6-metylopirydynodwukarboksylanu-3,5 3-etylowo-5-metylowego
KR880002704B1 (ko)	1988-12-26	1,4-디하이드로피리딘 화합물의 제조방법
GB2036722A (en)	1980-07-02	2-Methyl-dihydropyridines
US4450165A (en)	1984-05-22	Dihydropyridine compounds
US4556739A (en)	1985-12-03	3,4-Dialkoxy-2-alkylcarbonyl analino compounds
US4555570A (en)	1985-11-26	Substituted 4-alkyl-2-(1H) quinazolinone-1-alkanoic acid derivatives
CA1080223A (fr)	1980-06-24	Derives de la 1,4-dihydropyridine; leur preparation et les produits pharmaceutiques qui en derivent
US4616002A (en)	1986-10-07	Dihydro pyridine compounds, compositions and use
PL144351B1 (en)	1988-05-31	Method of obtaining new heterocyclic compounds
KR900004923B1 (ko)	1990-07-12	1,4-디히드로피리딘 유도체의 제조방법
EP0106276B1 (fr)	1988-10-26	Dérivés de 1,4-dihydropyridine
HK32395A (en)	1995-03-17	Substituted thiacycloalkeno [3,2-b] pyridines, methods of preparation, compositions and method of use
SE455701B (sv)	1988-08-01	Svavelhaltiga isokinolinderivat samt farmaceutiska beredningar innehalllande dem
US4525478A (en)	1985-06-25	Certain 4-aryl-1,4-dihydro-3,5-pyridinedicarboxylates having vasodilating and anti-hypertensive properties