NL8501046A - Farmaceutisch bruikbare dihydropyridinyldicarboxylaatamiden en esters. - Google Patents
Farmaceutisch bruikbare dihydropyridinyldicarboxylaatamiden en esters. Download PDFInfo
- Publication number
- NL8501046A NL8501046A NL8501046A NL8501046A NL8501046A NL 8501046 A NL8501046 A NL 8501046A NL 8501046 A NL8501046 A NL 8501046A NL 8501046 A NL8501046 A NL 8501046A NL 8501046 A NL8501046 A NL 8501046A
- Authority
- NL
- Netherlands
- Prior art keywords
- nitrophenyl
- piperazinyl
- dihydro
- dimethyl
- pyridinedicarboxylate
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 116
- -1 methylthiopyridyl Chemical group 0.000 claims description 85
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 8
- 239000005695 Ammonium acetate Substances 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 235000019257 ammonium acetate Nutrition 0.000 claims description 8
- 229940043376 ammonium acetate Drugs 0.000 claims description 8
- 230000003276 anti-hypertensive effect Effects 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 230000006870 function Effects 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 7
- 231100000252 nontoxic Toxicity 0.000 claims description 7
- 230000003000 nontoxic effect Effects 0.000 claims description 7
- 230000002253 anti-ischaemic effect Effects 0.000 claims description 6
- 238000009833 condensation Methods 0.000 claims description 6
- 230000005494 condensation Effects 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 230000024883 vasodilation Effects 0.000 claims description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 4
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 125000005518 carboxamido group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- QWEDYSHJZDVMLN-UHFFFAOYSA-N methyl 5-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propylcarbamoyl]-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)NCCCN2CCN(CC2)C=2C(=CC=CC=2)OC)C1C1=CC=CC([N+]([O-])=O)=C1 QWEDYSHJZDVMLN-UHFFFAOYSA-N 0.000 claims description 2
- 230000000304 vasodilatating effect Effects 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 17
- JPXPPUOCSLMCHK-UHFFFAOYSA-N 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 JPXPPUOCSLMCHK-UHFFFAOYSA-N 0.000 claims 3
- TZDPJNSHSWMCPN-UHFFFAOYSA-N 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 TZDPJNSHSWMCPN-UHFFFAOYSA-N 0.000 claims 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- ODODPKXHESNLMH-UHFFFAOYSA-N 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid;hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 ODODPKXHESNLMH-UHFFFAOYSA-N 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- HXDABULQCJTJHX-UHFFFAOYSA-N bis[3-[4-(2-methylphenyl)piperazin-1-yl]propyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCCN2CCN(CC2)C=2C(=CC=CC=2)C)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1C(=O)OCCCN(CC1)CCN1C1=CC=CC=C1C HXDABULQCJTJHX-UHFFFAOYSA-N 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 2
- OWEATIMWNOHHRL-UHFFFAOYSA-N 2,6-dimethyl-1-(3-nitrophenyl)-4h-pyridine-3,5-dicarboxylic acid Chemical compound CC1=C(C(O)=O)CC(C(O)=O)=C(C)N1C1=CC=CC([N+]([O-])=O)=C1 OWEATIMWNOHHRL-UHFFFAOYSA-N 0.000 claims 1
- NIKAJNOLEDWFSF-UHFFFAOYSA-N 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 NIKAJNOLEDWFSF-UHFFFAOYSA-N 0.000 claims 1
- KHNYCCBJPNXREL-UHFFFAOYSA-N 3-O-methyl 5-O-[3-[4-(2-methylphenyl)piperazin-1-yl]propyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCCN2CCN(CC2)C=2C(=CC=CC=2)C)C1C1=CC=CC([N+]([O-])=O)=C1 KHNYCCBJPNXREL-UHFFFAOYSA-N 0.000 claims 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- CARPRGVALGIIMO-UHFFFAOYSA-N Cl.CC=1NC(=C(C(C1C(=O)O)C1=CC(=CC=C1)[N+](=O)[O-])C(=O)O)C.Cl.Cl Chemical compound Cl.CC=1NC(=C(C(C1C(=O)O)C1=CC(=CC=C1)[N+](=O)[O-])C(=O)O)C.Cl.Cl CARPRGVALGIIMO-UHFFFAOYSA-N 0.000 claims 1
- 101100260565 Dictyostelium discoideum thyA gene Proteins 0.000 claims 1
- 206010047141 Vasodilatation Diseases 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- YADZPUAUOJITJG-UHFFFAOYSA-N bis[2-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethoxy]ethyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC1=CC=CC=C1N1CCN(CCOCCOC(=O)C=2C(C(=C(C)NC=2C)C(=O)OCCOCCN2CCN(CC2)C=2C(=CC=CC=2)OC)C=2C=C(C=CC=2)[N+]([O-])=O)CC1 YADZPUAUOJITJG-UHFFFAOYSA-N 0.000 claims 1
- VLOLGQQBGULNFN-UHFFFAOYSA-N bis[3-(4-pyrimidin-2-ylpiperazin-1-yl)propyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCCN2CCN(CC2)C=2N=CC=CN=2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1C(=O)OCCCN(CC1)CCN1C1=NC=CC=N1 VLOLGQQBGULNFN-UHFFFAOYSA-N 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- MPFLRYZEEAQMLQ-UHFFFAOYSA-N dinicotinic acid Chemical compound OC(=O)C1=CN=CC(C(O)=O)=C1 MPFLRYZEEAQMLQ-UHFFFAOYSA-N 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
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- 239000000543 intermediate Substances 0.000 description 33
- 239000000047 product Substances 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 16
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- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 10
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- 238000004458 analytical method Methods 0.000 description 9
- 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 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
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- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 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
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 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
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- YODZTKMDCQEPHD-UHFFFAOYSA-N thiodiglycol Chemical compound OCCSCCO YODZTKMDCQEPHD-UHFFFAOYSA-N 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 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
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59909784A | 1984-04-11 | 1984-04-11 | |
| US59909784 | 1984-04-11 | ||
| US06/693,426 US4755512A (en) | 1984-04-11 | 1985-01-22 | Pharmaceutically useful dihydropyridinyldicarboxylate amides and esters incorporating arylpiperazinylalkyl moities |
| US69342685 | 1985-01-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8501046A true NL8501046A (nl) | 1985-11-01 |
Family
ID=27083238
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8501046A NL8501046A (nl) | 1984-04-11 | 1985-04-10 | Farmaceutisch bruikbare dihydropyridinyldicarboxylaatamiden en esters. |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4755512A (ko) |
| JP (1) | JPS6117562A (ko) |
| KR (1) | KR920005742B1 (ko) |
| AU (1) | AU587182B2 (ko) |
| BE (1) | BE902154A (ko) |
| CA (1) | CA1320204C (ko) |
| CH (1) | CH664757A5 (ko) |
| DE (1) | DE3512995A1 (ko) |
| DK (1) | DK164594C (ko) |
| ES (2) | ES8607283A1 (ko) |
| FI (1) | FI84063C (ko) |
| FR (1) | FR2562892B1 (ko) |
| GB (1) | GB2158065B (ko) |
| GR (1) | GR850924B (ko) |
| IE (1) | IE58410B1 (ko) |
| IT (1) | IT1206730B (ko) |
| LU (1) | LU85847A1 (ko) |
| NL (1) | NL8501046A (ko) |
| PT (1) | PT80272B (ko) |
| SE (1) | SE465220B (ko) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3377352D1 (en) * | 1982-06-03 | 1988-08-18 | Pierrel Spa | Dihydropyridines with an antagonistic activity to calcium, process for their preparation, and pharmaceutical compositions containing them |
| EP0145956A1 (de) * | 1983-11-16 | 1985-06-26 | Ciba-Geigy Ag | Neue Amid-Verbindungen |
| NZ220022A (en) * | 1986-04-22 | 1990-04-26 | Byk Gulden Lomberg Chem Fab | 1,4-dihydropyridine derivatives and pharmaceutical compositions |
| 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 |
| JPH0725750B2 (ja) * | 1987-12-18 | 1995-03-22 | 富士レビオ株式会社 | １，４‐ジヒドロピリジン誘導体 |
| JPH02149563A (ja) * | 1988-11-30 | 1990-06-08 | Nisshin Flour Milling Co Ltd | ２−ハロエトキシカルボニル基を含有する１，４−ジヒドロピリジン誘導体の製造法 |
| US5286869A (en) * | 1988-12-15 | 1994-02-15 | Fujirebio Kabushiki Kaisha | 1,4-dihydropyridine derivatives |
| WO1990009377A1 (en) * | 1989-02-17 | 1990-08-23 | Institut Organicheskogo Sinteza Akademii Nauk Latviiskoi Ssr | Alcaline salts of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido) ethane sulphonic acid and method of obtaining them |
| WO1991009847A1 (fr) * | 1989-12-29 | 1991-07-11 | Kaken Pharmaceutical Co., Ltd. | Derive d'ethynylphenyle, production de ce derive et medicament de traitement des maladies des organes du systeme circulatoire contenant ce derive comme ingredient actif |
| CA2069877A1 (en) * | 1990-10-02 | 1992-04-03 | Michio Nakanishi | Ethynylphenyl derivative substituted by pyridazinone and medicament for circulatory disease containing the same as an effective ingredient |
| WO1993009774A1 (en) * | 1991-11-18 | 1993-05-27 | G.D. Searle & Co. | 2-(4-substituted)phenylmethylene derivatives and methods of use |
| US6211198B1 (en) | 1993-04-05 | 2001-04-03 | Synaptic Pharmaceutical Corporation | Dihydropyridines and new uses thereof |
| US5767131A (en) * | 1993-04-05 | 1998-06-16 | Synaptic Pharmaceutical Corporation | Dihydropyridines and new uses thereof |
| IL109220A0 (en) * | 1993-04-05 | 1994-07-31 | Synaptic Pharma Corp | Dihydropyridines and new uses thereof |
| US5700801A (en) * | 1994-12-23 | 1997-12-23 | Karl Thomae, Gmbh | Piperazine derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| US5635503A (en) * | 1995-06-07 | 1997-06-03 | Bristol-Myers Squibb Company | Dihydropyridine npy antagonists: piperazine derivatives |
| WO1997028152A1 (fr) * | 1996-01-29 | 1997-08-07 | Nikken Chemicals Co., Ltd. | Composes de dihydropyridine et composition medicinale les comprenant |
| US6566359B1 (en) | 2002-05-20 | 2003-05-20 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | 2,4,6-trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid esters as neuroprotective drugs |
| CN101215258A (zh) * | 2008-01-21 | 2008-07-09 | 中国药科大学 | 二氢吡啶类钙拮抗剂化合物及其制备方法与医药用途 |
| CN102557957A (zh) * | 2010-12-20 | 2012-07-11 | 四川科伦药物研究有限公司 | 一种2-(3-硝基苯亚甲基)乙酰乙酸异丙酯的制备方法 |
| CN102491902A (zh) * | 2011-11-30 | 2012-06-13 | 青岛黄海制药有限责任公司 | 一种2-(3-硝基亚苄基)乙酰乙酸异丙酯的制备方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670827C3 (de) * | 1967-03-20 | 1974-10-24 | Bayer Ag, 5090 Leverkusen | 4-(2'-Nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridin |
| GB1345449A (en) * | 1971-05-14 | 1974-01-30 | Science Union & Cie | Pyridylpiperazines and process for their preparation |
| US3974275A (en) * | 1972-04-18 | 1976-08-10 | Bayer Aktiengesellschaft | 1,4-Dihydropyridine carboxylic acid esters useful as coronary vessel dilators and anti-hypertensives |
| US3996234A (en) * | 1972-04-18 | 1976-12-07 | Bayer Aktiengesellschaft | 1,4-Dihydropyridine carboxylic acid esters |
| DE2218644C3 (de) * | 1972-04-18 | 1982-08-19 | Bayer Ag, 5090 Leverkusen | Basische Ester von 1,4-Dihydropyridinen, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel |
| US4307103A (en) * | 1978-09-08 | 1981-12-22 | Fujisawa Pharmaceutical Co., Ltd. | Dihydropyridine derivative, processes for preparation thereof and pharmaceutical composition comprising the same |
| CS228917B2 (en) * | 1981-03-14 | 1984-05-14 | Pfizer | Method of preparing substituted derivatives of 1,4-dihydropyridine |
| JPS57171968A (en) * | 1981-04-17 | 1982-10-22 | Kyowa Hakko Kogyo Co Ltd | 1,4-dihydropyridine derivative |
| WO1983003249A1 (en) * | 1982-03-17 | 1983-09-29 | Yoshitomi Pharmaceutical | 1,4-dihydropyridine-3,5-dicarboxylate derivatives |
| JPS58201765A (ja) * | 1982-05-10 | 1983-11-24 | Takeda Chem Ind Ltd | ジヒドロピリジン誘導体，その製造法および用途 |
| EP0094159B1 (en) * | 1982-05-10 | 1990-03-14 | Takeda Chemical Industries, Ltd. | Dihydropyridine derivatives, their production and use |
| DE3377352D1 (en) * | 1982-06-03 | 1988-08-18 | Pierrel Spa | Dihydropyridines with an antagonistic activity to calcium, process for their preparation, and pharmaceutical compositions containing them |
| IT1198377B (it) * | 1982-06-03 | 1988-12-21 | Pierrel Spa | Esteri basici ad attivita' calcioanatagonista,procedimenti per la loro preparazione e relative composizioni farmaceutiche |
| WO1985000169A1 (en) * | 1983-06-21 | 1985-01-17 | Sandoz Ag | 1,4-dihydropyridine derivatives, production thereof and pharmaceutical preparations containing them |
-
1985
- 1985-01-22 US US06/693,426 patent/US4755512A/en not_active Expired - Fee Related
- 1985-04-09 KR KR1019850002382A patent/KR920005742B1/ko not_active IP Right Cessation
- 1985-04-09 FI FI851404A patent/FI84063C/fi not_active IP Right Cessation
- 1985-04-09 IT IT8520276A patent/IT1206730B/it active
- 1985-04-09 CA CA000478537A patent/CA1320204C/en not_active Expired - Fee Related
- 1985-04-09 AU AU40949/85A patent/AU587182B2/en not_active Ceased
- 1985-04-10 SE SE8501767A patent/SE465220B/sv not_active IP Right Cessation
- 1985-04-10 NL NL8501046A patent/NL8501046A/nl not_active Application Discontinuation
- 1985-04-10 IE IE89885A patent/IE58410B1/en not_active IP Right Cessation
- 1985-04-10 LU LU85847A patent/LU85847A1/fr unknown
- 1985-04-10 DK DK162485A patent/DK164594C/da not_active IP Right Cessation
- 1985-04-10 BE BE0/214816A patent/BE902154A/fr not_active IP Right Cessation
- 1985-04-10 ES ES542120A patent/ES8607283A1/es not_active Expired
- 1985-04-10 GR GR850924A patent/GR850924B/el unknown
- 1985-04-11 JP JP60077517A patent/JPS6117562A/ja active Granted
- 1985-04-11 DE DE19853512995 patent/DE3512995A1/de not_active Ceased
- 1985-04-11 FR FR858505475A patent/FR2562892B1/fr not_active Expired
- 1985-04-11 PT PT80272A patent/PT80272B/pt not_active IP Right Cessation
- 1985-04-11 CH CH1556/85A patent/CH664757A5/de not_active IP Right Cessation
- 1985-04-11 GB GB08509250A patent/GB2158065B/en not_active Expired
-
1986
- 1986-02-01 ES ES551564A patent/ES8800928A1/es not_active Expired
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