CH650504A5 - Piperazinderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel. - Google Patents
Piperazinderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel. Download PDFInfo
- Publication number
- CH650504A5 CH650504A5 CH2213/82A CH221382A CH650504A5 CH 650504 A5 CH650504 A5 CH 650504A5 CH 2213/82 A CH2213/82 A CH 2213/82A CH 221382 A CH221382 A CH 221382A CH 650504 A5 CH650504 A5 CH 650504A5
- Authority
- CH
- Switzerland
- Prior art keywords
- compound
- carbonyl
- chain
- methyl
- oxirane
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 16
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 3
- 229940126601 medicinal product Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 58
- -1 2,3,4-trimethoxyphenylmethyl Chemical group 0.000 claims description 43
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 39
- OTGHWLKHGCENJV-UHFFFAOYSA-M oxirane-2-carboxylate Chemical compound [O-]C(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-M 0.000 claims description 34
- 238000002360 preparation method Methods 0.000 claims description 26
- 208000010125 myocardial infarction Diseases 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- OTGHWLKHGCENJV-UHFFFAOYSA-N glycidic acid Chemical compound OC(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 150000004885 piperazines Chemical class 0.000 claims description 12
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 5
- 125000003700 epoxy group Chemical group 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 82
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- 201000002674 obstructive nephropathy Diseases 0.000 description 66
- 125000003118 aryl group Chemical group 0.000 description 55
- 239000000203 mixture Substances 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 32
- 230000002829 reductive effect Effects 0.000 description 32
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 description 30
- 239000011734 sodium Substances 0.000 description 30
- 229910052708 sodium Inorganic materials 0.000 description 30
- 239000002904 solvent Substances 0.000 description 27
- 238000001816 cooling Methods 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 235000019441 ethanol Nutrition 0.000 description 23
- 239000000126 substance Substances 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 20
- 238000001914 filtration Methods 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000843 powder Substances 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 229910001868 water Inorganic materials 0.000 description 15
- 239000013078 crystal Substances 0.000 description 13
- 238000004821 distillation Methods 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 239000011345 viscous material Substances 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 229940088679 drug related substance Drugs 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000002198 insoluble material Substances 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- URQQEIOTRWJXBA-QRPNPIFTSA-N (2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid;hydrate Chemical compound O.CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C URQQEIOTRWJXBA-QRPNPIFTSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- DCEMCPAKSGRHCN-UHFFFAOYSA-N Epoxy-bernsteinsaeure Natural products OC(=O)C1OC1C(O)=O DCEMCPAKSGRHCN-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000013583 drug formulation Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- DCEMCPAKSGRHCN-JCYAYHJZSA-N trans-2,3-epoxysuccinic acid Chemical compound OC(=O)[C@@H]1O[C@H]1C(O)=O DCEMCPAKSGRHCN-JCYAYHJZSA-N 0.000 description 3
- JZQCTDNJDYIILV-JYJNAYRXSA-N (2S,3S)-3-ethyl-N-[(2S)-4-methyl-1-oxo-1-(4-pyrimidin-2-ylpiperazin-1-yl)pentan-2-yl]oxirane-2-carboxamide Chemical compound C(C)[C@@H]1O[C@@H]1C(N[C@@H](CC(C)C)C(=O)N1CCN(CC1)C1=NC=CC=N1)=O JZQCTDNJDYIILV-JYJNAYRXSA-N 0.000 description 2
- NDJVZFIVKIMJOF-ZDUSSCGKSA-N (2s)-2-amino-4-methyl-1-(4-pyridin-2-ylpiperazin-1-yl)pentan-1-one Chemical compound C1CN(C(=O)[C@@H](N)CC(C)C)CCN1C1=CC=CC=N1 NDJVZFIVKIMJOF-ZDUSSCGKSA-N 0.000 description 2
- 102100028138 F-box/WD repeat-containing protein 7 Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101001060231 Homo sapiens F-box/WD repeat-containing protein 7 Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 150000002148 esters Chemical group 0.000 description 2
- 239000007941 film coated tablet Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 229940095990 inderal Drugs 0.000 description 2
- 230000000053 inderal effect Effects 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- GQEPIMWWXJXAJG-DEOSSOPVSA-N tert-butyl n-[(2s)-1-(4-benzhydrylpiperazin-1-yl)-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1CN(C(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 GQEPIMWWXJXAJG-DEOSSOPVSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- JZQCTDNJDYIILV-ARFHVFGLSA-N (2R,3R)-3-ethyl-N-[(2S)-4-methyl-1-oxo-1-(4-pyrimidin-2-ylpiperazin-1-yl)pentan-2-yl]oxirane-2-carboxamide Chemical compound C(C)[C@H]1O[C@H]1C(N[C@@H](CC(C)C)C(=O)N1CCN(CC1)C1=NC=CC=N1)=O JZQCTDNJDYIILV-ARFHVFGLSA-N 0.000 description 1
- MECQEAQQQIVNBD-QPTUXGOLSA-N (2r,3r)-3-[[(2s)-1-(4-benzhydrylpiperazin-1-yl)-4-methyl-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid Chemical compound N([C@@H](CC(C)C)C(=O)N1CCN(CC1)C(C=1C=CC=CC=1)C=1C=CC=CC=1)C(=O)[C@@H]1O[C@H]1C(O)=O MECQEAQQQIVNBD-QPTUXGOLSA-N 0.000 description 1
- SIVITQWHOQLZMG-XUVXKRRUSA-N (2r,3r)-3-[[(2s)-4-methyl-1-oxo-1-[4-(3-phenylprop-2-enyl)piperazin-1-yl]pentan-2-yl]carbamoyl]oxirane-2-carboxylic acid Chemical compound N([C@@H](CC(C)C)C(=O)N1CCN(CC=CC=2C=CC=CC=2)CC1)C(=O)[C@@H]1O[C@H]1C(O)=O SIVITQWHOQLZMG-XUVXKRRUSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 1
- WGEIOMTZIIOUMA-QPJJXVBHSA-N 1-[(e)-3-phenylprop-2-enyl]piperazine Chemical compound C1CNCCN1C\C=C\C1=CC=CC=C1 WGEIOMTZIIOUMA-QPJJXVBHSA-N 0.000 description 1
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 description 1
- OLCIOXGQTLVZQT-UHFFFAOYSA-N 3-methylbutyl carbamate Chemical class CC(C)CCOC(N)=O OLCIOXGQTLVZQT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 101150046236 CNR1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 101001077374 Oryza sativa subsp. japonica UMP-CMP kinase 3 Proteins 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 102000009097 Phosphorylases Human genes 0.000 description 1
- 108010073135 Phosphorylases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- UHWVSEOVJBQKBE-UHFFFAOYSA-N Trimetazidine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 UHWVSEOVJBQKBE-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- SKKTUOZKZKCGTB-UHFFFAOYSA-N butyl carbamate Chemical compound CCCCOC(N)=O SKKTUOZKZKCGTB-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- LDFQMMUIJQDSAB-PHDIDXHHSA-N diethyl (2r,3r)-oxirane-2,3-dicarboxylate Chemical compound CCOC(=O)[C@@H]1O[C@H]1C(=O)OCC LDFQMMUIJQDSAB-PHDIDXHHSA-N 0.000 description 1
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 229940041476 lactose 100 mg Drugs 0.000 description 1
- 150000002613 leucine derivatives Chemical class 0.000 description 1
- 125000001998 leucyl group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- ORUIBWPALBXDOA-UHFFFAOYSA-L magnesium fluoride Chemical compound [F-].[F-].[Mg+2] ORUIBWPALBXDOA-UHFFFAOYSA-L 0.000 description 1
- 159000000003 magnesium salts Chemical class 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
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 229960004604 propranolol hydrochloride Drugs 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HAUJVFZPKVRLGM-QQBJDQAASA-M sodium;(2r,3r)-3-[[(2s)-1-(4-benzylpiperazin-1-yl)-4-methyl-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylate Chemical compound [Na+].N([C@@H](CC(C)C)C(=O)N1CCN(CC=2C=CC=CC=2)CC1)C(=O)[C@@H]1O[C@H]1C([O-])=O HAUJVFZPKVRLGM-QQBJDQAASA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- HQYUPYGIZOGJKN-IBGZPJMESA-N tert-butyl n-[(2s)-1-(4-benzylpiperazin-1-yl)-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1CN(C(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCN1CC1=CC=CC=C1 HQYUPYGIZOGJKN-IBGZPJMESA-N 0.000 description 1
- NHZKOJZSSMUILV-NRFANRHFSA-N tert-butyl n-[(2s)-4-methyl-1-oxo-1-[4-(3-phenylprop-2-enyl)piperazin-1-yl]pentan-2-yl]carbamate Chemical compound C1CN(C(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCN1CC=CC1=CC=CC=C1 NHZKOJZSSMUILV-NRFANRHFSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229960001177 trimetazidine Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/48—Compounds containing oxirane rings 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, e.g. ester or nitrile radicals
-
- 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
-
- 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
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56053116A JPS57169478A (en) | 1981-04-10 | 1981-04-10 | Piperazine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH650504A5 true CH650504A5 (de) | 1985-07-31 |
Family
ID=12933824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH2213/82A CH650504A5 (de) | 1981-04-10 | 1982-04-08 | Piperazinderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel. |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US4507297A (en, 2012) |
| JP (1) | JPS57169478A (en, 2012) |
| KR (1) | KR880000786B1 (en, 2012) |
| AU (1) | AU545938B2 (en, 2012) |
| BR (1) | BR8202085A (en, 2012) |
| CA (1) | CA1166637A (en, 2012) |
| CH (1) | CH650504A5 (en, 2012) |
| DD (1) | DD202567A5 (en, 2012) |
| DE (1) | DE3212882A1 (en, 2012) |
| ES (2) | ES8402288A1 (en, 2012) |
| FR (1) | FR2503709A1 (en, 2012) |
| GB (1) | GB2098204B (en, 2012) |
| HU (1) | HU189574B (en, 2012) |
| IT (1) | IT1156459B (en, 2012) |
| MX (1) | MX7583E (en, 2012) |
| NL (1) | NL191690C (en, 2012) |
| SU (1) | SU1318161A3 (en, 2012) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6087277A (ja) * | 1983-10-19 | 1985-05-16 | Taisho Pharmaceut Co Ltd | 光学活性トランス−エポキシコハク酸ジアルキルエステルの製造法 |
| FR2680508B1 (fr) * | 1991-08-20 | 1995-03-03 | Adir | Nouveaux composes amidiques des 1-(alcoxybenzyl)piperazines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| ES2062943B1 (es) * | 1993-03-23 | 1995-11-16 | Uriach & Cia Sa J | Nuevos derivados de la (2-metil-3-piridil) cianometilpiperazinas. |
| US5556853A (en) * | 1993-10-29 | 1996-09-17 | Takeda Chemical Industries, Ltd. | Epoxysuccinic acid derivatives |
| WO1997003060A1 (fr) * | 1995-07-13 | 1997-01-30 | Senju Pharmaceutical Co., Ltd. | Derives de la piperazine et leurs utilisations |
| US5733911A (en) * | 1996-01-26 | 1998-03-31 | Hitachi Chemical Co., Ltd. | Method for inducing death of neoplastic cells using piperazne derivatives |
| PT1022276E (pt) * | 1997-09-04 | 2003-10-31 | Nippon Chemiphar Co | Derivados de epoxissuccinamida |
| WO1999055688A1 (en) * | 1998-04-27 | 1999-11-04 | Warner-Lambert Company | Substituted diarylalkyl amides as calcium channel antagonists |
| RU2260431C2 (ru) * | 2003-12-15 | 2005-09-20 | Закрытое акционерное общество "Фармацевтическое предприятие "Оболенское" | Лекарственная форма, обладающая антиангинальным действием, и способ ее изготовления |
| RU2281772C1 (ru) * | 2005-02-14 | 2006-08-20 | Закрытое акционерное общество "Фармацевтическое предприятие "Оболенское" | Лекарственная форма, обладающая антиангинальным действием, и способ ее изготовления |
| US20090221603A1 (en) * | 2005-12-19 | 2009-09-03 | Hassan Pajouhesh | Heterocyclic amide derivatives as calcium channel blockers |
| EP2029135A4 (en) * | 2006-06-13 | 2011-08-17 | Univ Leland Stanford Junior | Epoxide inhibitors of cysteine proteases |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2963482A (en) * | 1957-09-09 | 1960-12-06 | Lilly Co Eli | Bis-epoxypropyldiamines |
| US2963483A (en) * | 1958-12-22 | 1960-12-06 | Union Carbide Corp | Nu-glycidylpiperazine and method of making it |
| US4032567A (en) * | 1972-02-16 | 1977-06-28 | Schering Aktiengesellschaft | Triiodoisophthalic acid monoamino acid amides, process for the preparation thereof, and use thereof as x-ray contrast media |
| GB1595168A (en) * | 1977-03-03 | 1981-08-12 | Taisho Pharmaceutical Co Ltd | Expoxysuccinic acid derivatives |
| JPS5547668A (en) * | 1978-09-30 | 1980-04-04 | Taisho Pharmaceut Co Ltd | Epoxysuccinamic acid |
| JPS55115878A (en) * | 1979-02-27 | 1980-09-06 | Taisho Pharmaceut Co Ltd | Epoxysuccinic acid derivative |
| JPS55153778A (en) * | 1979-05-17 | 1980-11-29 | Taisho Pharmaceut Co Ltd | Epoxysuccinylamino acid derivative |
| JPS58126879A (ja) * | 1982-01-25 | 1983-07-28 | Nippon Chemiphar Co Ltd | 光学活性なピペラジン誘導体ならびに心筋梗塞の予防および治療剤 |
-
1981
- 1981-04-10 JP JP56053116A patent/JPS57169478A/ja active Granted
-
1982
- 1982-03-25 US US06/361,506 patent/US4507297A/en not_active Expired - Lifetime
- 1982-04-01 AU AU82271/82A patent/AU545938B2/en not_active Ceased
- 1982-04-05 ES ES511174A patent/ES8402288A1/es not_active Expired
- 1982-04-06 DE DE19823212882 patent/DE3212882A1/de active Granted
- 1982-04-07 BR BR8202085A patent/BR8202085A/pt unknown
- 1982-04-07 MX MX82101934U patent/MX7583E/es unknown
- 1982-04-08 NL NL8201509A patent/NL191690C/xx not_active IP Right Cessation
- 1982-04-08 CH CH2213/82A patent/CH650504A5/de not_active IP Right Cessation
- 1982-04-08 CA CA000400711A patent/CA1166637A/en not_active Expired
- 1982-04-08 HU HU821081A patent/HU189574B/hu not_active IP Right Cessation
- 1982-04-08 GB GB8210562A patent/GB2098204B/en not_active Expired
- 1982-04-08 DD DD82238868A patent/DD202567A5/de not_active IP Right Cessation
- 1982-04-09 SU SU823419752A patent/SU1318161A3/ru active
- 1982-04-09 IT IT67485/82A patent/IT1156459B/it active
- 1982-04-09 FR FR8206239A patent/FR2503709A1/fr active Granted
- 1982-04-10 KR KR8201589A patent/KR880000786B1/ko not_active Expired
-
1983
- 1983-08-30 ES ES525245A patent/ES525245A0/es active Granted
-
1984
- 1984-03-08 US US06/587,545 patent/US4596803A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| NL8201509A (nl) | 1982-11-01 |
| ES8506304A1 (es) | 1985-07-16 |
| ES511174A0 (es) | 1984-01-16 |
| US4596803A (en) | 1986-06-24 |
| DE3212882A1 (de) | 1982-10-28 |
| US4507297A (en) | 1985-03-26 |
| IT1156459B (it) | 1987-02-04 |
| AU8227182A (en) | 1982-10-14 |
| NL191690B (nl) | 1995-11-01 |
| FR2503709A1 (fr) | 1982-10-15 |
| GB2098204B (en) | 1984-08-15 |
| BR8202085A (pt) | 1983-03-22 |
| JPH0154349B2 (en, 2012) | 1989-11-17 |
| AU545938B2 (en) | 1985-08-08 |
| DE3212882C2 (en, 2012) | 1991-02-07 |
| ES8402288A1 (es) | 1984-01-16 |
| FR2503709B1 (en, 2012) | 1985-03-22 |
| NL191690C (nl) | 1996-03-04 |
| ES525245A0 (es) | 1985-07-16 |
| HU189574B (en) | 1986-07-28 |
| GB2098204A (en) | 1982-11-17 |
| CA1166637A (en) | 1984-05-01 |
| IT8267485A0 (it) | 1982-04-09 |
| JPS57169478A (en) | 1982-10-19 |
| DD202567A5 (de) | 1983-09-21 |
| KR880000786B1 (ko) | 1988-05-09 |
| KR830010106A (ko) | 1983-12-26 |
| SU1318161A3 (ru) | 1987-06-15 |
| MX7583E (es) | 1989-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69317992T2 (de) | Aminoketonderivate | |
| EP0153277B1 (de) | Neue Pleuromutilinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung | |
| DE3005164A1 (de) | Antibiotisch wirksame beta -lactamverbindungen, verfahren zu deren herstellung und sie enthaltendes arzneimittel | |
| DE69104615T2 (de) | Diphenylpiperazinderivat. | |
| CH650504A5 (de) | Piperazinderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel. | |
| DE2846251C2 (en, 2012) | ||
| EP0217372B1 (de) | Neue polyoxygenierte Labdan-Derivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Medikamente | |
| DE2311131C3 (de) | Amidinopenicillansäureester, Verfahren zu deren Herstellung und pharmazeutische Mittel | |
| DE68910211T2 (de) | Estramustin-ester. | |
| DE3017684C2 (en, 2012) | ||
| DE2941288C2 (en, 2012) | ||
| US4933354A (en) | 2-pyrrolidone-5-carboxylic acid compounds useful for the treatment of mental disorders | |
| DE2653635C2 (de) | α-Aminoketonderivate, deren Herstellung und pharmazeutische Zusammensetzungen auf deren Basis | |
| DE1811518B2 (de) | Daunorubicinderivale, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen | |
| DE3139554C2 (en, 2012) | ||
| DE2413125C2 (de) | Indolylacetylaminosäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneipräparate | |
| DE2336671A1 (de) | Oxyessigsaeureaether von o-thymotinsaeureestern | |
| DD253616A5 (de) | Verfahren zur herstellung von neuen pleunromutilinderivaten | |
| DE3116250C2 (en, 2012) | ||
| DE2029510C3 (de) | Dibenzofuranderivate und deren pharmazeutisch verträgliche Säureadditionssalze sowie Verfahren zu deren Herstellung und Arzneimittel mit einem Gehalt dieser Verbindungen | |
| DE2513136B2 (de) | N-(I -Benzylpiperid-4-yl)-benzamide, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Präparate | |
| DE2725695A1 (de) | Arzneipraeparate fuer eine orale verabreichung | |
| EP0007347B1 (de) | Lipidsenkende Alkylenglykolderivate und Verfahren zu ihrer Herstellung | |
| DE1926754A1 (de) | Neue cyclische Verbindungen,ihre Herstellung und Verwendung | |
| DE3046017C2 (de) | Indolizin-Derivate, Verfahren zu deren Herstellung und pharmazeutische Zusammensetzung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |