DE3212882C2 - - Google Patents
Info
- Publication number
- DE3212882C2 DE3212882C2 DE3212882A DE3212882A DE3212882C2 DE 3212882 C2 DE3212882 C2 DE 3212882C2 DE 3212882 A DE3212882 A DE 3212882A DE 3212882 A DE3212882 A DE 3212882A DE 3212882 C2 DE3212882 C2 DE 3212882C2
- Authority
- DE
- Germany
- Prior art keywords
- carbonyl
- oxirane
- methyl
- butylcarbamoyl
- trans
- Prior art date
- 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 - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 claims description 51
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 42
- -1 2,3,4-trimethoxyphenylmethyl Chemical group 0.000 claims description 38
- OTGHWLKHGCENJV-UHFFFAOYSA-M oxirane-2-carboxylate Chemical compound [O-]C(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-M 0.000 claims description 24
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- OTGHWLKHGCENJV-UHFFFAOYSA-N glycidic acid Chemical compound OC(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-N 0.000 claims description 9
- 150000004885 piperazines Chemical class 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000003700 epoxy group Chemical group 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- RXSAQNDQVQSBLE-IHRRRGAJSA-N (2s,3s)-3-[[(2s)-4-methyl-1-oxo-1-(4-pyrimidin-2-ylpiperazin-1-yl)pentan-2-yl]carbamoyl]oxirane-2-carboxylic acid Chemical compound N([C@@H](CC(C)C)C(=O)N1CCN(CC1)C=1N=CC=CN=1)C(=O)[C@H]1O[C@@H]1C(O)=O RXSAQNDQVQSBLE-IHRRRGAJSA-N 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 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000000203 mixture Substances 0.000 description 36
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
- 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 28
- 239000011734 sodium Substances 0.000 description 28
- 229910052708 sodium Inorganic materials 0.000 description 28
- 239000002904 solvent Substances 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 22
- 235000019441 ethanol Nutrition 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000000126 substance Substances 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
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- 238000002360 preparation method 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000004821 distillation Methods 0.000 description 15
- 238000001914 filtration Methods 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 239000013078 crystal Substances 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 11
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- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 9
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
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- 238000000921 elemental analysis Methods 0.000 description 5
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- JJSRPMLZUUWVJC-YGICXTQQSA-M sodium;(2r,3r)-3-[[(2s)-1-(4-benzhydrylpiperazin-1-yl)-4-methyl-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylate Chemical compound [Na+].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 JJSRPMLZUUWVJC-YGICXTQQSA-M 0.000 description 5
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 5
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- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
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- UCQXHOZNZSIQIO-CDNPAEQRSA-N ethyl (2r,3r)-3-[[(2s)-4-methyl-1-oxo-1-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]pentan-2-yl]carbamoyl]oxirane-2-carboxylate Chemical compound CCOC(=O)[C@@H]1O[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1CCN(CC=2C(=C(OC)C(OC)=CC=2)OC)CC1 UCQXHOZNZSIQIO-CDNPAEQRSA-N 0.000 description 4
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- WGEIOMTZIIOUMA-UHFFFAOYSA-N 1-(3-phenylprop-2-enyl)piperazine Chemical compound C1CNCCN1CC=CC1=CC=CC=C1 WGEIOMTZIIOUMA-UHFFFAOYSA-N 0.000 description 2
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- 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
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- UHWVSEOVJBQKBE-UHFFFAOYSA-N Trimetazidine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 UHWVSEOVJBQKBE-UHFFFAOYSA-N 0.000 description 1
- VYFLPFGUVGMBEP-UHFFFAOYSA-N Trimetazidine hydrochloride Chemical compound Cl.Cl.COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 VYFLPFGUVGMBEP-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant 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
- 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
- VBICKXHEKHSIBG-UHFFFAOYSA-N beta-monoglyceryl stearate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
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- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
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- 210000000038 chest Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating 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
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 125000004185 ester group Chemical group 0.000 description 1
- RFLABOCLVWVMHD-SKBVVQJISA-N ethyl (2r,3r)-3-[[(2s)-1-(4-benzhydrylpiperazin-1-yl)-4-methyl-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylate Chemical compound CCOC(=O)[C@@H]1O[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RFLABOCLVWVMHD-SKBVVQJISA-N 0.000 description 1
- CMBFUJIOFDQSGW-CGTJXYLNSA-N ethyl (2r,3r)-3-[[(2s)-4-methyl-1-oxo-1-(4-pyridin-2-ylpiperazin-1-yl)pentan-2-yl]carbamoyl]oxirane-2-carboxylate Chemical compound CCOC(=O)[C@@H]1O[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1CCN(C=2N=CC=CC=2)CC1 CMBFUJIOFDQSGW-CGTJXYLNSA-N 0.000 description 1
- JVMZSMMQIXBCEQ-NMSOQDRXSA-N ethyl (2r,3r)-3-[[(2s)-4-methyl-1-oxo-1-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]pentan-2-yl]carbamoyl]oxirane-2-carboxylate;oxalic acid Chemical compound OC(=O)C(O)=O.CCOC(=O)[C@@H]1O[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1CCN(CC=2C(=C(OC)C(OC)=CC=2)OC)CC1 JVMZSMMQIXBCEQ-NMSOQDRXSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000945 filler 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
- 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
- 229940095990 inderal Drugs 0.000 description 1
- 230000000053 inderal effect Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
- 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
- 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
- 230000001338 necrotic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 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
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 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
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 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
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LJDSZVXDBHCRJF-AWEZNQCLSA-N tert-butyl n-[(2s)-1-(4-ethylpiperazin-1-yl)-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CCN1CCN(C(=O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)CC1 LJDSZVXDBHCRJF-AWEZNQCLSA-N 0.000 description 1
- CTWXIVRRMZXLDH-FQEVSTJZSA-N tert-butyl n-[(2s)-1-[4-[(4-methoxyphenyl)methyl]piperazin-1-yl]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CN1CCN(C(=O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)CC1 CTWXIVRRMZXLDH-FQEVSTJZSA-N 0.000 description 1
- VBKMWIFXRVLLAR-HNNXBMFYSA-N tert-butyl n-[(2s)-4-methyl-1-oxo-1-(4-pyrimidin-2-ylpiperazin-1-yl)pentan-2-yl]carbamate Chemical compound C1CN(C(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCN1C1=NC=CC=N1 VBKMWIFXRVLLAR-HNNXBMFYSA-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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-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
- 125000005270 trialkylamine group Chemical group 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
- 238000005303 weighing 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 (2)
| Publication Number | Publication Date |
|---|---|
| DE3212882A1 DE3212882A1 (de) | 1982-10-28 |
| DE3212882C2 true DE3212882C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-02-07 |
Family
ID=12933824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19823212882 Granted DE3212882A1 (de) | 1981-04-10 | 1982-04-06 | Piperazinderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
Country Status (17)
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 |
| CH650504A5 (de) | 1985-07-31 |
| GB2098204B (en) | 1984-08-15 |
| BR8202085A (pt) | 1983-03-22 |
| JPH0154349B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1989-11-17 |
| AU545938B2 (en) | 1985-08-08 |
| ES8402288A1 (es) | 1984-01-16 |
| FR2503709B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 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 |
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