JP4138489B2 - 脂肪酸の酸化防止剤としてのヘテロアリールアルキルピペラジン誘導体 - Google Patents
脂肪酸の酸化防止剤としてのヘテロアリールアルキルピペラジン誘導体 Download PDFInfo
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- JP4138489B2 JP4138489B2 JP2002564509A JP2002564509A JP4138489B2 JP 4138489 B2 JP4138489 B2 JP 4138489B2 JP 2002564509 A JP2002564509 A JP 2002564509A JP 2002564509 A JP2002564509 A JP 2002564509A JP 4138489 B2 JP4138489 B2 JP 4138489B2
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- 235000014113 dietary fatty acids Nutrition 0.000 title description 4
- 239000000194 fatty acid Substances 0.000 title description 4
- 229930195729 fatty acid Natural products 0.000 title description 4
- 150000004665 fatty acids Chemical class 0.000 title description 4
- 239000003963 antioxidant agent Substances 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 311
- 125000003118 aryl group Chemical group 0.000 claims description 222
- 150000001875 compounds Chemical class 0.000 claims description 217
- -1 piperazine compound Chemical class 0.000 claims description 180
- 229910052739 hydrogen Inorganic materials 0.000 claims description 166
- 239000001257 hydrogen Substances 0.000 claims description 143
- 125000005843 halogen group Chemical group 0.000 claims description 136
- 125000001424 substituent group Chemical group 0.000 claims description 129
- 125000001072 heteroaryl group Chemical group 0.000 claims description 127
- 150000002431 hydrogen Chemical class 0.000 claims description 90
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 70
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
- 125000004193 piperazinyl group Chemical group 0.000 claims description 51
- 125000000623 heterocyclic group Chemical group 0.000 claims description 50
- 125000003342 alkenyl group Chemical group 0.000 claims description 41
- 125000000304 alkynyl group Chemical group 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 33
- 125000004122 cyclic group Chemical group 0.000 claims description 29
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- 229910052736 halogen Chemical group 0.000 claims description 21
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- 125000005842 heteroatom Chemical group 0.000 claims description 21
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- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
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- 229910052717 sulfur Inorganic materials 0.000 claims description 14
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- 239000000126 substance Substances 0.000 claims description 13
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- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
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- 125000004950 trifluoroalkyl group Chemical group 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- QJOYTGCZTPWACL-UHFFFAOYSA-N 2-[4-[3-(1,3-benzothiazol-2-yloxy)-2-hydroxypropyl]piperazin-1-yl]-n-(2,6-dimethylphenyl)acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)COC=2SC3=CC=CC=C3N=2)CC1 QJOYTGCZTPWACL-UHFFFAOYSA-N 0.000 claims description 5
- VOBBYHJBAIAYRU-UHFFFAOYSA-N 2-[4-[3-(1,3-benzothiazol-6-yloxy)-2-hydroxypropyl]piperazin-1-yl]-n-(2,6-dimethylphenyl)acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)COC=2C=C3SC=NC3=CC=2)CC1 VOBBYHJBAIAYRU-UHFFFAOYSA-N 0.000 claims description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 5
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- BLZSDWMDBCVLPR-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-(2-hydroxy-3-quinolin-4-yloxypropyl)piperazin-1-yl]acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)COC=2C3=CC=CC=C3N=CC=2)CC1 BLZSDWMDBCVLPR-UHFFFAOYSA-N 0.000 claims description 5
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- TXYVYXLNUPKJEV-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-[(2-phenyl-1,3-benzothiazol-5-yl)oxy]propyl]piperazin-1-yl]acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)COC=2C=C3N=C(SC3=CC=2)C=2C=CC=CC=2)CC1 TXYVYXLNUPKJEV-UHFFFAOYSA-N 0.000 claims description 5
- OULDEVLLHJFRPR-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-[(2-phenyl-1,3-benzoxazol-5-yl)oxy]propyl]piperazin-1-yl]acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)COC=2C=C3N=C(OC3=CC=2)C=2C=CC=CC=2)CC1 OULDEVLLHJFRPR-UHFFFAOYSA-N 0.000 claims description 5
- RYTNTASXQAZPTK-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propyl]piperazin-1-yl]-n-(4-hydroxyphenyl)acetamide Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(=O)NC1=CC=C(O)C=C1 RYTNTASXQAZPTK-UHFFFAOYSA-N 0.000 claims description 4
- KNRLWMVXYOQGFW-UHFFFAOYSA-N 2-[4-[3-(1,3-benzothiazol-2-ylamino)-2-hydroxypropyl]piperazin-1-yl]-n-(2,6-dimethylphenyl)acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)CNC=2SC3=CC=CC=C3N=2)CC1 KNRLWMVXYOQGFW-UHFFFAOYSA-N 0.000 claims description 4
- ZHRAGUPUYMHBFK-UHFFFAOYSA-N 4-[3-[4-[2-(2,6-dimethylanilino)-2-oxoethyl]piperazin-1-yl]-2-hydroxypropoxy]-1h-indole-2-carboxamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)COC=2C=3C=C(NC=3C=CC=2)C(N)=O)CC1 ZHRAGUPUYMHBFK-UHFFFAOYSA-N 0.000 claims description 4
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- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 4
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- 238000006467 substitution reaction Methods 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- OPOHBZPGKPHACY-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-(2-hydroxy-3-pyridin-3-yloxypropyl)piperazin-1-yl]acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(CC(O)COC=2C=NC=CC=2)CC1 OPOHBZPGKPHACY-UHFFFAOYSA-N 0.000 claims description 3
- ZSJQEOXCZMMJFS-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propyl]-2-oxopiperazin-1-yl]acetamide Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1=O)CCN1CC(=O)NC1=C(C)C=CC=C1C ZSJQEOXCZMMJFS-UHFFFAOYSA-N 0.000 claims description 3
- HWCAHWFWTGNIBN-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-[(2-methyl-1,3-benzoxazol-5-yl)oxy]propyl]piperazin-1-yl]acetamide Chemical compound C=1C=C2OC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(=O)NC1=C(C)C=CC=C1C HWCAHWFWTGNIBN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 85
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- 239000000243 solution Substances 0.000 description 40
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- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
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- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- DCQXTYAFFMSNNH-UHFFFAOYSA-M sodium;2-[bis(2-hydroxyethyl)amino]ethanol;acetate Chemical compound [Na+].CC([O-])=O.OCCN(CCO)CCO DCQXTYAFFMSNNH-UHFFFAOYSA-M 0.000 description 1
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- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- 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
-
- 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—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
- 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
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
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- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
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- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
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- C07D241/44—Benzopyrazines 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 carbon atoms of the hetero ring
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- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
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- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
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- C07D277/68—Benzothiazoles 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 in position 2
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- C07D295/145—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
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- Engineering & Computer Science (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Physical Education & Sports Medicine (AREA)
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- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
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| PCT/US2001/051032 WO2002064576A1 (en) | 2000-10-23 | 2001-10-19 | Heteroaryl alkyl piperazine derivatives as fatty acid oxidation inhibitors |
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| US6573264B1 (en) * | 2000-10-23 | 2003-06-03 | Cv Therapeutics, Inc. | Heteroaryl alkyl piperazine derivatives |
| DK1406898T3 (da) * | 2001-07-19 | 2005-05-30 | Cv Therapeutics Inc | Substituerede piperazinforbindelser og anvendelse af disse som fedtsyreoxidationsinhibitorer |
| US7001909B2 (en) * | 2001-07-19 | 2006-02-21 | Cv Therapeutics, Inc. | Substituted heterocyclic compounds |
| US20030220344A1 (en) * | 2002-04-04 | 2003-11-27 | Luiz Belardinelli | Method of treating arrhythmias |
| US7056924B2 (en) * | 2002-07-18 | 2006-06-06 | Cv Therapeutics, Inc. | Substituted heterocyclic compounds |
| US7132539B2 (en) | 2002-10-23 | 2006-11-07 | The Procter & Gamble Company | Melanocortin receptor ligands |
| WO2004052887A2 (en) * | 2002-12-05 | 2004-06-24 | Cv Therapeutics, Inc. | Substituted piperazine compounds and their use as fatty acid oxidation inhibitors |
| EP1806346B1 (en) * | 2002-12-05 | 2009-07-22 | Cv Therapeutics, Inc. | Substituted piperazine compounds and their use as fatty acid oxidation inhibitors |
| KR20050086956A (ko) * | 2003-01-03 | 2005-08-30 | 씨브이 쎄러퓨틱스, 인코포레이티드 | 치환된 복소환 화합물 |
| KR20050100615A (ko) * | 2003-01-14 | 2005-10-19 | 싸이토키네틱스, 인코포레이티드 | 화합물, 조성물 및 방법 |
| NZ541306A (en) * | 2003-01-17 | 2008-07-31 | Cv Therapeutics Inc | Substituted piperazine and piperidine derivatives useful in the treatment of cardiovascular diseases |
| KR20060065586A (ko) * | 2003-06-23 | 2006-06-14 | 씨브이 쎄러퓨틱스, 인코포레이티드 | 지방산 산화 저해제로서의, 피페라진 및 피페리딘의 우레아유도체 |
| WO2005061470A1 (en) * | 2003-12-18 | 2005-07-07 | Cv Therapeutics, Inc. | 1-akan-2-ol substituted piperazine and piperidine compounds |
| US7163944B2 (en) * | 2004-01-26 | 2007-01-16 | Kowa Co., Ltd. | Cyclic diamine compound and pharmaceutical containing the same |
| CA2570999C (en) | 2004-06-17 | 2014-01-07 | Cytokinetics, Inc. | Compounds, compositions and methods |
| US7176222B2 (en) | 2004-07-27 | 2007-02-13 | Cytokinetics, Inc. | Syntheses of ureas |
| US7271169B2 (en) * | 2004-09-08 | 2007-09-18 | Cv Therapeutics, Inc. | Substituted heterocyclic compounds |
| US20060074105A1 (en) * | 2004-09-20 | 2006-04-06 | Serenex, Inc. | Substituted quinoline and quinazoline inhibitors of quinone reductase 2 |
| AU2006223212A1 (en) * | 2005-03-11 | 2006-09-21 | Hong Kong Nitric Oxide Limited | Combination therapy for endothelial dysfunction, angina and diabetes |
| US7538223B2 (en) * | 2005-08-04 | 2009-05-26 | Cytokinetics, Inc. | Compounds, compositions and methods |
| TW200808321A (en) | 2005-12-15 | 2008-02-16 | Cytokinetics Inc | Certain chemical entities, compositions and methods |
| US20070197505A1 (en) * | 2005-12-15 | 2007-08-23 | Morgan Bradley P | Certain chemical entities, compositions and methods |
| US7825120B2 (en) * | 2005-12-15 | 2010-11-02 | Cytokinetics, Inc. | Certain substituted ((piperazin-1-ylmethyl)benzyl)ureas |
| US20070208000A1 (en) * | 2005-12-15 | 2007-09-06 | Morgan Bradley P | Certain chemical entities, compositions and methods |
| EP1959962A2 (en) * | 2005-12-16 | 2008-08-27 | Cytokinetics, Inc. | Certain chemical entities, compositions, and methods |
| US7989455B2 (en) * | 2005-12-19 | 2011-08-02 | Cytokinetics, Inc. | Compounds, compositions and methods |
| TW200745025A (en) * | 2005-12-29 | 2007-12-16 | Schering Ag | Amide inhibitors of leukotriene A4 hydrolase |
| US8389500B2 (en) * | 2008-10-30 | 2013-03-05 | Gilead Sciences, Inc. | Fused heterocyclic compounds as ion channel modulators |
| CA2761771A1 (en) * | 2009-05-14 | 2010-11-18 | Gilead Sciences, Inc. | Ranolazine for the treatment of cns disorders |
| US8759382B2 (en) | 2010-09-29 | 2014-06-24 | Teva Pharmaceutical Industries Ltd. | Propargyl-trifluoromethoxy-aminobenzothiazole derivatives, their preparation and use |
| HRP20211778T1 (hr) | 2014-08-29 | 2022-03-18 | Chdi Foundation, Inc. | Kontrastna sredstva za slikovnu dijagnostiku huntingtin proteina |
| KR102704242B1 (ko) | 2017-06-20 | 2024-09-09 | 임브리아 파마슈티칼스, 인크. | 심장 대사의 효율을 증가시키기 위한 조성물 및 방법 |
| WO2020081361A1 (en) | 2018-10-17 | 2020-04-23 | Imbria Pharmaceuticals, Inc. | Methods of treating rheumatic diseases using trimetazidine-based compounds |
| RU2751878C2 (ru) * | 2018-12-06 | 2021-07-19 | Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова" | 1-(Метоксибензил)-4-[2-((метоксибензил)амино)этил]пиперазины, обладающие антиаритмической активностью |
| US11780811B2 (en) | 2020-06-30 | 2023-10-10 | Imbria Pharmaceuticals, Inc. | Methods of synthesizing 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11530184B2 (en) | 2020-06-30 | 2022-12-20 | Imbria Pharmaceuticals, Inc. | Crystal forms of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11883396B2 (en) | 2021-05-03 | 2024-01-30 | Imbria Pharmaceuticals, Inc. | Methods of treating kidney conditions using modified forms of trimetazidine |
| CN114805112A (zh) * | 2022-05-31 | 2022-07-29 | 常州大学 | 一种pde2抑制剂酰胺类衍生物及其制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4567264A (en) * | 1983-05-18 | 1986-01-28 | Syntex (U.S.A.) Inc. | Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry |
| IE80710B1 (en) | 1989-06-23 | 1998-12-16 | Syntex Inc | Ranolazine and related piperazines used in the treatment of tissues experiencing a physical or chemical insult |
| DE69033926T2 (de) * | 1989-11-22 | 2002-10-24 | Janssen Pharmaceutica N.V., Beerse | Verwendung von Piperazin-Acetamid-Derivaten gegen Reperfusionsschaden |
| US5455045A (en) * | 1993-05-13 | 1995-10-03 | Syntex (U.S.A.) Inc. | High dose formulations |
| WO2001062749A1 (en) | 2000-02-22 | 2001-08-30 | Cv Therapeutics, Inc. | Substituted piperazine compounds |
| US6573264B1 (en) * | 2000-10-23 | 2003-06-03 | Cv Therapeutics, Inc. | Heteroaryl alkyl piperazine derivatives |
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2001
- 2001-10-19 US US10/398,636 patent/US20040029889A1/en not_active Abandoned
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- 2001-10-19 CN CNB018177700A patent/CN1303074C/zh not_active Expired - Fee Related
- 2001-10-19 JP JP2002564509A patent/JP4138489B2/ja not_active Expired - Fee Related
- 2001-10-19 EP EP01271075A patent/EP1339701B1/en not_active Expired - Lifetime
- 2001-10-19 AT AT01271075T patent/ATE353882T1/de not_active IP Right Cessation
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- 2001-10-19 AU AU2002255466A patent/AU2002255466B2/en not_active Ceased
- 2001-10-23 AR ARP010104957A patent/AR034173A1/es unknown
- 2001-10-23 TW TW090126173A patent/TWI286135B/zh not_active IP Right Cessation
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2002
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- 2003-04-16 ZA ZA200302990A patent/ZA200302990B/xx unknown
- 2003-04-22 NO NO20031797A patent/NO325220B1/no not_active IP Right Cessation
- 2003-04-22 NO NO20031784A patent/NO20031784L/no unknown
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2004
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