CN1108240A - 兴奋性氨基酸受体拮抗剂 - Google Patents
兴奋性氨基酸受体拮抗剂 Download PDFInfo
- Publication number
- CN1108240A CN1108240A CN94119360A CN94119360A CN1108240A CN 1108240 A CN1108240 A CN 1108240A CN 94119360 A CN94119360 A CN 94119360A CN 94119360 A CN94119360 A CN 94119360A CN 1108240 A CN1108240 A CN 1108240A
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- Prior art keywords
- compound
- phenyl
- formula
- glutamic acid
- alkyl
- Prior art date
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- 229940123511 Excitatory amino acid receptor antagonist Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 282
- 238000002360 preparation method Methods 0.000 claims abstract description 92
- 102000018899 Glutamate Receptors Human genes 0.000 claims abstract description 27
- 108010027915 Glutamate Receptors Proteins 0.000 claims abstract description 27
- -1 7H-purinyl Chemical group 0.000 claims description 165
- 238000000034 method Methods 0.000 claims description 100
- 229910052760 oxygen Inorganic materials 0.000 claims description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000006239 protecting group Chemical group 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 239000001301 oxygen Substances 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000001425 triazolyl group Chemical group 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 6
- QACXMURHOPFKFS-UMJHXOGRSA-N (2s)-2-amino-3-(4-methylphenoxy)pentanedioic acid Chemical compound CC1=CC=C(OC(CC(O)=O)[C@H](N)C(O)=O)C=C1 QACXMURHOPFKFS-UMJHXOGRSA-N 0.000 claims description 5
- OPIQEWYOEHUKIV-PYMCNQPYSA-N (2s)-2-amino-3-naphthalen-2-yloxypentanedioic acid Chemical compound C1=CC=CC2=CC(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C21 OPIQEWYOEHUKIV-PYMCNQPYSA-N 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 230000005062 synaptic transmission Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 5
- 235000013922 glutamic acid Nutrition 0.000 claims 4
- 239000004220 glutamic acid Substances 0.000 claims 4
- 125000003107 substituted aryl group Chemical group 0.000 claims 4
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims 3
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 claims 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- KWQFQZGMLRXMCI-LWKPJOBUSA-N (2s)-2-amino-3-(9h-fluoren-2-yloxy)pentanedioic acid Chemical compound C1=CC=C2C3=CC=C(OC(CC(O)=O)[C@H](N)C(O)=O)C=C3CC2=C1 KWQFQZGMLRXMCI-LWKPJOBUSA-N 0.000 claims 1
- OPXGGRVTGCLFTM-NNBQYGFHSA-N (2s)-2-amino-3-[4-(3-phenylprop-2-enyl)phenoxy]pentanedioic acid Chemical compound C1=CC(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C1CC=CC1=CC=CC=C1 OPXGGRVTGCLFTM-NNBQYGFHSA-N 0.000 claims 1
- BVTYJDUQQIDSGH-IAXKEJLGSA-N (2s)-2-amino-3-[4-(6-phenylhexyl)phenoxy]pentanedioic acid Chemical compound C1=CC(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C1CCCCCCC1=CC=CC=C1 BVTYJDUQQIDSGH-IAXKEJLGSA-N 0.000 claims 1
- HBUBJSVUHMHUJW-DAFXYXGESA-N (2s)-2-amino-3-[4-[2-(4-nitrophenyl)ethenyl]phenoxy]pentanedioic acid Chemical compound C1=CC(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C1C=CC1=CC=C([N+]([O-])=O)C=C1 HBUBJSVUHMHUJW-DAFXYXGESA-N 0.000 claims 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000005530 alkylenedioxy group Chemical group 0.000 claims 1
- 125000005529 alkyleneoxy group Chemical group 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 abstract description 6
- 208000025966 Neurological disease Diseases 0.000 abstract description 6
- 238000010189 synthetic method Methods 0.000 abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 221
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 195
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 113
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 110
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 102
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
- 239000002585 base Substances 0.000 description 87
- 239000000203 mixture Substances 0.000 description 85
- 238000005160 1H NMR spectroscopy Methods 0.000 description 79
- 238000006243 chemical reaction Methods 0.000 description 79
- 239000011541 reaction mixture Substances 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
- 239000000243 solution Substances 0.000 description 67
- 238000001819 mass spectrum Methods 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 229960002989 glutamic acid Drugs 0.000 description 51
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 45
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 42
- 238000004458 analytical method Methods 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 29
- 239000012071 phase Substances 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 24
- 238000001914 filtration Methods 0.000 description 24
- 238000006460 hydrolysis reaction Methods 0.000 description 24
- 239000000463 material Substances 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- 239000000725 suspension Substances 0.000 description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 238000005406 washing Methods 0.000 description 21
- 239000002253 acid Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000003513 alkali Substances 0.000 description 15
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Chemical compound CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 15
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 14
- 230000007062 hydrolysis Effects 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 12
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
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- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 5
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
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- 239000003981 vehicle Substances 0.000 description 5
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 239000005864 Sulphur Substances 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
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- OKJQBJHYKVHRIS-UHFFFAOYSA-N methyl 4-hydroxy-5-oxopyrrolidine-2-carboxylate Chemical compound COC(=O)C1CC(O)C(=O)N1 OKJQBJHYKVHRIS-UHFFFAOYSA-N 0.000 description 1
- HQGPKMSGXAUKHT-UHFFFAOYSA-N methyl 5-oxopyrrolidine-2-carboxylate Chemical compound COC(=O)C1CCC(=O)N1 HQGPKMSGXAUKHT-UHFFFAOYSA-N 0.000 description 1
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- 238000012545 processing Methods 0.000 description 1
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- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
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- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical class O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
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- JXAZAUKOWVKTLO-UHFFFAOYSA-L sodium pyrosulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OS([O-])(=O)=O JXAZAUKOWVKTLO-UHFFFAOYSA-L 0.000 description 1
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- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
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- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- BJAARRARQJZURR-UHFFFAOYSA-N trimethylazanium;hydroxide Chemical compound O.CN(C)C BJAARRARQJZURR-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/24—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D207/28—2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
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- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
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- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- C07C2602/00—Systems containing two condensed rings
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- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
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| US08/322,632 US5576323A (en) | 1993-12-03 | 1994-10-13 | Excitatory amino acid receptor antagonists |
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| CN1108240A true CN1108240A (zh) | 1995-09-13 |
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| CN94119360A Pending CN1108240A (zh) | 1993-12-03 | 1994-12-02 | 兴奋性氨基酸受体拮抗剂 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102633657A (zh) * | 2012-03-30 | 2012-08-15 | 兰州中泰和生物科技有限公司 | 一种顺式3-氨基-环戊醇盐酸盐的制备方法 |
| CN102695701A (zh) * | 2009-12-21 | 2012-09-26 | 伊莱利利公司 | Mglu2激动剂 |
| CN104193612A (zh) * | 2014-08-12 | 2014-12-10 | 深圳市道尔顿电子材料有限公司 | 一种2,3,5-三羧基环戊基乙酸的制备方法 |
| CN107936040A (zh) * | 2017-12-08 | 2018-04-20 | 珠海联邦制药股份有限公司 | 一种替格瑞洛中间体的合成工艺 |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5824662A (en) * | 1996-09-27 | 1998-10-20 | Guilford Pharmaceuticals Inc. | Treatment of global and focal ischemia using naaladase inhibitors |
| US6017903A (en) | 1996-09-27 | 2000-01-25 | Guilford Pharmaceuticals Inc. | Pharmaceutical compositions and methods of treating a glutamate abnormality and effecting a neuronal activity in an animal using NAALADase inhibitors |
| IL128718A0 (en) | 1996-09-27 | 2000-01-31 | Guildford Pharmaceuticals Inc | Naaldase compositions |
| JP3936418B2 (ja) * | 1996-10-25 | 2007-06-27 | サントリー株式会社 | β−ヒドロキシアスパラギン酸誘導体 |
| EP0980247A1 (en) * | 1997-05-07 | 2000-02-23 | Algos Pharmaceutical Corporation | Composition and method combining an antidepressant with an nmda receptor antagonist, for treating neuropathic pain |
| DE19801647A1 (de) | 1998-01-17 | 1999-07-22 | Bayer Ag | Substituierte beta,gamma-annellierte Lactone |
| DE19801646A1 (de) | 1998-01-17 | 1999-07-22 | Bayer Ag | Substituierte alpha,beta-annellierte Butyrolactone |
| DE19801636A1 (de) | 1998-01-17 | 1999-07-22 | Bayer Ag | Substituierte bicyclische Lactone |
| US6307090B1 (en) | 1999-01-22 | 2001-10-23 | The United States Of America As Represented By The Department Of Health And Human Services | Acylated oligopeptide derivatives having cell signal inhibiting activity |
| US7226991B1 (en) * | 1999-03-23 | 2007-06-05 | United States Of America, Represented By The Secretary, Department Of Health And Human Services | Phenylalanine derivatives |
| WO2000056760A1 (en) * | 1999-03-23 | 2000-09-28 | The United States Of America, Represented By Secretary, Department Of Health And Human Services | Phenylalanine derivatives |
| AU2241400A (en) | 1999-04-06 | 2000-10-12 | Yamanouchi Pharmaceutical Co., Ltd. | Novel thiazolobenzoimidazole derivative |
| AU780697B2 (en) | 1999-10-22 | 2005-04-14 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Inhibition of cell motility and angiogenesis by inhibitors of the GRB2 SH2-domain |
| US7871981B2 (en) * | 1999-10-22 | 2011-01-18 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibition of cell motility, angiogenesis, and metastasis |
| US6362226B2 (en) | 1999-12-08 | 2002-03-26 | Vanderbilt University | Modulation of in vivo glutamine and glycine levels in the treatment of autism |
| US7425537B2 (en) * | 2000-08-22 | 2008-09-16 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | SH2 domain binding inhibitors |
| US6977241B2 (en) * | 2000-08-22 | 2005-12-20 | The United States Of America As Represented By The Department Of Health & Human Services | SH2 domain binding inhibitors |
| EP1397370B1 (en) | 2001-06-22 | 2014-07-23 | Suntory Holdings Limited | Beta-benzyloxyaspartate derivatives with amino group on benzene ring |
| US20040138104A1 (en) * | 2003-01-14 | 2004-07-15 | The Government Of The United States Of America Represented By The Secretary, | Peptides |
| US20050119163A1 (en) | 2003-09-18 | 2005-06-02 | The Government Of The United States Of America, As Represented By The Secretary, | SH2 domain binding inhibitors |
| US7423176B2 (en) * | 2004-04-13 | 2008-09-09 | Cephalon, Inc. | Bicyclic aromatic sulfinyl derivatives |
| PL2473492T3 (pl) * | 2009-08-31 | 2016-03-31 | Lonza Ag | Sposób wytwarzania (1S,4R)-2-oksa-3-azabicyklo[2.2.1]-hept-5-enów |
| DK2721012T3 (en) | 2011-06-17 | 2016-08-15 | Lilly Co Eli | Biclo (3.1.0) hexane-2,6-dicarboxylic acid derivatives as MGLU2 receptor agonist |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428960A (en) * | 1982-04-19 | 1984-01-31 | Merck & Co., Inc. | 3-Amino-6-substituted thio-1-azabicyclo(3.2.0)hept-6-en-2-one-7-carboxylic acids |
| DK160941C (da) * | 1988-06-28 | 1991-10-21 | Novo Nordisk As | Kondenserede 2,3-dihydroxypyraziner, fremgangsmaade til deres fremstilling og farmaceutiske praeparater, hvori forbindelserne indgaar |
| DE69019610D1 (de) * | 1989-07-06 | 1995-06-29 | Banyu Pharma Co Ltd | Cyclische Derivate des Amidinylthiocarbapenems. |
| GB9324872D0 (en) * | 1993-12-03 | 1994-01-19 | Univ Pasteur | Pharmaceutical compounds |
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1994
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- 1994-12-02 HU HU9403469A patent/HUT69181A/hu unknown
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1996
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102695701A (zh) * | 2009-12-21 | 2012-09-26 | 伊莱利利公司 | Mglu2激动剂 |
| CN102695701B (zh) * | 2009-12-21 | 2014-10-01 | 伊莱利利公司 | Mglu2激动剂 |
| CN102633657A (zh) * | 2012-03-30 | 2012-08-15 | 兰州中泰和生物科技有限公司 | 一种顺式3-氨基-环戊醇盐酸盐的制备方法 |
| CN104193612A (zh) * | 2014-08-12 | 2014-12-10 | 深圳市道尔顿电子材料有限公司 | 一种2,3,5-三羧基环戊基乙酸的制备方法 |
| CN104193612B (zh) * | 2014-08-12 | 2016-03-02 | 深圳市道尔顿电子材料有限公司 | 一种2,3,5-三羧基环戊基乙酸的制备方法 |
| CN107936040A (zh) * | 2017-12-08 | 2018-04-20 | 珠海联邦制药股份有限公司 | 一种替格瑞洛中间体的合成工艺 |
| CN107936040B (zh) * | 2017-12-08 | 2019-04-09 | 珠海联邦制药股份有限公司 | 一种替格瑞洛中间体的合成工艺 |
Also Published As
| Publication number | Publication date |
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| US5576323A (en) | 1996-11-19 |
| FI945704A7 (fi) | 1995-06-04 |
| EP0658539A1 (en) | 1995-06-21 |
| BR9404809A (pt) | 1995-08-01 |
| NO944578L (no) | 1995-06-06 |
| CA2136904A1 (en) | 1995-06-04 |
| JPH07267908A (ja) | 1995-10-17 |
| AU676781B2 (en) | 1997-03-20 |
| NO944578D0 (no) | 1994-11-29 |
| US5843997A (en) | 1998-12-01 |
| CO4290421A1 (es) | 1996-04-17 |
| CZ294794A3 (en) | 1995-12-13 |
| AU7915194A (en) | 1995-06-08 |
| PL306038A1 (en) | 1995-06-12 |
| KR950018015A (ko) | 1995-07-22 |
| IL111789A0 (en) | 1995-01-24 |
| YU70394A (sh) | 1997-12-05 |
| FI945704A0 (fi) | 1994-12-02 |
| HUT69181A (en) | 1995-08-28 |
| HU9403469D0 (en) | 1995-02-28 |
| ZA949405B (en) | 1996-05-28 |
| RU94042240A (ru) | 1996-10-10 |
| TW287157B (enExample) | 1996-10-01 |
| PE42595A1 (es) | 1995-12-12 |
| NZ270009A (en) | 1997-01-29 |
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