CA2941559A1 - Methods for the synthesis of chiral kynurenine compounds - Google Patents
Methods for the synthesis of chiral kynurenine compounds Download PDFInfo
- Publication number
- CA2941559A1 CA2941559A1 CA2941559A CA2941559A CA2941559A1 CA 2941559 A1 CA2941559 A1 CA 2941559A1 CA 2941559 A CA2941559 A CA 2941559A CA 2941559 A CA2941559 A CA 2941559A CA 2941559 A1 CA2941559 A1 CA 2941559A1
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- Prior art keywords
- compound
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- chloro
- afford
- amino
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 45
- YGPSJZOEDVAXAB-UHFFFAOYSA-N kynurenine Chemical class OC(=O)C(N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-UHFFFAOYSA-N 0.000 title abstract description 9
- 238000003786 synthesis reaction Methods 0.000 title description 12
- 230000015572 biosynthetic process Effects 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 58
- -1 acylated aniline compound Chemical class 0.000 claims description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical group [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 21
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 102000004190 Enzymes Human genes 0.000 claims description 16
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 14
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 claims description 13
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 12
- 229910052783 alkali metal Inorganic materials 0.000 claims description 12
- 230000002152 alkylating effect Effects 0.000 claims description 12
- 229910052782 aluminium Inorganic materials 0.000 claims description 12
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 12
- 229910052796 boron Inorganic materials 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 claims description 9
- VDLXWVJCSVAOKZ-UHFFFAOYSA-N 1-(2-amino-4-chlorophenyl)-2-chloroethanone Chemical compound NC1=CC(Cl)=CC=C1C(=O)CCl VDLXWVJCSVAOKZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 235000009518 sodium iodide Nutrition 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 7
- 241000981399 Aspergillus melleus Species 0.000 claims description 6
- 108010003977 aminoacylase I Proteins 0.000 claims description 6
- 230000000911 decarboxylating effect Effects 0.000 claims description 6
- OVTRJMNZIRSECO-UHFFFAOYSA-N 2-acetamido-4-(2-amino-4-chlorophenyl)-4-oxobutanoic acid Chemical compound CC(=O)NC(C(O)=O)CC(=O)C1=CC=C(Cl)C=C1N OVTRJMNZIRSECO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 2
- SBMIBRAEESOEIP-UHFFFAOYSA-N diethyl 2-acetamido-2-[2-(2-amino-4-chlorophenyl)-2-oxoethyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)(NC(C)=O)CC(=O)C1=CC=C(Cl)C=C1N SBMIBRAEESOEIP-UHFFFAOYSA-N 0.000 claims 3
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- HQLHZNDJQSRKDT-QMMMGPOBSA-N (2s)-2-amino-4-(2-amino-4-chlorophenyl)-4-oxobutanoic acid Chemical compound OC(=O)[C@@H](N)CC(=O)C1=CC=C(Cl)C=C1N HQLHZNDJQSRKDT-QMMMGPOBSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- HCZHHEIFKROPDY-UHFFFAOYSA-N kynurenic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 HCZHHEIFKROPDY-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 102100020870 La-related protein 6 Human genes 0.000 description 4
- 108050008265 La-related protein 6 Proteins 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108700023418 Amidases Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 102000005922 amidase Human genes 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 108091006629 SLC13A2 Proteins 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910052700 potassium Chemical class 0.000 description 2
- 239000011591 potassium Chemical class 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012070 reactive reagent Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- HQLHZNDJQSRKDT-UHFFFAOYSA-N 2-amino-4-(2-amino-4-chlorophenyl)-4-oxobutanoic acid Chemical compound OC(=O)C(N)CC(=O)C1=CC=C(Cl)C=C1N HQLHZNDJQSRKDT-UHFFFAOYSA-N 0.000 description 1
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- YGPSJZOEDVAXAB-QMMMGPOBSA-N L-kynurenine Chemical class OC(=O)[C@@H](N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-QMMMGPOBSA-N 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 108010062049 chirobiotic T Proteins 0.000 description 1
- KWTSZCJMWHGPOS-UHFFFAOYSA-M chloro(trimethyl)stannane Chemical compound C[Sn](C)(C)Cl KWTSZCJMWHGPOS-UHFFFAOYSA-M 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000001727 in vivo Methods 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
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000463 material Substances 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
- 125000000740 n-pentyl group Chemical group [H]C([H])([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
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000013341 scale-up Methods 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
- 238000000926 separation method Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/001—Amines; Imines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
- C07C227/20—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters by hydrolysis of N-acylated amino-acids or derivatives thereof, e.g. hydrolysis of carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
-
- 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
- C07C229/34—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 containing six-membered aromatic rings
- C07C229/36—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 containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/01—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in linear amides (3.5.1)
- C12Y305/01014—Aminoacylase (3.5.1.14)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361785807P | 2013-03-14 | 2013-03-14 | |
| US61/785,807 | 2013-03-14 | ||
| PCT/US2014/027694 WO2014152752A1 (en) | 2013-03-14 | 2014-03-14 | Methods for the synthesis of chiral kynurenine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2941559A1 true CA2941559A1 (en) | 2014-09-25 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2941559A Abandoned CA2941559A1 (en) | 2013-03-14 | 2014-03-14 | Methods for the synthesis of chiral kynurenine compounds |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US9834801B2 (enExample) |
| EP (1) | EP2970097B1 (enExample) |
| JP (2) | JP6340409B2 (enExample) |
| CN (2) | CN105164100B (enExample) |
| CA (1) | CA2941559A1 (enExample) |
| WO (1) | WO2014152752A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2941559A1 (en) | 2013-03-14 | 2014-09-25 | Vistagen Therapeutics, Inc. | Methods for the synthesis of chiral kynurenine compounds |
| SI3297619T1 (sl) | 2015-05-22 | 2023-02-28 | Vistagen Therapeutics, Inc., | Terapevtske uporabe L-4-klorokinurenina |
| EP3347346A1 (en) * | 2015-09-08 | 2018-07-18 | Cephalon, Inc. | Prodrugs of chlorokynurenines |
| US20190201360A1 (en) | 2016-08-31 | 2019-07-04 | Ampio Pharmaceuticals, Inc. | Treatment of disease with n-acetyl kynurenine |
| WO2018180116A1 (ja) | 2017-03-29 | 2018-10-04 | 富士フイルム株式会社 | 構造体および光センサ |
| CA3127220C (en) * | 2018-02-09 | 2024-11-19 | Vistagen Therapeutics Inc | SYNTHESIS OF 4-CHLOROKYNURENINS AND INTERMEDIARIES |
| CN113549661B (zh) * | 2020-04-26 | 2022-08-30 | 赤壁生合元科技有限公司 | 生物催化合成L-4-Cl-犬尿氨酸或L-4-Br-犬尿氨酸的方法及应用 |
| CN113549662B (zh) * | 2020-04-26 | 2022-06-03 | 赤壁市高质量发展研究院有限公司 | 一种用MOF载酶技术高效制备抗抑郁药前药L-4-Cl-犬尿氨酸的方法及应用 |
| AU2023300118A1 (en) | 2022-06-30 | 2025-01-09 | A-Clip Institute, Co., Ltd. | Method for testing diseased state of vasculitis or exacerbation risk of COVID-19, testing kit, companion diagnostic agent, and testing marker |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3766261A (en) | 1970-08-21 | 1973-10-16 | Us Agriculture | Process of producing kynurenine |
| US3702255A (en) * | 1970-08-21 | 1972-11-07 | Us Agriculture | Kynurenine derivatives as sweetening agents |
| US3765261A (en) * | 1973-01-02 | 1973-10-16 | Hurst Performance | Unitary stick transfer case shifter |
| US5519055A (en) | 1993-08-06 | 1996-05-21 | University Of Maryland At Baltimore | Substituted kynurenines and process for their preparation |
| US5789434A (en) * | 1994-11-15 | 1998-08-04 | Bayer Corporation | Derivatives of substituted 4-biarylbutyric acid as matrix metalloprotease inhibitors |
| GB9522615D0 (en) * | 1995-11-03 | 1996-01-03 | Pharmacia Spa | 4-Phenyl-4-oxo-butanoic acid derivatives with kynurenine-3-hydroxylase inhibiting activity |
| ITMI20041626A1 (it) | 2004-08-06 | 2004-11-06 | Roberto Pellicciari | Inibitori della chinurenina-ammino-trasferasi |
| US7622495B2 (en) * | 2006-10-03 | 2009-11-24 | Neurim Pharmaceuticals (1991) Ltd. | Substituted aryl-indole compounds and their kynurenine/kynuramine-like metabolites as therapeutic agents |
| WO2010067613A1 (ja) * | 2008-12-11 | 2010-06-17 | 東洋紡績株式会社 | Ｌ－サクシニルアミノアシラーゼ、およびこれを用いたｌ－アミノ酸の製造方法 |
| CA2941559A1 (en) | 2013-03-14 | 2014-09-25 | Vistagen Therapeutics, Inc. | Methods for the synthesis of chiral kynurenine compounds |
-
2014
- 2014-03-14 CA CA2941559A patent/CA2941559A1/en not_active Abandoned
- 2014-03-14 WO PCT/US2014/027694 patent/WO2014152752A1/en not_active Ceased
- 2014-03-14 CN CN201480023992.8A patent/CN105164100B/zh not_active Expired - Fee Related
- 2014-03-14 US US14/775,287 patent/US9834801B2/en active Active
- 2014-03-14 JP JP2016502520A patent/JP6340409B2/ja not_active Expired - Fee Related
- 2014-03-14 CN CN201710718531.8A patent/CN107417558A/zh active Pending
- 2014-03-14 EP EP14770640.2A patent/EP2970097B1/en not_active Not-in-force
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2017
- 2017-11-14 US US15/812,599 patent/US10294502B2/en active Active
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2018
- 2018-05-14 JP JP2018093249A patent/JP6618569B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20180171372A1 (en) | 2018-06-21 |
| US10294502B2 (en) | 2019-05-21 |
| EP2970097A1 (en) | 2016-01-20 |
| JP6340409B2 (ja) | 2018-06-06 |
| EP2970097A4 (en) | 2016-11-16 |
| HK1218414A1 (zh) | 2017-02-17 |
| WO2014152752A1 (en) | 2014-09-25 |
| JP2018139608A (ja) | 2018-09-13 |
| CN105164100A (zh) | 2015-12-16 |
| EP2970097B1 (en) | 2018-10-31 |
| CN107417558A (zh) | 2017-12-01 |
| US9834801B2 (en) | 2017-12-05 |
| CN105164100B (zh) | 2017-09-15 |
| JP6618569B2 (ja) | 2019-12-11 |
| JP2016513709A (ja) | 2016-05-16 |
| US20160032334A1 (en) | 2016-02-04 |
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