NO821037L - Fremgangsmaate ved fremstilling av n-substituerte amidoaminosyrer - Google Patents
Fremgangsmaate ved fremstilling av n-substituerte amidoaminosyrerInfo
- Publication number
- NO821037L NO821037L NO821037A NO821037A NO821037L NO 821037 L NO821037 L NO 821037L NO 821037 A NO821037 A NO 821037A NO 821037 A NO821037 A NO 821037A NO 821037 L NO821037 L NO 821037L
- Authority
- NO
- Norway
- Prior art keywords
- lower alkyl
- amino
- carbon atoms
- aryl
- hydroxy
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 19
- 238000000034 method Methods 0.000 title claims description 19
- 150000007513 acids Chemical class 0.000 title claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- -1 methylenedioxy Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 6
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 6
- 239000012433 hydrogen halide Substances 0.000 claims description 6
- 125000005592 polycycloalkyl group Polymers 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Chemical group 0.000 claims description 5
- 150000003573 thiols Chemical class 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 150000002466 imines Chemical class 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 3
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 claims description 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000003367 polycyclic group Chemical group 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000005027 hydroxyaryl group Chemical group 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 239000000243 solution Substances 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 239000000047 product Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 26
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 239000004471 Glycine Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 229960002449 glycine Drugs 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 description 7
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000007864 aqueous solution Substances 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
- 239000012043 crude product Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 description 4
- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 229940107700 pyruvic acid Drugs 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
- JWSBIOGYWXJAEF-SFVWDYPZSA-N (4s)-4-amino-2-[cyclopentyl(phenylmethoxycarbonyl)amino]-3-oxopentanoic acid Chemical compound C=1C=CC=CC=1COC(=O)N(C(C(=O)[C@@H](N)C)C(O)=O)C1CCCC1 JWSBIOGYWXJAEF-SFVWDYPZSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- CTFOHWIEFNJZHC-UHFFFAOYSA-N 2-(4-methylanilino)acetic acid Chemical compound CC1=CC=C(NCC(O)=O)C=C1 CTFOHWIEFNJZHC-UHFFFAOYSA-N 0.000 description 2
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000000370 acceptor Substances 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000004716 alpha keto acids Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 2
- 239000000292 calcium oxide Substances 0.000 description 2
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- OETYRQRYGOUTAY-UHFFFAOYSA-N ethyl 2-(2,3-dihydro-1h-inden-2-ylamino)acetate Chemical compound C1=CC=C2CC(NCC(=O)OCC)CC2=C1 OETYRQRYGOUTAY-UHFFFAOYSA-N 0.000 description 2
- IDCLWTLFGKJVQO-UHFFFAOYSA-N ethyl 2-(2,3-dihydro-1h-inden-5-ylamino)acetate Chemical compound CCOC(=O)CNC1=CC=C2CCCC2=C1 IDCLWTLFGKJVQO-UHFFFAOYSA-N 0.000 description 2
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
- 229940117360 ethyl pyruvate Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 229960001269 glycine hydrochloride Drugs 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229940076788 pyruvate Drugs 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- ZMUXBMQOKPPQPM-YGYNJSFOSA-N (2s)-2-[(3,4-dimethoxyphenyl)methyl-[(2s)-2-[(1-ethoxy-5-methyl-1-oxohexan-2-yl)amino]propanoyl]amino]propanoic acid Chemical compound CCOC(=O)C(CCC(C)C)N[C@@H](C)C(=O)N([C@@H](C)C(O)=O)CC1=CC=C(OC)C(OC)=C1 ZMUXBMQOKPPQPM-YGYNJSFOSA-N 0.000 description 1
- RRONHWAVOYADJL-HNNXBMFYSA-N (2s)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-HNNXBMFYSA-N 0.000 description 1
- JSHXJPFZKBRLFU-JQWIXIFHSA-N (2s,3s)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 JSHXJPFZKBRLFU-JQWIXIFHSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- XEHNLVMHWYPNEQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-amine;hydron;chloride Chemical compound Cl.C1=CC=C2CC(N)CC2=C1 XEHNLVMHWYPNEQ-UHFFFAOYSA-N 0.000 description 1
- LEWZOBYWGWKNCK-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-amine Chemical compound NC1=CC=C2CCCC2=C1 LEWZOBYWGWKNCK-UHFFFAOYSA-N 0.000 description 1
- OTAMPNDOKJPRRH-FVGYRXGTSA-N 2-(N-[(2S)-2-aminopropanoyl]-4-methylanilino)acetic acid hydrobromide Chemical compound Br.C[C@H](N)C(=O)N(CC(O)=O)C1=CC=C(C)C=C1 OTAMPNDOKJPRRH-FVGYRXGTSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
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- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
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- 241000400611 Eucalyptus deanei Species 0.000 description 1
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
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- 241000700159 Rattus Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
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- 230000000397 acetylating effect Effects 0.000 description 1
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- 125000002252 acyl group Chemical group 0.000 description 1
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- 239000003513 alkali Substances 0.000 description 1
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
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- 239000006286 aqueous extract Substances 0.000 description 1
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- 230000000903 blocking effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical class C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 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
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ULOLIZHBYWAICY-UHFFFAOYSA-N ethyl 2-(benzylamino)acetate Chemical compound CCOC(=O)CNCC1=CC=CC=C1 ULOLIZHBYWAICY-UHFFFAOYSA-N 0.000 description 1
- STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 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
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 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
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 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
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- AJWUSVUOAIUDGZ-UHFFFAOYSA-N tert-butyl 2-(cyclopentylamino)acetate Chemical compound CC(C)(C)OC(=O)CNC1CCCC1 AJWUSVUOAIUDGZ-UHFFFAOYSA-N 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/248,172 US4820729A (en) | 1981-03-30 | 1981-03-30 | N-substituted-amido-amino acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO821037L true NO821037L (no) | 1982-10-01 |
Family
ID=22938008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO821037A NO821037L (no) | 1981-03-30 | 1982-03-29 | Fremgangsmaate ved fremstilling av n-substituerte amidoaminosyrer |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US4820729A (ko) |
| JP (1) | JPS57176941A (ko) |
| KR (1) | KR830008999A (ko) |
| AU (1) | AU559023B2 (ko) |
| BE (1) | BE892669A (ko) |
| CH (1) | CH661931A5 (ko) |
| DE (1) | DE3211569A1 (ko) |
| DK (1) | DK142482A (ko) |
| ES (2) | ES8307719A1 (ko) |
| FI (1) | FI821080L (ko) |
| FR (1) | FR2502614B1 (ko) |
| GB (1) | GB2095682B (ko) |
| HK (1) | HK25386A (ko) |
| IE (1) | IE52790B1 (ko) |
| IL (1) | IL65346A0 (ko) |
| IN (1) | IN156595B (ko) |
| IT (1) | IT1151125B (ko) |
| MX (1) | MX7222E (ko) |
| MY (1) | MY8600419A (ko) |
| NL (1) | NL8201326A (ko) |
| NO (1) | NO821037L (ko) |
| NZ (1) | NZ200164A (ko) |
| PH (1) | PH18663A (ko) |
| SE (1) | SE8201854L (ko) |
| SG (1) | SG93585G (ko) |
| ZA (1) | ZA821869B (ko) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU543804B2 (en) * | 1980-10-31 | 1985-05-02 | Takeda Chemical Industries Ltd. | Amides having bicyclic substituents on nitrogen |
| US4766110A (en) * | 1981-08-21 | 1988-08-23 | Ryan James W | Novel complex amido and imido derivatives of carboxyalkyl peptides |
| DE3226768A1 (de) * | 1981-11-05 | 1983-05-26 | Hoechst Ag, 6230 Frankfurt | Derivate der cis, endo-2-azabicyclo-(3.3.0)-octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
| IE55867B1 (en) * | 1981-12-29 | 1991-02-14 | Hoechst Ag | New derivatives of bicyclic aminoacids,processes for their preparation,agents containing these compounds and their use,and new bicyclic aminoacids as intermediates and processes for their preparation |
| US4555502A (en) * | 1982-09-30 | 1985-11-26 | Merck & Co., Inc. | Aminoacyl-containing dipeptide derivatives useful as antihypertensives |
| US4686295A (en) * | 1982-03-10 | 1987-08-11 | Usv Pharmaceutical Corporation | N-carboxy anhydride intermediates |
| US4555503A (en) * | 1982-05-05 | 1985-11-26 | Merck & Co., Inc. | N2 -(Substituted)carboxymethyl-N6 -(substituted)-lysyl-and αε-aminoalkyl)glycyl amino acid antihypertensive agents |
| US4617291A (en) * | 1982-05-14 | 1986-10-14 | Mead Johnson & Company | Angiotensin-converting enzyme inhibiting dipeptide derivatives |
| AU560285B2 (en) * | 1982-07-19 | 1987-04-02 | Imperial Chemical Industries Plc | Heterocyclyl carbonyl sulphonamides |
| US4487716A (en) * | 1982-08-23 | 1984-12-11 | American Home Products Corporation | N-(1-Carboxy-3-phenylpropyl)-dipeptides |
| US4587234A (en) * | 1982-11-18 | 1986-05-06 | E. R. Squibb & Sons, Inc. | Carboxy and substituted carboxy alkanoyl and cycloalkanoyl peptides |
| US4499079A (en) * | 1982-11-18 | 1985-02-12 | E. R. Squibb & Sons, Inc. | Carboxy and substituted carboxy alkanoyl and cycloalkanoyl peptides |
| US4482544A (en) * | 1982-11-29 | 1984-11-13 | Usv Pharmaceutical Corporation | Compounds for treating hypertension |
| US4496541A (en) * | 1983-01-12 | 1985-01-29 | Usv Pharmaceutical Corporation | Compounds for treating hypertension |
| US5175306A (en) * | 1983-01-31 | 1992-12-29 | Hoechst Aktiengesellschaft | Process for the resolution of racemates of optically active bicyclic imino-α-carboxylic esters |
| US4666906A (en) * | 1983-03-16 | 1987-05-19 | Usv Pharmaceutical Corporation | Compounds for treating hypertension |
| US4596791A (en) * | 1983-03-16 | 1986-06-24 | Usv Pharmaceutical Corp. | Compounds for treating hypertension |
| GB8311286D0 (en) * | 1983-04-26 | 1983-06-02 | Searle & Co | Carboxyalkyl peptide derivatives |
| DE3333454A1 (de) * | 1983-09-16 | 1985-04-11 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von n-alkylierten dipeptiden und deren estern |
| DE3333455A1 (de) * | 1983-09-16 | 1985-04-11 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung n-alkylierter dipeptide und deren estern |
| US5684016A (en) * | 1984-04-12 | 1997-11-04 | Hoechst Aktiengesellschaft | Method of treating cardiac insufficiency |
| DE3413710A1 (de) * | 1984-04-12 | 1985-10-24 | Hoechst Ag, 6230 Frankfurt | Verfahren zur behandlung der herzinsuffizienz |
| DE3431541A1 (de) * | 1984-08-28 | 1986-03-06 | Hoechst Ag, 6230 Frankfurt | Cis,endo-2-azabicycloalkan-3-carbonsaeure-derivate, verfahren zu deren herstellung, deren verwendung sowie zwischenprodukte bei deren herstellung |
| EP0187037A3 (en) * | 1984-12-21 | 1988-03-23 | Takeda Chemical Industries, Ltd. | Piperidine derivatives, their production and use |
| JPS6248696A (ja) * | 1985-08-27 | 1987-03-03 | Kanegafuchi Chem Ind Co Ltd | Ｎ−〔１（ｓ）−エトキシカルボニル−３−フエニルプロピル〕−ｌ−アラニル−ｌ−プロリンの製造法 |
| US5231080A (en) * | 1985-10-15 | 1993-07-27 | Hoechst Aktiengesellschaft | Method for the treatment of atherosclerosis, thrombosis, and peripheral vessel disease |
| US5231084A (en) * | 1986-03-27 | 1993-07-27 | Hoechst Aktiengesellschaft | Compounds having a cognition adjuvant action, agents containing them, and the use thereof for the treatment and prophylaxis of cognitive dysfuncitons |
| EP0566157A1 (en) | 1986-06-20 | 1993-10-20 | Schering Corporation | Neutral metalloendopeptidase inhibitors in the treatment of hypertension |
| US4749688A (en) * | 1986-06-20 | 1988-06-07 | Schering Corporation | Use of neutral metalloendopeptidase inhibitors in the treatment of hypertension |
| EP0254032A3 (en) * | 1986-06-20 | 1990-09-05 | Schering Corporation | Neutral metalloendopeptidase inhibitors in the treatment of hypertension |
| DE3633496A1 (de) * | 1986-10-02 | 1988-04-14 | Hoechst Ag | Kombination von angiotensin-converting-enzyme-hemmern mit calciumantagonisten sowie deren verwendung in arzneimitteln |
| DE3639879A1 (de) * | 1986-11-21 | 1988-06-01 | Hoechst Ag | Verfahren zur herstellung von mono-, bi- und tricyclischen aminosaeuren, zwischenprodukte dieses verfahrens sowie ein verfahren zu deren herstellung |
| DK100788A (da) * | 1987-03-04 | 1988-09-05 | Takeda Chemical Industries Ltd | Fremgangsmaade til fremstilling af indanderivater |
| US5262436A (en) * | 1987-03-27 | 1993-11-16 | Schering Corporation | Acylamino acid antihypertensives in the treatment of congestive heart failure |
| DE3722007A1 (de) * | 1987-07-03 | 1989-01-12 | Hoechst Ag | Verfahren zur herstellung bicyclischer aminocarbonsaeuren, zwischenprodukte dieses verfahrens und deren verwendung |
| ZA902661B (en) * | 1989-04-10 | 1991-01-30 | Schering Corp | Mercapto-acyl amino acids |
| GB8910550D0 (en) * | 1989-05-08 | 1989-06-21 | Ici America Inc | Substituted amides |
| US5389610A (en) * | 1989-11-21 | 1995-02-14 | Schering Corporation | Carboxyalkylcarbonyl aminoacid endopeptidase inhibitors |
| US5075302A (en) * | 1990-03-09 | 1991-12-24 | Schering Corporation | Mercaptoacyl aminolactam endopeptidase inhibitors |
| US5173506A (en) * | 1990-08-16 | 1992-12-22 | Schering Corporation | N-(mercaptoalkyl)ureas and carbamates |
| US5232920A (en) * | 1990-12-21 | 1993-08-03 | Schering Corporation | N-(mercaptoalkyl)amides |
| AU2002258794A1 (en) * | 2001-04-10 | 2003-10-20 | Transtech Pharma, Inc. | Probes, systems and methods for drug discovery |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2799670A (en) * | 1954-04-13 | 1957-07-16 | Laufer Louis | Method of preparing cysteinylglycine |
| US3607859A (en) * | 1968-06-12 | 1971-09-21 | Monsanto Co | Furylacryloylgly-clycyl-l-leucinamide and relateo peptides and use thereof in spectrophotometric assay for neutral protease |
| US3799918A (en) * | 1972-04-26 | 1974-03-26 | Searle & Co | Alkyl esters of alpha-aspartyl alpha-alkyl aliphatic amino acid dipeptides |
| US4076705A (en) * | 1974-08-06 | 1978-02-28 | Shionogi & Co., Ltd. | Dipeptide derivatives and their production |
| US4116768A (en) * | 1975-04-29 | 1978-09-26 | (Zaidanhojin) Sagami Chemical Research Center | Process for producing a peptide |
| US4086136A (en) * | 1975-10-23 | 1978-04-25 | (Zaidanhojin) Sagami Chemical Research Center | Process for producing a peptide using a serine or thiol proteinase |
| CH626872A5 (ko) * | 1976-06-21 | 1981-12-15 | Hoffmann La Roche | |
| CH627735A5 (de) * | 1976-06-25 | 1982-01-29 | Hoffmann La Roche | Verfahren zur herstellung von dipeptidderivaten. |
| DE2801238C2 (de) * | 1977-01-27 | 1986-06-05 | (Zaidanhojin) Sagami Chemical Research Center, Tokio/Tokyo | Verfahren zur Herstellung von Salzen aus L,L-Dipeptiden und Phenylalaninestern |
| US4183910A (en) * | 1978-04-20 | 1980-01-15 | Levine Bernard B | Method for testing to predict and/or diagnose allergy to penicillins, and compounds and compositions for use in such tests |
| IL58849A (en) * | 1978-12-11 | 1983-03-31 | Merck & Co Inc | Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them |
| US4256761A (en) * | 1979-07-13 | 1981-03-17 | Usv Pharmaceutical Corporation | Antihypertensive amides |
| US4238392A (en) * | 1979-10-29 | 1980-12-09 | Pfizer Inc. | Purification of L-aspartyl-L-phenylalanine alkyl esters |
| AU556932B2 (en) * | 1981-03-30 | 1986-11-27 | Usv Pharmaceutical Corp. | Dipetide with heterocyclic groiup |
-
1981
- 1981-03-30 US US06/248,172 patent/US4820729A/en not_active Expired - Fee Related
-
1982
- 1982-03-19 IN IN309/CAL/82A patent/IN156595B/en unknown
- 1982-03-19 ZA ZA821869A patent/ZA821869B/xx unknown
- 1982-03-19 GB GB8208150A patent/GB2095682B/en not_active Expired
- 1982-03-22 AU AU81791/82A patent/AU559023B2/en not_active Ceased
- 1982-03-23 SE SE8201854A patent/SE8201854L/ not_active Application Discontinuation
- 1982-03-24 PH PH27051A patent/PH18663A/en unknown
- 1982-03-25 IL IL65346A patent/IL65346A0/xx unknown
- 1982-03-25 MX MX829994U patent/MX7222E/es unknown
- 1982-03-26 FR FR8205207A patent/FR2502614B1/fr not_active Expired
- 1982-03-26 CH CH1886/82A patent/CH661931A5/de not_active IP Right Cessation
- 1982-03-26 FI FI821080A patent/FI821080L/fi not_active Application Discontinuation
- 1982-03-29 IT IT20454/82A patent/IT1151125B/it active
- 1982-03-29 BE BE0/207690A patent/BE892669A/fr not_active IP Right Cessation
- 1982-03-29 ES ES511408A patent/ES8307719A1/es not_active Expired
- 1982-03-29 NO NO821037A patent/NO821037L/no unknown
- 1982-03-29 NZ NZ200164A patent/NZ200164A/en unknown
- 1982-03-29 DK DK142482A patent/DK142482A/da not_active IP Right Cessation
- 1982-03-29 DE DE19823211569 patent/DE3211569A1/de not_active Withdrawn
- 1982-03-30 JP JP57050266A patent/JPS57176941A/ja active Pending
- 1982-03-30 NL NL8201326A patent/NL8201326A/nl not_active Application Discontinuation
- 1982-03-30 IE IE753/82A patent/IE52790B1/en unknown
- 1982-03-30 KR KR1019820001388A patent/KR830008999A/ko unknown
-
1983
- 1983-04-15 ES ES521491A patent/ES521491A0/es active Granted
-
1985
- 1985-12-06 SG SG935/85A patent/SG93585G/en unknown
-
1986
- 1986-04-10 HK HK253/86A patent/HK25386A/xx unknown
- 1986-12-30 MY MY419/86A patent/MY8600419A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IT8220454A0 (it) | 1982-03-29 |
| PH18663A (en) | 1985-08-29 |
| IE820753L (en) | 1982-09-30 |
| NL8201326A (nl) | 1982-10-18 |
| IN156595B (ko) | 1985-09-14 |
| BE892669A (fr) | 1982-09-29 |
| KR830008999A (ko) | 1983-12-16 |
| FR2502614A1 (fr) | 1982-10-01 |
| JPS57176941A (en) | 1982-10-30 |
| FI821080L (fi) | 1982-10-01 |
| ES511408A0 (es) | 1983-08-01 |
| US4820729A (en) | 1989-04-11 |
| DK142482A (da) | 1982-10-01 |
| ES8405364A1 (es) | 1984-06-16 |
| FR2502614B1 (fr) | 1988-01-29 |
| NZ200164A (en) | 1985-08-16 |
| AU8179182A (en) | 1982-10-07 |
| IT1151125B (it) | 1986-12-17 |
| ES8307719A1 (es) | 1983-08-01 |
| MY8600419A (en) | 1986-12-31 |
| GB2095682A (en) | 1982-10-06 |
| IE52790B1 (en) | 1988-03-02 |
| ZA821869B (en) | 1983-01-26 |
| HK25386A (en) | 1986-04-18 |
| ES521491A0 (es) | 1984-06-16 |
| GB2095682B (en) | 1985-04-24 |
| SE8201854L (sv) | 1982-10-01 |
| MX7222E (es) | 1988-01-18 |
| SG93585G (en) | 1986-07-25 |
| CH661931A5 (de) | 1987-08-31 |
| FI821080A0 (fi) | 1982-03-26 |
| DE3211569A1 (de) | 1982-11-11 |
| IL65346A0 (en) | 1982-05-31 |
| AU559023B2 (en) | 1987-02-19 |
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