FI66840C - Foerfarande foer framstaellning av nya terapeutiskt anvaendbara alfa-fluormetyl-alfa-aminoalkansyror - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt anvaendbara alfa-fluormetyl-alfa-aminoalkansyror Download PDFInfo
- Publication number
- FI66840C FI66840C FI781674A FI781674A FI66840C FI 66840 C FI66840 C FI 66840C FI 781674 A FI781674 A FI 781674A FI 781674 A FI781674 A FI 781674A FI 66840 C FI66840 C FI 66840C
- Authority
- FI
- Finland
- Prior art keywords
- fluoromethyl
- hydroxymethyl
- formula
- tyrosine
- compound
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 49
- 239000002253 acid Substances 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229960003104 ornithine Drugs 0.000 claims description 4
- GEQODLSAFKKFCC-ZETCQYMHSA-N (2s)-3-(3,4-dihydroxyphenyl)-2-(fluoromethylamino)propanoic acid Chemical compound FCN[C@H](C(=O)O)CC1=CC=C(O)C(O)=C1 GEQODLSAFKKFCC-ZETCQYMHSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical compound CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 claims description 3
- PYSFCFGTQFSVRE-UHFFFAOYSA-N 2,5-diamino-2-(fluoromethyl)pentanoic acid Chemical compound NCCCC(N)(CF)C(O)=O PYSFCFGTQFSVRE-UHFFFAOYSA-N 0.000 claims description 2
- 239000004475 Arginine Substances 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- YOBKOMUDGCEWIN-ZETCQYMHSA-N (2S)-3-(3,4-dihydroxyphenyl)-2-(hydroxymethylamino)propanoic acid Chemical compound OCN[C@@H](CC1=CC(=C(C=C1)O)O)C(=O)O YOBKOMUDGCEWIN-ZETCQYMHSA-N 0.000 claims 1
- QHSCIWIRXWFIGH-LURJTMIESA-N (2s)-2-amino-2-methylpentanedioic acid Chemical compound OC(=O)[C@](N)(C)CCC(O)=O QHSCIWIRXWFIGH-LURJTMIESA-N 0.000 claims 1
- LYHXEKFXCOWLEE-PVPKANODSA-N FCC([C@H](N)C(=O)O)CC(=O)O Chemical compound FCC([C@H](N)C(=O)O)CC(=O)O LYHXEKFXCOWLEE-PVPKANODSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 37
- 239000000047 product Substances 0.000 description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000203 mixture Substances 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000007788 liquid Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- 239000007789 gas Substances 0.000 description 16
- 239000011347 resin Substances 0.000 description 14
- 229920005989 resin Polymers 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 12
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 11
- 230000003287 optical effect Effects 0.000 description 11
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- FOYXZVHDLXZETB-LBPRGKRZSA-N (2s)-2-(benzylazaniumyl)-3-(1h-imidazol-5-yl)propanoate Chemical compound C([C@@H](C(=O)O)NCC=1C=CC=CC=1)C1=CNC=N1 FOYXZVHDLXZETB-LBPRGKRZSA-N 0.000 description 9
- 102000004031 Carboxy-Lyases Human genes 0.000 description 9
- 108090000489 Carboxy-Lyases Proteins 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000003729 cation exchange resin Substances 0.000 description 9
- 239000010949 copper Substances 0.000 description 9
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000013522 chelant Substances 0.000 description 6
- 238000006114 decarboxylation reaction Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 229960002885 histidine Drugs 0.000 description 6
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 5
- 229910052802 copper Inorganic materials 0.000 description 5
- 238000005906 dihydroxylation reaction Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- KWGRBVOPPLSCSI-PSASIEDQSA-N (1s,2r)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-PSASIEDQSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- -1 inorganic acid salts Chemical class 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VKFQSSQEWFZWND-YFKPBYRVSA-N (2s)-5-amino-2-(fluoromethylamino)pentanoic acid Chemical compound NCCC[C@@H](C(O)=O)NCF VKFQSSQEWFZWND-YFKPBYRVSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 2
- 241001279009 Strychnos toxifera Species 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000002983 circular dichroism Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 229960004502 levodopa Drugs 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229960005453 strychnine Drugs 0.000 description 2
- QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- GZBUOYOUHBVLGP-LURJTMIESA-N (2S)-2-(chloromethylamino)-3-(1H-imidazol-5-yl)propanoic acid Chemical compound OC(=O)[C@H](Cc1cnc[nH]1)NCCl GZBUOYOUHBVLGP-LURJTMIESA-N 0.000 description 1
- XQBQSFRFBOVIAA-JTQLQIEISA-N (2S)-2-(hydroxymethylamino)-3-(4-methoxyphenyl)propanoic acid Chemical compound COC1=CC=C(C[C@H](NCO)C(=O)O)C=C1 XQBQSFRFBOVIAA-JTQLQIEISA-N 0.000 description 1
- ZSOMKTOYRKMTJS-YFKPBYRVSA-N (2S)-5-(diaminomethylideneamino)-2-(fluoromethylamino)pentanoic acid Chemical compound FCN[C@@H](CCCNC(N)=N)C(=O)O ZSOMKTOYRKMTJS-YFKPBYRVSA-N 0.000 description 1
- QMZHDWXCDDBKJY-SECBINFHSA-N (2r)-2-(hydroxymethylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound OCN[C@@H](C(O)=O)CC1=CC=C(O)C=C1 QMZHDWXCDDBKJY-SECBINFHSA-N 0.000 description 1
- PRGJINCWXXDFRZ-LURJTMIESA-N (2s)-2-(fluoromethylamino)-3-(1h-imidazol-5-yl)propanoic acid Chemical compound FCN[C@H](C(=O)O)CC1=CNC=N1 PRGJINCWXXDFRZ-LURJTMIESA-N 0.000 description 1
- QMZHDWXCDDBKJY-VIFPVBQESA-N (2s)-2-(hydroxymethylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound OCN[C@H](C(O)=O)CC1=CC=C(O)C=C1 QMZHDWXCDDBKJY-VIFPVBQESA-N 0.000 description 1
- NRNSHPCDKHOUOE-SNVBAGLBSA-N (2s)-2-amino-2-[(3,4-dihydroxyphenyl)methyl]-3-fluoropropanoic acid Chemical compound FC[C@@](N)(C(O)=O)CC1=CC=C(O)C(O)=C1 NRNSHPCDKHOUOE-SNVBAGLBSA-N 0.000 description 1
- SLEAPJHLNGFZHW-SCSAIBSYSA-N (2s)-2-amino-3-fluoro-2-methylpropanoic acid Chemical compound FC[C@](N)(C)C(O)=O SLEAPJHLNGFZHW-SCSAIBSYSA-N 0.000 description 1
- WDHVINJIFFFJFA-UHFFFAOYSA-N 2-acetamido-2-[(3,4-dimethoxyphenyl)methyl]-3-hydroxypropanoic acid Chemical compound COC1=CC=C(CC(CO)(NC(C)=O)C(O)=O)C=C1OC WDHVINJIFFFJFA-UHFFFAOYSA-N 0.000 description 1
- CDUUKBXTEOFITR-SCSAIBSYSA-N 2-methyl-D-serine Chemical compound OC[C@](N)(C)C(O)=O CDUUKBXTEOFITR-SCSAIBSYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- DBXBTMSZEOQQDU-UHFFFAOYSA-N 3-hydroxyisobutyric acid Chemical compound OCC(C)C(O)=O DBXBTMSZEOQQDU-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 206010027654 Allergic conditions Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102100038238 Aromatic-L-amino-acid decarboxylase Human genes 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- YRFAAXZTKALHNO-PIJUOVFKSA-N COC1=CC=C(C([C@@H](NC(C)=O)C(=O)O)CO)C=C1 Chemical compound COC1=CC=C(C([C@@H](NC(C)=O)C(=O)O)CO)C=C1 YRFAAXZTKALHNO-PIJUOVFKSA-N 0.000 description 1
- WBJCRPPJPSXLPB-GFCCVEGCSA-N COC1=CC=C(C[C@@H](N(CO)C(C)=O)C(=O)O)C=C1 Chemical compound COC1=CC=C(C[C@@H](N(CO)C(C)=O)C(=O)O)C=C1 WBJCRPPJPSXLPB-GFCCVEGCSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- NVYRLQBYHXDQPM-WCCKRBBISA-N Cl.FCN[C@@H](CCC(=O)O)C(=O)O Chemical compound Cl.FCN[C@@H](CCC(=O)O)C(=O)O NVYRLQBYHXDQPM-WCCKRBBISA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PLSKEFLAZZJOQZ-AKGZTFGVSA-N FCC([C@H](N)C(=O)O)CCN Chemical class FCC([C@H](N)C(=O)O)CCN PLSKEFLAZZJOQZ-AKGZTFGVSA-N 0.000 description 1
- OAEHUMVJQVOSGS-BYPYZUCNSA-N FCN[C@@H](CCC(=O)O)C(=O)O Chemical compound FCN[C@@H](CCC(=O)O)C(=O)O OAEHUMVJQVOSGS-BYPYZUCNSA-N 0.000 description 1
- OAEHUMVJQVOSGS-SCSAIBSYSA-N FCN[C@H](CCC(=O)O)C(=O)O Chemical compound FCN[C@H](CCC(=O)O)C(=O)O OAEHUMVJQVOSGS-SCSAIBSYSA-N 0.000 description 1
- QEDIOQINCOMOQI-ZETCQYMHSA-N FCOC1=C(C=C(C[C@H](N)C(=O)O)C=C1)O Chemical compound FCOC1=C(C=C(C[C@H](N)C(=O)O)C=C1)O QEDIOQINCOMOQI-ZETCQYMHSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000008214 Glutamate decarboxylase Human genes 0.000 description 1
- 108091022930 Glutamate decarboxylase Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000005909 Kieselgur Substances 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AXDLCFOOGCNDST-UHFFFAOYSA-N N-methyl-DL-tyrosine Natural products CNC(C(O)=O)CC1=CC=C(O)C=C1 AXDLCFOOGCNDST-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- MPUOJTCVKAOGDF-RZKHNPSRSA-N OCC([C@H](N)C(=O)O)C1=CNC=N1 Chemical compound OCC([C@H](N)C(=O)O)C1=CNC=N1 MPUOJTCVKAOGDF-RZKHNPSRSA-N 0.000 description 1
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 1
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108010035075 Tyrosine decarboxylase Proteins 0.000 description 1
- VSYMNDBTCKIDLT-UHFFFAOYSA-N [2-(carbamoyloxymethyl)-2-ethylbutyl] carbamate Chemical compound NC(=O)OCC(CC)(CC)COC(N)=O VSYMNDBTCKIDLT-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- OVFCVRIJCCDFNQ-UHFFFAOYSA-N carbonic acid;copper Chemical compound [Cu].OC(O)=O OVFCVRIJCCDFNQ-UHFFFAOYSA-N 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910000009 copper(II) carbonate Inorganic materials 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000011646 cupric carbonate Substances 0.000 description 1
- 235000019854 cupric carbonate Nutrition 0.000 description 1
- 239000003954 decarboxylase inhibitor Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N dopa Chemical compound OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- XIXSGKWDOQJOHK-YFKPBYRVSA-N fluoromethyl (2S)-2-amino-5-(diaminomethylideneamino)pentanoate Chemical compound FCOC(=O)[C@@H](N)CCCN=C(N)N XIXSGKWDOQJOHK-YFKPBYRVSA-N 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000004220 glutamic acid Substances 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
- 229960001340 histamine Drugs 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 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
- 230000003902 lesion Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000004079 stearyl 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])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
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 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
- 238000012360 testing method Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 description 1
- 238000006227 trimethylsilylation reaction Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 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
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80238977A | 1977-06-01 | 1977-06-01 | |
| US80238977 | 1977-06-01 | ||
| US05/802,391 US4325961A (en) | 1977-06-01 | 1977-06-01 | Fluorinated amino acids |
| US80239177 | 1977-06-01 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI781674A7 FI781674A7 (fi) | 1978-12-02 |
| FI66840B FI66840B (fi) | 1984-08-31 |
| FI66840C true FI66840C (fi) | 1984-12-10 |
Family
ID=27122442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI781674A FI66840C (fi) | 1977-06-01 | 1978-05-26 | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara alfa-fluormetyl-alfa-aminoalkansyror |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS5416423A (en, 2012) |
| AR (1) | AR223463A1 (en, 2012) |
| AT (1) | AT360509B (en, 2012) |
| AU (1) | AU518479B2 (en, 2012) |
| CA (1) | CA1120040A (en, 2012) |
| CH (1) | CH639639A5 (en, 2012) |
| DD (1) | DD138651A5 (en, 2012) |
| DE (1) | DE2824116A1 (en, 2012) |
| DK (1) | DK149841C (en, 2012) |
| ES (1) | ES470296A1 (en, 2012) |
| FI (1) | FI66840C (en, 2012) |
| FR (1) | FR2392958A1 (en, 2012) |
| GB (1) | GB1602525A (en, 2012) |
| GR (1) | GR64495B (en, 2012) |
| HK (1) | HK18184A (en, 2012) |
| HU (1) | HU181911B (en, 2012) |
| IE (1) | IE46983B1 (en, 2012) |
| IT (1) | IT1104709B (en, 2012) |
| LU (1) | LU79750A1 (en, 2012) |
| NL (1) | NL190485C (en, 2012) |
| NO (1) | NO147382C (en, 2012) |
| NZ (1) | NZ187377A (en, 2012) |
| PL (1) | PL115731B1 (en, 2012) |
| PT (1) | PT68102B (en, 2012) |
| SE (1) | SE7806440L (en, 2012) |
| YU (1) | YU129178A (en, 2012) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL59481A0 (en) * | 1977-07-11 | 1980-05-30 | Merrell Toraude & Co | -halomethyl amino acids |
| CA1091661A (en) * | 1977-07-11 | 1980-12-16 | Philippe Bey | .alpha.-HALOMETHYL DERIVATIVES OF .alpha.-AMINO ACIDS |
| ZA783273B (en) * | 1977-07-11 | 1979-06-27 | Merrell Toraude & Co | A-halomethyl amino acids |
| US4315095A (en) * | 1977-07-28 | 1982-02-09 | Merrell Toraude Et Compagnie | α-Halomethyl derivatives of amino acids |
| ATE3282T1 (de) * | 1978-07-24 | 1983-05-15 | Merck & Co. Inc. | Alpha-difluormethyl-alpha-aminosaeuren und sie enthaltende pharmazeutische zusammensetzung. |
| IE49522B1 (en) * | 1979-04-26 | 1985-10-16 | Merrell Toraude & Co | Alpha-halomethylaminoacids |
| CA1158657A (en) * | 1979-07-26 | 1983-12-13 | Philippe Bey | Preparation of fluorinated methyl aminoalkanoic acids and novel process intermediates |
| ZA813018B (en) * | 1980-05-09 | 1982-05-26 | Merrell Toraude & Co | Fluoromethylated tyrosine methyl ester |
| CA1174603A (en) * | 1980-06-16 | 1984-09-18 | Albert Sjoerdsma | Method of inhibiting the growth of protozoa |
| US4421767A (en) * | 1981-06-01 | 1983-12-20 | Merrell Toraude Et Compagnie | Compounds and methods for treating depression |
| GB9325368D0 (en) * | 1993-12-10 | 1994-02-16 | Univ Bristol | Organic compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3046300A (en) * | 1960-10-21 | 1962-07-24 | Merck & Co Inc | alpha-trifluoromethyloxyphenylalanines |
-
1978
- 1978-05-25 FR FR7815567A patent/FR2392958A1/fr active Granted
- 1978-05-25 GR GR56328A patent/GR64495B/el unknown
- 1978-05-25 NZ NZ187377A patent/NZ187377A/xx unknown
- 1978-05-26 FI FI781674A patent/FI66840C/fi not_active IP Right Cessation
- 1978-05-26 AR AR272336A patent/AR223463A1/es active
- 1978-05-29 AU AU36586/78A patent/AU518479B2/en not_active Expired
- 1978-05-29 CA CA000304318A patent/CA1120040A/en not_active Expired
- 1978-05-29 ES ES470296A patent/ES470296A1/es not_active Expired
- 1978-05-30 GB GB24330/78A patent/GB1602525A/en not_active Expired
- 1978-05-30 PT PT68102A patent/PT68102B/pt unknown
- 1978-05-30 DK DK237978A patent/DK149841C/da not_active IP Right Cessation
- 1978-05-30 DD DD78205669A patent/DD138651A5/xx unknown
- 1978-05-30 AT AT393278A patent/AT360509B/de not_active IP Right Cessation
- 1978-05-30 YU YU01291/78A patent/YU129178A/xx unknown
- 1978-05-30 IE IE1078/78A patent/IE46983B1/en unknown
- 1978-05-30 HU HU78ME2169A patent/HU181911B/hu unknown
- 1978-05-31 PL PL1978207242A patent/PL115731B1/pl unknown
- 1978-05-31 NO NO781892A patent/NO147382C/no unknown
- 1978-05-31 IT IT49637/78A patent/IT1104709B/it active
- 1978-05-31 CH CH597978A patent/CH639639A5/de not_active IP Right Cessation
- 1978-06-01 NL NLAANVRAGE7805981,A patent/NL190485C/xx not_active IP Right Cessation
- 1978-06-01 JP JP6501678A patent/JPS5416423A/ja active Granted
- 1978-06-01 SE SE7806440A patent/SE7806440L/xx unknown
- 1978-06-01 LU LU79750A patent/LU79750A1/xx unknown
- 1978-06-01 DE DE19782824116 patent/DE2824116A1/de active Granted
-
1984
- 1984-03-01 HK HK181/84A patent/HK18184A/en not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4325961A (en) | Fluorinated amino acids | |
| FI66840C (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara alfa-fluormetyl-alfa-aminoalkansyror | |
| HU228197B1 (en) | Stable salts of 3,3-diphenylpropylamines derivatives and preparation thereof | |
| UA66359C2 (uk) | Спосіб одержання рацемічних або оптично активних сполук | |
| US4297282A (en) | Resolution of mercaptopropionic acids | |
| EP3022183A1 (en) | Method of racemisation of undesired enantiomers | |
| JP2012521352A (ja) | ［２−（８，９−ジオキソ−２，６−ジアザビシクロ［５．２．０］ノナ−１（７）−エン−２−イル）エチル］ホスホン酸およびその前駆体を調製するための方法 | |
| US4695588A (en) | Fluorinated amino acids | |
| US5171752A (en) | Benzhydryl derivatives having calmodulin inhibitor properties | |
| HU229188B1 (hu) | Új eljárás N-[(S)-1-karboxibutil]-(S)-alanin-észterek elõállítására, és a perindopril szintézisnél történõ alkalmazása | |
| US4451473A (en) | 3,7-Diazabicyclo [3.3.1] nonanes having anti-arrhythmic activity | |
| de Meijere et al. | Convenient Syntheses of Novel α‐and β‐Amino Acids with Spiropentyl Groups | |
| EP0000034B1 (en) | Fluorinated amines, compositions and process for preparing said compounds | |
| EP0000035A1 (en) | Alpha-amino acids, compositions and process for preparing said compounds | |
| US4325886A (en) | Optical resolution of acylthiopropionic acid | |
| EP0000036B1 (en) | Fluorinated alkylamines and process for preparing same | |
| US4176183A (en) | Novel naphthyridines | |
| EP0007600B1 (en) | Alpha-difluoromethyl amino acids and pharmaceutical composition containing the same | |
| US4288601A (en) | Fluorination process | |
| DK172006B1 (da) | Fremgangsmåde til syntese af optisk aktive aminosyrer | |
| US4347374A (en) | Acid addition salts of N-trityl-α-fluoromethylhistidine enantiomer derivatives | |
| US4411836A (en) | Racemization of an α-methyl-β-acylthiopropionic acid | |
| US4431821A (en) | Fluorinated tryptamines | |
| US4215221A (en) | Fluorination process | |
| US4431817A (en) | Fluorinated imidazolyl alkylamines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: MERCK & CO., INC. |