NO782128L - Fremgangsmaate for fremstilling av fysiologisk aktive isonikotinsyrederivater - Google Patents
Fremgangsmaate for fremstilling av fysiologisk aktive isonikotinsyrederivaterInfo
- Publication number
- NO782128L NO782128L NO782128A NO782128A NO782128L NO 782128 L NO782128 L NO 782128L NO 782128 A NO782128 A NO 782128A NO 782128 A NO782128 A NO 782128A NO 782128 L NO782128 L NO 782128L
- Authority
- NO
- Norway
- Prior art keywords
- group
- compound
- general formula
- acid
- hydrogen
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 23
- 239000002253 acid Substances 0.000 title claims description 14
- 238000000034 method Methods 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 80
- 150000003839 salts Chemical class 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229940125890 compound Ia Drugs 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- -1 formic acid ester Chemical class 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000000286 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 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 235000019253 formic acid Nutrition 0.000 claims description 6
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- KRVDMABBKYMBHG-UHFFFAOYSA-N Isoguvacine Chemical compound OC(=O)C1=CCNCC1 KRVDMABBKYMBHG-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 3
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 claims description 3
- YVIHCEXQAJNSKX-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=CCNCC1 YVIHCEXQAJNSKX-UHFFFAOYSA-N 0.000 claims description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 2
- 150000008064 anhydrides Chemical class 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 239000002516 radical scavenger Substances 0.000 claims 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 46
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 23
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 23
- 239000000243 solution Substances 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- ZJQHPWUVQPJPQT-UHFFFAOYSA-N muscimol Chemical compound NCC1=CC(=O)NO1 ZJQHPWUVQPJPQT-UHFFFAOYSA-N 0.000 description 15
- 238000002844 melting Methods 0.000 description 14
- 230000008018 melting Effects 0.000 description 14
- 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
- 230000000694 effects Effects 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- PFVFXDVOCHMQDU-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine-4-carboxylic acid Chemical compound OC(=O)C1CCNC=C1 PFVFXDVOCHMQDU-UHFFFAOYSA-N 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 102000003946 Prolactin Human genes 0.000 description 4
- 108010057464 Prolactin Proteins 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000008499 blood brain barrier function Effects 0.000 description 4
- 210000001218 blood-brain barrier Anatomy 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 230000007257 malfunction Effects 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 229940097325 prolactin Drugs 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical class CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 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
- 150000002148 esters Chemical class 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 150000002990 phenothiazines Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- RLJKFAMYSYWMND-GRTNUQQKSA-M (6r)-6-[(5s)-6,6-dimethyl-7,8-dihydro-5h-[1,3]dioxolo[4,5-g]isoquinolin-6-ium-5-yl]-6h-furo[3,4-g][1,3]benzodioxol-8-one;chloride Chemical compound [Cl-].O([C@H]1[C@@H]2C3=CC=4OCOC=4C=C3CC[N+]2(C)C)C(=O)C2=C1C=CC1=C2OCO1 RLJKFAMYSYWMND-GRTNUQQKSA-M 0.000 description 2
- WKYGMSYBNGFBEX-UHFFFAOYSA-N 1,2,3,6-tetrahydropyridine-4-carboxylic acid;hydrobromide Chemical compound Br.OC(=O)C1=CCNCC1 WKYGMSYBNGFBEX-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FTCQLFBQQZDCQA-UHFFFAOYSA-N 1-trityl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound C1CC(C(=O)O)=CCN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 FTCQLFBQQZDCQA-UHFFFAOYSA-N 0.000 description 2
- MZWLADOOFUTXPI-UHFFFAOYSA-N 2,2-dimethylpropanoyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate;hydrobromide Chemical compound Br.CC(C)(C)C(=O)OCOC(=O)C1=CCNCC1 MZWLADOOFUTXPI-UHFFFAOYSA-N 0.000 description 2
- ICJWWLYKZUYLCT-UHFFFAOYSA-N 3-hydroxypiperidine-4-carboxylic acid;hydrochloride Chemical compound Cl.OC1CNCCC1C(O)=O ICJWWLYKZUYLCT-UHFFFAOYSA-N 0.000 description 2
- 241000134914 Amanita muscaria Species 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
- 102000005915 GABA Receptors Human genes 0.000 description 2
- 108010005551 GABA Receptors Proteins 0.000 description 2
- 229940121909 GABA receptor agonist Drugs 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010062767 Hypophysitis Diseases 0.000 description 2
- 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 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- 206010034010 Parkinsonism Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 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
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 230000035873 hypermotility Effects 0.000 description 2
- 239000000960 hypophysis hormone Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical class OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- ISHLCKAQWKBMAU-UHFFFAOYSA-N tert-butyl n-diazocarbamate Chemical compound CC(C)(C)OC(=O)N=[N+]=[N-] ISHLCKAQWKBMAU-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- YWJLYDGNYAZLTN-UHFFFAOYSA-N (2-phenylacetyl)oxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound C=1CNCCC=1C(=O)OCOC(=O)CC1=CC=CC=C1 YWJLYDGNYAZLTN-UHFFFAOYSA-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
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- SMNWDTHJSPTXJT-UHFFFAOYSA-N 1-(4-chlorophenoxy)carbonyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound C1CC(C(=O)O)=CCN1C(=O)OC1=CC=C(Cl)C=C1 SMNWDTHJSPTXJT-UHFFFAOYSA-N 0.000 description 1
- GMCOILLDURLTQK-UHFFFAOYSA-N 1-(4-methoxyphenoxy)carbonyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1OC(=O)N1CC=C(C(O)=O)CC1 GMCOILLDURLTQK-UHFFFAOYSA-N 0.000 description 1
- ULIZLOYJESBEQP-UHFFFAOYSA-N 1-(4-methylphenoxy)carbonyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound C1=CC(C)=CC=C1OC(=O)N1CC=C(C(O)=O)CC1 ULIZLOYJESBEQP-UHFFFAOYSA-N 0.000 description 1
- VXFNKGMGJZDHCD-UHFFFAOYSA-N 1-acetyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound CC(=O)N1CCC(C(O)=O)=CC1 VXFNKGMGJZDHCD-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- BNRJEFPEEYASCL-UHFFFAOYSA-N 1-butoxycarbonyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound CCCCOC(=O)N1CCC(C(O)=O)=CC1 BNRJEFPEEYASCL-UHFFFAOYSA-N 0.000 description 1
- MHIKJQMGPHGMEZ-UHFFFAOYSA-N 1-ethoxycarbonyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound CCOC(=O)N1CCC(C(O)=O)=CC1 MHIKJQMGPHGMEZ-UHFFFAOYSA-N 0.000 description 1
- AYQAKNRNHIUKIY-UHFFFAOYSA-N 1-methyl-3,6-dihydro-2h-pyridine-4-carboxylic acid;hydrochloride Chemical compound [Cl-].C[NH+]1CCC(C(O)=O)=CC1 AYQAKNRNHIUKIY-UHFFFAOYSA-N 0.000 description 1
- HGIVSKXVQGXEAV-UHFFFAOYSA-N 1-phenoxycarbonyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound C1CC(C(=O)O)=CCN1C(=O)OC1=CC=CC=C1 HGIVSKXVQGXEAV-UHFFFAOYSA-N 0.000 description 1
- FRWCNDVEBMIVDG-UHFFFAOYSA-N 1-phenylmethoxycarbonyl-3,6-dihydro-2h-pyridine-4-carboxylic acid Chemical compound C1CC(C(=O)O)=CCN1C(=O)OCC1=CC=CC=C1 FRWCNDVEBMIVDG-UHFFFAOYSA-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
- OCDFFPRVRQLOAE-UHFFFAOYSA-N 2-acetyloxypropan-2-yl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CC(=O)OC(C)(C)OC(=O)C1=CCNCC1 OCDFFPRVRQLOAE-UHFFFAOYSA-N 0.000 description 1
- JEJFXQFDECUFAX-UHFFFAOYSA-N 2-ethylbutanoyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CCC(CC)C(=O)OCOC(=O)C1=CCNCC1 JEJFXQFDECUFAX-UHFFFAOYSA-N 0.000 description 1
- NJPPWBLCPTZCOL-UHFFFAOYSA-N 2-methylpropanoyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CC(C)C(=O)OCOC(=O)C1=CCNCC1 NJPPWBLCPTZCOL-UHFFFAOYSA-N 0.000 description 1
- 239000003148 4 aminobutyric acid receptor blocking agent Substances 0.000 description 1
- MVQROXPEZULQEP-UHFFFAOYSA-N 4-o-ethyl 1-o-methyl 3-hydroxypiperidine-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC)CC1O MVQROXPEZULQEP-UHFFFAOYSA-N 0.000 description 1
- PTKLDHADMDDGDN-UHFFFAOYSA-N 4-o-ethyl 1-o-methyl 3-oxopiperidine-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC)CC1=O PTKLDHADMDDGDN-UHFFFAOYSA-N 0.000 description 1
- PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical compound C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010047141 Vasodilatation Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- MHLMRBVCMNDOCW-UHFFFAOYSA-N acetic acid;butan-1-ol;hydrate Chemical compound O.CC(O)=O.CCCCO MHLMRBVCMNDOCW-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- UNQJZCVCDPKMAK-UHFFFAOYSA-N acetyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CC(=O)OCOC(=O)C1=CCNCC1 UNQJZCVCDPKMAK-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- JFWIRJZMFJWEKQ-UHFFFAOYSA-N benzoyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound C=1CNCCC=1C(=O)OCOC(=O)C1=CC=CC=C1 JFWIRJZMFJWEKQ-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 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
- KTTYCCHHKLNNMY-UHFFFAOYSA-N butanoyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CCCC(=O)OCOC(=O)C1=CCNCC1 KTTYCCHHKLNNMY-UHFFFAOYSA-N 0.000 description 1
- PDQOMVCEIFSXDN-UHFFFAOYSA-N butyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CCCCOC(=O)C1=CCNCC1 PDQOMVCEIFSXDN-UHFFFAOYSA-N 0.000 description 1
- IYVYJDZFDIOPRN-UHFFFAOYSA-N butyl 1,2,3,6-tetrahydropyridine-4-carboxylate;hydrobromide Chemical compound Br.CCCCOC(=O)C1=CCNCC1 IYVYJDZFDIOPRN-UHFFFAOYSA-N 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
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- XKMYLRYRMPTNPE-UHFFFAOYSA-N diethyl 3,6-dihydro-2h-pyridine-1,4-dicarboxylate Chemical compound CCOC(=O)N1CCC(C(=O)OCC)=CC1 XKMYLRYRMPTNPE-UHFFFAOYSA-N 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000003400 hallucinatory effect Effects 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229960003350 isoniazid Drugs 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- YJBXHMHSOCHRLV-UHFFFAOYSA-N methyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound COC(=O)C1=CCNCC1 YJBXHMHSOCHRLV-UHFFFAOYSA-N 0.000 description 1
- BJLGIRWBYKEMDX-UHFFFAOYSA-N methyl 1,2,3,6-tetrahydropyridine-4-carboxylate;hydrobromide Chemical compound Br.COC(=O)C1=CCNCC1 BJLGIRWBYKEMDX-UHFFFAOYSA-N 0.000 description 1
- YTSAAQMJVBJTJS-UHFFFAOYSA-N methyl 1,2,3,6-tetrahydropyridine-4-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1=CCNCC1 YTSAAQMJVBJTJS-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- LKVYWSOUXPAASC-UHFFFAOYSA-N propan-2-yl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CC(C)OC(=O)C1=CCNCC1 LKVYWSOUXPAASC-UHFFFAOYSA-N 0.000 description 1
- QFPHZWKUUXPCHL-UHFFFAOYSA-N propanoyloxymethyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CCC(=O)OCOC(=O)C1=CCNCC1 QFPHZWKUUXPCHL-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- PBMDISAJJZPQKQ-UHFFFAOYSA-N propyl 1,2,3,6-tetrahydropyridine-4-carboxylate Chemical compound CCCOC(=O)C1=CCNCC1 PBMDISAJJZPQKQ-UHFFFAOYSA-N 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000015149 toffees Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2574077 | 1977-06-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO782128L true NO782128L (no) | 1978-12-21 |
Family
ID=10232513
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO782128A NO782128L (no) | 1977-06-20 | 1978-06-19 | Fremgangsmaate for fremstilling av fysiologisk aktive isonikotinsyrederivater |
| NO782127A NO152049C (no) | 1977-06-20 | 1978-06-19 | Analogifremgangsmaate for fremstilling av den farmasoeytisk anvendelige forbindelse 4,5,6,7-tetrahydroisoksazolo (5,4-c)pyridin-3-ol |
| NO792839A NO792839L (no) | 1977-06-20 | 1979-09-03 | Mellomprodukt for anvendelse ved fremstilling av fysiologisk aktive isonikotinsyrederivater |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO782127A NO152049C (no) | 1977-06-20 | 1978-06-19 | Analogifremgangsmaate for fremstilling av den farmasoeytisk anvendelige forbindelse 4,5,6,7-tetrahydroisoksazolo (5,4-c)pyridin-3-ol |
| NO792839A NO792839L (no) | 1977-06-20 | 1979-09-03 | Mellomprodukt for anvendelse ved fremstilling av fysiologisk aktive isonikotinsyrederivater |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US4278676A (de) |
| EP (4) | EP0027279A1 (de) |
| JP (2) | JPS5436275A (de) |
| AT (1) | AT368505B (de) |
| AU (2) | AU3724478A (de) |
| CA (1) | CA1107736A (de) |
| DK (2) | DK270278A (de) |
| ES (2) | ES470912A1 (de) |
| FI (2) | FI64376C (de) |
| IE (1) | IE47200B1 (de) |
| IT (2) | IT7868449A0 (de) |
| NO (3) | NO782128L (de) |
| NZ (1) | NZ187615A (de) |
| ZA (2) | ZA783492B (de) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3145474A1 (de) * | 1980-11-27 | 1982-09-02 | Kefalas A/S, Koebenhavn-Valby | 3-substituierte 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridinverbindungen, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| DE3145473A1 (de) * | 1980-11-27 | 1982-08-26 | Kefalas A/S, Koebenhavn-Valby | 2-substituierte 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-on-verbindungen, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| EP0083378A1 (de) * | 1981-12-22 | 1983-07-13 | Chugai Seiyaku Kabushiki Kaisha | Tetrahydronicotinsäureamide, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen |
| GB8314391D0 (en) * | 1983-05-24 | 1983-06-29 | Kefalas As | Heterocyclic compounds |
| IT1228426B (it) * | 1987-07-20 | 1991-06-17 | Ausimont Spa | Perossiacidi eterociclici |
| US4859666A (en) * | 1988-07-06 | 1989-08-22 | Bristol-Myers Company | THAZ derivatives for enhancement of cerebral function |
| CN1043051C (zh) * | 1994-07-22 | 1999-04-21 | 国际壳牌研究有限公司 | 制备氢化石蜡的方法 |
| US20050234093A1 (en) * | 2003-06-25 | 2005-10-20 | H. Lundbeck A/S | Treatment of depression and other affective disorders |
| WO2004112786A2 (en) | 2003-06-25 | 2004-12-29 | H. Lundbeck A/S | Gaboxadol for treating depression and other affective disorders |
| AR045540A1 (es) | 2003-09-05 | 2005-11-02 | Lundbeck & Co As H | Metodo de elaboracion de 4,5,6,7 tetrahidroisoxazol [5,4-c] piridin-3-ol (thip) |
| EP1691811B1 (de) | 2003-12-11 | 2014-07-23 | Sunovion Pharmaceuticals Inc. | Kombination aus einem sedativum und einem neurotransmitter-modulator und verfahren zur verbesserung der schlafqualität und zur behandlung von depression |
| US20050137222A1 (en) * | 2003-12-18 | 2005-06-23 | H. Lundbeck A/S | Treatment of insomnia in human patients |
| US20050215521A1 (en) * | 2003-12-22 | 2005-09-29 | Karim Lalji | Modafinil combination therapy for improving sleep quality |
| AU2004308962A1 (en) * | 2003-12-24 | 2005-07-14 | Sepracor Inc. | Melatonin combination therapy for improving sleep quality |
| GB0402118D0 (en) * | 2004-01-30 | 2004-03-03 | Merck Sharp & Dohme | Polymorphic forms of a GABAA agonist |
| DE602005018763D1 (de) * | 2004-02-18 | 2010-02-25 | Sepracor Inc | Dopamin-agonisten-kombinationstherapie mit sedativa zur verbesserung der schlafqualität |
| GB0417558D0 (en) * | 2004-08-06 | 2004-09-08 | Merck Sharp & Dohme | Novel combination therapy |
| EP1848420A4 (de) | 2005-01-28 | 2008-01-23 | Merck & Co Inc | Polymorphe formen eines gabaa-agonisten |
| EP1906953A4 (de) * | 2005-04-29 | 2009-05-20 | Lundbeck & Co As H | Säure- und basensalzformen von gaboxadol |
| JP2009506069A (ja) | 2005-08-26 | 2009-02-12 | ブレインセルス，インコーポレイティド | ムスカリン性受容体調節による神経発生 |
| EP2258359A3 (de) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenese durch Modulation des Muscarinrezeptors mit Sabcomelin |
| AU2006304787A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
| CA2625210A1 (en) * | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20070203216A1 (en) * | 2006-02-14 | 2007-08-30 | Bjarke Ebert | Method of treating inflammatory diseases |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| AU2007249399A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| US7678808B2 (en) | 2006-05-09 | 2010-03-16 | Braincells, Inc. | 5 HT receptor mediated neurogenesis |
| EP2068872A1 (de) | 2006-09-08 | 2009-06-17 | Braincells, Inc. | Kombinationen mit einem 4-acylaminopyridin-derivat |
| US20100193652A1 (en) * | 2009-02-02 | 2010-08-05 | William Stajos | Wall Display System And Method Of Providing The Same |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| US8784835B2 (en) * | 2012-07-02 | 2014-07-22 | Trent Austin | Method for producing muscimol and/or reducing ibotenic acid from amanita tissue |
| CN104974175A (zh) * | 2014-04-11 | 2015-10-14 | 天津药物研究院 | 一种氨甲基羟异恶唑类似物的制备方法 |
| MX2016016136A (es) | 2014-06-06 | 2017-07-05 | Ovid Therapeutics Inc | Metodos para incrementar la inhibicion tonica y para tratar insomnio secundario. |
| SI3274331T1 (sl) | 2015-03-24 | 2020-08-31 | H. Lundbeck A/S | Izdelava 4,5,6,7-tetrahidroizozaksolo (5,4-C)piridin-3-ol |
| IL305342A (en) | 2015-07-17 | 2023-10-01 | Ovid Therapeutics Inc | Methods for treating developmental disorders with gaboxadol |
| US9682069B2 (en) | 2015-07-17 | 2017-06-20 | Ovid Therapeutics Inc | Methods of treating Dravet syndrome |
| US9399034B1 (en) | 2015-08-11 | 2016-07-26 | Ovid Therapeutics Inc | Methods of sedation during critical care treatment |
| AU2017311412B2 (en) | 2016-08-11 | 2023-05-18 | Ovid Therapeutics Inc. | Methods and compositions for treatment of epileptic disorders |
| US10071083B2 (en) | 2017-02-03 | 2018-09-11 | Ovid Therapeutics Inc | Use of gaboxadol in the treatment of tinnitus |
| US20180338959A1 (en) | 2017-05-24 | 2018-11-29 | Ovid Therapeutics Inc. | Treatment of depressive disorders |
| US10813918B2 (en) | 2017-08-04 | 2020-10-27 | Ovid Therapeutics Inc. | Use of Gaboxadol in the treatment of diabetes and related conditions |
| JP2022501384A (ja) | 2018-09-20 | 2022-01-06 | オービッド・セラピューティクス・インコーポレイテッドOvid Therapeutics Inc. | トゥレット症候群、チックおよび吃音の処置のためのガボキサドールの使用 |
| WO2020106927A1 (en) | 2018-11-21 | 2020-05-28 | Certego Therapeutics | Gaboxadol for reducing risk of suicide and rapid relief of depression |
| CA3123876A1 (en) | 2018-12-17 | 2020-06-25 | Ovid Therapeutics Inc. | Use of gaboxadol for the treatment of non-24 hour sleep-wake disorder |
| IL298334A (en) | 2020-05-20 | 2023-01-01 | Certego Therapeutics Inc | A canceled gaboxadol ring and its use for the treatment of psychiatric disorders |
| CN114292224B (zh) * | 2022-03-07 | 2022-05-20 | 中国农业科学院农产品加工研究所 | 一种大麻二酚-2-（n-乙酰基）哌啶酸酯及其应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2784190A (en) * | 1952-03-28 | 1957-03-05 | Upjohn Co | Alkyl piperidinepropionates |
| CA762455A (en) * | 1962-03-22 | 1967-07-04 | Dr. Karl Thomae Gesellschaft Mit Beschrankter Haftung | Pyrido-pyrimidines |
| US3381016A (en) * | 1966-03-04 | 1968-04-30 | Upjohn Co | Isoxazolo[5, 4-b]pyridine derivatives and a method for their preparation |
| DE2221770A1 (de) * | 1972-05-04 | 1973-11-15 | Bayer Ag | Verfahren zur herstellung von tetrahydropyridinen |
| DK62791A (da) * | 1991-04-09 | 1992-11-09 | Tulip Int As | Fremgangsmaade til saltning af koed samt anlaeg til brug ved udoevelse af fremgangsmaaden |
-
1978
- 1978-06-15 DK DK270278A patent/DK270278A/da unknown
- 1978-06-15 DK DK270378A patent/DK270378A/da unknown
- 1978-06-19 FI FI781954A patent/FI64376C/fi not_active IP Right Cessation
- 1978-06-19 ES ES470912A patent/ES470912A1/es not_active Expired
- 1978-06-19 FI FI781955A patent/FI781955A/fi not_active Application Discontinuation
- 1978-06-19 EP EP80106497A patent/EP0027279A1/de not_active Withdrawn
- 1978-06-19 NO NO782128A patent/NO782128L/no unknown
- 1978-06-19 NZ NZ187615A patent/NZ187615A/xx unknown
- 1978-06-19 IE IE1234/78A patent/IE47200B1/en unknown
- 1978-06-19 NO NO782127A patent/NO152049C/no unknown
- 1978-06-19 ES ES470913A patent/ES470913A1/es not_active Expired
- 1978-06-19 EP EP78100190A patent/EP0000167A1/de not_active Withdrawn
- 1978-06-19 ZA ZA00783492A patent/ZA783492B/xx unknown
- 1978-06-19 US US05/917,118 patent/US4278676A/en not_active Expired - Lifetime
- 1978-06-19 AU AU37244/78A patent/AU3724478A/en active Pending
- 1978-06-19 ZA ZA00783493A patent/ZA783493B/xx unknown
- 1978-06-19 EP EP80106498A patent/EP0028017A1/de not_active Withdrawn
- 1978-06-19 EP EP78100191A patent/EP0000338B1/de not_active Expired
- 1978-06-20 JP JP7479978A patent/JPS5436275A/ja active Pending
- 1978-06-20 IT IT7868449A patent/IT7868449A0/it unknown
- 1978-06-20 AT AT0448678A patent/AT368505B/de not_active IP Right Cessation
- 1978-06-20 CA CA305,798A patent/CA1107736A/en not_active Expired
- 1978-06-20 IT IT68450/78A patent/IT1159739B/it active
- 1978-06-20 JP JP7480078A patent/JPS5436290A/ja active Pending
- 1978-06-20 AU AU37298/78A patent/AU521040B2/en not_active Expired
-
1979
- 1979-09-03 NO NO792839A patent/NO792839L/no unknown
- 1979-12-17 US US06/104,080 patent/US4301287A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US4278676A (en) | 1981-07-14 |
| ATA448678A (de) | 1982-02-15 |
| ES470912A1 (es) | 1979-02-01 |
| ZA783492B (en) | 1979-06-27 |
| IE47200B1 (en) | 1984-01-11 |
| DK270378A (da) | 1978-12-21 |
| EP0000338A2 (de) | 1979-01-24 |
| EP0000167A1 (de) | 1979-01-10 |
| US4301287A (en) | 1981-11-17 |
| NO152049C (no) | 1985-07-24 |
| FI64376C (fi) | 1983-11-10 |
| AT368505B (de) | 1982-10-25 |
| JPS5436275A (en) | 1979-03-16 |
| NZ187615A (en) | 1981-12-15 |
| CA1107736A (en) | 1981-08-25 |
| JPS5436290A (en) | 1979-03-16 |
| NO152049B (no) | 1985-04-15 |
| FI64376B (fi) | 1983-07-29 |
| NO782127L (no) | 1978-12-21 |
| IE781234L (en) | 1978-12-20 |
| FI781955A (fi) | 1978-12-21 |
| IT7868450A0 (it) | 1978-06-20 |
| IT1159739B (it) | 1987-03-04 |
| ES470913A1 (es) | 1979-02-01 |
| EP0000338B1 (de) | 1981-11-25 |
| ZA783493B (en) | 1979-06-27 |
| EP0027279A1 (de) | 1981-04-22 |
| IT7868449A0 (it) | 1978-06-20 |
| EP0028017A1 (de) | 1981-05-06 |
| DK270278A (da) | 1978-12-21 |
| EP0000338A3 (en) | 1979-06-27 |
| NO792839L (no) | 1978-12-21 |
| FI781954A (fi) | 1978-12-21 |
| AU521040B2 (en) | 1982-03-11 |
| AU3724478A (en) | 1980-01-03 |
| AU3729878A (en) | 1980-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO782128L (no) | Fremgangsmaate for fremstilling av fysiologisk aktive isonikotinsyrederivater | |
| JP7565078B2 (ja) | Ａｌｋタンパク質分解剤及びそれらの癌療法における使用 | |
| KR880000042B1 (ko) | 신규 유기 아마이드 화합물의 제법 | |
| EP0595610B1 (de) | Benzokondensierte Lactame | |
| SE445352B (sv) | Forfarande for framstellning av dipeptider, vilka inhiberar overforing av angiotensin i till angiotensin ii | |
| JPS6058751B2 (ja) | プロリン関連化合物ならびにその製法 | |
| EP2600866A1 (de) | Verfahren zur herstellung von tubulysinen | |
| DD201782A5 (de) | Verfahren zur herstellung von octahydro-1-(omega-mercaptoalkanoyl)-1h-indol 2-carbonsaeure-verbindungen | |
| SK283233B6 (sk) | Deriváty benzazepinon-N-octovej kyseliny substituované kyselinou fosfónovou, ako aj spôsob ich výroby a liečivá obsahujúce tieto zlúčeniny | |
| AU2008320718B2 (en) | Indol-2-one derivatives disubstituted in the 3-position, preparation thereof and therapeutic use thereof | |
| CS621585A2 (en) | Method of analynprolinone derivatives production | |
| FR2701708A1 (fr) | Dérivés de 2-amido-4-phénylthiazoles polysubstitués, procédé de préparation, composition pharmaceutique et utilisation de ces dérivés pour la préparation d'un médicament. | |
| JP6180432B2 (ja) | アザアダマンタン誘導体およびその使用 | |
| KR20220127839A (ko) | Khk 억제 효과를 갖는 화합물 | |
| SU1308196A3 (ru) | Способ получени 5,11-дигидро-11- @ (1-метил-4-пиперидинил)-амино @ -карбонил @ -6 @ -дибенз ( @ , @ )азепин-6-она или его солей | |
| US5312826A (en) | N,3-disubstituted alaninamide derivatives | |
| US4968670A (en) | Pyridine-2,4- and 2,5-dicarboxylic acid derivatives, a process for their preparation, the use thereof, and medicaments based on these compounds | |
| MXPA99003106A (es) | Compuestos azaheterociclicos n-sustituidos. | |
| JP7007381B2 (ja) | 細胞外クエン酸の取込みの阻害剤としてのスルホンアミド | |
| CS230562B2 (en) | Production method of halogen n-/mepkaptoacyl/proline derivatives | |
| CA3155114A1 (en) | Semicarbazide-sensitive amino oxidase inhibitors and use thereof | |
| FI68841B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara erotpeptidalkaloidderivat | |
| EP0145304B1 (de) | Tetrahydro-beta-carbolinderivate und Verfahren zu ihrer Herstellung | |
| IE904434A1 (en) | "New thiophene derivatives, the process for the preparation thereof and the pharmaceutical compositions containing them" | |
| CS236782B2 (en) | Processing of 5 s-(2r-butyl)peptidergotalkaloid |