CA1064942A - Pyroglutamy compounds having antidepressive activity and process for their manufacture - Google Patents
Pyroglutamy compounds having antidepressive activity and process for their manufactureInfo
- Publication number
- CA1064942A CA1064942A CA227,255A CA227255A CA1064942A CA 1064942 A CA1064942 A CA 1064942A CA 227255 A CA227255 A CA 227255A CA 1064942 A CA1064942 A CA 1064942A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- acid
- pyroglutamyl
- compound
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000001430 anti-depressive effect Effects 0.000 title description 4
- 238000004519 manufacturing process Methods 0.000 title description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 125000005518 carboxamido group Chemical group 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 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 claims abstract description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 19
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 13
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 8
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 claims description 7
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 7
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- DAZRVKBSFHYTLI-GDVGLLTNSA-N 4-amino-2-[(2S)-5-oxopyrrolidine-2-carbonyl]butanoic acid Chemical compound NCCC(C(O)=O)C(=O)[C@@H]1CCC(=O)N1 DAZRVKBSFHYTLI-GDVGLLTNSA-N 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- DEPSACIPTIZHFP-QMMMGPOBSA-N (2,4,5-trichlorophenyl) (2s)-5-oxopyrrolidine-2-carboxylate Chemical compound C1=C(Cl)C(Cl)=CC(Cl)=C1OC(=O)[C@H]1NC(=O)CC1 DEPSACIPTIZHFP-QMMMGPOBSA-N 0.000 claims description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 4
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 claims description 4
- 239000003125 aqueous solvent Substances 0.000 claims description 4
- 150000002308 glutamine derivatives Chemical class 0.000 claims description 4
- 150000003141 primary amines Chemical class 0.000 claims description 4
- 230000002035 prolonged effect Effects 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- GOUUUUODJNNJAL-GDVGLLTNSA-N 4-amino-2-[(2s)-5-oxopyrrolidine-2-carbonyl]butanamide Chemical compound NCCC(C(N)=O)C(=O)[C@@H]1CCC(=O)N1 GOUUUUODJNNJAL-GDVGLLTNSA-N 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 150000001718 carbodiimides Chemical class 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 2
- 238000011282 treatment Methods 0.000 abstract description 3
- 208000028017 Psychotic disease Diseases 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- -1 2,4,5-trichloro-phenyl Chemical group 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- OMSBLEXGRIBBNL-VIFPVBQESA-N (2s)-n-hexyl-5-oxopyrrolidine-2-carboxamide Chemical compound CCCCCCNC(=O)[C@@H]1CCC(=O)N1 OMSBLEXGRIBBNL-VIFPVBQESA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- SJTNUDPSFMEUGP-UHFFFAOYSA-N 4-amino-2-phenylmethoxycarbonylbutanoic acid Chemical compound NCCC(C(O)=O)C(=O)OCC1=CC=CC=C1 SJTNUDPSFMEUGP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- UICDNADSGVMHKL-ZETCQYMHSA-N (2s)-n-butyl-5-oxopyrrolidine-2-carboxamide Chemical compound CCCCNC(=O)[C@@H]1CCC(=O)N1 UICDNADSGVMHKL-ZETCQYMHSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229960001407 sodium bicarbonate Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000001646 thyrotropic effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- CLNSLBYOSNFAOC-WHFBIAKZSA-N (2s)-n-[(2s)-1-amino-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide Chemical compound NC(=O)[C@H](C)NC(=O)[C@@H]1CCC(=O)N1 CLNSLBYOSNFAOC-WHFBIAKZSA-N 0.000 description 2
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000007098 aminolysis reaction Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- PZSJOBKRSVRODF-UHFFFAOYSA-N vanillin acetate Chemical compound COC1=CC(C=O)=CC=C1OC(C)=O PZSJOBKRSVRODF-UHFFFAOYSA-N 0.000 description 2
- FMROFZXZHJKSRK-QMMMGPOBSA-N (2s)-5-oxo-n-pentylpyrrolidine-2-carboxamide Chemical compound CCCCCNC(=O)[C@@H]1CCC(=O)N1 FMROFZXZHJKSRK-QMMMGPOBSA-N 0.000 description 1
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical group [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- MVEPJLNIXKEKMI-UHFFFAOYSA-N 4-aminobutanamide;hydrochloride Chemical compound Cl.NCCCC(N)=O MVEPJLNIXKEKMI-UHFFFAOYSA-N 0.000 description 1
- OLZNNLDEATYBNR-MQWKRIRWSA-N 6-amino-2-[(2S)-5-oxopyrrolidine-2-carbonyl]hexanamide Chemical compound NCCCCC(C(N)=O)C(=O)[C@@H]1CCC(=O)N1 OLZNNLDEATYBNR-MQWKRIRWSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 241000905957 Channa melasoma Species 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- 241000699670 Mus sp. Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FIAINKIUSZGVGX-DKWTVANSSA-N [(2s)-1-amino-1-oxopropan-2-yl]azanium;chloride Chemical compound Cl.C[C@H](N)C(N)=O FIAINKIUSZGVGX-DKWTVANSSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- ZUDYPQRUOYEARG-UHFFFAOYSA-L barium(2+);dihydroxide;octahydrate Chemical compound O.O.O.O.O.O.O.O.[OH-].[OH-].[Ba+2] ZUDYPQRUOYEARG-UHFFFAOYSA-L 0.000 description 1
- LUASUXTWFMUYIE-UHFFFAOYSA-N benzyl 4-amino-2-carbamoylbutanoate Chemical compound NCCC(C(N)=O)C(=O)OCC1=CC=CC=C1 LUASUXTWFMUYIE-UHFFFAOYSA-N 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000007106 menorrhagia Diseases 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- IODNYRVZHKRFIW-UHFFFAOYSA-N methyl 2-aminopentanoate;hydrochloride Chemical compound Cl.CCCC(N)C(=O)OC IODNYRVZHKRFIW-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D207/28—2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06173—Dipeptides with the first amino acid being heterocyclic and Glp-amino acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2423390A DE2423390A1 (de) | 1974-05-14 | 1974-05-14 | Pyroglutamylverbindungen mit antidepressiver wirkung und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1064942A true CA1064942A (en) | 1979-10-23 |
Family
ID=5915523
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA227,255A Expired CA1064942A (en) | 1974-05-14 | 1975-05-13 | Pyroglutamy compounds having antidepressive activity and process for their manufacture |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JPS50157362A (en:Method) |
| AT (2) | AT352707B (en:Method) |
| BE (1) | BE829059A (en:Method) |
| CA (1) | CA1064942A (en:Method) |
| CH (2) | CH612180A5 (en:Method) |
| DE (1) | DE2423390A1 (en:Method) |
| DK (1) | DK209575A (en:Method) |
| FR (1) | FR2270866B1 (en:Method) |
| GB (1) | GB1472154A (en:Method) |
| IE (1) | IE41145B1 (en:Method) |
| IL (1) | IL47258A (en:Method) |
| LU (1) | LU72450A1 (en:Method) |
| NL (1) | NL7505473A (en:Method) |
| SE (1) | SE405113B (en:Method) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU3184395A (en) * | 1994-08-05 | 1996-03-04 | Warwick International Group Limited | Bleach activators |
| US6420427B1 (en) * | 1997-10-09 | 2002-07-16 | Ono Pharmaceutical Co., Ltd. | Aminobutyric acid derivatives |
| RU2232578C1 (ru) * | 2003-04-10 | 2004-07-20 | Ахапкина Валентина Ивановна | Вещество, обладающее антидепрессивной активностью |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5220996B2 (en:Method) * | 1972-01-14 | 1977-06-07 | ||
| JPS5015793B2 (en:Method) * | 1972-06-07 | 1975-06-07 |
-
1974
- 1974-05-14 DE DE2423390A patent/DE2423390A1/de not_active Withdrawn
-
1975
- 1975-05-08 IL IL47258A patent/IL47258A/xx unknown
- 1975-05-09 NL NL7505473A patent/NL7505473A/xx not_active Application Discontinuation
- 1975-05-12 CH CH608075A patent/CH612180A5/xx not_active IP Right Cessation
- 1975-05-12 CH CH85079A patent/CH613689A5/xx not_active IP Right Cessation
- 1975-05-12 LU LU72450A patent/LU72450A1/xx unknown
- 1975-05-12 GB GB1984075A patent/GB1472154A/en not_active Expired
- 1975-05-13 AT AT364875A patent/AT352707B/de not_active IP Right Cessation
- 1975-05-13 DK DK209575A patent/DK209575A/da not_active Application Discontinuation
- 1975-05-13 IE IE1069/75A patent/IE41145B1/xx unknown
- 1975-05-13 CA CA227,255A patent/CA1064942A/en not_active Expired
- 1975-05-14 BE BE156337A patent/BE829059A/xx not_active IP Right Cessation
- 1975-05-14 FR FR7515026A patent/FR2270866B1/fr not_active Expired
- 1975-05-14 JP JP50056232A patent/JPS50157362A/ja active Pending
- 1975-05-14 SE SE7505546A patent/SE405113B/xx unknown
-
1979
- 1979-01-08 AT AT0013179A patent/AT364875B/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AT364875B (de) | 1979-03-15 |
| JPS50157362A (en:Method) | 1975-12-19 |
| DK209575A (da) | 1975-11-15 |
| IE41145B1 (en) | 1979-10-24 |
| GB1472154A (en) | 1977-05-04 |
| BE829059A (fr) | 1975-11-14 |
| IL47258A0 (en) | 1975-07-28 |
| ATA13179A (de) | 1981-04-15 |
| FR2270866B1 (en:Method) | 1978-08-04 |
| SE7505546L (sv) | 1975-11-17 |
| CH613689A5 (en) | 1979-10-15 |
| ATA364875A (de) | 1979-03-15 |
| FR2270866A1 (en:Method) | 1975-12-12 |
| IL47258A (en) | 1978-07-31 |
| LU72450A1 (en:Method) | 1977-02-09 |
| SE405113B (sv) | 1978-11-20 |
| NL7505473A (nl) | 1975-11-18 |
| IE41145L (en) | 1975-11-14 |
| CH612180A5 (en) | 1979-07-13 |
| AT352707B (de) | 1979-10-10 |
| DE2423390A1 (de) | 1975-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4053588A (en) | Pharmaceutical preparations having psychotropic activity and process for their manufacture | |
| US4619916A (en) | Tripeptide compounds containing pyroglutamic acid and tryptophan, process for their production and therapeutic applications | |
| JPH06340691A (ja) | ペプチド類 | |
| GB1592552A (en) | Pseudopeptides used as medicaments | |
| US4298523A (en) | Methods and compositions for preparation of H-ARG-X-Z-Y-TYR-R | |
| CH650519A5 (de) | Auf das zentrale nervensystem wirkende tripeptide und verfahren zur herstellung derselben. | |
| US4216209A (en) | Tripeptide angiotensin converting enzyme inhibitors | |
| GB2127830A (en) | Amides of tripeptides and tetrapeptides | |
| GB2086912A (en) | Enkephalin derivatives production thereof and pharmaceutical compositions | |
| CA1064942A (en) | Pyroglutamy compounds having antidepressive activity and process for their manufacture | |
| NZ202784A (en) | Enkephalin derivatives and pharmaceutical compositions | |
| JPS5811941B2 (ja) | ブラディキニン環状類似体 | |
| CA1158236A (en) | Process for the preparation of novel substituted phenylacetic acid amide compounds | |
| CA1062250A (en) | Tripeptide derivatives with central nervous system activity and preparation thereof | |
| DE1518133B1 (de) | Verfahren zur Herstellung eines neuen hypotensiv wirkenden Hendekapeptids | |
| JPH0647599B2 (ja) | ヘプタノイル―Ｇｌｕ―Ａｓｐ―Ａｌａ―アミノ酸系免疫賦活薬 | |
| US3780014A (en) | Octapeptide intermediate to gonadotropin releasing hormone | |
| US4369137A (en) | N-Protected pentapeptides useful as intermediates in the preparation of thymopoietin pentapeptide | |
| GB2130590A (en) | Peptides | |
| DE3340208A1 (de) | Neue biologisch aktive peptide, verfahren zu deren herstellung und veterinaerpraeparate, welche diese enthalten | |
| EP0004394B1 (en) | Psychopharmacological peptides, process for their preparation and their pharmaceutical formulations | |
| FI64349B (fi) | Foerfarande foer framstaellning av ett terapeutiskt anvaendbart l-pyroglutamyl-l-histidyl-glycin och dess salter | |
| DE68913936T2 (de) | Retro-Inverso-Thrymopentin-Analoge, Verfahren zu deren Herstellung und deren Verwendung für die Zubereitung von pharmazeutischen Zusammensetzungen. | |
| US3790555A (en) | Octapeptide derivative of gonadotropinreleasing hormone | |
| EP0015036B1 (en) | Psycho-pharmacological peptides, process for their preparation and therapeutical compositions containing them |