HU193373B - Process for preparing cyclic 9'-thiapeptide-ergot alkaloids - Google Patents
Process for preparing cyclic 9'-thiapeptide-ergot alkaloids Download PDFInfo
- Publication number
- HU193373B HU193373B HU851921A HU192185A HU193373B HU 193373 B HU193373 B HU 193373B HU 851921 A HU851921 A HU 851921A HU 192185 A HU192185 A HU 192185A HU 193373 B HU193373 B HU 193373B
- Authority
- HU
- Hungary
- Prior art keywords
- culture
- compounds
- thia
- medium
- ergotamine
- Prior art date
Links
- 125000004122 cyclic group Chemical group 0.000 title abstract description 3
- 229960003133 ergot alkaloid Drugs 0.000 title description 6
- 238000004519 manufacturing process Methods 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 238000009630 liquid culture Methods 0.000 claims abstract description 3
- 241000221751 Claviceps purpurea Species 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000000945 filler Substances 0.000 claims 1
- DZLNHFMRPBPULJ-GSVOUGTGSA-N D-thioproline Chemical compound OC(=O)[C@H]1CSCN1 DZLNHFMRPBPULJ-GSVOUGTGSA-N 0.000 abstract description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 4
- 230000001430 anti-depressive effect Effects 0.000 abstract description 2
- 239000000935 antidepressant agent Substances 0.000 abstract description 2
- 229940005513 antidepressants Drugs 0.000 abstract description 2
- 229960003638 dopamine Drugs 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000002609 medium Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 229960004943 ergotamine Drugs 0.000 description 17
- 229920001817 Agar Polymers 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000008272 agar Substances 0.000 description 15
- 244000052616 bacterial pathogen Species 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 229930013930 alkaloid Natural products 0.000 description 11
- 150000003797 alkaloid derivatives Chemical class 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 5
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000008223 sterile water Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- VBIXEXWLHSRNKB-UHFFFAOYSA-N ammonium oxalate Chemical compound [NH4+].[NH4+].[O-]C(=O)C([O-])=O VBIXEXWLHSRNKB-UHFFFAOYSA-N 0.000 description 3
- OWEUDBYTKOYTAD-MKTPKCENSA-N ergocristine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@@H]1C=C2C3=CC=CC4=NC=C([C]34)C[C@H]2N(C)C1)C(C)C)C1=CC=CC=C1 OWEUDBYTKOYTAD-MKTPKCENSA-N 0.000 description 3
- HEFIYUQVAZFDEE-UHFFFAOYSA-N ergocristinine Natural products N12C(=O)C(C(C)C)(NC(=O)C3C=C4C=5C=CC=C6NC=C(C=56)CC4N(C)C3)OC2(O)C2CCCN2C(=O)C1CC1=CC=CC=C1 HEFIYUQVAZFDEE-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- 231100000219 mutagenic Toxicity 0.000 description 3
- 230000003505 mutagenic effect Effects 0.000 description 3
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 235000011164 potassium chloride Nutrition 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RZLVQBNCHSJZPX-UHFFFAOYSA-L zinc sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Zn+2].[O-]S([O-])(=O)=O RZLVQBNCHSJZPX-UHFFFAOYSA-L 0.000 description 3
- ZHJGWYRLJUCMRT-UHFFFAOYSA-N 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide Chemical compound C=1C=CC=C(C(F)(F)F)C=1C(C)OC(=C(S1)C(N)=O)C=C1N(C1=C2)C=NC1=CC=C2CN1CCN(C)CC1 ZHJGWYRLJUCMRT-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 235000005811 Viola adunca Nutrition 0.000 description 2
- 240000009038 Viola odorata Species 0.000 description 2
- 235000013487 Viola odorata Nutrition 0.000 description 2
- 235000002254 Viola papilionacea Nutrition 0.000 description 2
- 244000172533 Viola sororia Species 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000003727 cerebral blood flow Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052500 inorganic mineral Chemical class 0.000 description 2
- 230000006651 lactation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Chemical class 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 235000020095 red wine Nutrition 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000209200 Bromus Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 206010017600 Galactorrhoea Diseases 0.000 description 1
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241000364057 Peoria Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 206010036832 Prolactinoma Diseases 0.000 description 1
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 1
- 244000082988 Secale cereale Species 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 229950001817 alpha-ergocryptine Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000001263 anti-prolactin effect Effects 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- YDOTUXAWKBPQJW-UHFFFAOYSA-N ergocryptine Chemical compound C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000010365 information processing Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229930015720 peptide alkaloid Natural products 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 208000030153 prolactin-producing pituitary gland adenoma Diseases 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/02—Ergot alkaloids of the cyclic peptide type
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (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)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH5104/81A CH649300A5 (de) | 1981-08-07 | 1981-08-07 | Ergopeptinderivate, ihre herstellung und verwendung. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT37960A HUT37960A (en) | 1986-03-28 |
| HU193373B true HU193373B (en) | 1987-09-28 |
Family
ID=4287999
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU851921A HU193373B (en) | 1981-08-07 | 1982-08-06 | Process for preparing cyclic 9'-thiapeptide-ergot alkaloids |
| HU822537A HU190405B (en) | 1981-08-07 | 1982-08-06 | Process for producing cyclic 9'-thia-ergopeptine derivatives |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU822537A HU190405B (en) | 1981-08-07 | 1982-08-06 | Process for producing cyclic 9'-thia-ergopeptine derivatives |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US4542135A (en, 2012) |
| JP (1) | JPS5843982A (en, 2012) |
| AT (1) | AT382156B (en, 2012) |
| AU (1) | AU558414B2 (en, 2012) |
| BE (1) | BE894046A (en, 2012) |
| CA (1) | CA1191802A (en, 2012) |
| CH (1) | CH649300A5 (en, 2012) |
| CS (1) | CS235303B2 (en, 2012) |
| DD (2) | DD211582A5 (en, 2012) |
| DE (1) | DE3228230A1 (en, 2012) |
| DK (1) | DK352082A (en, 2012) |
| ES (2) | ES514766A0 (en, 2012) |
| FI (1) | FI72979C (en, 2012) |
| FR (1) | FR2511003B1 (en, 2012) |
| GB (1) | GB2109795B (en, 2012) |
| GR (1) | GR77262B (en, 2012) |
| HU (2) | HU193373B (en, 2012) |
| IE (1) | IE53647B1 (en, 2012) |
| IL (1) | IL66471A (en, 2012) |
| IT (1) | IT1152489B (en, 2012) |
| MY (1) | MY8600311A (en, 2012) |
| NL (1) | NL8203067A (en, 2012) |
| NZ (1) | NZ201504A (en, 2012) |
| PH (1) | PH22998A (en, 2012) |
| PT (1) | PT75384B (en, 2012) |
| SE (1) | SE452011B (en, 2012) |
| ZA (1) | ZA825727B (en, 2012) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH649300A5 (de) * | 1981-08-07 | 1985-05-15 | Sandoz Ag | Ergopeptinderivate, ihre herstellung und verwendung. |
| JPS60104129A (ja) * | 1983-11-11 | 1985-06-08 | Hitachi Ltd | フッ素含有ポリアミド酸誘導体及びポリイミドの製造方法 |
| NL8600161A (nl) * | 1985-02-05 | 1986-09-01 | Sandoz Ag | Farmaceutische preparaten die 9,10-dihydroergotalkaloiden bevatten. |
| HU193317B (en) * | 1985-06-12 | 1987-09-28 | Richter Gedeon Vegyeszet | Process for producing 2-bromo-alpha-ergochristin |
| PT628042E (pt) * | 1992-12-24 | 2002-01-30 | Pharmacia & Upjohn Spa | Derivados de ergolina serotoninergicos |
| DE10041478A1 (de) | 2000-08-24 | 2002-03-14 | Sanol Arznei Schwarz Gmbh | Neue pharmazeutische Zusammensetzung |
| DE10334188B4 (de) * | 2003-07-26 | 2007-07-05 | Schwarz Pharma Ag | Verwendung von Rotigotin zur Behandlung von Depressionen |
| DE10334187A1 (de) * | 2003-07-26 | 2005-03-03 | Schwarz Pharma Ag | Substituierte 2-Aminotetraline zur Behandlung von Depressionen |
| DE10361258A1 (de) * | 2003-12-24 | 2005-07-28 | Schwarz Pharma Ag | Verwendung von substituierten 2-Aminotetralinen zur vorbeugenden Behandlung von Morbus Parkinson |
| US20050197385A1 (en) * | 2004-02-20 | 2005-09-08 | Schwarz Pharma Ag | Use of rotigotine for treatment or prevention of dopaminergic neuron loss |
| DE102004014841B4 (de) * | 2004-03-24 | 2006-07-06 | Schwarz Pharma Ag | Verwendung von Rotigotin zur Behandlung und Prävention des Parkinson-Plus-Syndroms |
| US20070022720A1 (en) * | 2005-07-27 | 2007-02-01 | The Toro Company | Cleaner for cooling system screen of outdoor power equipment unit |
| WO2011079313A1 (en) * | 2009-12-23 | 2011-06-30 | Map Pharmaceuticals, Inc. | Novel ergoline analogs |
| US8604035B2 (en) | 2011-06-23 | 2013-12-10 | Map Pharmaceuticals, Inc. | Fluoroergoline analogs |
| WO2013095707A1 (en) | 2011-12-19 | 2013-06-27 | Map Pharmaceuticals, Inc. | Novel iso-ergoline derivatives |
| EP2793583A4 (en) | 2011-12-21 | 2015-08-12 | Map Pharmaceuticals Inc | NOVEL NEUROMODULATORY CONNECTIONS |
| US9012640B2 (en) | 2012-06-22 | 2015-04-21 | Map Pharmaceuticals, Inc. | Cabergoline derivatives |
| CZ304709B6 (cs) * | 2013-07-25 | 2014-09-03 | Teva Czech Industries S.R.O. | Izolovaný kmen houby Claviceps purpurea (Fr.) Tul., CCM 8404 |
| CN113308442B (zh) * | 2021-04-28 | 2023-06-27 | 天津大学 | 重组酿酒酵母菌株及其构建方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3314959A (en) * | 1961-05-10 | 1967-04-18 | Sandoz Ltd | Intermediates for the synthesis of ergot alkaloids |
| FR2292M (fr) * | 1962-06-27 | 1964-01-27 | Sandoz Sa | Médicament a base d'une combinaison de dihydro-ergotamine, de caféine et d'une hydantoine. |
| CH602766A5 (en) * | 1974-09-27 | 1978-07-31 | Sandoz Ag | 10-Alpha-methoxy-di:hydro-beta-ergosine derivs. |
| CH602765A5 (en, 2012) * | 1974-09-27 | 1978-07-31 | Sandoz Ag | |
| DE2750090A1 (de) * | 1976-11-19 | 1978-06-01 | Sandoz Ag | Neue verabreichungsformen fuer organische verbindungen |
| CH626373A5 (en, 2012) * | 1977-02-22 | 1981-11-13 | Sandoz Ag | |
| GB1584464A (en) * | 1977-04-19 | 1981-02-11 | Farmaceutici Italia | Ergot alkaloids |
| DE2717953A1 (de) * | 1977-04-22 | 1978-10-26 | Sandoz Ag | Neue therapeutische mischung und verfahren zu deren herstellung |
| YU216177A (en) * | 1977-09-09 | 1984-02-29 | Rudolf Rucman | Process for preparing 2-bromo ergosine |
| CH636011A5 (en) * | 1978-01-01 | 1983-05-13 | Sandoz Ag | Administration forms for organic compounds |
| EP0003286B1 (de) * | 1978-01-20 | 1982-03-24 | Sandoz Ag | Ergopeptidalkaloid-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen |
| DE2803543A1 (de) * | 1978-01-27 | 1979-08-02 | Sandoz Ag | Ergopeptidalkaloidderivate, ihre verwendung und herstellung |
| YU40046B (en) * | 1978-09-04 | 1985-06-30 | Lek Tovarna Farmacevtskih | Process for preparing 2-bromo-9,10-dihydroergosine |
| US4609731A (en) * | 1979-10-10 | 1986-09-02 | Sandoz Ltd. | Process for brominating ergot alkaloids |
| DD200571A1 (de) * | 1981-07-22 | 1983-05-18 | Alfred Baumert | Verfahren zur herstellung von ergopeptinen mit modifiziertem prolinteil |
| CH649300A5 (de) * | 1981-08-07 | 1985-05-15 | Sandoz Ag | Ergopeptinderivate, ihre herstellung und verwendung. |
-
1981
- 1981-08-07 CH CH5104/81A patent/CH649300A5/de not_active IP Right Cessation
-
1982
- 1982-07-28 DE DE19823228230 patent/DE3228230A1/de not_active Ceased
- 1982-07-30 FI FI822670A patent/FI72979C/fi not_active IP Right Cessation
- 1982-08-02 NL NL8203067A patent/NL8203067A/nl not_active Application Discontinuation
- 1982-08-03 US US06/404,832 patent/US4542135A/en not_active Expired - Fee Related
- 1982-08-04 GB GB08222490A patent/GB2109795B/en not_active Expired
- 1982-08-05 NZ NZ201504A patent/NZ201504A/en unknown
- 1982-08-05 GR GR68967A patent/GR77262B/el unknown
- 1982-08-05 JP JP57137147A patent/JPS5843982A/ja active Granted
- 1982-08-05 SE SE8204585A patent/SE452011B/sv not_active IP Right Cessation
- 1982-08-05 ES ES514766A patent/ES514766A0/es active Granted
- 1982-08-05 PT PT75384A patent/PT75384B/pt unknown
- 1982-08-05 FR FR8213834A patent/FR2511003B1/fr not_active Expired
- 1982-08-05 AU AU86785/82A patent/AU558414B2/en not_active Ceased
- 1982-08-05 CA CA000408786A patent/CA1191802A/en not_active Expired
- 1982-08-05 IL IL66471A patent/IL66471A/xx unknown
- 1982-08-05 DK DK352082A patent/DK352082A/da not_active Application Discontinuation
- 1982-08-06 ZA ZA825727A patent/ZA825727B/xx unknown
- 1982-08-06 DD DD82256213A patent/DD211582A5/de unknown
- 1982-08-06 BE BE1/10569A patent/BE894046A/fr not_active IP Right Cessation
- 1982-08-06 IT IT22768/82A patent/IT1152489B/it active
- 1982-08-06 AT AT0302682A patent/AT382156B/de not_active IP Right Cessation
- 1982-08-06 HU HU851921A patent/HU193373B/hu not_active IP Right Cessation
- 1982-08-06 CS CS825871A patent/CS235303B2/cs unknown
- 1982-08-06 HU HU822537A patent/HU190405B/hu not_active IP Right Cessation
- 1982-08-06 IE IE1906/82A patent/IE53647B1/en unknown
- 1982-08-06 PH PH27690A patent/PH22998A/en unknown
- 1982-08-06 DD DD82242325A patent/DD206379A5/de unknown
-
1983
- 1983-09-29 ES ES526119A patent/ES526119A0/es active Granted
-
1985
- 1985-07-02 US US06/751,272 patent/US4681880A/en not_active Expired - Fee Related
-
1986
- 1986-12-30 MY MY311/86A patent/MY8600311A/xx unknown
-
1987
- 1987-05-05 US US07/047,362 patent/US4804660A/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HU193373B (en) | Process for preparing cyclic 9'-thiapeptide-ergot alkaloids | |
| US6596518B2 (en) | Percyquinnin, a process for its production and its use as a pharmaceutical | |
| US20020143021A1 (en) | Phenylahistin and the phenylahistin analogs, a new class of anti-tumor compounds | |
| EP1751272B1 (en) | Production of tacrolimus (fk-506) using new streptomyces species | |
| SU735154A3 (ru) | Способ получени алкалоидов спорыньи | |
| EP0703917A1 (en) | Indolocarbazole compound useful as proteinkinase c inhibitor | |
| KR101764349B1 (ko) | 펩티드 디포밀라제 저해 및 항균 활성을 갖는 신규한 프라비마이신 화합물 | |
| RU2261254C2 (ru) | Мемнопептиды, способ их получения и их применение | |
| JPH09508271A (ja) | インドールジテルペンアルカロイド化合物 | |
| US5756536A (en) | Microbial transformation of taxol and cephalomannine | |
| US4803217A (en) | Hapalindolinone compounds as vassopressin antagonists | |
| TOKI et al. | PS-990, A NOVEL NEURITOGENIC COMPOUND FROM Acremoniums p. | |
| US5079376A (en) | Novel substance uct-1003 and process for producing the same | |
| JP2002518057A (ja) | ムンバイスタチン、その製造法およびその医薬としての使用 | |
| HU215146B (hu) | Eljárás új balhimicin antibiotikum és ezt tartalmazó gyógyszerkészítmény előállítására | |
| US5236929A (en) | Compound uca1064-b | |
| JPH05331172A (ja) | 生物活性プソイロチンａおよびｄ、アスペルギルス・フミガタスから得られる新規な代謝産物、その調製方法およびその使用 | |
| JP3733163B2 (ja) | 化合物ｔａｎ−２１７７、その製造法および用途 | |
| JPH05306271A (ja) | 新規なアルカロイドおよびその製造方法 | |
| FI75188B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 9'-tiaergopeptinderivat. | |
| KR20040025902A (ko) | Ｃｎｓ 장애 치료용 의약의 제조시 티오루틴 디옥사이드및 이의 유도체의 용도 및 이의 제조방법 | |
| JP3564543B2 (ja) | フロピリジン抗細菌剤 | |
| JP2002509444A (ja) | Ｗｆ１４５７３またはその塩、それらの製法および用途 | |
| CA2008628C (en) | Substance uct-1003 and process for producing the same | |
| CS235340B2 (cs) | Způsob výroby derivátů ergopeptinu |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |