NO303939B1 - Oktadecyl-£2-(N-metylpiperidiono)-etyl|-fosfat og fremstilling derav, legemiddel omfattende forbindelsen og rensemetode for denne - Google Patents

Oktadecyl-£2-(N-metylpiperidiono)-etyl|-fosfat og fremstilling derav, legemiddel omfattende forbindelsen og rensemetode for denne Download PDF

Info

Publication number: NO303939B1
Authority: NO; Norway
Prior art keywords: octadecyl; phosphate; ethyl; methylpiperidino; solvent
Prior art date: 1991-07-04

Application number

NO922642A

Other languages

English (en)

Norwegian (no)

Other versions

NO922642D0 (no

NO922642L (no

Inventor

Wolfgang Schumacher

J Rgen Engel

Ssner Gerhard N

Bernhard Kutscher

Jurij Stekar

Peter Hilgard

Original Assignee

Asta Medica Ag

Priority date (The priority date 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 date listed.)

1991-07-04

Filing date

1992-07-03

Publication date

1998-09-28

1992-07-03 Application filed by Asta Medica Ag filed Critical Asta Medica Ag

1992-07-03 Publication of NO922642D0 publication Critical patent/NO922642D0/no

1993-01-05 Publication of NO922642L publication Critical patent/NO922642L/no

1998-09-28 Publication of NO303939B1 publication Critical patent/NO303939B1/no

Links

238000000034 method Methods 0.000 title claims description 30
238000000746 purification Methods 0.000 title claims description 9
239000003814 drug Substances 0.000 title claims description 5
229940079593 drug Drugs 0.000 title claims description 3
150000001875 compounds Chemical class 0.000 title description 25
229910019142 PO4 Inorganic materials 0.000 title description 12
239000010452 phosphate Substances 0.000 title description 12
238000002360 preparation method Methods 0.000 title description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 title 1
239000000126 substance Substances 0.000 claims description 28
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 26
239000002904 solvent Substances 0.000 claims description 24
CUQJLYFFQBHUGW-UHFFFAOYSA-N 2-(1-methylpiperidin-1-ium-1-yl)ethyl octadecyl phosphate Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+]1(C)CCCCC1 CUQJLYFFQBHUGW-UHFFFAOYSA-N 0.000 claims description 22
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 20
150000002500 ions Chemical class 0.000 claims description 19
230000002378 acidificating effect Effects 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
230000007062 hydrolysis Effects 0.000 claims description 7
238000006460 hydrolysis reaction Methods 0.000 claims description 7
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
229940126601 medicinal product Drugs 0.000 claims description 4
230000000118 anti-neoplastic effect Effects 0.000 claims description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
239000000969 carrier Substances 0.000 claims description 2
150000005690 diesters Chemical class 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
238000002955 isolation Methods 0.000 claims description 2
239000003960 organic solvent Substances 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims 1
239000008024 pharmaceutical diluent Substances 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
-1 acyclic ethers Chemical class 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical class CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 13
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
229920001429 chelating resin Polymers 0.000 description 11
239000000203 mixture Substances 0.000 description 11
239000000047 product Substances 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
229920002125 Sokalan® Polymers 0.000 description 10
150000001298 alcohols Chemical class 0.000 description 10
239000003513 alkali Substances 0.000 description 9
150000003839 salts Chemical class 0.000 description 9
238000003756 stirring Methods 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
230000000259 anti-tumor effect Effects 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
150000002430 hydrocarbons Chemical group 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
238000001816 cooling Methods 0.000 description 7
229930195733 hydrocarbon Natural products 0.000 description 7
239000007788 liquid Substances 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
206010028980 Neoplasm Diseases 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
125000001931 aliphatic group Chemical group 0.000 description 6
150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
150000008282 halocarbons Chemical class 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
235000011114 ammonium hydroxide Nutrition 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
150000004292 cyclic ethers Chemical class 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000005406 washing Methods 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
239000013543 active substance Substances 0.000 description 4
229910052784 alkaline earth metal Inorganic materials 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
150000004649 carbonic acid derivatives Chemical class 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
239000011159 matrix material Substances 0.000 description 4
238000002156 mixing Methods 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
VZEOMTOGOOFQRF-UHFFFAOYSA-N 2-octadecoxy-1,3,2$l^{5}-dioxaphospholane 2-oxide Chemical compound CCCCCCCCCCCCCCCCCCOP1(=O)OCCO1 VZEOMTOGOOFQRF-UHFFFAOYSA-N 0.000 description 3
GNNUMBNFLKFKRG-UHFFFAOYSA-N 2-piperidin-1-ylicosyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCCCC(COP(O)(O)=O)N1CCCCC1 GNNUMBNFLKFKRG-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000001309 chloro group Chemical group Cl* 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
RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 3
238000001035 drying Methods 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
150000003053 piperidines Chemical class 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
239000011591 potassium Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 description 2
ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
VFZRZRDOXPRTSC-UHFFFAOYSA-N DMBA Natural products COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
241000699660 Mus musculus Species 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
239000004793 Polystyrene Substances 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
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 2
150000007513 acids Chemical class 0.000 description 2
229910001854 alkali hydroxide Inorganic materials 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
150000001408 amides Chemical group 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
238000000605 extraction Methods 0.000 description 2
230000009036 growth inhibition Effects 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
150000002367 halogens Chemical group 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
239000003456 ion exchange resin Substances 0.000 description 2
229920003303 ion-exchange polymer Polymers 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
239000012528 membrane Substances 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
230000011987 methylation Effects 0.000 description 2
238000007069 methylation reaction Methods 0.000 description 2
239000011707 mineral Substances 0.000 description 2
238000011580 nude mouse model Methods 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
229920002223 polystyrene Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
229930195734 saturated hydrocarbon Natural products 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 description 1
AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 1
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
IPEPLPGOLSCCNI-UHFFFAOYSA-M 4-methylbenzenesulfonate;2-(1-methylpiperidin-1-ium-1-yl)ethanol Chemical compound OCC[N+]1(C)CCCCC1.CC1=CC=C(S([O-])(=O)=O)C=C1 IPEPLPGOLSCCNI-UHFFFAOYSA-M 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
238000006418 Brown reaction Methods 0.000 description 1
AEFXDGGNILQRDU-UHFFFAOYSA-N C1(=C(C(=CC(=C1)C)C)S(=O)(=O)N1N=NN=[C-]1)C Chemical compound C1(=C(C(=CC(=C1)C)C)S(=O)(=O)N1N=NN=[C-]1)C AEFXDGGNILQRDU-UHFFFAOYSA-N 0.000 description 1
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
102000003820 Lipoxygenases Human genes 0.000 description 1
108090000128 Lipoxygenases Proteins 0.000 description 1
241001465754 Metazoa 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
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
229910019213 POCl3 Inorganic materials 0.000 description 1
102000015439 Phospholipases Human genes 0.000 description 1
108010064785 Phospholipases Proteins 0.000 description 1
241000700159 Rattus Species 0.000 description 1
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000004996 alkyl benzenes Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
230000000843 anti-fungal effect Effects 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
229940117389 dichlorobenzene Drugs 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000012010 growth Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
QDUXDCXILAPLAG-UHFFFAOYSA-N hydron;1-methylpiperidine;chloride Chemical compound Cl.CN1CCCCC1 QDUXDCXILAPLAG-UHFFFAOYSA-N 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Chemical group 0.000 description 1
239000011630 iodine Chemical group 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
210000000214 mouth Anatomy 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000003672 processing method Methods 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
239000012264 purified product Substances 0.000 description 1
JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical compound C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
150000003388 sodium compounds Chemical class 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical group OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
150000003511 tertiary amides Chemical class 0.000 description 1
150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
230000007306 turnover Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Medicinal Preparation (AREA)
Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)

NO922642A 1991-07-04 1992-07-03 Oktadecyl-£2-(N-metylpiperidiono)-etyl|-fosfat og fremstilling derav, legemiddel omfattende forbindelsen og rensemetode for denne NO303939B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE4122140		1991-07-04
DE4129364		1991-09-04

Publications (3)

Publication Number	Publication Date
NO922642D0 NO922642D0 (no)	1992-07-03
NO922642L NO922642L (no)	1993-01-05
NO303939B1 true NO303939B1 (no)	1998-09-28

Family

ID=25905206

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO922642A NO303939B1 (no)	1991-07-04	1992-07-03	Oktadecyl-£2-(N-metylpiperidiono)-etyl\|-fosfat og fremstilling derav, legemiddel omfattende forbindelsen og rensemetode for denne

Country Status (19)

Country	Link
US (1)	US5219866A (zh)
EP (1)	EP0521353B1 (zh)
JP (1)	JP3176720B2 (zh)
KR (1)	KR100255436B1 (zh)
CN (1)	CN1030658C (zh)
AT (1)	ATE136783T1 (zh)
AU (1)	AU651224B2 (zh)
CA (1)	CA2073146C (zh)
DE (2)	DE59205998D1 (zh)
DK (1)	DK0521353T3 (zh)
EG (1)	EG20082A (zh)
ES (1)	ES2086026T3 (zh)
FI (1)	FI108035B (zh)
GR (1)	GR3019776T3 (zh)
HU (2)	HUT61561A (zh)
IE (1)	IE73200B1 (zh)
IL (1)	IL102380A (zh)
NO (1)	NO303939B1 (zh)
PL (3)	PL173869B1 (zh)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2369535T3 (es) *	2002-07-30	2011-12-01	Eterna Zentaris Gmbh	Uso de alquilfosfocolinas en combinación con medicamentos antitumorales.
US8383605B2 (en) *	2002-07-30	2013-02-26	Aeterna Zentaris Gmbh	Use of alkylphosphocholines in combination with antimetabolites for the treatment of benign and malignant oncoses in humans and mammals
UA99434C2 (ru) *	2005-12-19	2012-08-27	Аетерна Центаріс Гмбх	Применение производных алкилфосфолипидов со сниженной цитотоксичностью
PL1962862T3 (pl) *	2005-12-19	2014-01-31	Aeterna Zentaris Gmbh	Pochodne alkilofosfolipidów o ograniczonej cytotoksyczności i ich zastosowania
JP5068630B2 (ja) *	2007-11-15	2012-11-07	オルガノ株式会社	アルコール含有溶液中のアルデヒド化合物の除去方法及び該方法により精製された醸造酒
MX2011011596A (es)	2010-03-31	2012-02-01	Keryx Biopharmaceuticals Inc	Perifosina y capecitabina como un tratamiento combinado para cancer.

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SU301951A1 (ru) *	1970-06-01	1973-04-05	В. А. Чернов, Т. С. Сафонова, Н. В. Сазонов, А. А. Кропачева,	Лекарственное средство
JPS5984824A (ja) *	1982-11-08	1984-05-16	Takeda Chem Ind Ltd	抗腫瘍剤
ATE158295T1 (de) *	1991-07-04	1997-10-15	Asta Medica Ag	Verfahren zur herstellung von alkylphosphocholinen und reinherstellung derselben

1992
- 1992-06-19 ES ES92110347T patent/ES2086026T3/es not_active Expired - Lifetime
- 1992-06-19 DE DE59205998T patent/DE59205998D1/de not_active Expired - Fee Related
- 1992-06-19 DE DE4219972A patent/DE4219972A1/de not_active Withdrawn
- 1992-06-19 DK DK92110347.9T patent/DK0521353T3/da active
- 1992-06-19 EP EP92110347A patent/EP0521353B1/de not_active Expired - Lifetime
- 1992-06-19 AT AT92110347T patent/ATE136783T1/de not_active IP Right Cessation
- 1992-07-01 US US07/907,025 patent/US5219866A/en not_active Expired - Lifetime
- 1992-07-01 EG EG34592A patent/EG20082A/xx active
- 1992-07-02 PL PL92311788A patent/PL173869B1/pl not_active IP Right Cessation
- 1992-07-02 PL PL92295128A patent/PL173905B1/pl not_active IP Right Cessation
- 1992-07-02 PL PL92311787A patent/PL173794B1/pl not_active IP Right Cessation
- 1992-07-02 IL IL10238092A patent/IL102380A/en not_active IP Right Cessation
- 1992-07-03 AU AU19435/92A patent/AU651224B2/en not_active Ceased
- 1992-07-03 CA CA002073146A patent/CA2073146C/en not_active Expired - Fee Related
- 1992-07-03 JP JP17691592A patent/JP3176720B2/ja not_active Expired - Fee Related
- 1992-07-03 FI FI923088A patent/FI108035B/fi active
- 1992-07-03 NO NO922642A patent/NO303939B1/no unknown
- 1992-07-03 IE IE922183A patent/IE73200B1/en not_active IP Right Cessation
- 1992-07-03 CN CN92105452A patent/CN1030658C/zh not_active Expired - Fee Related
- 1992-07-03 KR KR1019920011821A patent/KR100255436B1/ko not_active Expired - Fee Related
- 1992-07-03 HU HU9202232A patent/HUT61561A/hu unknown
1995
- 1995-06-16 HU HU95P/P00233P patent/HU211483A9/hu unknown
1996
- 1996-04-29 GR GR960401156T patent/GR3019776T3/el unknown

Also Published As

Publication number	Publication date
KR100255436B1 (ko)	2000-05-01
PL173869B1 (pl)	1998-05-29
EP0521353A1 (de)	1993-01-07
HU211483A9 (en)	1995-11-28
IL102380A (en)	1996-10-16
PL173905B1 (pl)	1998-05-29
HUT61561A (en)	1993-01-28
NO922642D0 (no)	1992-07-03
EG20082A (en)	1997-05-31
DE4219972A1 (de)	1993-01-07
AU1943592A (en)	1993-03-11
FI923088A0 (fi)	1992-07-03
IE922183A1 (en)	1993-01-13
EP0521353B1 (de)	1996-04-17
PL173794B1 (pl)	1998-05-29
JPH05213980A (ja)	1993-08-24
CA2073146A1 (en)	1993-01-05
HU9202232D0 (en)	1992-10-28
CA2073146C (en)	2002-05-28
AU651224B2 (en)	1994-07-14
DK0521353T3 (da)	1996-05-13
KR930001909A (ko)	1993-02-22
IL102380A0 (en)	1993-01-14
PL295128A1 (en)	1993-08-23
FI923088L (fi)	1993-01-05
GR3019776T3 (en)	1996-07-31
CN1068119A (zh)	1993-01-20
JP3176720B2 (ja)	2001-06-18
CN1030658C (zh)	1996-01-10
DE59205998D1 (de)	1996-05-23
NO922642L (no)	1993-01-05
ATE136783T1 (de)	1996-05-15
IE73200B1 (en)	1997-05-07
FI108035B (fi)	2001-11-15
ES2086026T3 (es)	1996-06-16
US5219866A (en)	1993-06-15

Publication	Publication Date	Title
DE69606840T2 (de)	2000-10-12	Monohydrate von Aminobenzensulfonsäurederivaten und Verfahren zu ihrer Herstellung
IE882108L (en)	1989-01-09	Azithromycin dihydrate
DE69811930T2 (de)	2003-12-18	Tricyclische triazolobenzazepinderivate, verfahren zu ihrer herstellung und antiallergische mittel
US4609653A (en)	1986-09-02	Crystalline cephem-acid addition salts and processes for their preparation
AU1816900A (en)	2000-05-29	Therapeutic polymorphs of a gaba-a alpha-5 inverse agonist and pamoate formulations of the same
US7994320B2 (en)	2011-08-09	Narcistatin prodrugs
NO303939B1 (no)	1998-09-28	Oktadecyl-£2-(N-metylpiperidiono)-etyl\|-fosfat og fremstilling derav, legemiddel omfattende forbindelsen og rensemetode for denne
CA2107439C (en)	2006-08-15	Phospholipid derivatives containing phosphorous, arsenic, antimony or bismuth
US6436955B1 (en)	2002-08-20	Crystal modification A of 8-cyano-1-cyclopropyl-7-(is,6s-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
CZ290863B6 (cs)	2002-11-13	Deriváty fosfolipidů, způsob jejich výroby, léčiva a jejich pouľití a způsob výroby těchto léčiv
ZA200106289B (en)	2002-07-31	Crystal modification C of 8-cyano-1-cyclopropyl-7-(IS,6S-2,8-diazabicyclo-[4.3.0]nonan-8-YL)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic.
EP1598347A1 (en)	2005-11-23	Polymorphs of pantoprazole sodium salt and process for the preparation thereof
EP0548834B1 (en)	1995-11-22	Stable hexahydrate of etoposide 4'-phosphate disodium salt
DE3881146T2 (de)	1993-10-21	Thiazetidin-Derivate.
CS208746B2 (en)	1981-09-15	Method of making the 3,6-disubstituted-1,2,4-triazin 5-ons
NO304232B1 (no)	1998-11-16	FremgangsmÕte for fremstilling av C14-C18-alkylfosfokoliner
EP0254167A1 (en)	1988-01-27	1-Hydroxy-5-oxo-5H-pyrido(3,2-a)-phenoxazine-3-carboxylic acid esters
CN111039984A (zh)	2020-04-21	康泰唑胺酯的药物晶体及其制备方法和应用
KR19980033013A (ko)	1998-07-25	세팔로스포린 피리디늄 유도체
HK1051693A1 (zh)	2003-08-15	制备阿德福韦的方法
HK1051693B (zh)	2005-05-20	制备阿德福韦的方法