IL102380A - Octadecyl] -N-2-methylpipridino (ethyl-phosphate, its preparation and pharmaceutical preparations containing - Google Patents
Octadecyl] -N-2-methylpipridino (ethyl-phosphate, its preparation and pharmaceutical preparations containingInfo
- Publication number
- IL102380A IL102380A IL10238092A IL10238092A IL102380A IL 102380 A IL102380 A IL 102380A IL 10238092 A IL10238092 A IL 10238092A IL 10238092 A IL10238092 A IL 10238092A IL 102380 A IL102380 A IL 102380A
- Authority
- IL
- Israel
- Prior art keywords
- octadecyl
- phosphate
- ethyl
- methylpiperidinio
- methyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 229910019142 PO4 Inorganic materials 0.000 title claims description 19
- 239000010452 phosphate Substances 0.000 title claims description 19
- 238000000034 method Methods 0.000 claims abstract description 27
- 230000000118 anti-neoplastic effect Effects 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 claims description 35
- -1 octadecyl- [ 2- (N-methylpiperidinio)- ethyl ] Chemical class 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 28
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 24
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 19
- 150000002500 ions Chemical class 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 17
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 15
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
- 239000012442 inert solvent Substances 0.000 claims description 7
- 238000000746 purification Methods 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 229910052740 iodine Chemical group 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 239000011630 iodine Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 239000012050 conventional carrier Substances 0.000 claims 1
- 239000012059 conventional drug carrier Substances 0.000 claims 1
- 150000005690 diesters Chemical class 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 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 abstract description 2
- ZJXZSIYSNXKHEA-UHFFFAOYSA-N ethyl dihydrogen phosphate Chemical compound CCOP(O)(O)=O ZJXZSIYSNXKHEA-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 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
- 125000004432 carbon atom Chemical group C* 0.000 description 17
- 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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
- 150000001298 alcohols Chemical class 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
- 239000000047 product Substances 0.000 description 12
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000003513 alkali Substances 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
- 230000000694 effects Effects 0.000 description 8
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- 238000003756 stirring Methods 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000000259 anti-tumor effect Effects 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
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- 150000002430 hydrocarbons 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 150000004292 cyclic ethers Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 150000008282 halocarbons Chemical class 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
- 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 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
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- 230000009036 growth inhibition Effects 0.000 description 3
- 235000011167 hydrochloric acid Nutrition 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 150000003053 piperidines Chemical class 0.000 description 3
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- 238000001953 recrystallisation Methods 0.000 description 3
- KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- CESWEUWSELBVOI-UHFFFAOYSA-N 2-bromoicosyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCCCC(Br)COP(O)(O)=O CESWEUWSELBVOI-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
- GNNUMBNFLKFKRG-UHFFFAOYSA-N 2-piperidin-1-ylicosyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCCCC(COP(O)(O)=O)N1CCCCC1 GNNUMBNFLKFKRG-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
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- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- 102100037611 Lysophospholipase Human genes 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
- WPPONCHFOIIFIJ-UHFFFAOYSA-N N1N=NN=[C-]1 Chemical compound N1N=NN=[C-]1 WPPONCHFOIIFIJ-UHFFFAOYSA-N 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 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
- 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
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 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
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000004907 gland Anatomy 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
- 230000005764 inhibitory process Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 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
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder 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
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 150000003388 sodium compounds Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 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
- 238000005303 weighing Methods 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (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)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4122140 | 1991-07-04 | ||
| DE4129364 | 1991-09-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL102380A0 IL102380A0 (en) | 1993-01-14 |
| IL102380A true IL102380A (en) | 1996-10-16 |
Family
ID=25905206
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10238092A IL102380A (en) | 1991-07-04 | 1992-07-02 | Octadecyl] -N-2-methylpipridino (ethyl-phosphate, its preparation and pharmaceutical preparations containing |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5219866A (fi) |
| EP (1) | EP0521353B1 (fi) |
| JP (1) | JP3176720B2 (fi) |
| KR (1) | KR100255436B1 (fi) |
| CN (1) | CN1030658C (fi) |
| AT (1) | ATE136783T1 (fi) |
| AU (1) | AU651224B2 (fi) |
| CA (1) | CA2073146C (fi) |
| DE (2) | DE4219972A1 (fi) |
| DK (1) | DK0521353T3 (fi) |
| EG (1) | EG20082A (fi) |
| ES (1) | ES2086026T3 (fi) |
| FI (1) | FI108035B (fi) |
| GR (1) | GR3019776T3 (fi) |
| HU (2) | HUT61561A (fi) |
| IE (1) | IE73200B1 (fi) |
| IL (1) | IL102380A (fi) |
| NO (1) | NO303939B1 (fi) |
| PL (3) | PL173794B1 (fi) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| KR20130016413A (ko) * | 2002-07-30 | 2013-02-14 | 아에테르나 젠타리스 게엠베하 | 항종양 약제와 조합하여 사용하기 위한 알킬포스포콜린의 약물 제품 |
| AR058397A1 (es) * | 2005-12-19 | 2008-01-30 | Zentaris Gmbh | Derivados de alquilfosfolipidos con citotoxicidad reducida y usos de los mismos |
| US20070167408A1 (en) * | 2005-12-19 | 2007-07-19 | Zentaris Gmbh | Novel alkyl phospholipid derivatives with reduced cytotoxicity and uses thereof |
| 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 |
| CA2794513A1 (en) | 2010-03-31 | 2011-10-06 | Aeterna Zentaris Gmbh | Perifosine and capecitabine as a combined treatment for cancer |
Family Cites Families (3)
| 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 |
| ES2108715T3 (es) * | 1991-07-04 | 1998-01-01 | Asta Medica Ag | Procedimiento para la preparacion de alquilfosfocolinas y purificacion de las mismas. |
-
1992
- 1992-06-19 DK DK92110347.9T patent/DK0521353T3/da active
- 1992-06-19 DE DE4219972A patent/DE4219972A1/de not_active Withdrawn
- 1992-06-19 DE DE59205998T patent/DE59205998D1/de not_active Expired - Fee Related
- 1992-06-19 ES ES92110347T patent/ES2086026T3/es not_active Expired - Lifetime
- 1992-06-19 AT AT92110347T patent/ATE136783T1/de not_active IP Right Cessation
- 1992-06-19 EP EP92110347A patent/EP0521353B1/de not_active Expired - Lifetime
- 1992-07-01 EG EG34592A patent/EG20082A/xx active
- 1992-07-01 US US07/907,025 patent/US5219866A/en not_active Expired - Lifetime
- 1992-07-02 PL PL92311787A patent/PL173794B1/pl not_active IP Right Cessation
- 1992-07-02 PL PL92295128A patent/PL173905B1/pl not_active IP Right Cessation
- 1992-07-02 PL PL92311788A patent/PL173869B1/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 FI FI923088A patent/FI108035B/fi active
- 1992-07-03 HU HU9202232A patent/HUT61561A/hu unknown
- 1992-07-03 JP JP17691592A patent/JP3176720B2/ja not_active Expired - Fee Related
- 1992-07-03 IE IE922183A patent/IE73200B1/en not_active IP Right Cessation
- 1992-07-03 KR KR1019920011821A patent/KR100255436B1/ko not_active IP Right Cessation
- 1992-07-03 NO NO922642A patent/NO303939B1/no unknown
- 1992-07-03 CA CA002073146A patent/CA2073146C/en not_active Expired - Fee Related
- 1992-07-03 CN CN92105452A patent/CN1030658C/zh not_active Expired - Fee Related
-
1995
- 1995-06-16 HU HU95P/P00233P patent/HU211483A9/hu unknown
-
1996
- 1996-04-29 GR GR960401156T patent/GR3019776T3/el unknown
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Legal Events
| Date | Code | Title | Description |
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| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| HP | Change in proprietorship | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |