IL98524A - R (-2-] -Octadecyloxymethyl tetrahydropuran-2-yl-methoxyhydroxy [N N N its, their preparation and pharmaceutical preparations containing them - Google Patents
R (-2-] -Octadecyloxymethyl tetrahydropuran-2-yl-methoxyhydroxy [N N N its, their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL98524A IL98524A IL9852491A IL9852491A IL98524A IL 98524 A IL98524 A IL 98524A IL 9852491 A IL9852491 A IL 9852491A IL 9852491 A IL9852491 A IL 9852491A IL 98524 A IL98524 A IL 98524A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- formula
- enantiomer
- tetrahydrofuran
- preparation
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 title claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 229950004354 phosphorylcholine Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- 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 claims abstract description 19
- 238000010511 deprotection reaction Methods 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 19
- -1 2-octadecyloxymethyltetrahydrofuran-2-ylmethoxy Chemical group 0.000 claims description 15
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 27
- 239000000543 intermediate Substances 0.000 abstract description 7
- 229910052799 carbon Inorganic materials 0.000 abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- IXZHWGJCHBDVLV-UHFFFAOYSA-N C(CCC)(=O)O.C(CCC)(=O)O.OCC1(OCCC1)CO Chemical compound C(CCC)(=O)O.C(CCC)(=O)O.OCC1(OCCC1)CO IXZHWGJCHBDVLV-UHFFFAOYSA-N 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 2
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 201000006417 multiple sclerosis Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 11
- 239000003480 eluent Substances 0.000 description 10
- 239000003960 organic solvent Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 230000003287 optical effect Effects 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 108090001060 Lipase Proteins 0.000 description 5
- 239000004367 Lipase Substances 0.000 description 5
- 102000004882 Lipase Human genes 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 235000019421 lipase Nutrition 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011369 resultant mixture Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 4
- WSULSMOGMLRGKU-UHFFFAOYSA-N 1-bromooctadecane Chemical compound CCCCCCCCCCCCCCCCCCBr WSULSMOGMLRGKU-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 150000004292 cyclic ethers Chemical class 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000498617 Mucor javanicus Species 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 101001003495 Pseudomonas fluorescens Lipase Proteins 0.000 description 2
- 101001064559 Pseudomonas fluorescens Lipase Proteins 0.000 description 2
- DDUCSZMYPQLRNL-UHFFFAOYSA-N [2-(hydroxymethyl)oxolan-2-yl]methanol Chemical compound OCC1(CO)CCCO1 DDUCSZMYPQLRNL-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- 238000006884 silylation reaction Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 2
- OPZURGNJJBQSCY-HKBQPEDESA-N (2s)-2-(phenylmethoxymethyl)-2-(trityloxymethyl)oxolane Chemical compound C=1C=CC=CC=1COC[C@]1(COC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCCO1 OPZURGNJJBQSCY-HKBQPEDESA-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
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 241000235015 Yarrowia lipolytica Species 0.000 description 1
- CVBYQXBQHNZALC-XMMPIXPASA-N [(2r)-2-(octadecoxymethyl)oxolan-2-yl]methanol Chemical compound CCCCCCCCCCCCCCCCCCOC[C@]1(CO)CCCO1 CVBYQXBQHNZALC-XMMPIXPASA-N 0.000 description 1
- YCZZQSFWHFBKMU-OLQVQODUSA-N [(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]methanol Chemical compound OC[C@H]1CC[C@@H](CO)O1 YCZZQSFWHFBKMU-OLQVQODUSA-N 0.000 description 1
- 241000179532 [Candida] cylindracea Species 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- RZJRJXONCZWCBN-NJFSPNSNSA-N octadecane Chemical class CCCCCCCCCCCCCCCCC[14CH3] RZJRJXONCZWCBN-NJFSPNSNSA-N 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 108010079522 solysime Proteins 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 238000005866 tritylation reaction Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/12—Radicals substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
-
- 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
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/6574—Esters of oxyacids of phosphorus
- C07F9/65742—Esters of oxyacids of phosphorus non-condensed with carbocyclic rings or heterocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54043890A | 1990-06-19 | 1990-06-19 | |
| US64739691A | 1991-01-29 | 1991-01-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL98524A0 IL98524A0 (en) | 1992-07-15 |
| IL98524A true IL98524A (en) | 1995-12-31 |
Family
ID=27066435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9852491A IL98524A (en) | 1990-06-19 | 1991-06-17 | R (-2-] -Octadecyloxymethyl tetrahydropuran-2-yl-methoxyhydroxy [N N N its, their preparation and pharmaceutical preparations containing them |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0462935B1 (pl) |
| JP (1) | JP2709330B2 (pl) |
| KR (1) | KR920000772A (pl) |
| AT (1) | ATE125261T1 (pl) |
| AU (2) | AU649681B2 (pl) |
| CA (1) | CA2044786A1 (pl) |
| CS (1) | CS185191A3 (pl) |
| DE (1) | DE69111311T2 (pl) |
| DK (1) | DK0462935T3 (pl) |
| ES (1) | ES2076502T3 (pl) |
| FI (1) | FI912964A (pl) |
| GR (1) | GR3017437T3 (pl) |
| HK (1) | HK111996A (pl) |
| HU (1) | HU210548B (pl) |
| IE (1) | IE68417B1 (pl) |
| IL (1) | IL98524A (pl) |
| MY (1) | MY107022A (pl) |
| NZ (1) | NZ238573A (pl) |
| PL (1) | PL164981B1 (pl) |
| PT (1) | PT97994B (pl) |
| TW (1) | TW255897B (pl) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5208352A (en) * | 1992-04-02 | 1993-05-04 | Sandoz Ltd. | Process for preparing the R- and S-isomers of 2-hydroxy-methyl-2-octadecyloxymethyl-tetrahydrofuran and their use in preparing stereoisomers of pharmacologically active compounds |
| ATE225982T1 (de) * | 1998-07-17 | 2002-10-15 | Fuji Photo Film Co Ltd | Photozelle und photoelektrochemische zelle |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0178261A3 (en) * | 1984-10-10 | 1986-12-30 | Sandoz Ag | Substituted 2-furanyl or 5-oxo-2-furanyl-alkoxy phosphoryl alkyl cyclimmonium salts |
| US4601987A (en) * | 1985-02-27 | 1986-07-22 | Massachusetts Institute Of Technology | Enzymatic production of optical isomers of 2-halopropionic acids |
| DE3666435D1 (en) * | 1985-08-30 | 1989-11-23 | Sandoz Ag | Substituted hydroxy-heterocyclyl-alkoxy phosphinyloxy trialkylaminium hydroxide inner salt oxides, processes for their preparation and their use as pharmaceuticals |
| US4673672A (en) * | 1985-10-28 | 1987-06-16 | Sandoz Pharmaceuticals Corp. | Substituted-[hydroxy(tetrahydro)-5-oxo-(2- and 3-furanyl or 2-thienyl)alkoxyphosphinyloxy]-alkanaminium hydroxide, inner salt oxides |
| US4868319A (en) * | 1987-12-22 | 1989-09-19 | Sandoz Pharm. Corp. | Process for the preparation of monoalkylcarbamate group-containing compounds |
-
1991
- 1991-06-06 HU HU911882A patent/HU210548B/hu not_active IP Right Cessation
- 1991-06-17 NZ NZ238573A patent/NZ238573A/en unknown
- 1991-06-17 AU AU78439/91A patent/AU649681B2/en not_active Ceased
- 1991-06-17 CS CS911851A patent/CS185191A3/cs unknown
- 1991-06-17 IL IL9852491A patent/IL98524A/en not_active IP Right Cessation
- 1991-06-17 CA CA002044786A patent/CA2044786A1/en not_active Abandoned
- 1991-06-17 PT PT97994A patent/PT97994B/pt not_active IP Right Cessation
- 1991-06-18 IE IE208191A patent/IE68417B1/en not_active IP Right Cessation
- 1991-06-18 KR KR1019910010079A patent/KR920000772A/ko not_active Application Discontinuation
- 1991-06-18 FI FI912964A patent/FI912964A/fi not_active Application Discontinuation
- 1991-06-18 PL PL91290719A patent/PL164981B1/pl unknown
- 1991-06-18 MY MYPI91001089A patent/MY107022A/en unknown
- 1991-06-18 JP JP3173245A patent/JP2709330B2/ja not_active Expired - Lifetime
- 1991-06-19 AT AT91810477T patent/ATE125261T1/de not_active IP Right Cessation
- 1991-06-19 DE DE69111311T patent/DE69111311T2/de not_active Expired - Fee Related
- 1991-06-19 DK DK91810477.9T patent/DK0462935T3/da active
- 1991-06-19 ES ES91810477T patent/ES2076502T3/es not_active Expired - Lifetime
- 1991-06-19 EP EP91810477A patent/EP0462935B1/en not_active Expired - Lifetime
- 1991-07-09 TW TW080105309A patent/TW255897B/zh active
-
1994
- 1994-08-23 AU AU71407/94A patent/AU677403B2/en not_active Ceased
-
1995
- 1995-09-18 GR GR950402562T patent/GR3017437T3/el unknown
-
1996
- 1996-06-27 HK HK111996A patent/HK111996A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ES2076502T3 (es) | 1995-11-01 |
| HUT58340A (en) | 1992-02-28 |
| JPH04270276A (ja) | 1992-09-25 |
| NZ238573A (en) | 1993-11-25 |
| FI912964A0 (fi) | 1991-06-18 |
| JP2709330B2 (ja) | 1998-02-04 |
| HU911882D0 (en) | 1991-12-30 |
| CS185191A3 (en) | 1992-01-15 |
| HU210548B (en) | 1995-05-29 |
| MY107022A (en) | 1995-08-30 |
| PT97994B (pt) | 1998-11-30 |
| CA2044786A1 (en) | 1991-12-20 |
| EP0462935B1 (en) | 1995-07-19 |
| AU649681B2 (en) | 1994-06-02 |
| HK111996A (en) | 1996-07-05 |
| ATE125261T1 (de) | 1995-08-15 |
| IL98524A0 (en) | 1992-07-15 |
| DE69111311D1 (de) | 1995-08-24 |
| PT97994A (pt) | 1992-03-31 |
| IE68417B1 (en) | 1996-06-12 |
| DE69111311T2 (de) | 1996-03-14 |
| EP0462935A1 (en) | 1991-12-27 |
| KR920000772A (ko) | 1992-01-29 |
| DK0462935T3 (da) | 1995-11-06 |
| TW255897B (pl) | 1995-09-01 |
| PL164981B1 (pl) | 1994-10-31 |
| AU677403B2 (en) | 1997-04-24 |
| IE912081A1 (en) | 1992-01-01 |
| PL290719A1 (en) | 1992-07-27 |
| AU7843991A (en) | 1992-01-02 |
| FI912964A (fi) | 1991-12-20 |
| AU7140794A (en) | 1994-11-03 |
| GR3017437T3 (en) | 1995-12-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| HC | Change of name of proprietor(s) | ||
| MM9K | Patent not in force due to non-payment of renewal fees |