JP2002514632A - モルホリノエーテル類 - Google Patents
モルホリノエーテル類Info
- Publication number
- JP2002514632A JP2002514632A JP2000548316A JP2000548316A JP2002514632A JP 2002514632 A JP2002514632 A JP 2002514632A JP 2000548316 A JP2000548316 A JP 2000548316A JP 2000548316 A JP2000548316 A JP 2000548316A JP 2002514632 A JP2002514632 A JP 2002514632A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- optionally substituted
- branched
- formyl
- indacene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- LBILFEKNFGGWDY-UHFFFAOYSA-N 4-morpholin-4-yloxymorpholine Chemical class C1COCCN1ON1CCOCC1 LBILFEKNFGGWDY-UHFFFAOYSA-N 0.000 title abstract description 3
- -1 propadienyl Chemical group 0.000 claims abstract description 183
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 34
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 125000005843 halogen group Chemical group 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 10
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 8
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 6
- 125000003302 alkenyloxy group Chemical group 0.000 claims abstract description 5
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims abstract description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 5
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 3
- 125000001589 carboacyl group Chemical group 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 218
- 238000006243 chemical reaction Methods 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 39
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 12
- 208000031888 Mycoses Diseases 0.000 claims description 10
- 206010017533 Fungal infection Diseases 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 230000002538 fungal effect Effects 0.000 claims description 9
- 125000005394 methallyl group Chemical group 0.000 claims description 9
- 125000003172 aldehyde group Chemical group 0.000 claims description 8
- 150000001299 aldehydes Chemical class 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 238000006268 reductive amination reaction Methods 0.000 claims description 8
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000005336 allyloxy group Chemical group 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- AJSOAVVAYLEJRI-VUOYKSBVSA-N 2-[[(2R,6R)-4-cyclopropyl-6-methylmorpholin-2-yl]oxymethyl]-9-formyl-5-methyl-13-propan-2-yltetracyclo[7.4.0.02,11.04,8]tridec-12-ene-1-carboxylic acid Chemical compound C1(CC1)N1C[C@@H](O[C@@H](C1)C)OCC12CC3C(CCC3C3(C2(C(=CC1C3)C(C)C)C(=O)O)C=O)C AJSOAVVAYLEJRI-VUOYKSBVSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims description 3
- 125000004462 3,4-difluorophenylmethyl group Chemical group FC=1C=C(C=CC1F)C* 0.000 claims description 2
- VSBNCJVQGGHYAU-XDSCNKDDSA-N 9-formyl-5-methyl-2-[[(2R,6R)-6-methyl-4-prop-2-ynylmorpholin-2-yl]oxymethyl]-13-propan-2-yltetracyclo[7.4.0.02,11.04,8]tridec-12-ene-1-carboxylic acid Chemical compound C(C#C)N1C[C@@H](O[C@@H](C1)C)OCC12CC3C(CCC3C3(C2(C(=CC1C3)C(C)C)C(=O)O)C=O)C VSBNCJVQGGHYAU-XDSCNKDDSA-N 0.000 claims description 2
- DRCUSVNZAUVMRT-DLYQAWBXSA-N C(C=C=C)N1C[C@@H](O[C@@H](C1)C)OCC12CC3C(CCC3C3(C2(C(=CC1C3)C(C)C)C(=O)O)C=O)C Chemical compound C(C=C=C)N1C[C@@H](O[C@@H](C1)C)OCC12CC3C(CCC3C3(C2(C(=CC1C3)C(C)C)C(=O)O)C=O)C DRCUSVNZAUVMRT-DLYQAWBXSA-N 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 208000010362 Protozoan Infections Diseases 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000002207 metabolite Substances 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 128
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 198
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 168
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 153
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 151
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 131
- 239000000203 mixture Substances 0.000 description 106
- 239000000243 solution Substances 0.000 description 95
- 238000005160 1H NMR spectroscopy Methods 0.000 description 80
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 239000002904 solvent Substances 0.000 description 61
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- 239000007787 solid Substances 0.000 description 43
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- 238000004440 column chromatography Methods 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 239000012044 organic layer Substances 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 239000000843 powder Substances 0.000 description 26
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 239000000725 suspension Substances 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
- 239000012267 brine Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 22
- 235000011152 sodium sulphate Nutrition 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- 239000002244 precipitate Substances 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 17
- 239000012043 crude product Substances 0.000 description 17
- 239000012279 sodium borohydride Substances 0.000 description 17
- 229910000033 sodium borohydride Inorganic materials 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 16
- 235000019441 ethanol Nutrition 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000004809 thin layer chromatography Methods 0.000 description 15
- 239000008186 active pharmaceutical agent Substances 0.000 description 14
- 229940088679 drug related substance Drugs 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 239000010410 layer Substances 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 238000012544 monitoring process Methods 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 235000020357 syrup Nutrition 0.000 description 11
- 239000006188 syrup Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 238000012746 preparative thin layer chromatography Methods 0.000 description 9
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 8
- 241000222122 Candida albicans Species 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000007796 conventional method Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 201000003984 candidiasis Diseases 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000002808 molecular sieve Substances 0.000 description 6
- 230000036961 partial effect Effects 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 5
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical class NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 5
- 206010007134 Candida infections Diseases 0.000 description 5
- 241000233866 Fungi Species 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 230000000845 anti-microbial effect Effects 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- YNJQKNVVBBIPBA-UHFFFAOYSA-M tetrabutylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.CCCC[N+](CCCC)(CCCC)CCCC YNJQKNVVBBIPBA-UHFFFAOYSA-M 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 244000060011 Cocos nucifera Species 0.000 description 4
- 235000013162 Cocos nucifera Nutrition 0.000 description 4
- 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 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 208000002003 vulvitis Diseases 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
- UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98500117 | 1998-05-11 | ||
| EP98500117.1 | 1998-05-11 | ||
| EP98500204.7 | 1998-09-18 | ||
| EP98500204 | 1998-09-18 | ||
| PCT/EP1999/003139 WO1999058512A1 (fr) | 1998-05-11 | 1999-05-07 | Ethers de morpholine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002514632A true JP2002514632A (ja) | 2002-05-21 |
Family
ID=26151831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000548316A Pending JP2002514632A (ja) | 1998-05-11 | 1999-05-07 | モルホリノエーテル類 |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1077959A1 (fr) |
| JP (1) | JP2002514632A (fr) |
| KR (1) | KR100625146B1 (fr) |
| CN (1) | CN1174971C (fr) |
| AR (1) | AR016261A1 (fr) |
| AU (1) | AU763088B2 (fr) |
| BR (1) | BR9910377A (fr) |
| CA (1) | CA2331584A1 (fr) |
| MA (1) | MA26628A1 (fr) |
| PE (1) | PE20000479A1 (fr) |
| TR (1) | TR200003301T2 (fr) |
| TW (1) | TW585858B (fr) |
| WO (1) | WO1999058512A1 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002023541A1 (fr) * | 2000-09-13 | 2002-03-21 | Sankyo Company, Limited | Dérivés de zofimarin présentant un noyau oxazépame |
| RU2259825C9 (ru) | 2001-06-18 | 2006-04-10 | БиоДием Лимитед | Вещества, проявляющие антимикробную, антигрибковую, антипротозойную активности |
| JP6640750B2 (ja) * | 2015-01-30 | 2020-02-05 | 日油株式会社 | カチオン性脂質 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH465771A (de) * | 1965-12-06 | 1968-11-30 | Sandoz Ag | Verfahren zur Herstellung eines neuen Antibioticums |
| JPH0615555B2 (ja) * | 1985-08-14 | 1994-03-02 | 三共株式会社 | 抗生物質ゾフイマリン |
| EP0711783A1 (fr) * | 1994-11-08 | 1996-05-15 | Glaxo, S.A. | Dérivés de Sordarin antifongiques |
| EP0711784A1 (fr) * | 1994-11-08 | 1996-05-15 | Glaxo, S.A. | Dérivés de Sordarin antifongiques |
| ZA959362B (en) * | 1994-11-08 | 1996-05-08 | Glaxo Wellcome Sa | Carbocyclic compounds |
| EP0712859A1 (fr) * | 1994-11-08 | 1996-05-22 | Glaxo, S.A. | Dérivés de Sordarin antifongiques |
| EP0901493A1 (fr) * | 1996-05-08 | 1999-03-17 | Glaxo Wellcome S.A. | Procede de preparation d'un compose d'indacene |
| ES2196364T3 (es) * | 1996-09-18 | 2003-12-16 | Merck & Co Inc | Sordarina y sus derivados para uso como agentes antifungicos en cultivos. |
| ES2215220T3 (es) * | 1996-10-07 | 2004-10-01 | MERCK & CO., INC. | Derivados de sordarina. |
| SK2082000A3 (en) * | 1997-08-22 | 2001-02-12 | Merck & Co Inc | 4-cyano-4-deformylsordaricin derivatives, process for the preparation thereof and agricultural agent containing the same and use thereof |
| JP4339505B2 (ja) * | 1997-08-22 | 2009-10-07 | メルク エンド カムパニー インコーポレーテッド | ４−シアノ−４−デホルミルソルダリン誘導体 |
-
1999
- 1999-05-05 MA MA25570A patent/MA26628A1/fr unknown
- 1999-05-06 AR ARP990102128A patent/AR016261A1/es not_active Application Discontinuation
- 1999-05-06 PE PE1999000371A patent/PE20000479A1/es not_active Application Discontinuation
- 1999-05-07 BR BR9910377-0A patent/BR9910377A/pt not_active Application Discontinuation
- 1999-05-07 CA CA002331584A patent/CA2331584A1/fr not_active Abandoned
- 1999-05-07 CN CNB998085146A patent/CN1174971C/zh not_active Expired - Fee Related
- 1999-05-07 TR TR2000/03301T patent/TR200003301T2/xx unknown
- 1999-05-07 AU AU42588/99A patent/AU763088B2/en not_active Ceased
- 1999-05-07 WO PCT/EP1999/003139 patent/WO1999058512A1/fr active IP Right Grant
- 1999-05-07 EP EP99950344A patent/EP1077959A1/fr not_active Withdrawn
- 1999-05-07 JP JP2000548316A patent/JP2002514632A/ja active Pending
- 1999-05-07 KR KR1020007012581A patent/KR100625146B1/ko not_active IP Right Cessation
- 1999-05-17 TW TW088107988A patent/TW585858B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CN1174971C (zh) | 2004-11-10 |
| AU763088B2 (en) | 2003-07-10 |
| BR9910377A (pt) | 2001-01-16 |
| CA2331584A1 (fr) | 1999-11-18 |
| WO1999058512A1 (fr) | 1999-11-18 |
| TR200003301T2 (tr) | 2001-02-21 |
| AR016261A1 (es) | 2001-06-20 |
| PE20000479A1 (es) | 2000-05-29 |
| TW585858B (en) | 2004-05-01 |
| KR20010025009A (ko) | 2001-03-26 |
| KR100625146B1 (ko) | 2006-09-20 |
| AU4258899A (en) | 1999-11-29 |
| EP1077959A1 (fr) | 2001-02-28 |
| MA26628A1 (fr) | 2004-12-20 |
| CN1309651A (zh) | 2001-08-22 |
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