JPH0749428B2 - 〔〔４−〔４−（４−フエニル−１−ピペラジニル）フエノキシメチル〕−１，３−ジオキソラン−２−イル〕メチル〕−１ｈ−イミダゾ−ル類及び１ｈ−１，２，４−トリアゾ−ル類の新規な誘導体 - Google Patents
〔〔４−〔４−（４−フエニル−１−ピペラジニル）フエノキシメチル〕−１，３−ジオキソラン−２−イル〕メチル〕−１ｈ−イミダゾ−ル類及び１ｈ−１，２，４−トリアゾ−ル類の新規な誘導体Info
- Publication number
- JPH0749428B2 JPH0749428B2 JP61305542A JP30554286A JPH0749428B2 JP H0749428 B2 JPH0749428 B2 JP H0749428B2 JP 61305542 A JP61305542 A JP 61305542A JP 30554286 A JP30554286 A JP 30554286A JP H0749428 B2 JPH0749428 B2 JP H0749428B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- formula
- group
- substituted
- hydrogen
- 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.)
- Expired - Fee Related
Links
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 title description 5
- RGZZBDSVWHYNGT-UHFFFAOYSA-N 1-[4-[[2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-phenylpiperazine Chemical class C1OC(CN2C=NC=C2)OC1COC(C=C1)=CC=C1N(CC1)CCN1C1=CC=CC=C1 RGZZBDSVWHYNGT-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 131
- 239000002253 acid Substances 0.000 claims abstract description 61
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 37
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 185
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 151
- 239000000203 mixture Substances 0.000 claims description 99
- -1 nitro, amino Chemical group 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 66
- 125000003118 aryl group Chemical group 0.000 claims description 65
- 125000003545 alkoxy group Chemical group 0.000 claims description 52
- 239000000543 intermediate Substances 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 44
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 34
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 31
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 239000002585 base Substances 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 16
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 14
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000001894 2,4,6-trinitrophenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O 0.000 claims description 12
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 231100000252 nontoxic Toxicity 0.000 claims description 9
- 230000003000 nontoxic effect Effects 0.000 claims description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 241000894006 Bacteria Species 0.000 claims description 7
- 241000233866 Fungi Species 0.000 claims description 7
- 239000012442 inert solvent Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000006477 desulfuration reaction Methods 0.000 claims description 4
- 230000023556 desulfurization Effects 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 150000000180 1,2-diols Chemical class 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 125000003700 epoxy group Chemical group 0.000 claims description 2
- 229910044991 metal oxide Inorganic materials 0.000 claims description 2
- 150000004706 metal oxides Chemical class 0.000 claims description 2
- 244000005700 microbiome Species 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 239000003513 alkali Substances 0.000 claims 8
- 239000012458 free base Substances 0.000 claims 8
- 125000004185 ester group Chemical group 0.000 claims 5
- 239000012876 carrier material Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
- 239000004599 antimicrobial Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 140
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 79
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
- 239000000047 product Substances 0.000 description 72
- 230000008018 melting Effects 0.000 description 69
- 238000002844 melting Methods 0.000 description 69
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 53
- 239000003480 eluent Substances 0.000 description 52
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- 229960001701 chloroform Drugs 0.000 description 39
- 239000000243 solution Substances 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 32
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- 238000004440 column chromatography Methods 0.000 description 23
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 238000001816 cooling Methods 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 19
- 238000003756 stirring Methods 0.000 description 18
- 239000000284 extract Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 16
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 14
- 150000002148 esters Chemical class 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 230000000845 anti-microbial effect Effects 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000010934 O-alkylation reaction Methods 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- ISJVOEOJQLKSJU-HYQHGBLTSA-N O=C1N([C@H](C)[C@H](O)C)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 Chemical group O=C1N([C@H](C)[C@H](O)C)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 ISJVOEOJQLKSJU-HYQHGBLTSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- OIMRLHCSLQUXLL-UHFFFAOYSA-N 3-chlorobutan-2-one Chemical compound CC(Cl)C(C)=O OIMRLHCSLQUXLL-UHFFFAOYSA-N 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000222122 Candida albicans Species 0.000 description 3
- 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 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000007126 N-alkylation reaction Methods 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 201000007096 Vulvovaginal Candidiasis Diseases 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 229940095731 candida albicans Drugs 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 150000004679 hydroxides Chemical class 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 3
- 238000005907 ketalization reaction Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- MDTUWBLTRPRXBX-UHFFFAOYSA-N 1,2,4-triazol-3-one Chemical compound O=C1N=CN=N1 MDTUWBLTRPRXBX-UHFFFAOYSA-N 0.000 description 2
- NPFLZNXRZCFFJP-UHFFFAOYSA-N 1-[4-[4-(4-hydroxyphenyl)piperazin-1-yl]phenyl]-3-(3-oxobutan-2-yl)imidazolidin-2-one Chemical compound O=C1N(C(C)C(C)=O)CCN1C1=CC=C(N2CCN(CC2)C=2C=CC(O)=CC=2)C=C1 NPFLZNXRZCFFJP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- BZLVPSLGJCWYBB-UHFFFAOYSA-N 2-methyl-2-(methylamino)propanoic acid;hydrochloride Chemical compound Cl.CNC(C)(C)C(O)=O BZLVPSLGJCWYBB-UHFFFAOYSA-N 0.000 description 2
- BNHYDULILNJFFY-UHFFFAOYSA-N 4-[4-(4-nitrophenyl)piperazin-1-yl]phenol Chemical compound C1=CC(O)=CC=C1N1CCN(C=2C=CC(=CC=2)[N+]([O-])=O)CC1 BNHYDULILNJFFY-UHFFFAOYSA-N 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
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- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-M undecanoate Chemical compound CCCCCCCCCCC([O-])=O ZDPHROOEEOARMN-UHFFFAOYSA-M 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81267085A | 1985-12-23 | 1985-12-23 | |
| US812670 | 1985-12-23 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6302729A Division JP2574656B2 (ja) | 1985-12-23 | 1994-11-14 | 置換（４−フエニル−１−ピペラジニル）フエノール誘導体及びその製造方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62158275A JPS62158275A (ja) | 1987-07-14 |
| JPH0749428B2 true JPH0749428B2 (ja) | 1995-05-31 |
Family
ID=25210297
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61305542A Expired - Fee Related JPH0749428B2 (ja) | 1985-12-23 | 1986-12-23 | 〔〔４−〔４−（４−フエニル−１−ピペラジニル）フエノキシメチル〕−１，３−ジオキソラン−２−イル〕メチル〕−１ｈ−イミダゾ−ル類及び１ｈ−１，２，４−トリアゾ−ル類の新規な誘導体 |
| JP6302729A Expired - Fee Related JP2574656B2 (ja) | 1985-12-23 | 1994-11-14 | 置換（４−フエニル−１−ピペラジニル）フエノール誘導体及びその製造方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6302729A Expired - Fee Related JP2574656B2 (ja) | 1985-12-23 | 1994-11-14 | 置換（４−フエニル−１−ピペラジニル）フエノール誘導体及びその製造方法 |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP0228125B1 (en, 2012) |
| JP (2) | JPH0749428B2 (en, 2012) |
| AT (1) | ATE73799T1 (en, 2012) |
| AU (2) | AU589726B2 (en, 2012) |
| CA (1) | CA1292472C (en, 2012) |
| CY (1) | CY1825A (en, 2012) |
| DE (1) | DE3684431D1 (en, 2012) |
| DK (2) | DK164167C (en, 2012) |
| ES (1) | ES2032381T3 (en, 2012) |
| FI (1) | FI88505C (en, 2012) |
| GR (1) | GR3004114T3 (en, 2012) |
| HK (1) | HK46295A (en, 2012) |
| IE (1) | IE59564B1 (en, 2012) |
| IL (1) | IL81054A (en, 2012) |
| NO (1) | NO167917C (en, 2012) |
| NZ (1) | NZ218553A (en, 2012) |
| PT (1) | PT84007B (en, 2012) |
| ZA (1) | ZA869637B (en, 2012) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ223799A (en) * | 1987-03-25 | 1989-12-21 | Janssen Pharmaceutica Nv | Azolylmethyl-dioxolanylmethoxyphenyl-piperazinyl-phenyl-triazolones and antimicrobial compositions |
| CA1331757C (en) | 1988-02-29 | 1994-08-30 | Janssen Pharmaceutica Naamloze Vennootschap | 5-lipoxygenase inhibiting 4-(4-phenyl-1-piperazinyl)phenols |
| GR1000330B (el) * | 1988-07-01 | 1992-06-25 | Janssen Pharmaceutica Nv | Μεθοδος παρασκευης παραγωγων 2,4 διυδρο-3η-1,2,4-τριαζολ-3-ονης. |
| GR1000302B (el) * | 1988-07-01 | 1992-05-12 | Janssen Pharmaceutica Nv | Μεθοδος παρασκευης παραγωγων 2,4-διυδρο-3η-1,2,4-τριαζολ-3-ονης. |
| GR1000298B (el) * | 1988-07-01 | 1992-05-12 | Janssen Pharmaceutica Nv | Μεθοδος παρασκευης παραγωγων 2,4-διυδρο-3η-1,2,4-τριαζολ-3-ονης. |
| GR1000297B (el) * | 1988-07-01 | 1992-05-12 | Janssen Pharmaceutica Nv | Μεθοδος παρασκευης παραγωγων 2,4-διυδρο-3η-1,2,4-τριαζολ-3-ονης. |
| GB8903592D0 (en) * | 1989-02-16 | 1989-04-05 | Boots Co Plc | Therapeutic agents |
| NZ233502A (en) * | 1989-06-09 | 1991-11-26 | Janssen Pharmaceutica Nv | 4-(1,2,4-triazole- or imidazole-phenyl-substituted) -1-(1,3-dioxolan-4-ylmethoxyphenyl) piperazine derivatives; preparatory processes: fungicidal and antiviral compositions |
| CA2076257A1 (en) * | 1991-09-13 | 1993-03-14 | Jan Heeres | 4-¬4-¬4-(4-hydroxyphenyl)-1- piperazinyl|phenyl|-5-methyl-3h -1,2,4-triazol-3-one derivatives |
| TW279864B (en, 2012) * | 1993-02-19 | 1996-07-01 | Janssen Pharmaceutica Nv | |
| HU225062B1 (en) * | 1993-12-21 | 2006-05-29 | Schering Corp | Tetrahydrofuran derivatives with antifungal- effect, pharmaceutical compositions containing them and process for their preparation |
| CN1078210C (zh) * | 1994-01-24 | 2002-01-23 | 詹森药业有限公司 | 水溶性吡咯系杀真菌剂 |
| US5571811A (en) * | 1994-07-12 | 1996-11-05 | Janssen Pharmaceutica N.V. | Sulfonamide derivatives of azolones |
| AU697744C (en) * | 1994-10-27 | 2002-08-22 | Elanco Animal Health Ireland Limited | Apolipoprotein-B synthesis inhibitors |
| US5625064A (en) * | 1995-04-19 | 1997-04-29 | Schering Corporation | Process for the preparation of triazolones |
| TW457240B (en) * | 1995-04-20 | 2001-10-01 | Janssen Pharmaceutica Nv | Novel triazolones as apolipoprotein-B synthesis inhibitors |
| AU6257596A (en) * | 1995-06-19 | 1997-01-15 | Schering Corporation | Hydroxyalkyl-substituted triazolones antifungals |
| AU773405B2 (en) * | 1996-11-12 | 2004-05-27 | Sepracor, Inc. | Hydroxyitraconazole enantiomer mixtures |
| JP2001504121A (ja) * | 1996-11-12 | 2001-03-27 | セプラコール，インク． | ２ｒ，４ｓ，ｒ，ｓ―および２ｓ，４ｒ，ｒ，ｓ―ヒドロキシイトラコナゾール―およびヒドロキシサパーコナゾール誘導体 |
| TW593312B (en) * | 1997-07-11 | 2004-06-21 | Janssen Pharmaceutica Nv | 2,4,4-trisubstituted-1,3-dioxolane antifungals |
| CN100343249C (zh) * | 1997-07-11 | 2007-10-17 | 詹森药业有限公司 | 2,4,4－三取代的1,3－二氧环戊烷抗真菌剂 |
| AU9592998A (en) * | 1997-10-07 | 1999-04-27 | Schering Corporation | Crystalline antifungal glycine ester polymorph |
| CN1349540A (zh) * | 1999-05-04 | 2002-05-15 | 詹森药业有限公司 | 抗真菌的醚类 |
| KR100342383B1 (ko) * | 1999-06-17 | 2002-12-06 | 한국화학연구원 | 이소옥사졸리딘 유도체, 그의 제조 방법 및 그를 포함하는 살균제 조성물 |
| MX342850B (es) * | 2010-05-19 | 2016-10-14 | Sandoz Ag | Proceso para la preparacion de triazolonas quirales. |
| ES2790875T3 (es) | 2014-12-05 | 2020-10-29 | Pulmocide Ltd | Compuesto antimicótico |
| HUE048843T2 (hu) | 2015-05-21 | 2020-08-28 | Pulmocide Ltd | Gombaölõ szer 4-(4-(4-(((3R,5R)-5-((1H -1,2,4-triazol-1-YL)metil)-5-(2,4-difluor-fenil)tetra-hidro-furán-3-YL)metoxi)-3 metilfenil)piperazin-1-il)-n -(2-hidroxi-ciklohexil)benzamid, vagy annak gyógyszerészetileg elfogadható sója |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4144346A (en) * | 1977-01-31 | 1979-03-13 | Janssen Pharmaceutica N.V. | Novel 1-(1,3-dioxolan-2-ylmethyl)-1H-imidazoles |
| US4218458A (en) * | 1978-06-23 | 1980-08-19 | Janssen Pharmaceutica, N.V. | Heterocyclic derivatives of (4-aryloxy-methyl-1,3-dioxolan-2-yl)methyl-1H-imidazoles and 1H-1,2,4-triazoles |
| US4619931A (en) * | 1983-02-28 | 1986-10-28 | Janssen Pharmaceutica, N.V. | [[4-[4-(4-phenyl-1-piperazinyl)phenoxymethyl]-1,3-dioxolan-2-yl]methyl]-1H-imidazoles and 1H-1,2,4-triazoles |
-
1986
- 1986-11-13 CA CA000522852A patent/CA1292472C/en not_active Expired - Fee Related
- 1986-12-09 NZ NZ218553A patent/NZ218553A/xx unknown
- 1986-12-10 ES ES198686202230T patent/ES2032381T3/es not_active Expired - Lifetime
- 1986-12-10 AT AT86202230T patent/ATE73799T1/de not_active IP Right Cessation
- 1986-12-10 DE DE8686202230T patent/DE3684431D1/de not_active Expired - Fee Related
- 1986-12-10 EP EP86202230A patent/EP0228125B1/en not_active Expired - Lifetime
- 1986-12-22 AU AU66853/86A patent/AU589726B2/en not_active Ceased
- 1986-12-22 FI FI865257A patent/FI88505C/fi not_active IP Right Cessation
- 1986-12-22 NO NO865235A patent/NO167917C/no unknown
- 1986-12-22 DK DK625586A patent/DK164167C/da not_active IP Right Cessation
- 1986-12-22 IE IE336986A patent/IE59564B1/en not_active IP Right Cessation
- 1986-12-22 IL IL81054A patent/IL81054A/xx not_active IP Right Cessation
- 1986-12-23 JP JP61305542A patent/JPH0749428B2/ja not_active Expired - Fee Related
- 1986-12-23 ZA ZA869637A patent/ZA869637B/xx unknown
- 1986-12-23 PT PT84007A patent/PT84007B/pt not_active IP Right Cessation
-
1988
- 1988-05-12 AU AU16076/88A patent/AU593736B2/en not_active Ceased
-
1991
- 1991-04-23 DK DK074691A patent/DK167356B1/da not_active IP Right Cessation
-
1992
- 1992-03-19 GR GR920400484T patent/GR3004114T3/el unknown
-
1994
- 1994-11-14 JP JP6302729A patent/JP2574656B2/ja not_active Expired - Fee Related
-
1995
- 1995-03-30 HK HK46295A patent/HK46295A/en not_active IP Right Cessation
- 1995-12-01 CY CY182595A patent/CY1825A/xx unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |