LV12634B - WATER SOLUBLE ANTIMICOTICS OF AZOLA - Google Patents

WATER SOLUBLE ANTIMICOTICS OF AZOLA Download PDF

Info

Publication number: LV12634B
Authority: LV; Latvia
Prior art keywords: formula; phenyl; hydrogen; compound; triazol
Prior art date: 1994-01-24

Application number

LVP-00-153A

Other languages

English (en)

Latvian (lv)

Other versions

LV12634A (lv

Inventor

Jan Heeres

Leo Jacobus Jozef Backx

Luc Alfons Leo Van Der Eycken

Frank Christopher Odds

Jean Louis Mesens

Original Assignee

Janssen Pharmaceutica N.V.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1994-01-24

Filing date

2000-11-09

Publication date

2001-07-20

2000-11-09 Application filed by Janssen Pharmaceutica N.V. filed Critical Janssen Pharmaceutica N.V.

2001-03-20 Publication of LV12634A publication Critical patent/LV12634A/xx

2001-07-20 Publication of LV12634B publication Critical patent/LV12634B/en

Links

229940121375 antifungal agent Drugs 0.000 title description 11
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 97
150000003839 salts Chemical class 0.000 claims abstract description 31
239000002253 acid Substances 0.000 claims abstract description 29
238000011282 treatment Methods 0.000 claims abstract description 12
238000004519 manufacturing process Methods 0.000 claims abstract description 6
241001465754 Metazoa Species 0.000 claims abstract description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 87
239000000203 mixture Substances 0.000 claims description 83
239000001257 hydrogen Substances 0.000 claims description 30
229910052739 hydrogen Inorganic materials 0.000 claims description 30
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 30
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
-1 1,2,4-triazol-1-ylmethyl Chemical group 0.000 claims description 20
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 16
239000002585 base Substances 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
238000000034 method Methods 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 9
241000233866 Fungi Species 0.000 claims description 8
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
125000004193 piperazinyl group Chemical group 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
125000005059 halophenyl group Chemical group 0.000 claims description 7
150000004885 piperazines Chemical group 0.000 claims description 7
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 4
208000015181 infectious disease Diseases 0.000 claims description 4
238000006366 phosphorylation reaction Methods 0.000 claims description 4
238000005917 acylation reaction Methods 0.000 claims description 3
239000012458 free base Substances 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 2
125000000524 functional group Chemical group 0.000 claims description 2
230000026731 phosphorylation Effects 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims 7
150000002367 halogens Chemical group 0.000 claims 7
125000000217 alkyl group Chemical group 0.000 claims 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
230000006179 O-acylation Effects 0.000 claims 2
239000003153 chemical reaction reagent Substances 0.000 claims 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
230000010933 acylation Effects 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 1
230000001857 anti-mycotic effect Effects 0.000 claims 1
229910052801 chlorine Inorganic materials 0.000 claims 1
239000000460 chlorine Substances 0.000 claims 1
229910052731 fluorine Inorganic materials 0.000 claims 1
239000011737 fluorine Substances 0.000 claims 1
230000000843 anti-fungal effect Effects 0.000 abstract description 5
239000012871 anti-fungal composition Substances 0.000 abstract 1
150000007980 azole derivatives Chemical class 0.000 abstract 1
230000001747 exhibiting effect Effects 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 123
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 77
239000000543 intermediate Substances 0.000 description 34
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000000243 solution Substances 0.000 description 31
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
150000003254 radicals Chemical class 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
239000002904 solvent Substances 0.000 description 21
239000002244 precipitate Substances 0.000 description 20
239000012044 organic layer Substances 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
229910001868 water Inorganic materials 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
239000003480 eluent Substances 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 13
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 13
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
125000005843 halogen group Chemical group 0.000 description 12
241000222120 Candida <Saccharomycetales> Species 0.000 description 11
206010017533 Fungal infection Diseases 0.000 description 11
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 11
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
208000031888 Mycoses Diseases 0.000 description 10
238000003756 stirring Methods 0.000 description 10
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000010410 layer Substances 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
238000004440 column chromatography Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
150000002431 hydrogen Chemical group 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
239000011521 glass Substances 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000000047 product Substances 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000003826 tablet Substances 0.000 description 6
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 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
241000699666 Mus <mouse, genus> Species 0.000 description 5
229940079593 drug Drugs 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
230000009885 systemic effect Effects 0.000 description 5
241001225321 Aspergillus fumigatus Species 0.000 description 4
241000222122 Candida albicans Species 0.000 description 4
201000007336 Cryptococcosis Diseases 0.000 description 4
241000221204 Cryptococcus neoformans Species 0.000 description 4
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
230000000845 anti-microbial effect Effects 0.000 description 4
229940095731 candida albicans Drugs 0.000 description 4
239000013078 crystal Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
230000002538 fungal effect Effects 0.000 description 4
230000003902 lesion Effects 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 3
VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)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 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 3
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
241000893980 Microsporum canis Species 0.000 description 3
241000699670 Mus sp. Species 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
229940091771 aspergillus fumigatus Drugs 0.000 description 3
125000001246 bromo group Chemical group Br* 0.000 description 3
201000003984 candidiasis Diseases 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
229960004130 itraconazole Drugs 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
150000004682 monohydrates Chemical class 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
JNIIMKZIYBVWAH-UHFFFAOYSA-N 2-(2-hydroxy-3,3-dimethylbutyl)-4-[4-[4-(4-hydroxyphenyl)piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N(CC(O)C(C)(C)C)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(O)=CC=2)C=C1 JNIIMKZIYBVWAH-UHFFFAOYSA-N 0.000 description 2
HUADITLKOCMHSB-AVQIMAJZSA-N 2-butan-2-yl-4-[4-[4-[4-[[(2s,4r)-2-(2,4-difluorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N(C(C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3O[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 HUADITLKOCMHSB-AVQIMAJZSA-N 0.000 description 2
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
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241000894006 Bacteria Species 0.000 description 2
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
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241000223205 Coccidioides immitis Species 0.000 description 2
229920000858 Cyclodextrin Polymers 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
206010061598 Immunodeficiency Diseases 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
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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 2
208000002474 Tinea Diseases 0.000 description 2
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230000002152 alkylating effect Effects 0.000 description 2
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239000002775 capsule Substances 0.000 description 2
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208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
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RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 2
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238000006460 hydrolysis reaction Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
230000000865 phosphorylative effect Effects 0.000 description 2
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HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
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239000007787 solid Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
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FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
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YGTMDEGZMDIKET-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)acetic acid;dihydrochloride Chemical compound Cl.Cl.CN1CCN(CC(O)=O)CC1 YGTMDEGZMDIKET-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
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LVQFHDAKZHGEAJ-UHFFFAOYSA-M 4-methylbenzenesulfonate Chemical compound [CH2]C1=CC=C(S([O-])(=O)=O)C=C1 LVQFHDAKZHGEAJ-UHFFFAOYSA-M 0.000 description 1
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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
- 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
- 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
- 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
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Detergent Compositions (AREA)
Separation Of Suspended Particles By Flocculating Agents (AREA)
External Artificial Organs (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Footwear And Its Accessory, Manufacturing Method And Apparatuses (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)

LVP-00-153A 1994-01-24 2000-11-09 WATER SOLUBLE ANTIMICOTICS OF AZOLA LV12634B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US18535294A	1994-01-24	1994-01-24

Publications (2)

Publication Number	Publication Date
LV12634A LV12634A (lv)	2001-03-20
LV12634B true LV12634B (en)	2001-07-20

Family

ID=22680644

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LVP-00-153A LV12634B (en)	1994-01-24	2000-11-09	WATER SOLUBLE ANTIMICOTICS OF AZOLA

Country Status (31)

Country	Link
US (1)	US5707977A (fi)
EP (1)	EP0741737B1 (fi)
JP (1)	JP3764750B2 (fi)
KR (1)	KR100352147B1 (fi)
CN (1)	CN1078210C (fi)
AT (1)	ATE186540T1 (fi)
AU (1)	AU688455B2 (fi)
CA (1)	CA2179640C (fi)
CY (1)	CY2176B1 (fi)
CZ (1)	CZ288544B6 (fi)
DE (1)	DE69513279T2 (fi)
DK (1)	DK0741737T3 (fi)
ES (1)	ES2141329T3 (fi)
FI (1)	FI116057B (fi)
GR (1)	GR3032550T3 (fi)
HU (1)	HU227281B1 (fi)
IL (1)	IL112413A (fi)
LV (1)	LV12634B (fi)
MY (1)	MY111814A (fi)
NO (1)	NO308412B1 (fi)
NZ (1)	NZ278882A (fi)
PH (1)	PH31664A (fi)
PL (1)	PL181947B1 (fi)
PT (1)	PT741737E (fi)
RU (1)	RU2156764C2 (fi)
SG (1)	SG48386A1 (fi)
SI (1)	SI0741737T1 (fi)
SK (1)	SK282059B6 (fi)
TW (1)	TW376385B (fi)
WO (1)	WO1995019983A1 (fi)
ZA (1)	ZA95521B (fi)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TW457240B (en)	1995-04-20	2001-10-01	Janssen Pharmaceutica Nv	Novel triazolones as apolipoprotein-B synthesis inhibitors
AR002751A1 (es) *	1995-06-02	1998-04-29	Schering Corp	Antifungicos de tetrahidrofurano, composiciones farmaceuticas que los contienen y el uso de los compuestos para preparar composiciones farmaceuticas utiles para el tratamiento de infecciones fungicas
US5698557A (en) *	1995-06-19	1997-12-16	Schering Corporation	Hydroxy-substituted antifungals
WO1997000255A1 (en) *	1995-06-19	1997-01-03	Schering Corporation	Tetrahydrofuran antifungals
GB9602080D0 (en) *	1996-02-02	1996-04-03	Pfizer Ltd	Pharmaceutical compounds
NZ328607A (en) *	1996-09-09	1999-08-30	Hoffmann La Roche	Heterocyclically substituted n-benzyl-azolium derivatives and fungicidal compositions
AU5251298A (en) *	1996-11-12	1998-06-03	Sepracor, Inc.	(2r,4s,s,r-) and (2s,4r,s,r-)hydroxyitraconazole
WO1998021205A1 (en) *	1996-11-12	1998-05-22	Sepracor, Inc.	2r,4s,r,r- and 2s,4r,r,r-hydroxyitraconazole
JP2001504465A (ja) *	1996-11-12	2001-04-03	セプラコール，インク．	２ｒ，４ｓ，ｓ，ｓ―および２ｓ，４ｒ，ｓ，ｓ―ヒドロキシイトラコナゾール
CA2269617A1 (en) *	1996-11-12	1998-05-22	Chris H. Senanayake	2r,4s,r,s- and 2s,4r,r,s-hydroxyitraconazole- and hydroxysaperconazole derivatives
JP4347911B2 (ja) *	1997-02-11	2009-10-21	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	アミノ酸エステル含有アゾール抗真菌剤
TW593312B (en) *	1997-07-11	2004-06-21	Janssen Pharmaceutica Nv	2,4,4-trisubstituted-1,3-dioxolane antifungals
UA63954C2 (en) *	1997-07-11	2004-02-16	Janssen Pharmaceutica Nv	(+/-) norcisapride, a process for the preparation thereof, intermediate compounds, composition based thereon for use in the manufacture of medicaments for treating gastro-intestinal disorders
ZA989063B (en) *	1997-10-07	1999-04-06	Schering Corp	Crystalline antifungal polymorph
EP0957101A1 (en)	1998-05-14	1999-11-17	Janssen Pharmaceutica N.V.	Water soluble azoles as broad-spectrum antifungals
US6265584B1 (en) *	1998-05-22	2001-07-24	Bristol-Myers Squibb Company	Water soluble prodrugs of azole compounds
WO2000030655A1 (en)	1998-11-20	2000-06-02	Bristol-Myers Squibb Company	Water soluble prodrugs of azole compounds
US6362172B2 (en)	2000-01-20	2002-03-26	Bristol-Myers Squibb Company	Water soluble prodrugs of azole compounds
US6448401B1 (en)	2000-11-20	2002-09-10	Bristol-Myers Squibb Company	Process for water soluble azole compounds
AR052342A1 (es) *	2004-12-21	2007-03-14	Janssen Pharmaceutica Nv	Derivados sustituidos de triazolona,tetrazolona e imidazolona con actividad selectiva antagonista de alfa2c-adenoreceptores
JO2691B1 (en) *	2005-05-03	2013-03-03	ايساي آر آند دي مانجمنت كو.، ليمتد	Monolysine salts for azole compounds
EP2343980A4 (en) *	2008-09-08	2012-06-06	Nian Wu	ANTIFUNGAL AGENTS BASED ON TRIAZOLE
RU2563811C1 (ru) *	2014-08-08	2015-09-20	Федеральное государственное бюджетное учреждение науки Институт химической физики им. Н.Н. Семенова Российской академии наук (ИХФ РАН)	Фармацевтическая композиция для лечения грибковых заболеваний
CN106243087B (zh) *	2016-09-12	2018-10-09	三峡大学	一种***吡咯烷酮类杀菌剂，合成方法及其应用
CN111138421A (zh) *	2019-12-26	2020-05-12	上海英诺富成生物科技有限公司	抗真菌水溶性化合物及其制备方法与应用

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
CA1292472C (en) *	1985-12-03	1991-11-26	Alfonsus Guilielmus Knaeps	Derivatives of ¬¬4-¬4-(4-phenyl-1-piperazinyl)- phenoxymethyl\|-1,3-dioxolan-2-yl\|methyl\|-1h-imidazoles and 1h-1,2,4-triazoles
US4791111A (en) *	1985-12-23	1988-12-13	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 having anti-microbial properties
NZ223799A (en) *	1987-03-25	1989-12-21	Janssen Pharmaceutica Nv	Azolylmethyl-dioxolanylmethoxyphenyl-piperazinyl-phenyl-triazolones and antimicrobial compositions
US5039676A (en) *	1990-05-11	1991-08-13	Schering Corporation	Tri- and tetra-substituted-oxetanes and tetrahydrofurans and intermediates thereof
IL103558A0 (en) *	1991-10-30	1993-03-15	Schering Corp	Tri-substituted tetrahydrofuran antifungals
CZ294823B6 (cs) *	1993-12-21	2005-03-16	Schering Corporation	Fungicidní tetrahydrofurany

1995
- 1995-01-17 SI SI9530327T patent/SI0741737T1/xx unknown
- 1995-01-17 RU RU96117244/04A patent/RU2156764C2/ru active
- 1995-01-17 AT AT95906968T patent/ATE186540T1/de active
- 1995-01-17 US US08/666,270 patent/US5707977A/en not_active Expired - Lifetime
- 1995-01-17 CZ CZ19961956A patent/CZ288544B6/cs not_active IP Right Cessation
- 1995-01-17 DE DE69513279T patent/DE69513279T2/de not_active Expired - Lifetime
- 1995-01-17 SK SK896-96A patent/SK282059B6/sk not_active IP Right Cessation
- 1995-01-17 SG SG1996009270A patent/SG48386A1/en unknown
- 1995-01-17 AU AU15355/95A patent/AU688455B2/en not_active Expired
- 1995-01-17 CA CA002179640A patent/CA2179640C/en not_active Expired - Lifetime
- 1995-01-17 HU HU9602008A patent/HU227281B1/hu unknown
- 1995-01-17 KR KR1019960703394A patent/KR100352147B1/ko not_active IP Right Cessation
- 1995-01-17 DK DK95906968T patent/DK0741737T3/da active
- 1995-01-17 PT PT95906968T patent/PT741737E/pt unknown
- 1995-01-17 EP EP95906968A patent/EP0741737B1/en not_active Expired - Lifetime
- 1995-01-17 CN CN95191237A patent/CN1078210C/zh not_active Expired - Lifetime
- 1995-01-17 PL PL95315558A patent/PL181947B1/pl unknown
- 1995-01-17 JP JP51933795A patent/JP3764750B2/ja not_active Expired - Lifetime
- 1995-01-17 NZ NZ278882A patent/NZ278882A/en not_active IP Right Cessation
- 1995-01-17 ES ES95906968T patent/ES2141329T3/es not_active Expired - Lifetime
- 1995-01-17 WO PCT/EP1995/000174 patent/WO1995019983A1/en active IP Right Grant
- 1995-01-19 PH PH49798A patent/PH31664A/en unknown
- 1995-01-20 MY MYPI95000141A patent/MY111814A/en unknown
- 1995-01-23 ZA ZA95521A patent/ZA95521B/xx unknown
- 1995-01-23 TW TW084100675A patent/TW376385B/zh not_active IP Right Cessation
- 1995-01-23 IL IL11241395A patent/IL112413A/xx not_active IP Right Cessation
1996
- 1996-07-23 NO NO963073A patent/NO308412B1/no not_active IP Right Cessation
- 1996-07-23 FI FI962947A patent/FI116057B/fi not_active IP Right Cessation
2000
- 2000-02-02 GR GR20000400246T patent/GR3032550T3/el unknown
- 2000-06-16 CY CY0000029A patent/CY2176B1/xx unknown
- 2000-11-09 LV LVP-00-153A patent/LV12634B/en unknown

Also Published As

Publication number	Publication date
HU227281B1 (en)	2011-01-28
FI116057B (fi)	2005-09-15
FI962947A (fi)	1996-07-23
CZ288544B6 (cs)	2001-07-11
IL112413A (en)	1999-11-30
NZ278882A (en)	1997-06-24
CA2179640C (en)	2005-11-15
WO1995019983A1 (en)	1995-07-27
JPH09508360A (ja)	1997-08-26
NO963073D0 (no)	1996-07-23
CN1138862A (zh)	1996-12-25
JP3764750B2 (ja)	2006-04-12
EP0741737A1 (en)	1996-11-13
DE69513279D1 (de)	1999-12-16
EP0741737B1 (en)	1999-11-10
HUT75943A (en)	1997-05-28
PH31664A (en)	1999-01-12
DE69513279T2 (de)	2000-07-13
MY111814A (en)	2001-01-31
SK89696A3 (en)	1998-02-04
TW376385B (en)	1999-12-11
CN1078210C (zh)	2002-01-23
PL315558A1 (en)	1996-11-12
HU9602008D0 (en)	1996-09-30
SK282059B6 (sk)	2001-10-08
SI0741737T1 (en)	2000-02-29
CY2176B1 (en)	2002-08-23
ZA95521B (en)	1996-07-23
RU2156764C2 (ru)	2000-09-27
GR3032550T3 (en)	2000-05-31
ATE186540T1 (de)	1999-11-15
LV12634A (lv)	2001-03-20
PT741737E (pt)	2000-04-28
AU1535595A (en)	1995-08-08
US5707977A (en)	1998-01-13
IL112413A0 (en)	1995-03-30
NO963073L (no)	1996-07-23
DK0741737T3 (da)	2000-05-22
NO308412B1 (no)	2000-09-11
SG48386A1 (en)	1998-04-17
PL181947B1 (en)	2001-10-31
AU688455B2 (en)	1998-03-12
FI962947A0 (fi)	1996-07-23
KR100352147B1 (ko)	2002-11-11
CA2179640A1 (en)	1995-07-27
CZ195696A3 (en)	1997-02-12
ES2141329T3 (es)	2000-03-16

Publication	Publication Date	Title
LV12634B (en)	2001-07-20	WATER SOLUBLE ANTIMICOTICS OF AZOLA
EP0973768B1 (en)	2003-07-09	Azole compounds, their production and their use
JPH10512599A (ja)	1998-12-02	治療において有用なトリアゾール誘導体
HU189143B (en)	1986-06-30	Process for preparing 2-/2,4-difluoro-phenyl/-1,3-bis/1h-1,2,4-triazol-1-yl/-propan-2-ol derivatives
AU2835201A (en)	2001-05-14	N-substituted carbamoyloxyalkyl-azolium derivatives
WO1999045008A1 (en)	1999-09-10	3-[4-(4-cyanophenyl)thiazol-2-y)]-1-(1h-1,2,4-triazol-1-yl)-butan-2-ol derivatives having antifungal activity
HU191528B (en)	1987-03-30	Process for preparing bis-triazole derivatives and pharmaceutical compositions containing such compounds as active ingredients
CA1257276A (en)	1989-07-11	1,3-bis(1h-1,2,4-triazol-1-yl)-1,1-propan-2-ol
EP0115400B1 (en)	1986-03-26	Triazole antifungal agents
NZ207509A (en)	1986-07-11	Triazole derivatives;antifungal agents
EP0115416A2 (en)	1984-08-08	Triazole antifungal agents
CS241073B2 (en)	1986-03-13	Fungicide for plants protection and method of active substances production
EP0102727B1 (en)	1988-01-20	Chloropyridyl antifungal agents
FI83777C (fi)	1991-08-26	Foerfarande foer framstaellning av terapeutiskt anvaendbara 1-aryl-1-(fluorhydroxialkyl eller perfluoralkanoyl)-2-(1h-1,2,4-triazol-1-yl) etanoler.
HU192296B (en)	1987-05-28	Process for producing triazol derivatives
PL186247B1 (pl)	2003-12-31	Związki azolowe do zastosowania jako leki
CS241098B2 (cs)	1986-03-13	Způsob výroby nových bis-triazolových derivátů