NO318328B1 - Disubstituerte 1,3-dioksolan-antifungale midler, deres fremstilling, farmasoytiske sammensetninger inneholdende dem og deres anvendelse - Google Patents

Disubstituerte 1,3-dioksolan-antifungale midler, deres fremstilling, farmasoytiske sammensetninger inneholdende dem og deres anvendelse Download PDF

Info

Publication number: NO318328B1
Authority: NO; Norway
Prior art keywords: formula; compound; compounds; alkyl; mixture
Prior art date: 1997-07-11

Application number

NO20000114A

Other languages

English (en)

Norwegian (no)

Other versions

NO20000114D0 (no

NO20000114L (no

Inventor

Jan Heeres

Hugo Florent Adolf Van Bossche

Louis Jozef Elisabeth Va Veken

Frank ODDS

Lieven Meerpoel

Original Assignee

Janssen Pharmaceutica Nv

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.)

1997-07-11

Filing date

2000-01-10

Publication date

2005-03-07

2000-01-10 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2000-01-10 Publication of NO20000114D0 publication Critical patent/NO20000114D0/no

2000-03-13 Publication of NO20000114L publication Critical patent/NO20000114L/no

2005-03-07 Publication of NO318328B1 publication Critical patent/NO318328B1/no

Links

229940121375 antifungal agent Drugs 0.000 title claims description 24
238000002360 preparation method Methods 0.000 title claims description 22
239000008194 pharmaceutical composition Substances 0.000 title claims description 12
-1 their preparation Substances 0.000 title description 25
239000003429 antifungal agent Substances 0.000 title description 14
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical class C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims description 136
239000002904 solvent Substances 0.000 claims description 44
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
238000000034 method Methods 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 19
230000000843 anti-fungal effect Effects 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
239000002585 base Substances 0.000 claims description 12
238000003756 stirring Methods 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 9
239000012442 inert solvent Substances 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
125000006091 1,3-dioxolane group Chemical group 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
206010017533 Fungal infection Diseases 0.000 claims description 4
208000031888 Mycoses Diseases 0.000 claims description 4
239000003153 chemical reaction reagent Substances 0.000 claims description 4
229940079593 drug Drugs 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
239000000376 reactant Substances 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
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
125000000815 N-oxide group Chemical group 0.000 claims description 3
239000003377 acid catalyst Substances 0.000 claims description 3
230000002152 alkylating effect Effects 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
239000012298 atmosphere Substances 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
150000002989 phenols Chemical class 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
150000000180 1,2-diols Chemical class 0.000 claims description 2
125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 2
239000003513 alkali Substances 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
239000012948 isocyanate Substances 0.000 claims description 2
150000002513 isocyanates Chemical class 0.000 claims description 2
231100000252 nontoxic Toxicity 0.000 claims description 2
230000003000 nontoxic effect Effects 0.000 claims description 2
230000009466 transformation Effects 0.000 claims description 2
238000000844 transformation Methods 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
239000000203 mixture Substances 0.000 description 80
239000000543 intermediate Substances 0.000 description 63
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
239000000243 solution Substances 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 31
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
238000012360 testing method Methods 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
239000003480 eluent Substances 0.000 description 15
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
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 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
239000000460 chlorine Substances 0.000 description 13
229960004125 ketoconazole Drugs 0.000 description 13
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
235000019439 ethyl acetate Nutrition 0.000 description 12
229920000858 Cyclodextrin Polymers 0.000 description 11
230000000694 effects Effects 0.000 description 11
235000019441 ethanol Nutrition 0.000 description 11
239000002244 precipitate Substances 0.000 description 11
150000003254 radicals Chemical class 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
239000000725 suspension Substances 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
208000015181 infectious disease Diseases 0.000 description 10
239000000047 product Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
150000001241 acetals Chemical class 0.000 description 8
239000006185 dispersion Substances 0.000 description 8
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
238000004440 column chromatography Methods 0.000 description 7
239000008213 purified water Substances 0.000 description 7
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 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
238000002156 mixing Methods 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
239000007921 spray Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
241000222122 Candida albicans Species 0.000 description 5
241000893980 Microsporum canis Species 0.000 description 5
OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
229940095731 candida albicans Drugs 0.000 description 5
150000001721 carbon Chemical group 0.000 description 5
229940126086 compound 21 Drugs 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229960004063 propylene glycol Drugs 0.000 description 5
239000007962 solid dispersion Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
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 4
229920001817 Agar Polymers 0.000 description 4
241000222120 Candida <Saccharomycetales> Species 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
238000004566 IR spectroscopy Methods 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
241000223229 Trichophyton rubrum Species 0.000 description 4
239000008272 agar Substances 0.000 description 4
238000000576 coating method Methods 0.000 description 4
239000006071 cream Substances 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000011521 glass Substances 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
238000004949 mass spectrometry Methods 0.000 description 4
239000002609 medium Substances 0.000 description 4
239000003607 modifier Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000002245 particle Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000007787 solid Substances 0.000 description 4
VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical compound CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 description 3
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
241000233866 Fungi Species 0.000 description 3
241000250507 Gigaspora candida Species 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
241000555688 Malassezia furfur Species 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
238000010934 O-alkylation reaction Methods 0.000 description 3
240000004808 Saccharomyces cerevisiae Species 0.000 description 3
239000000654 additive Substances 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000011248 coating agent Substances 0.000 description 3
238000004090 dissolution Methods 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000008103 glucose Substances 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
235000015141 kefir Nutrition 0.000 description 3
239000000463 material Substances 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
239000000843 powder Substances 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000012258 stirred mixture Substances 0.000 description 3
238000003420 transacetalization reaction Methods 0.000 description 3
229920003169 water-soluble polymer Polymers 0.000 description 3
LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 2
GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
241001480043 Arthrodermataceae Species 0.000 description 2
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
241000700198 Cavia Species 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
229930040373 Paraformaldehyde Natural products 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
241001045770 Trichophyton mentagrophytes Species 0.000 description 2
241001609979 Trichophyton quinckeanum Species 0.000 description 2
201000007096 Vulvovaginal Candidiasis Diseases 0.000 description 2
238000006359 acetalization reaction Methods 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000000969 carrier Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
229940097362 cyclodextrins Drugs 0.000 description 2
229940075894 denatured ethanol Drugs 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
230000037304 dermatophytes Effects 0.000 description 2
108010037444 diisopropylglutathione ester Proteins 0.000 description 2
HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000001125 extrusion Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
230000002538 fungal effect Effects 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
239000008240 homogeneous mixture Substances 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
229920001477 hydrophilic polymer Polymers 0.000 description 2
229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000011081 inoculation Methods 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
230000003902 lesion Effects 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
XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
239000003921 oil Substances 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000003973 paint Substances 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
229920002866 paraformaldehyde Polymers 0.000 description 2
150000002978 peroxides Chemical class 0.000 description 2
XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
229940068196 placebo Drugs 0.000 description 2
239000000902 placebo Substances 0.000 description 2
239000004033 plastic Substances 0.000 description 2
229920003023 plastic Polymers 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000010956 selective crystallization Methods 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000006104 solid solution Substances 0.000 description 2
238000005507 spraying Methods 0.000 description 2
229910001220 stainless steel Inorganic materials 0.000 description 2
239000010935 stainless steel Substances 0.000 description 2
230000000707 stereoselective effect Effects 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
238000007910 systemic administration Methods 0.000 description 2
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
238000001665 trituration Methods 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
HFGZFHCWKKQGIS-NOZJJQNGSA-N (2r,3r)-2-(2,4-difluorophenyl)-3-methylsulfonyl-1-(1,2,4-triazol-1-yl)butan-2-ol Chemical compound C([C@@](O)([C@@H](C)S(C)(=O)=O)C=1C(=CC(F)=CC=1)F)N1C=NC=N1 HFGZFHCWKKQGIS-NOZJJQNGSA-N 0.000 description 1
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
MPIPASJGOJYODL-SFHVURJKSA-N (R)-isoconazole Chemical compound ClC1=CC(Cl)=CC=C1[C@@H](OCC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 MPIPASJGOJYODL-SFHVURJKSA-N 0.000 description 1
CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 1
MPTJIDOGFUQSQH-UHFFFAOYSA-N 1-(2,4-dichloro-10,11-dihydrodibenzo[a,d][7]annulen-5-yl)imidazole Chemical compound C12=CC=CC=C2CCC2=CC(Cl)=CC(Cl)=C2C1N1C=CN=C1 MPTJIDOGFUQSQH-UHFFFAOYSA-N 0.000 description 1
AFNXATANNDIXLG-SFHVURJKSA-N 1-[(2r)-2-[(4-chlorophenyl)methylsulfanyl]-2-(2,4-dichlorophenyl)ethyl]imidazole Chemical compound C1=CC(Cl)=CC=C1CS[C@H](C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 AFNXATANNDIXLG-SFHVURJKSA-N 0.000 description 1
ZCJYUTQZBAIHBS-UHFFFAOYSA-N 1-[2-(2,4-dichlorophenyl)-2-{[4-(phenylsulfanyl)benzyl]oxy}ethyl]imidazole Chemical compound ClC1=CC(Cl)=CC=C1C(OCC=1C=CC(SC=2C=CC=CC=2)=CC=1)CN1C=NC=C1 ZCJYUTQZBAIHBS-UHFFFAOYSA-N 0.000 description 1
KKRSCLXGAAJHDK-UHFFFAOYSA-N 1-[4-[4-(4-hydroxyphenyl)piperazin-1-yl]phenyl]-3-propan-2-ylimidazolidin-2-one Chemical compound O=C1N(C(C)C)CCN1C1=CC=C(N2CCN(CC2)C=2C=CC(O)=CC=2)C=C1 KKRSCLXGAAJHDK-UHFFFAOYSA-N 0.000 description 1
LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 description 1
QXHHHPZILQDDPS-UHFFFAOYSA-N 1-{2-[(2-chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound S1C=CC(COC(CN2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1Cl QXHHHPZILQDDPS-UHFFFAOYSA-N 0.000 description 1
JLGKQTAYUIMGRK-UHFFFAOYSA-N 1-{2-[(7-chloro-1-benzothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound ClC1=CC(Cl)=CC=C1C(OCC=1C2=CC=CC(Cl)=C2SC=1)CN1C=NC=C1 JLGKQTAYUIMGRK-UHFFFAOYSA-N 0.000 description 1
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
CJXQAYQWVNXIQE-UHFFFAOYSA-N 2,2-dimethylpropanedioyl dichloride Chemical compound ClC(=O)C(C)(C)C(Cl)=O CJXQAYQWVNXIQE-UHFFFAOYSA-N 0.000 description 1
SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
SPHILNHUYNCNSY-UHFFFAOYSA-N 2-(chloromethyl)-2-(2,4-difluorophenyl)oxirane Chemical compound FC1=CC(F)=CC=C1C1(CCl)OC1 SPHILNHUYNCNSY-UHFFFAOYSA-N 0.000 description 1
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
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 1
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 1
UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 1
PBIUDEUWYGBHDW-UHFFFAOYSA-N 2-chloro-1-pyridin-3-ylethanone;hydrochloride Chemical compound Cl.ClCC(=O)C1=CC=CN=C1 PBIUDEUWYGBHDW-UHFFFAOYSA-N 0.000 description 1
LODHFNUFVRVKTH-ZHACJKMWSA-N 2-hydroxy-n'-[(e)-3-phenylprop-2-enoyl]benzohydrazide Chemical compound OC1=CC=CC=C1C(=O)NNC(=O)\C=C\C1=CC=CC=C1 LODHFNUFVRVKTH-ZHACJKMWSA-N 0.000 description 1
LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
OBKYMVGMCNKPJI-UHFFFAOYSA-N 3-chloro-2-(2,4-difluorophenyl)propane-1,2-diol Chemical compound OCC(O)(CCl)C1=CC=C(F)C=C1F OBKYMVGMCNKPJI-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
FGRPDYHWSQMGNO-UHFFFAOYSA-N 4-(chloromethyl)-4-(4-chlorophenyl)-2,2-dimethyl-1,3-dioxolane Chemical compound O1C(C)(C)OCC1(CCl)C1=CC=C(Cl)C=C1 FGRPDYHWSQMGNO-UHFFFAOYSA-N 0.000 description 1
SQALLFXXNCQEQX-UHFFFAOYSA-N 4-(chloromethyl)-4-(4-fluorophenyl)-2,2-dimethyl-1,3-dioxolane Chemical compound O1C(C)(C)OCC1(CCl)C1=CC=C(F)C=C1 SQALLFXXNCQEQX-UHFFFAOYSA-N 0.000 description 1
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 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-UHFFFAOYSA-N 0.000 description 1
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
KBIWNQVZKHSHTI-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,4-diamine;oxalic acid Chemical compound OC(=O)C(O)=O.CN(C)C1=CC=C(N)C=C1 KBIWNQVZKHSHTI-UHFFFAOYSA-N 0.000 description 1
AKZAGHOFDGJXCC-UHFFFAOYSA-N 5-(3-iodoprop-2-ynoxy)-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=C(OCC#CI)C=N1 AKZAGHOFDGJXCC-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
229910002012 Aerosil® Inorganic materials 0.000 description 1
229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
241000228212 Aspergillus Species 0.000 description 1
241000228197 Aspergillus flavus Species 0.000 description 1
241001225321 Aspergillus fumigatus Species 0.000 description 1
241000228245 Aspergillus niger Species 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
241000222173 Candida parapsilosis Species 0.000 description 1
241000222178 Candida tropicalis Species 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
201000007336 Cryptococcosis Diseases 0.000 description 1
241000221204 Cryptococcus neoformans Species 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
208000001840 Dandruff Diseases 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 1
241001480036 Epidermophyton floccosum Species 0.000 description 1
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 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
238000012404 In vitro experiment Methods 0.000 description 1
SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
244000285963 Kluyveromyces fragilis Species 0.000 description 1
ZRTQSJFIDWNVJW-WYMLVPIESA-N Lanoconazole Chemical compound ClC1=CC=CC=C1C(CS\1)SC/1=C(\C#N)N1C=NC=C1 ZRTQSJFIDWNVJW-WYMLVPIESA-N 0.000 description 1
102100026038 Lens fiber membrane intrinsic protein Human genes 0.000 description 1
101710115990 Lens fiber membrane intrinsic protein Proteins 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
244000062730 Melissa officinalis Species 0.000 description 1
235000010654 Melissa officinalis Nutrition 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
JFNKOBKWTRBYDT-UHFFFAOYSA-N O(C1=CC=CC=C1)ClOC(Cl)(Cl)Cl Chemical compound O(C1=CC=CC=C1)ClOC(Cl)(Cl)Cl JFNKOBKWTRBYDT-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
239000001888 Peptone Substances 0.000 description 1
108010080698 Peptones Proteins 0.000 description 1
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 1
241000235645 Pichia kudriavzevii Species 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
239000006159 Sabouraud's agar Substances 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Natural products OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
241001149963 Sporothrix schenckii Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930182558 Sterol Natural products 0.000 description 1
229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
241000223238 Trichophyton Species 0.000 description 1
XRKCQBAPGILDOG-UHFFFAOYSA-N [4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]urea Chemical compound C1=CC(OC)=CC=C1N1CCN(C=2C=CC(NC(N)=O)=CC=2)CC1 XRKCQBAPGILDOG-UHFFFAOYSA-N 0.000 description 1
241000222126 [Candida] glabrata Species 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000004974 alkaline earth metal peroxides Chemical class 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
XZKWIPVTHGWDCF-KUZYQSSXSA-N amorolfine hydrochloride Chemical compound Cl.C1=CC(C(C)(C)CC)=CC=C1CC(C)CN1C[C@@H](C)O[C@@H](C)C1 XZKWIPVTHGWDCF-KUZYQSSXSA-N 0.000 description 1
229940101006 anhydrous sodium sulfite Drugs 0.000 description 1
239000003945 anionic surfactant Substances 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
229940091771 aspergillus fumigatus Drugs 0.000 description 1
239000011324 bead Substances 0.000 description 1
230000008901 benefit Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
235000015895 biscuits Nutrition 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
229960002962 butenafine Drugs 0.000 description 1
ABJKWBDEJIDSJZ-UHFFFAOYSA-N butenafine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)CC1=CC=C(C(C)(C)C)C=C1 ABJKWBDEJIDSJZ-UHFFFAOYSA-N 0.000 description 1
BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
239000000292 calcium oxide Substances 0.000 description 1
ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
208000032343 candida glabrata infection Diseases 0.000 description 1
229940055022 candida parapsilosis Drugs 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
239000000679 carrageenan Substances 0.000 description 1
235000010418 carrageenan Nutrition 0.000 description 1
229920001525 carrageenan Polymers 0.000 description 1
229940113118 carrageenan Drugs 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
238000010568 chiral column chromatography Methods 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
229960003749 ciclopirox Drugs 0.000 description 1
SCKYRAXSEDYPSA-UHFFFAOYSA-N ciclopirox Chemical compound ON1C(=O)C=C(C)C=C1C1CCCCC1 SCKYRAXSEDYPSA-UHFFFAOYSA-N 0.000 description 1
KDULJHFMZBRAHO-UHFFFAOYSA-N cioteronel Chemical compound C1C(=O)CC2C(CCCCC(CC)OC)CCC21 KDULJHFMZBRAHO-UHFFFAOYSA-N 0.000 description 1
229950000970 cioteronel Drugs 0.000 description 1
229960004022 clotrimazole Drugs 0.000 description 1
VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
229920001688 coating polymer Polymers 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
239000008139 complexing agent Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
CEJLBZWIKQJOAT-UHFFFAOYSA-N dichloroisocyanuric acid Chemical compound ClN1C(=O)NC(=O)N(Cl)C1=O CEJLBZWIKQJOAT-UHFFFAOYSA-N 0.000 description 1
FAMGJMYDHOESPR-UHFFFAOYSA-M dilithium;carbanide;bromide Chemical compound [Li+].[Li+].[CH3-].[Br-] FAMGJMYDHOESPR-UHFFFAOYSA-M 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
229960003062 eberconazole Drugs 0.000 description 1
229960003913 econazole Drugs 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
229960004766 estradiol valerate Drugs 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229960001274 fenticonazole Drugs 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229960004884 fluconazole Drugs 0.000 description 1
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 1
125000001153 fluoro group Chemical group F* 0.000 description 1
229960000690 flutrimazole Drugs 0.000 description 1
QHMWCHQXCUNUAK-UHFFFAOYSA-N flutrimazole Chemical compound C1=CC(F)=CC=C1C(N1C=NC=C1)(C=1C(=CC=CC=1)F)C1=CC=CC=C1 QHMWCHQXCUNUAK-UHFFFAOYSA-N 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000000499 gel Substances 0.000 description 1
229960004275 glycolic acid Drugs 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
238000000227 grinding Methods 0.000 description 1
238000011554 guinea pig model Methods 0.000 description 1
230000009931 harmful effect Effects 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
235000012907 honey Nutrition 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
229960004849 isoconazole Drugs 0.000 description 1
229960005280 isotretinoin Drugs 0.000 description 1
229960004130 itraconazole Drugs 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229950010163 lanoconazole Drugs 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000000865 liniment Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229960002509 miconazole Drugs 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
VWOIKFDZQQLJBJ-DTQAZKPQSA-N neticonazole Chemical compound CCCCCOC1=CC=CC=C1\C(=C/SC)N1C=NC=C1 VWOIKFDZQQLJBJ-DTQAZKPQSA-N 0.000 description 1
229950010757 neticonazole Drugs 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
229960004031 omoconazole Drugs 0.000 description 1
JMFOSJNGKJCTMJ-ZHZULCJRSA-N omoconazole Chemical compound C1=CN=CN1C(/C)=C(C=1C(=CC(Cl)=CC=1)Cl)\OCCOC1=CC=C(Cl)C=C1 JMFOSJNGKJCTMJ-ZHZULCJRSA-N 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
229940100688 oral solution Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000001451 organic peroxides Chemical class 0.000 description 1
229960003483 oxiconazole Drugs 0.000 description 1
QRJJEGAJXVEBNE-MOHJPFBDSA-N oxiconazole Chemical compound ClC1=CC(Cl)=CC=C1CO\N=C(C=1C(=CC(Cl)=CC=1)Cl)\CN1C=NC=C1 QRJJEGAJXVEBNE-MOHJPFBDSA-N 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
239000006072 paste Substances 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
235000019319 peptone Nutrition 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
238000003408 phase transfer catalysis Methods 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229940113124 polysorbate 60 Drugs 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
239000002243 precursor Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000011552 rat model Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
238000005096 rolling process Methods 0.000 description 1
102220151657 rs763546006 Human genes 0.000 description 1
239000012449 sabouraud dextrose agar Substances 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
229950005137 saperconazole Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000007789 sealing Methods 0.000 description 1
208000008742 seborrheic dermatitis Diseases 0.000 description 1
229960005429 sertaconazole Drugs 0.000 description 1
239000002453 shampoo Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
239000001587 sorbitan monostearate Substances 0.000 description 1
235000011076 sorbitan monostearate Nutrition 0.000 description 1
229940035048 sorbitan monostearate Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
150000003432 sterols Chemical class 0.000 description 1
235000003702 sterols Nutrition 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229960002607 sulconazole Drugs 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
230000001502 supplementing effect Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
229960002722 terbinafine Drugs 0.000 description 1
DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
229960004214 tioconazole Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
229940042129 topical gel Drugs 0.000 description 1
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
238000004879 turbidimetry Methods 0.000 description 1
229960004740 voriconazole Drugs 0.000 description 1
BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic 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)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Epidemiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Tropical Medicine & Parasitology (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Pyrrole Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

NO20000114A 1997-07-11 2000-01-10 Disubstituerte 1,3-dioksolan-antifungale midler, deres fremstilling, farmasoytiske sammensetninger inneholdende dem og deres anvendelse NO318328B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97202181		1997-07-11
PCT/EP1998/004194 WO1999002523A1 (en)	1997-07-11	1998-07-07	2,4,4-trisubstituted-1,3-dioxolane antifungals

Publications (3)

Publication Number	Publication Date
NO20000114D0 NO20000114D0 (no)	2000-01-10
NO20000114L NO20000114L (no)	2000-03-13
NO318328B1 true NO318328B1 (no)	2005-03-07

Family

ID=8228553

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20000114A NO318328B1 (no)	1997-07-11	2000-01-10	Disubstituerte 1,3-dioksolan-antifungale midler, deres fremstilling, farmasoytiske sammensetninger inneholdende dem og deres anvendelse

Country Status (33)

Country	Link
US (1)	US6387906B1 (cs)
EP (1)	EP1068200B1 (cs)
KR (1)	KR100540460B1 (cs)
AP (1)	AP1379A (cs)
AR (1)	AR015130A1 (cs)
AT (1)	ATE289303T1 (cs)
AU (1)	AU749760B2 (cs)
BG (1)	BG64314B1 (cs)
BR (1)	BRPI9811679B8 (cs)
CA (1)	CA2295090C (cs)
CZ (1)	CZ297453B6 (cs)
DE (1)	DE69829082T2 (cs)
DK (1)	DK1068200T3 (cs)
EA (1)	EA002828B1 (cs)
EE (1)	EE04155B1 (cs)
ES (1)	ES2238765T3 (cs)
GE (1)	GEP20033054B (cs)
HR (1)	HRP20000007B1 (cs)
HU (1)	HU225159B1 (cs)
ID (1)	ID23783A (cs)
IL (1)	IL133919A (cs)
MY (1)	MY118844A (cs)
NO (1)	NO318328B1 (cs)
NZ (1)	NZ501982A (cs)
PL (1)	PL193703B1 (cs)
PT (1)	PT1068200E (cs)
SI (1)	SI1068200T1 (cs)
SK (1)	SK285321B6 (cs)
TR (1)	TR200000154T2 (cs)
TW (1)	TW593312B (cs)
UA (1)	UA71543C2 (cs)
WO (1)	WO1999002523A1 (cs)
ZA (1)	ZA986160B (cs)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19945982A1 (de)	1999-09-24	2001-03-29	Knoll Ag	Geschwindigkeitsbestimmte Partikel
US20040086567A1 (en) *	2002-10-30	2004-05-06	Pawan Seth	Bioequivalent composition of itraconazole and a hydrophilic polymer
WO2009114080A2 (en) *	2008-03-03	2009-09-17	Stiefel Laboratories, Inc.	Processes for preparing enantiomerically pure diol and dioxolane compounds
US8431699B2 (en) *	2009-02-27	2013-04-30	Vertichem Corporation	Method for manufacture of 2-oxoimidazolidines
CN105777486B (zh) *	2016-03-30	2018-09-11	浙江大学宁波理工学院	一种2-[2-(2，4-二氟苯基)-2-丙烯-1-基]-1，3-丙二醇的合成方法

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
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
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
US4788190A (en) *	1986-12-24	1988-11-29	Schering Corporation	2,4,4-tri- and 2,2,4,4-tetra substituted-1,3-dioxolane antifungal, antiallergy compounds
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
IL103558A0 (en) *	1991-10-30	1993-03-15	Schering Corp	Tri-substituted tetrahydrofuran antifungals
SG48386A1 (en) *	1994-01-24	1998-04-17	Janssen Pharmaceutica Nv	Watersoluble azole antifungals

1998
- 1998-07-06 TW TW087110868A patent/TW593312B/zh not_active IP Right Cessation
- 1998-07-07 HU HU0004459A patent/HU225159B1/hu unknown
- 1998-07-07 WO PCT/EP1998/004194 patent/WO1999002523A1/en not_active Ceased
- 1998-07-07 UA UA2000010162A patent/UA71543C2/uk unknown
- 1998-07-07 AT AT98940160T patent/ATE289303T1/de active
- 1998-07-07 EE EEP200000020A patent/EE04155B1/xx unknown
- 1998-07-07 HR HR20000007A patent/HRP20000007B1/xx not_active IP Right Cessation
- 1998-07-07 EA EA200000116A patent/EA002828B1/ru not_active IP Right Cessation
- 1998-07-07 EP EP98940160A patent/EP1068200B1/en not_active Expired - Lifetime
- 1998-07-07 MY MYPI98003075A patent/MY118844A/en unknown
- 1998-07-07 TR TR2000/00154T patent/TR200000154T2/xx unknown
- 1998-07-07 BR BRPI9811679A patent/BRPI9811679B8/pt not_active IP Right Cessation
- 1998-07-07 SI SI9830764T patent/SI1068200T1/xx unknown
- 1998-07-07 GE GEAP19985200A patent/GEP20033054B/en unknown
- 1998-07-07 US US09/462,588 patent/US6387906B1/en not_active Expired - Lifetime
- 1998-07-07 ES ES98940160T patent/ES2238765T3/es not_active Expired - Lifetime
- 1998-07-07 PT PT98940160T patent/PT1068200E/pt unknown
- 1998-07-07 AU AU88576/98A patent/AU749760B2/en not_active Expired
- 1998-07-07 DE DE69829082T patent/DE69829082T2/de not_active Expired - Lifetime
- 1998-07-07 CA CA002295090A patent/CA2295090C/en not_active Expired - Lifetime
- 1998-07-07 DK DK98940160T patent/DK1068200T3/da active
- 1998-07-07 AP APAP/P/2000/001730A patent/AP1379A/en active
- 1998-07-07 NZ NZ501982A patent/NZ501982A/xx not_active IP Right Cessation
- 1998-07-07 KR KR1019997012503A patent/KR100540460B1/ko not_active Expired - Lifetime
- 1998-07-07 SK SK1841-99A patent/SK285321B6/sk not_active IP Right Cessation
- 1998-07-07 CZ CZ0463799A patent/CZ297453B6/cs not_active IP Right Cessation
- 1998-07-07 ID IDW20000032A patent/ID23783A/id unknown
- 1998-07-07 PL PL98338009A patent/PL193703B1/pl unknown
- 1998-07-07 IL IL13391998A patent/IL133919A/en not_active IP Right Cessation
- 1998-07-10 ZA ZA9806160A patent/ZA986160B/xx unknown
- 1998-07-10 AR ARP980103376A patent/AR015130A1/es active IP Right Grant
1999
- 1999-12-10 BG BG103982A patent/BG64314B1/bg unknown
2000
- 2000-01-10 NO NO20000114A patent/NO318328B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
PT1068200E (pt)	2005-07-29
BG103982A (en)	2000-08-31
PL193703B1 (pl)	2007-03-30
AU8857698A (en)	1999-02-08
SK285321B6 (sk)	2006-11-03
BG64314B1 (bg)	2004-09-30
SI1068200T1 (cs)	2005-08-31
AP1379A (en)	2005-03-29
BRPI9811679B8 (pt)	2021-05-25
BR9811679A (pt)	2000-09-19
ES2238765T3 (es)	2005-09-01
DE69829082T2 (de)	2005-12-29
CZ463799A3 (cs)	2000-04-12
EE200000020A (et)	2000-10-16
BRPI9811679B1 (pt)	2016-10-18
TW593312B (en)	2004-06-21
CA2295090A1 (en)	1999-01-21
HRP20000007A2 (en)	2000-12-31
CA2295090C (en)	2009-09-08
HUP0004459A3 (en)	2002-11-28
MY118844A (en)	2005-01-31
EP1068200A1 (en)	2001-01-17
AP2000001730A0 (en)	2000-03-31
US6387906B1 (en)	2002-05-14
ATE289303T1 (de)	2005-03-15
ZA986160B (en)	2000-01-10
EP1068200B1 (en)	2005-02-16
WO1999002523A1 (en)	1999-01-21
KR100540460B1 (ko)	2006-01-12
HK1032404A1 (en)	2001-07-20
HUP0004459A2 (hu)	2002-04-29
IL133919A0 (en)	2001-04-30
NO20000114D0 (no)	2000-01-10
SK184199A3 (en)	2000-07-11
ID23783A (id)	2000-05-11
NO20000114L (no)	2000-03-13
EA002828B1 (ru)	2002-10-31
UA71543C2 (uk)	2004-12-15
HRP20000007B1 (en)	2008-12-31
DK1068200T3 (da)	2005-06-20
AU749760B2 (en)	2002-07-04
IL133919A (en)	2002-02-10
NZ501982A (en)	2000-10-27
DE69829082D1 (de)	2005-03-24
TR200000154T2 (tr)	2000-06-21
AR015130A1 (es)	2001-04-18
EE04155B1 (et)	2003-10-15
KR20010020576A (ko)	2001-03-15
EA200000116A1 (ru)	2000-08-28
CZ297453B6 (cs)	2006-12-13
PL338009A1 (en)	2000-09-25
HU225159B1 (en)	2006-07-28
GEP20033054B (en)	2003-08-25

Legal Events

Date	Code	Title	Description
2018-08-13	MK1K	Patent expired

Publication	Publication Date	Title
CZ20004108A3 (en)	2001-05-16	Water soluble azoles exhibiting wide spectrum of antifungal activity
CA2295090C (en)	2009-09-08	2,4,4-trisubstituted-1,3-dioxolane antifungals
EP1177192B1 (en)	2003-03-19	Antifungal ethers
HK1032404B (en)	2005-05-20	2,4,4-trisubstituted-1,3-dioxolane antifungals
MXPA00000453A (en)	2001-11-21	2,4,4-trisubstituted-1,3-dioxolane antifungals
JP4473350B2 (ja)	2010-06-02	２，４，４−三置換−１，３−ジオキソラン抗菌・抗カビ剤