BG64388B1 - Водоразтворими азоли като антифунгали с широк спектър на действие - Google Patents
Водоразтворими азоли като антифунгали с широк спектър на действие Download PDFInfo
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- BG64388B1 BG64388B1 BG104717A BG10471700A BG64388B1 BG 64388 B1 BG64388 B1 BG 64388B1 BG 104717 A BG104717 A BG 104717A BG 10471700 A BG10471700 A BG 10471700A BG 64388 B1 BG64388 B1 BG 64388B1
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- Prior art keywords
- alkyl
- formula
- radical
- amino
- aryl
- Prior art date
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- 229940121375 antifungal agent Drugs 0.000 title abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 32
- 150000003851 azoles Chemical class 0.000 title description 2
- -1 1,2,3,4-tetrahydronaphthalenyl Chemical group 0.000 claims abstract description 140
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- 238000000034 method Methods 0.000 claims abstract description 47
- 125000003118 aryl group Chemical group 0.000 claims abstract description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 10
- 125000000815 N-oxide group Chemical group 0.000 claims abstract description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
- DUAJIKVIRGATIW-UHFFFAOYSA-N trinitrogen(.) Chemical compound [N]=[N+]=[N-] DUAJIKVIRGATIW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims abstract description 4
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims abstract description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 3
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims abstract description 3
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 130
- 239000002904 solvent Substances 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 13
- 208000031888 Mycoses Diseases 0.000 claims description 11
- 239000002585 base Substances 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 206010017533 Fungal infection Diseases 0.000 claims description 10
- 125000003386 piperidinyl group Chemical group 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 238000007126 N-alkylation reaction Methods 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229910052736 halogen Chemical group 0.000 claims description 5
- 150000003335 secondary amines Chemical class 0.000 claims description 5
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 238000000844 transformation Methods 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 5
- 239000012442 inert solvent Substances 0.000 claims 2
- 101100450138 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) hat-2 gene Proteins 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 38
- 239000000543 intermediate Substances 0.000 description 91
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- 150000003254 radicals Chemical class 0.000 description 36
- 229920000858 Cyclodextrin Polymers 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229960004592 isopropanol Drugs 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 125000005843 halogen group Chemical group 0.000 description 11
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 229940097362 cyclodextrins Drugs 0.000 description 9
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 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 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 238000005917 acylation reaction Methods 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 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 7
- 241000233866 Fungi Species 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 230000000843 anti-fungal effect Effects 0.000 description 7
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- 239000002552 dosage form Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
- 229920003169 water-soluble polymer Polymers 0.000 description 7
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 6
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- 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
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
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- 230000000707 stereoselective effect Effects 0.000 description 6
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- 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
-
- 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
- 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
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98201588A EP0957101A1 (en) | 1998-05-14 | 1998-05-14 | Water soluble azoles as broad-spectrum antifungals |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BG104717A BG104717A (en) | 2001-07-31 |
| BG64388B1 true BG64388B1 (bg) | 2004-12-30 |
Family
ID=8233724
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG104717A BG64388B1 (bg) | 1998-05-14 | 2000-08-28 | Водоразтворими азоли като антифунгали с широк спектър на действие |
| BG104933A BG64954B1 (bg) | 1998-05-14 | 2000-11-09 | Водоразтворими азоли като антифунгали с широк спектър на действие |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG104933A BG64954B1 (bg) | 1998-05-14 | 2000-11-09 | Водоразтворими азоли като антифунгали с широк спектър на действие |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US6448244B1 (cs) |
| EP (3) | EP0957101A1 (cs) |
| JP (2) | JP2002514645A (cs) |
| KR (2) | KR100593395B1 (cs) |
| CN (2) | CN1137118C (cs) |
| AR (2) | AR016482A1 (cs) |
| AT (2) | ATE221884T1 (cs) |
| AU (2) | AU758876B2 (cs) |
| BG (2) | BG64388B1 (cs) |
| BR (2) | BR9911057A (cs) |
| CA (2) | CA2331141C (cs) |
| CO (1) | CO5021227A1 (cs) |
| CZ (2) | CZ299481B6 (cs) |
| DE (2) | DE69907171T2 (cs) |
| DK (1) | DK1077976T3 (cs) |
| EE (2) | EE04346B1 (cs) |
| ES (2) | ES2198915T3 (cs) |
| HR (2) | HRP20000740B1 (cs) |
| HU (2) | HUP0103536A3 (cs) |
| IL (2) | IL139649A (cs) |
| MY (2) | MY122147A (cs) |
| NO (2) | NO319851B1 (cs) |
| NZ (2) | NZ507965A (cs) |
| PL (2) | PL194085B1 (cs) |
| PT (1) | PT1077976E (cs) |
| SI (1) | SI1077976T1 (cs) |
| SK (2) | SK285763B6 (cs) |
| TR (2) | TR200003323T2 (cs) |
| TW (2) | TW572899B (cs) |
| WO (2) | WO1999058529A1 (cs) |
| ZA (2) | ZA200007173B (cs) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0957101A1 (en) * | 1998-05-14 | 1999-11-17 | Janssen Pharmaceutica N.V. | Water soluble azoles as broad-spectrum antifungals |
| EP1278755A2 (en) * | 2000-03-07 | 2003-01-29 | Ranbaxy Laboratories, Limited | Azole compounds as therapeutic agents for fungal infections |
| EP1413301A1 (fr) * | 2002-10-24 | 2004-04-28 | Bayer CropScience SA | Médicaments antifongiques à base de dérivés d'arylamidine |
| ITMI20032020A1 (it) | 2003-10-17 | 2005-04-18 | Italfarmaco Spa | Nuovi agenti antifungini azolici con diminuita interazione con i citocromi metabolici |
| 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 |
| AU2011254654B2 (en) * | 2010-05-19 | 2016-01-07 | Sandoz Ag | Process for the preparation of chiral triazolones |
| US9346791B2 (en) | 2011-09-07 | 2016-05-24 | The Johns Hopkins University | Itraconazole analogs and use thereof |
| US11028078B2 (en) * | 2011-09-07 | 2021-06-08 | The Johns Hopkins University | Itraconazole analogs and use thereof |
| ES2991873T3 (es) | 2013-06-07 | 2024-12-05 | Scripps Research Inst | Análogos del itraconazol como inhibidores de fibrosis |
| EP3227278B1 (en) | 2014-12-05 | 2020-02-05 | Pulmocide Limited | Antimycotic compound |
| KR102548066B1 (ko) | 2014-12-10 | 2023-06-26 | 더 스크립스 리서치 인스티튜트 | 섬유증의 소분자 억제제 |
| NZ735783A (en) * | 2015-05-21 | 2021-12-24 | Pulmocide Ltd | Antifungal 4-(4-(4-(((3r,5r)-5-((1 h -1,2,4-triazol-1 -yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methoxy)- 3-methylphenyl)piperazin-1 -yl )-n -(2-h yd roxycyc lo h exyl) b e nzam i d e, or a pharmaceutically acceptable salt thereof. |
| CN105237392B (zh) * | 2015-11-24 | 2017-12-12 | 辽宁渤大化工有限公司 | 芳烷基水杨酸及其衍生物的制备方法 |
| US11390613B2 (en) | 2017-08-20 | 2022-07-19 | University Of Connecticut | Azole analogues and methods of use thereof |
| 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 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4267179A (en) * | 1978-06-23 | 1981-05-12 | Janssen Pharmaceutica, N.V. | Heterocyclic derivatives of (4-phenylpiperazin-1-yl-aryloxymethyl-1,3-dioxolan-2-yl)methyl-1H-imidazoles and 1H-1,2,4-triazoles |
| WO1993019061A1 (en) * | 1992-03-18 | 1993-09-30 | Janssen Pharmaceutica N.V. | Itraconazole and saperconazole stereoisomers |
| WO1995017407A1 (en) * | 1993-12-21 | 1995-06-29 | Schering Corporation | Tetrahydrofuran antifungals |
| WO1995019983A1 (en) * | 1994-01-24 | 1995-07-27 | Janssen Pharmaceutica N.V. | Watersoluble azole antifungals |
| WO1996003843A2 (en) * | 1994-07-20 | 1996-02-08 | Nokia Telecommunications Oy | Starting a short message transmission in a cellular communication system |
| WO1997000255A1 (en) * | 1995-06-19 | 1997-01-03 | Schering Corporation | Tetrahydrofuran antifungals |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ59497A3 (en) * | 1995-06-02 | 1997-08-13 | Schering Corp | Tetrahydrofuran derivative and pharmaceutical composition containing thereof |
| IL128513A (en) * | 1997-02-11 | 2002-11-10 | Janssen Pharmaceutica Nv | Aster derivatives of amino acids of Azuli substance against fungi, their preparation and pharmaceutical preparations containing them |
| EP0957101A1 (en) * | 1998-05-14 | 1999-11-17 | Janssen Pharmaceutica N.V. | Water soluble azoles as broad-spectrum antifungals |
-
1998
- 1998-05-14 EP EP98201588A patent/EP0957101A1/en not_active Withdrawn
-
1999
- 1999-05-06 EP EP99924942A patent/EP1077975B1/en not_active Expired - Lifetime
- 1999-05-06 JP JP2000548333A patent/JP2002514645A/ja active Pending
- 1999-05-06 AT AT99926304T patent/ATE221884T1/de active
- 1999-05-06 KR KR1020007009640A patent/KR100593395B1/ko not_active Expired - Fee Related
- 1999-05-06 PT PT99926304T patent/PT1077976E/pt unknown
- 1999-05-06 BR BR9911057-1A patent/BR9911057A/pt not_active Application Discontinuation
- 1999-05-06 IL IL13964999A patent/IL139649A/en not_active IP Right Cessation
- 1999-05-06 EP EP99926304A patent/EP1077976B1/en not_active Expired - Lifetime
- 1999-05-06 NZ NZ507965A patent/NZ507965A/en not_active IP Right Cessation
- 1999-05-06 WO PCT/EP1999/003242 patent/WO1999058529A1/en active IP Right Grant
- 1999-05-06 CZ CZ20004108A patent/CZ299481B6/cs not_active IP Right Cessation
- 1999-05-06 CN CNB998059560A patent/CN1137118C/zh not_active Expired - Fee Related
- 1999-05-06 SK SK1682-2000A patent/SK285763B6/sk not_active IP Right Cessation
- 1999-05-06 IL IL13964799A patent/IL139647A0/xx not_active IP Right Cessation
- 1999-05-06 HU HU0103536A patent/HUP0103536A3/hu unknown
- 1999-05-06 EE EEP200000651A patent/EE04346B1/xx not_active IP Right Cessation
- 1999-05-06 WO PCT/EP1999/003243 patent/WO1999058530A1/en active IP Right Grant
- 1999-05-06 US US09/700,166 patent/US6448244B1/en not_active Expired - Lifetime
- 1999-05-06 ES ES99924942T patent/ES2198915T3/es not_active Expired - Lifetime
- 1999-05-06 SK SK1681-2000A patent/SK286156B6/sk not_active IP Right Cessation
- 1999-05-06 BR BR9910448-2A patent/BR9910448A/pt not_active Application Discontinuation
- 1999-05-06 AU AU43615/99A patent/AU758876B2/en not_active Ceased
- 1999-05-06 JP JP2000548334A patent/JP2002514646A/ja active Pending
- 1999-05-06 AT AT99924942T patent/ATE238296T1/de not_active IP Right Cessation
- 1999-05-06 CA CA002331141A patent/CA2331141C/en not_active Expired - Fee Related
- 1999-05-06 ES ES99926304T patent/ES2182531T3/es not_active Expired - Lifetime
- 1999-05-06 CN CNB998060690A patent/CN1135229C/zh not_active Expired - Fee Related
- 1999-05-06 HR HR20000740A patent/HRP20000740B1/xx not_active IP Right Cessation
- 1999-05-06 NZ NZ507966A patent/NZ507966A/xx not_active IP Right Cessation
- 1999-05-06 PL PL99344047A patent/PL194085B1/pl unknown
- 1999-05-06 AU AU41417/99A patent/AU751135B2/en not_active Ceased
- 1999-05-06 DK DK99926304T patent/DK1077976T3/da active
- 1999-05-06 HR HR20000741A patent/HRP20000741B1/xx not_active IP Right Cessation
- 1999-05-06 TR TR2000/03323T patent/TR200003323T2/xx unknown
- 1999-05-06 EE EEP200000657A patent/EE04311B1/xx not_active IP Right Cessation
- 1999-05-06 CZ CZ20004109A patent/CZ298702B6/cs not_active IP Right Cessation
- 1999-05-06 US US09/700,251 patent/US6384030B1/en not_active Expired - Lifetime
- 1999-05-06 DE DE69907171T patent/DE69907171T2/de not_active Expired - Lifetime
- 1999-05-06 DE DE69902461T patent/DE69902461T2/de not_active Expired - Lifetime
- 1999-05-06 KR KR1020007011624A patent/KR100575147B1/ko not_active Expired - Fee Related
- 1999-05-06 HU HU0102031A patent/HUP0102031A3/hu unknown
- 1999-05-06 SI SI9930131T patent/SI1077976T1/xx unknown
- 1999-05-06 TR TR2000/03322T patent/TR200003322T2/xx unknown
- 1999-05-06 CA CA002331187A patent/CA2331187C/en not_active Expired - Fee Related
- 1999-05-06 PL PL99344037A patent/PL194086B1/pl unknown
- 1999-05-10 TW TW088107504A patent/TW572899B/zh not_active IP Right Cessation
- 1999-05-10 TW TW088107505A patent/TWI259835B/zh not_active IP Right Cessation
- 1999-05-11 MY MYPI99001862A patent/MY122147A/en unknown
- 1999-05-11 MY MYPI99001861A patent/MY120248A/en unknown
- 1999-05-13 CO CO99029778A patent/CO5021227A1/es unknown
- 1999-05-13 AR ARP990102276A patent/AR016482A1/es active IP Right Grant
- 1999-05-13 AR ARP990102270A patent/AR016480A1/es active IP Right Grant
-
2000
- 2000-08-28 BG BG104717A patent/BG64388B1/bg unknown
- 2000-11-09 BG BG104933A patent/BG64954B1/bg unknown
- 2000-11-13 NO NO20005712A patent/NO319851B1/no not_active IP Right Cessation
- 2000-11-13 NO NO20005713A patent/NO319760B1/no not_active IP Right Cessation
- 2000-12-04 ZA ZA200007173A patent/ZA200007173B/en unknown
- 2000-12-13 ZA ZA200007459A patent/ZA200007459B/xx unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4267179A (en) * | 1978-06-23 | 1981-05-12 | Janssen Pharmaceutica, N.V. | Heterocyclic derivatives of (4-phenylpiperazin-1-yl-aryloxymethyl-1,3-dioxolan-2-yl)methyl-1H-imidazoles and 1H-1,2,4-triazoles |
| WO1993019061A1 (en) * | 1992-03-18 | 1993-09-30 | Janssen Pharmaceutica N.V. | Itraconazole and saperconazole stereoisomers |
| WO1995017407A1 (en) * | 1993-12-21 | 1995-06-29 | Schering Corporation | Tetrahydrofuran antifungals |
| WO1995019983A1 (en) * | 1994-01-24 | 1995-07-27 | Janssen Pharmaceutica N.V. | Watersoluble azole antifungals |
| WO1996003843A2 (en) * | 1994-07-20 | 1996-02-08 | Nokia Telecommunications Oy | Starting a short message transmission in a cellular communication system |
| WO1997000255A1 (en) * | 1995-06-19 | 1997-01-03 | Schering Corporation | Tetrahydrofuran antifungals |
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