ZA200007173B - Water soluble azoles as broad-spectrum antifungals. - Google Patents
Water soluble azoles as broad-spectrum antifungals. Download PDFInfo
- Publication number
- ZA200007173B ZA200007173B ZA200007173A ZA200007173A ZA200007173B ZA 200007173 B ZA200007173 B ZA 200007173B ZA 200007173 A ZA200007173 A ZA 200007173A ZA 200007173 A ZA200007173 A ZA 200007173A ZA 200007173 B ZA200007173 B ZA 200007173B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- 4alkyl
- amino
- radical
- mono
- Prior art date
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- 229940121375 antifungal agent Drugs 0.000 title description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title description 23
- 150000003851 azoles Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 129
- -1 hydroxy, mercapto Chemical class 0.000 claims description 127
- 239000000203 mixture Substances 0.000 claims description 61
- 238000000034 method Methods 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 206010017533 Fungal infection Diseases 0.000 claims description 10
- 208000031888 Mycoses Diseases 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000000815 N-oxide group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 8
- 239000012442 inert solvent Substances 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002911 monocyclic heterocycle 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
- 125000004193 piperazinyl group Chemical group 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
- 238000010511 deprotection reaction Methods 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 150000003335 secondary amines Chemical class 0.000 claims description 5
- DUAJIKVIRGATIW-UHFFFAOYSA-N trinitrogen(.) Chemical compound [N]=[N+]=[N-] DUAJIKVIRGATIW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
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- 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
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- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
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- 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
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- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 claims description 2
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 2
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- 125000000850 2H-chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 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
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- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
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- 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
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- 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
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
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- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
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- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
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- 238000004519 manufacturing process Methods 0.000 claims description 2
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- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
- 125000002265 phtalazinyl group Chemical group 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
- 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
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- 125000001166 thiolanyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 238000000844 transformation Methods 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 6
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 92
- 150000003254 radicals Chemical class 0.000 description 38
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- 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
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- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
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- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
- 239000004544 spot-on Substances 0.000 description 1
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- 235000003702 sterols Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
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- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- MDDPTCUZZASZIQ-UHFFFAOYSA-N tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] MDDPTCUZZASZIQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
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 (1)
| Publication Number | Publication Date |
|---|---|
| ZA200007173B true ZA200007173B (en) | 2002-03-04 |
Family
ID=8233724
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200007173A ZA200007173B (en) | 1998-05-14 | 2000-12-04 | Water soluble azoles as broad-spectrum antifungals. |
| ZA200007459A ZA200007459B (en) | 1998-05-14 | 2000-12-13 | Water soluble azoles as broad-spectrum antifungals. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200007459A ZA200007459B (en) | 1998-05-14 | 2000-12-13 | Water soluble azoles as broad-spectrum antifungals. |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US6384030B1 (et) |
| EP (3) | EP0957101A1 (et) |
| JP (2) | JP2002514646A (et) |
| KR (2) | KR100575147B1 (et) |
| CN (2) | CN1137118C (et) |
| AR (2) | AR016480A1 (et) |
| AT (2) | ATE221884T1 (et) |
| AU (2) | AU751135B2 (et) |
| BG (2) | BG64388B1 (et) |
| BR (2) | BR9911057A (et) |
| CA (2) | CA2331141C (et) |
| CO (1) | CO5021227A1 (et) |
| CZ (2) | CZ298702B6 (et) |
| DE (2) | DE69907171T2 (et) |
| DK (1) | DK1077976T3 (et) |
| EE (2) | EE04311B1 (et) |
| ES (2) | ES2182531T3 (et) |
| HK (2) | HK1033312A1 (et) |
| HR (2) | HRP20000740B1 (et) |
| HU (2) | HUP0103536A3 (et) |
| IL (2) | IL139647A0 (et) |
| MY (2) | MY120248A (et) |
| NO (2) | NO319851B1 (et) |
| NZ (2) | NZ507965A (et) |
| PL (2) | PL194085B1 (et) |
| PT (1) | PT1077976E (et) |
| SI (1) | SI1077976T1 (et) |
| SK (2) | SK286156B6 (et) |
| TR (2) | TR200003323T2 (et) |
| TW (2) | TWI259835B (et) |
| WO (2) | WO1999058530A1 (et) |
| ZA (2) | ZA200007173B (et) |
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 |
| NZ521241A (en) * | 2000-03-07 | 2004-02-27 | Ranbaxy Lab Ltd | 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 |
| RU2585760C2 (ru) * | 2010-05-19 | 2016-06-10 | Сандоз Аг | Способ получения хиральных триазолонов |
| US11028078B2 (en) | 2011-09-07 | 2021-06-08 | The Johns Hopkins University | Itraconazole analogs and use thereof |
| WO2013036866A1 (en) * | 2011-09-07 | 2013-03-14 | The Johns Hopkins University | Itraconazole analogs and use thereof |
| SG11201510011VA (en) | 2013-06-07 | 2016-01-28 | California Inst Biomedical Res | Small molecule inhibitors of fibrosis |
| EP3227277B1 (en) | 2014-12-05 | 2020-02-05 | Pulmocide Limited | Antimycotic compound |
| US10336735B2 (en) | 2014-12-10 | 2019-07-02 | The Scripps Research Institute | Small molecule inhibitors of fibrosis |
| KR102653821B1 (ko) * | 2015-05-21 | 2024-04-02 | 풀모사이드 리미티드 | 항진균성 4-(4-(4-(((3r,5r)-5-((1h-1,2,4-트리아졸-1-일)메틸)-5-(2,4-디플루오로페닐)테트라하이드로푸란-3-일)메톡시)-3-메틸페닐)피페라진-1-일)-n-(2-하이드록시사이클로헥실)벤즈아미드 또는 이의 약학적으로 허용가능한 염. |
| 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 |
| WO2019040363A1 (en) * | 2017-08-20 | 2019-02-28 | University Of Connecticut | AZOLE-TYPE COMPOUND ANALOGUES AND METHODS OF USE |
| CN111138421A (zh) * | 2019-12-26 | 2020-05-12 | 上海英诺富成生物科技有限公司 | 抗真菌水溶性化合物及其制备方法与应用 |
Family Cites Families (9)
| 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 |
| HU221189B1 (en) * | 1992-03-18 | 2002-08-28 | Janssen Pharmaceutica Nv | Itraconazole and saperconazole stereoisomers, their cyclodextrin complexes and pharmaceutical compositions containing them and process for producing them |
| ES2159623T3 (es) * | 1993-12-21 | 2001-10-16 | Schering Corp | Antifungicos de tetrahidrofurano. |
| WO1995019983A1 (en) * | 1994-01-24 | 1995-07-27 | Janssen Pharmaceutica N.V. | Watersoluble azole antifungals |
| FI98688C (fi) * | 1994-07-20 | 1997-07-25 | Nokia Telecommunications Oy | Menetelmä lyhytsanomalähetyksen käynnistämiseksi solukkoradiojärjestelmässä, solukkoradiojärjestelmä sekä solukkoradiojärjestelmän tilaajarekisteri |
| CA2197672C (en) * | 1995-06-02 | 2011-05-17 | Anil K. Saksena | Tetrahydrofuran antifungals |
| AU6257396A (en) * | 1995-06-19 | 1997-01-15 | Schering Corporation | Tetrahydrofuran antifungals |
| US6262052B1 (en) * | 1997-02-11 | 2001-07-17 | Janssen Pharmaceutica N.V. | Amino acid ester containing azole antifungals |
| EP0957101A1 (en) * | 1998-05-14 | 1999-11-17 | Janssen Pharmaceutica N.V. | Water soluble azoles as broad-spectrum antifungals |
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1998
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