NO319760B1 - Vannloselige azoler som bredspektrede antifungale midler, deres fremstilling og anvendelse samt farmasoytiske sammensetninger omfattende dem - Google Patents

Vannloselige azoler som bredspektrede antifungale midler, deres fremstilling og anvendelse samt farmasoytiske sammensetninger omfattende dem Download PDF

Info

Publication number: NO319760B1
Authority: NO; Norway
Prior art keywords: phenyl; triazol; amino; piperazinyl; formula
Prior art date: 1998-05-14

Application number

NO20005713A

Other languages

English (en)

Norwegian (no)

Other versions

NO20005713L (no

NO20005713D0 (no

Inventor

Jan Heeres

Louis Jozef Elisabeth Va Veken

Leo Jacobus Jozef Backx

Frank Christopher 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.)

1998-05-14

Filing date

2000-11-13

Publication date

2005-09-12

2000-11-13 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2000-11-13 Publication of NO20005713D0 publication Critical patent/NO20005713D0/no

2001-01-11 Publication of NO20005713L publication Critical patent/NO20005713L/no

2005-09-12 Publication of NO319760B1 publication Critical patent/NO319760B1/no

Links

238000002360 preparation method Methods 0.000 title claims description 19
239000008194 pharmaceutical composition Substances 0.000 title claims description 8
229940121375 antifungal agent Drugs 0.000 title description 29
239000003429 antifungal agent Substances 0.000 title description 27
150000003851 azoles Chemical class 0.000 title description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 170
150000001875 compounds Chemical class 0.000 claims description 161
-1 hydroxy, mercapto Chemical class 0.000 claims description 145
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 86
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 86
125000000217 alkyl group Chemical group 0.000 claims description 62
229910052739 hydrogen Inorganic materials 0.000 claims description 44
239000001257 hydrogen Substances 0.000 claims description 44
238000000034 method Methods 0.000 claims description 41
125000003118 aryl group Chemical group 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 30
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 23
125000001424 substituent group Chemical group 0.000 claims description 21
150000002431 hydrogen Chemical class 0.000 claims description 19
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 13
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
125000001475 halogen functional group Chemical group 0.000 claims description 12
239000002585 base Substances 0.000 claims description 11
206010017533 Fungal infection Diseases 0.000 claims description 10
208000031888 Mycoses Diseases 0.000 claims description 10
239000004480 active ingredient Substances 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
125000003386 piperidinyl group Chemical group 0.000 claims description 10
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 8
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
125000004104 aryloxy group Chemical group 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
238000010511 deprotection reaction Methods 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
239000012442 inert solvent Substances 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
DUAJIKVIRGATIW-UHFFFAOYSA-N trinitrogen(.) Chemical compound [N]=[N+]=[N-] DUAJIKVIRGATIW-UHFFFAOYSA-N 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 5
125000004193 piperazinyl group Chemical group 0.000 claims description 5
150000003335 secondary amines Chemical class 0.000 claims description 5
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239000003513 alkali Substances 0.000 claims description 3
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
239000012458 free base Substances 0.000 claims description 3
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
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230000003000 nontoxic effect Effects 0.000 claims description 3
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125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 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
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
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230000008569 process Effects 0.000 claims description 2
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125000001544 thienyl group Chemical group 0.000 claims description 2
238000000844 transformation Methods 0.000 claims description 2
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239000003480 eluent Substances 0.000 description 45
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239000003054 catalyst Substances 0.000 description 38
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ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 32
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108010037444 diisopropylglutathione ester Proteins 0.000 description 30
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VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 26
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KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 22
238000004440 column chromatography Methods 0.000 description 22
239000000706 filtrate Substances 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
239000012074 organic phase Substances 0.000 description 21
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241000233866 Fungi Species 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
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125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
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150000004862 dioxolanes Chemical group 0.000 description 7
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WWJFFVUVFNBJTN-VHDFTHOZSA-N nikkomycin Z Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)[C@H](NC(=O)[C@@H](N)[C@H](C)[C@H](O)C=2N=CC(O)=CC=2)C(O)=O)C=CC(=O)NC1=O WWJFFVUVFNBJTN-VHDFTHOZSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
239000003921 oil Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000001451 organic peroxides Chemical class 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
108010058641 papulacandins Proteins 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
239000001814 pectin Chemical class 0.000 description 1
229920001277 pectin Chemical class 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000012071 phase Substances 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
NTGBUUXKGAZMSE-UHFFFAOYSA-N phenyl n-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1CCN(C=2C=CC(NC(=O)OC=3C=CC=CC=3)=CC=2)CC1 NTGBUUXKGAZMSE-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920000233 poly(alkylene oxides) Polymers 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
230000002265 prevention Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
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
239000001294 propane Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
JADFCQKRKICRKI-UHFFFAOYSA-N quinoline;sulfane Chemical compound S.N1=CC=CC2=CC=CC=C21 JADFCQKRKICRKI-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000007789 sealing Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000002453 shampoo Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
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
PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
150000003432 sterols Chemical class 0.000 description 1
235000003702 sterols Nutrition 0.000 description 1
238000003756 stirring Methods 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
JTDQWSANBKDIGJ-UHFFFAOYSA-N tert-butyl n-benzyl-n-[3-(methylamino)butan-2-yl]carbamate Chemical compound CNC(C)C(C)N(C(=O)OC(C)(C)C)CC1=CC=CC=C1 JTDQWSANBKDIGJ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Natural products NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 1
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
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
238000001665 trituration Methods 0.000 description 1
238000004879 turbidimetry Methods 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
239000004474 valine Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-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
- 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)

NO20005713A 1998-05-14 2000-11-13 Vannloselige azoler som bredspektrede antifungale midler, deres fremstilling og anvendelse samt farmasoytiske sammensetninger omfattende dem NO319760B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP98201588A EP0957101A1 (de)	1998-05-14	1998-05-14	Wasserlösliche Azole als Breitspektrum-antifungus
PCT/EP1999/003243 WO1999058530A1 (en)	1998-05-14	1999-05-06	Water soluble azoles as broad-spectrum antifungals

Publications (3)

Publication Number	Publication Date
NO20005713D0 NO20005713D0 (no)	2000-11-13
NO20005713L NO20005713L (no)	2001-01-11
NO319760B1 true NO319760B1 (no)	2005-09-12

Family

ID=8233724

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20005713A NO319760B1 (no)	1998-05-14	2000-11-13	Vannloselige azoler som bredspektrede antifungale midler, deres fremstilling og anvendelse samt farmasoytiske sammensetninger omfattende dem
NO20005712A NO319851B1 (no)	1998-05-14	2000-11-13	Vannloselige azoler som bredspektrede antifungale midler

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20005712A NO319851B1 (no)	1998-05-14	2000-11-13	Vannloselige azoler som bredspektrede antifungale midler

Country Status (31)

Country	Link
US (2)	US6448244B1 (de)
EP (3)	EP0957101A1 (de)
JP (2)	JP2002514645A (de)
KR (2)	KR100575147B1 (de)
CN (2)	CN1137118C (de)
AR (2)	AR016480A1 (de)
AT (2)	ATE238296T1 (de)
AU (2)	AU751135B2 (de)
BG (2)	BG64388B1 (de)
BR (2)	BR9911057A (de)
CA (2)	CA2331187C (de)
CO (1)	CO5021227A1 (de)
CZ (2)	CZ298702B6 (de)
DE (2)	DE69907171T2 (de)
DK (1)	DK1077976T3 (de)
EE (2)	EE04311B1 (de)
ES (2)	ES2198915T3 (de)
HR (2)	HRP20000741B1 (de)
HU (2)	HUP0102031A3 (de)
IL (2)	IL139647A0 (de)
MY (2)	MY122147A (de)
NO (2)	NO319760B1 (de)
NZ (2)	NZ507965A (de)
PL (2)	PL194085B1 (de)
PT (1)	PT1077976E (de)
SI (1)	SI1077976T1 (de)
SK (2)	SK286156B6 (de)
TR (2)	TR200003322T2 (de)
TW (2)	TWI259835B (de)
WO (2)	WO1999058530A1 (de)
ZA (2)	ZA200007173B (de)

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EP0957101A1 (de) *	1998-05-14	1999-11-17	Janssen Pharmaceutica N.V.	Wasserlösliche Azole als Breitspektrum-antifungus
NZ521241A (en) *	2000-03-07	2004-02-27	Ranbaxy Lab Ltd	Azole compounds as therapeutic agents for fungal infections
EP1413301A1 (de) *	2002-10-24	2004-04-28	Bayer CropScience SA	Antimykotische Medikamente auf der Basis von Arylamidinderivaten
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
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
EA201592157A1 (ru)	2013-06-07	2016-05-31	Дзе Калифорния Инститъют Фор Биомедикал Рисёрч	Низкомолекулярные ингибиторы фиброза
WO2016087880A1 (en)	2014-12-05	2016-06-09	Pulmocide Limited	Antimycotic compound
EP3250036B1 (de)	2014-12-10	2021-05-12	The Scripps Research Institute	Kleinmolekül-hemmer von fibrose
ES2790723T3 (es) *	2015-05-21	2020-10-29	Pulmocide Ltd	Antifúngico 4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-il)metil)-5-(2,4-difluorofenil)tetrahidrofurano-3-il)metoxi)-3-metilfenil)piperazina-1-il)-N -(2-hidroxiciclohexil)benzamida, o una sal farmacéuticamente aceptable del mismo
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
CA3073228A1 (en) *	2017-08-20	2019-02-28	University Of Connecticut	Azole analogues and methods of use thereof
WO2021030174A1 (en)	2019-08-09	2021-02-18	University Of Connecticut	Truncated itraconazole analogues and methods of use thereof
GB201917867D0 (en)	2019-12-06	2020-01-22	Pulmocide Ltd	Polymorphs
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

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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
EP0631578B1 (de) *	1992-03-18	2001-05-23	Janssen Pharmaceutica N.V.	Itraconazol- und saperconazolstereoisomere
DK0736030T3 (da) *	1993-12-21	2001-10-29	Schering Corp	Fungicide tetrahydrofuraner
SG48386A1 (en) *	1994-01-24	1998-04-17	Janssen Pharmaceutica Nv	Watersoluble azole antifungals
FI98688C (fi) *	1994-07-20	1997-07-25	Nokia Telecommunications Oy	Menetelmä lyhytsanomalähetyksen käynnistämiseksi solukkoradiojärjestelmässä, solukkoradiojärjestelmä sekä solukkoradiojärjestelmän tilaajarekisteri
ES2199291T3 (es) *	1995-06-02	2004-02-16	Schering Corporation	Antifungicos de tetrahidrofurano.
MX9710270A (es) *	1995-06-19	1998-08-30	Schering Corp	Fungicidas de tetrahidrofurano.
CN1238353C (zh)	1997-02-11	2006-01-25	詹森药业有限公司	含氨基酸酯之唑类抗真菌剂
EP0957101A1 (de) *	1998-05-14	1999-11-17	Janssen Pharmaceutica N.V.	Wasserlösliche Azole als Breitspektrum-antifungus

1998
- 1998-05-14 EP EP98201588A patent/EP0957101A1/de not_active Withdrawn
1999
- 1999-05-06 WO PCT/EP1999/003243 patent/WO1999058530A1/en not_active Ceased
- 1999-05-06 IL IL13964799A patent/IL139647A0/xx not_active IP Right Cessation
- 1999-05-06 BR BR9911057-1A patent/BR9911057A/pt not_active Application Discontinuation
- 1999-05-06 PL PL99344047A patent/PL194085B1/pl unknown
- 1999-05-06 DE DE69907171T patent/DE69907171T2/de not_active Expired - Lifetime
- 1999-05-06 SI SI9930131T patent/SI1077976T1/xx unknown
- 1999-05-06 CZ CZ20004109A patent/CZ298702B6/cs not_active IP Right Cessation
- 1999-05-06 HR HR20000741A patent/HRP20000741B1/xx not_active IP Right Cessation
- 1999-05-06 US US09/700,166 patent/US6448244B1/en not_active Expired - Lifetime
- 1999-05-06 NZ NZ507965A patent/NZ507965A/en not_active IP Right Cessation
- 1999-05-06 HU HU0102031A patent/HUP0102031A3/hu unknown
- 1999-05-06 TR TR2000/03322T patent/TR200003322T2/xx unknown
- 1999-05-06 KR KR1020007011624A patent/KR100575147B1/ko not_active Expired - Fee Related
- 1999-05-06 CA CA002331187A patent/CA2331187C/en not_active Expired - Fee Related
- 1999-05-06 IL IL13964999A patent/IL139649A/en not_active IP Right Cessation
- 1999-05-06 ES ES99924942T patent/ES2198915T3/es not_active Expired - Lifetime
- 1999-05-06 PT PT99926304T patent/PT1077976E/pt unknown
- 1999-05-06 SK SK1681-2000A patent/SK286156B6/sk not_active IP Right Cessation
- 1999-05-06 KR KR1020007009640A patent/KR100593395B1/ko not_active Expired - Fee Related
- 1999-05-06 HR HR20000740A patent/HRP20000740B1/xx not_active IP Right Cessation
- 1999-05-06 AT AT99924942T patent/ATE238296T1/de not_active IP Right Cessation
- 1999-05-06 DE DE69902461T patent/DE69902461T2/de not_active Expired - Lifetime
- 1999-05-06 US US09/700,251 patent/US6384030B1/en not_active Expired - Lifetime
- 1999-05-06 WO PCT/EP1999/003242 patent/WO1999058529A1/en not_active Ceased
- 1999-05-06 EE EEP200000657A patent/EE04311B1/xx not_active IP Right Cessation
- 1999-05-06 EE EEP200000651A patent/EE04346B1/xx not_active IP Right Cessation
- 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 AU AU41417/99A patent/AU751135B2/en not_active Ceased
- 1999-05-06 CN CNB998060690A patent/CN1135229C/zh not_active Expired - Fee Related
- 1999-05-06 HU HU0103536A patent/HUP0103536A3/hu unknown
- 1999-05-06 NZ NZ507966A patent/NZ507966A/xx not_active IP Right Cessation
- 1999-05-06 PL PL99344037A patent/PL194086B1/pl unknown
- 1999-05-06 JP JP2000548333A patent/JP2002514645A/ja active Pending
- 1999-05-06 BR BR9910448-2A patent/BR9910448A/pt not_active Application Discontinuation
- 1999-05-06 AT AT99926304T patent/ATE221884T1/de active
- 1999-05-06 JP JP2000548334A patent/JP2002514646A/ja active Pending
- 1999-05-06 AU AU43615/99A patent/AU758876B2/en not_active Ceased
- 1999-05-06 TR TR2000/03323T patent/TR200003323T2/xx unknown
- 1999-05-06 EP EP99926304A patent/EP1077976B1/de not_active Expired - Lifetime
- 1999-05-06 SK SK1682-2000A patent/SK285763B6/sk not_active IP Right Cessation
- 1999-05-06 DK DK99926304T patent/DK1077976T3/da active
- 1999-05-06 EP EP99924942A patent/EP1077975B1/de not_active Expired - Lifetime
- 1999-05-06 ES ES99926304T patent/ES2182531T3/es not_active Expired - Lifetime
- 1999-05-06 CA CA002331141A patent/CA2331141C/en not_active Expired - Fee Related
- 1999-05-10 TW TW088107505A patent/TWI259835B/zh not_active IP Right Cessation
- 1999-05-10 TW TW088107504A patent/TW572899B/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 ARP990102270A patent/AR016480A1/es active IP Right Grant
- 1999-05-13 AR ARP990102276A patent/AR016482A1/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 NO20005713A patent/NO319760B1/no not_active IP Right Cessation
- 2000-11-13 NO NO20005712A patent/NO319851B1/no not_active IP Right Cessation
- 2000-12-04 ZA ZA200007173A patent/ZA200007173B/en unknown
- 2000-12-13 ZA ZA200007459A patent/ZA200007459B/xx unknown

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HRP20000740B1 (en)	2003-12-31
CZ299481B6 (cs)	2008-08-13
US6448244B1 (en)	2002-09-10
SK285763B6 (sk)	2007-07-06
HRP20000741B1 (hr)	2009-02-28
NZ507966A (en)	2002-10-25
KR100593395B1 (ko)	2006-06-28
HUP0103536A2 (hu)	2002-07-29
IL139647A0 (en)	2002-02-10
ES2182531T3 (es)	2003-03-01
HRP20000741A2 (en)	2001-06-30
DE69902461T2 (de)	2003-04-10
SK16822000A3 (sk)	2001-07-10
CZ20004108A3 (en)	2001-05-16
EP1077976B1 (de)	2002-08-07
NO20005713L (no)	2001-01-11
EE04346B1 (et)	2004-08-16
CZ20004109A3 (en)	2001-05-16
NZ507965A (en)	2002-05-31
DE69907171D1 (de)	2003-05-28
ZA200007173B (en)	2002-03-04
AU4141799A (en)	1999-11-29
HUP0102031A3 (en)	2002-10-28
CN1135229C (zh)	2004-01-21
KR100575147B1 (ko)	2006-05-03
TR200003323T2 (tr)	2001-02-21
NO20005713D0 (no)	2000-11-13
MY120248A (en)	2005-09-30
PL194085B1 (pl)	2007-04-30
HK1032781A1 (en)	2001-08-03
JP2002514645A (ja)	2002-05-21
EP0957101A1 (de)	1999-11-17
BG64954B1 (bg)	2006-10-31
NO20005712L (no)	2000-12-07
CN1137118C (zh)	2004-02-04
WO1999058529A1 (en)	1999-11-18
SK286156B6 (sk)	2008-04-07
HRP20000740A2 (en)	2001-10-31
CN1300287A (zh)	2001-06-20
ES2198915T3 (es)	2004-02-01
DE69907171T2 (de)	2004-02-05
IL139649A0 (en)	2002-02-10
ZA200007459B (en)	2002-09-13
EE200000657A (et)	2002-04-15
KR20010042852A (ko)	2001-05-25
ATE238296T1 (de)	2003-05-15
KR20010041480A (ko)	2001-05-25
BR9910448A (pt)	2001-01-02
AR016480A1 (es)	2001-07-04
SK16812000A3 (sk)	2001-08-06
BG104717A (en)	2001-07-31
CZ298702B6 (cs)	2007-12-27
ATE221884T1 (de)	2002-08-15
MY122147A (en)	2006-03-31
PT1077976E (pt)	2002-12-31
AR016482A1 (es)	2001-07-04
PL194086B1 (pl)	2007-04-30
CA2331187C (en)	2008-11-18
SI1077976T1 (en)	2003-02-28
NO319851B1 (no)	2005-09-19
EP1077975A1 (de)	2001-02-28
BG104933A (en)	2001-10-31
DE69902461D1 (de)	2002-09-12
AU758876B2 (en)	2003-04-03
DK1077976T3 (da)	2002-12-02
TWI259835B (en)	2006-08-11
TR200003322T2 (tr)	2001-02-21
PL344037A1 (en)	2001-09-24
NO20005712D0 (no)	2000-11-13
US6384030B1 (en)	2002-05-07
PL344047A1 (en)	2001-09-24
EE04311B1 (et)	2004-06-15
HUP0102031A2 (hu)	2002-05-29
CO5021227A1 (es)	2001-03-27
AU4361599A (en)	1999-11-29
CA2331141C (en)	2008-10-28
HK1033312A1 (en)	2001-08-24
CA2331141A1 (en)	1999-11-18
BR9911057A (pt)	2001-02-06
BG64388B1 (bg)	2004-12-30
EE200000651A (et)	2002-04-15
JP2002514646A (ja)	2002-05-21
CN1300288A (zh)	2001-06-20
WO1999058530A1 (en)	1999-11-18
EP1077976A1 (de)	2001-02-28
CA2331187A1 (en)	1999-11-18
TW572899B (en)	2004-01-21
AU751135B2 (en)	2002-08-08
EP1077975B1 (de)	2003-04-23
HUP0103536A3 (en)	2002-08-28
IL139649A (en)	2004-09-27

Legal Events

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Publication	Publication Date	Title
NO316173B1 (no)	2003-12-22	Tetrahydrofuran-antifungale midler
CZ297769B6 (cs)	2007-03-28	N-[4-(heteroarylmetyl)fenyl]-heteroarylaminy, zpusob jejich prípravy a jejich pouzití jako léciva
KR100575147B1 (ko)	2006-05-03	광범위-스펙트럼 항진균제로서의 수용성 아졸
NO971218L (no)	1997-03-17	Tetrahydrofuran-antifungale midler
CZ328897A3 (cs)	1998-01-14	Nové triazolony jako inhibitory syntézy apolipoproteinu-B
CA2372691C (en)	2009-11-17	Antifungal ethers
MXPA00011152A (en)	2001-07-31	Water soluble azoles as broad-spectrum antifungals
HK1033312B (en)	2003-02-21	Water soluble azoles as broad-spectrum antifungals
MXPA00011155A (es)	2001-07-31	Azoles solubles en agua como antifungicos de amplio espectro