JP2004507501A - ベンジリデンチアゾリジンジオンおよび抗真菌剤としてのそれらの使用 - Google Patents
ベンジリデンチアゾリジンジオンおよび抗真菌剤としてのそれらの使用 Download PDFInfo
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- JP2004507501A JP2004507501A JP2002522888A JP2002522888A JP2004507501A JP 2004507501 A JP2004507501 A JP 2004507501A JP 2002522888 A JP2002522888 A JP 2002522888A JP 2002522888 A JP2002522888 A JP 2002522888A JP 2004507501 A JP2004507501 A JP 2004507501A
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- Prior art keywords
- phenyl
- branched
- phenylmethoxy
- methylene
- oxo
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
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- 229940121375 antifungal agent Drugs 0.000 title claims description 15
- 239000003429 antifungal agent Substances 0.000 title claims description 11
- SGIZECXZFLAGBW-UHFFFAOYSA-N 5-benzylidene-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC1=CC=CC=C1 SGIZECXZFLAGBW-UHFFFAOYSA-N 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 59
- 239000001257 hydrogen Substances 0.000 claims abstract description 53
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 206010017533 Fungal infection Diseases 0.000 claims abstract description 12
- 208000031888 Mycoses Diseases 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims abstract description 5
- 150000002431 hydrogen Chemical class 0.000 claims abstract 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 128
- 150000001875 compounds Chemical class 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 91
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 89
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 77
- 238000000034 method Methods 0.000 claims description 74
- -1 phenylmethoxy Chemical group 0.000 claims description 72
- 125000005975 2-phenylethyloxy group Chemical group 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- 125000004076 pyridyl group Chemical group 0.000 claims description 20
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 125000001544 thienyl group Chemical group 0.000 claims description 18
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 7
- 239000005695 Ammonium acetate Substances 0.000 claims description 7
- 229940043376 ammonium acetate Drugs 0.000 claims description 7
- 235000019257 ammonium acetate Nutrition 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- MQCZHTDGFLSFOD-UHFFFAOYSA-N 2-[4-oxo-5-[[4-(2-phenylethoxy)-3-phenylmethoxyphenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCCC1=CC=CC=C1 MQCZHTDGFLSFOD-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 101100533877 Hypocrea jecorina (strain QM6a) sor8 gene Proteins 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
- MFCHSBDIWCBMFE-LJQANCHMSA-N 2-[4-oxo-5-[[3-phenylmethoxy-4-[(2s)-2-phenylpropoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound C([C@@H](C)C=1C=CC=CC=1)OC(C(=C1)OCC=2C=CC=CC=2)=CC=C1C=C1SC(=S)N(CC(O)=O)C1=O MFCHSBDIWCBMFE-LJQANCHMSA-N 0.000 claims description 4
- QBKDSAYHKBXKQL-UHFFFAOYSA-N 2-[4-oxo-5-[[3-phenylmethoxy-4-[[4-(trifluoromethoxy)phenyl]methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=C(OC(F)(F)F)C=C1 QBKDSAYHKBXKQL-UHFFFAOYSA-N 0.000 claims description 4
- KWYBOLDSAURJIK-UHFFFAOYSA-N 2-[4-oxo-5-[[3-phenylmethoxy-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=C(C(F)(F)F)C=C1 KWYBOLDSAURJIK-UHFFFAOYSA-N 0.000 claims description 4
- LHYRKNFTTKMDNQ-DWXRJYCRSA-N 2-[4-oxo-5-[[4-[(2s)-2-phenylpropoxy]-3-[(1s)-2,2,2-trifluoro-1-phenylethoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound C([C@@H](C)C=1C=CC=CC=1)OC(C(=C1)O[C@@H](C=2C=CC=CC=2)C(F)(F)F)=CC=C1C=C1SC(=S)N(CC(O)=O)C1=O LHYRKNFTTKMDNQ-DWXRJYCRSA-N 0.000 claims description 4
- XTFYPIJXZLFEAR-UHFFFAOYSA-N 2-[5-[[3,4-bis[(2,4-difluorophenyl)methoxy]phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C(=CC(F)=CC=2)F)=CC=C1OCC1=CC=C(F)C=C1F XTFYPIJXZLFEAR-UHFFFAOYSA-N 0.000 claims description 4
- XGNWOQWQTFJAQN-UHFFFAOYSA-N 2-[5-[[3,4-bis[(4-fluorophenyl)methoxy]phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC(F)=CC=2)=CC=C1OCC1=CC=C(F)C=C1 XGNWOQWQTFJAQN-UHFFFAOYSA-N 0.000 claims description 4
- JDVBNGAJBKGNLT-UHFFFAOYSA-N 2-[5-[[3-[(3,4-difluorophenyl)methoxy]-4-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=C(F)C(F)=CC=2)=CC=C1OCC1=CC=CC=C1 JDVBNGAJBKGNLT-UHFFFAOYSA-N 0.000 claims description 4
- RYINIELRRQTSQL-UHFFFAOYSA-N 2-[5-[[4-(2-cyclohexylethoxy)-3-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCCC1CCCCC1 RYINIELRRQTSQL-UHFFFAOYSA-N 0.000 claims description 4
- SSKLGZLYOABIDO-UHFFFAOYSA-N 2-[5-[[4-[2-(4-chlorophenyl)ethoxy]-3-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCCC1=CC=C(Cl)C=C1 SSKLGZLYOABIDO-UHFFFAOYSA-N 0.000 claims description 4
- FXPLNNDKZYARSZ-UHFFFAOYSA-N 2-[5-[[4-[2-(4-fluorophenyl)ethoxy]-3-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCCC1=CC=C(F)C=C1 FXPLNNDKZYARSZ-UHFFFAOYSA-N 0.000 claims description 4
- YNOGAFPQUMNNHQ-UHFFFAOYSA-N 2-[5-[[4-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-3-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 YNOGAFPQUMNNHQ-UHFFFAOYSA-N 0.000 claims description 4
- 241001480037 Microsporum Species 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- YAHWWUNPHNZBOT-UHFFFAOYSA-N 2-[4-oxo-5-[[4-(2,2,3,3,3-pentafluoropropoxy)-3-phenylmethoxyphenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC1=CC=C(OCC(F)(F)C(F)(F)F)C(OCC=2C=CC=CC=2)=C1 YAHWWUNPHNZBOT-UHFFFAOYSA-N 0.000 claims description 3
- LHYRKNFTTKMDNQ-QYBDOPJKSA-N 2-[4-oxo-5-[[4-[(2r)-2-phenylpropoxy]-3-[(1s)-2,2,2-trifluoro-1-phenylethoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound C([C@H](C)C=1C=CC=CC=1)OC(C(=C1)O[C@@H](C=2C=CC=CC=2)C(F)(F)F)=CC=C1C=C1SC(=S)N(CC(O)=O)C1=O LHYRKNFTTKMDNQ-QYBDOPJKSA-N 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 241000223238 Trichophyton Species 0.000 claims description 3
- 150000003935 benzaldehydes Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- KOYJKQFGCGIFEU-UHFFFAOYSA-N 2-[4-oxo-5-[[3-(phenoxymethyl)-4-phenylmethoxyphenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1COC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 KOYJKQFGCGIFEU-UHFFFAOYSA-N 0.000 claims description 2
- GIHSGMSTRANTBM-UHFFFAOYSA-N 2-[4-oxo-5-[[3-phenylmethoxy-4-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=CC(C(F)(F)F)=C1 GIHSGMSTRANTBM-UHFFFAOYSA-N 0.000 claims description 2
- AOAROSLFYLNGCD-UHFFFAOYSA-N 2-[4-oxo-5-[[4-(2-phenylethoxy)-3-(2,2,2-trifluoro-1-phenylethoxy)phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OC(C=2C=CC=CC=2)C(F)(F)F)=CC=C1OCCC1=CC=CC=C1 AOAROSLFYLNGCD-UHFFFAOYSA-N 0.000 claims description 2
- IUBJVPOPUFQYOQ-UHFFFAOYSA-N 2-[5-[[3-[2-(dibutylamino)-2-oxo-1-phenylethoxy]-4-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound C=1C=CC=CC=1C(C(=O)N(CCCC)CCCC)OC(C(=CC=1)OCC=2C=CC=CC=2)=CC=1C=C1SC(=S)N(CC(O)=O)C1=O IUBJVPOPUFQYOQ-UHFFFAOYSA-N 0.000 claims description 2
- ICNYEXXENSBATD-UHFFFAOYSA-N 2-[5-[[4-[(3,4-difluorophenyl)methoxy]-3-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=C(F)C(F)=C1 ICNYEXXENSBATD-UHFFFAOYSA-N 0.000 claims description 2
- OWSLGYWEPUDVAT-UHFFFAOYSA-N 2-[5-[[4-[(4-chlorophenyl)methoxy]-3-phenylmethoxyphenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C=C1 OWSLGYWEPUDVAT-UHFFFAOYSA-N 0.000 claims description 2
- 241000228197 Aspergillus flavus Species 0.000 claims description 2
- 241001225321 Aspergillus fumigatus Species 0.000 claims description 2
- 229940091771 aspergillus fumigatus Drugs 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
- 101100495911 Arabidopsis thaliana CHR10 gene Proteins 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- FFYJVTLTZYPAAB-UQQQWYQISA-N 5-[[3-(1-phenylethoxy)-4-(2-phenylethoxy)phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid Chemical compound C=1C=CC=CC=1C(C)OC(C(=CC=1)OCCC=2C=CC=CC=2)=CC=1\C=C1/SC(=S)N(CC(O)=O)C1=O FFYJVTLTZYPAAB-UQQQWYQISA-N 0.000 claims 1
- 201000007336 Cryptococcosis Diseases 0.000 claims 1
- 241000221204 Cryptococcus neoformans Species 0.000 claims 1
- 238000005815 base catalysis Methods 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 285
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 219
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 180
- 239000000047 product Substances 0.000 description 73
- 239000000843 powder Substances 0.000 description 65
- 239000000243 solution Substances 0.000 description 64
- 239000003208 petroleum Substances 0.000 description 62
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- 238000005160 1H NMR spectroscopy Methods 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 35
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
- 229910052938 sodium sulfate Inorganic materials 0.000 description 32
- 235000011152 sodium sulphate Nutrition 0.000 description 32
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 27
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- 239000000741 silica gel Substances 0.000 description 26
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- 229910000024 caesium carbonate Inorganic materials 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
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- OAOJBMHAQUUUTE-UHFFFAOYSA-N 3-hydroxy-4-(2-phenylethoxy)benzaldehyde Chemical compound OC1=CC(C=O)=CC=C1OCCC1=CC=CC=C1 OAOJBMHAQUUUTE-UHFFFAOYSA-N 0.000 description 6
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- OOENNZREZDKUHB-UHFFFAOYSA-N 2-[5-[[3,4-bis(phenylmethoxy)phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1OCC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 OOENNZREZDKUHB-UHFFFAOYSA-N 0.000 description 5
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- 235000011187 glycerol Nutrition 0.000 description 1
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- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
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- 239000008309 hydrophilic cream Substances 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
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- 238000001990 intravenous administration Methods 0.000 description 1
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- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
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- 235000019341 magnesium sulphate Nutrition 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- AMYIBYTXYMGLMV-QRPNPIFTSA-N methane (2R)-2-phenylpropane-1-sulfonic acid Chemical compound C1(=CC=CC=C1)[C@H](CS(=O)(=O)O)C.C AMYIBYTXYMGLMV-QRPNPIFTSA-N 0.000 description 1
- AMYIBYTXYMGLMV-DDWIOCJRSA-N methane (2S)-2-phenylpropane-1-sulfonic acid Chemical compound C1(=CC=CC=C1)[C@@H](CS(=O)(=O)O)C.C AMYIBYTXYMGLMV-DDWIOCJRSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 238000003808 methanol extraction Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
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- 238000002156 mixing Methods 0.000 description 1
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- 235000010460 mustard Nutrition 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 230000037125 natural defense Effects 0.000 description 1
- WWJFFVUVFNBJTN-UHFFFAOYSA-N neopolyoxin C Natural products C=1C=C(O)C=NC=1C(O)C(C)C(N)C(=O)NC(C(O)=O)C(C(C1O)O)OC1N1C=CC(=O)NC1=O WWJFFVUVFNBJTN-UHFFFAOYSA-N 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 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
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
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- 235000010603 pastilles Nutrition 0.000 description 1
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- 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
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- 230000028327 secretion Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ZMRHBJQLCDZMAH-UHFFFAOYSA-M sodium chloride hydrate hydrochloride Chemical compound [OH-].[Na+].Cl.Cl ZMRHBJQLCDZMAH-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
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- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
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- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003548 thiazolidines Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
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- 239000011701 zinc Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
-
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0021421.3A GB0021421D0 (en) | 2000-08-31 | 2000-08-31 | Compounds |
| PCT/GB2001/003862 WO2002017915A1 (en) | 2000-08-31 | 2001-08-30 | Benzylidene thiazolidinediones and their use as antimycotic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004507501A true JP2004507501A (ja) | 2004-03-11 |
| JP2004507501A5 JP2004507501A5 (enExample) | 2005-04-14 |
Family
ID=9898616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002522888A Pending JP2004507501A (ja) | 2000-08-31 | 2001-08-30 | ベンジリデンチアゾリジンジオンおよび抗真菌剤としてのそれらの使用 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7105554B2 (enExample) |
| EP (1) | EP1313471B1 (enExample) |
| JP (1) | JP2004507501A (enExample) |
| AT (1) | ATE359073T1 (enExample) |
| AU (1) | AU2001284190A1 (enExample) |
| DE (1) | DE60127845T2 (enExample) |
| ES (1) | ES2282283T3 (enExample) |
| GB (1) | GB0021421D0 (enExample) |
| WO (1) | WO2002017915A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011520968A (ja) * | 2008-05-20 | 2011-07-21 | メルク・シャープ・エンド・ドーム・コーポレイション | マンノシルトランスフェラーゼ阻害剤を使用した異種蛋白質の効率的生産 |
| WO2014024897A1 (ja) * | 2012-08-06 | 2014-02-13 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | チアゾリジンジオンおよびピロリジンジオン誘導体、並びにそれらを有効成分としてなる殺菌剤 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0204252D0 (en) * | 2002-02-23 | 2002-04-10 | Oxford Glycosciences Uk Ltd | Novel compounds |
| WO2003070238A1 (en) * | 2002-02-23 | 2003-08-28 | Oxford Glycosciences (Uk) Ltd | Thiazolidine antifungal agents |
| AU2005225632B2 (en) | 2004-03-23 | 2011-08-04 | Pfizer Inc. | Formamide derivatives useful as adrenoceptor |
| EP1954815B1 (en) * | 2005-11-15 | 2015-02-25 | GlycoFi, Inc. | Production of glycoproteins with reduced o-glycosylation |
| WO2007079466A2 (en) * | 2006-01-04 | 2007-07-12 | Nano Mist International, Llc | Air driven delivery system for sprayable media |
| US8637435B2 (en) * | 2007-11-16 | 2014-01-28 | Merck Sharp & Dohme Corp. | Eukaryotic cell display systems |
| WO2009111183A1 (en) * | 2008-03-03 | 2009-09-11 | Glycofi, Inc. | Surface display of recombinant proteins in lower eukaryotes |
| US8067339B2 (en) | 2008-07-09 | 2011-11-29 | Merck Sharp & Dohme Corp. | Surface display of whole antibodies in eukaryotes |
| JP2011530311A (ja) | 2008-08-12 | 2011-12-22 | グライコフィ， インコーポレイテッド | タンパク質製造のための改良されたベクターおよび酵母株：Ｃａ２＋ＡＴＰアーゼ過剰発現 |
| US8936918B2 (en) | 2011-02-25 | 2015-01-20 | Merck Sharp & Dohme Corp. | Yeast strain for the production of proteins with modified O-glycosylation |
| MX336268B (es) * | 2011-07-29 | 2016-01-13 | Toyama Chemical Co Ltd | Compuesto de amidina o sal del mismo. |
| US9261497B2 (en) | 2012-10-16 | 2016-02-16 | New York University | Method of treating cancer with modulators of SCFSkp2 |
| WO2015001049A1 (en) | 2013-07-04 | 2015-01-08 | Novartis Ag | O-mannosyltransferase deficient filamentous fungal cells and methods of use thereof |
| CN108064266A (zh) | 2014-07-21 | 2018-05-22 | 格利科斯芬兰公司 | 在丝状真菌中具有哺乳动物样n-聚糖的糖蛋白的制备 |
| JP2019523229A (ja) * | 2016-06-14 | 2019-08-22 | ヴェルシテック リミテッド | 抗微生物化合物及びその使用方法 |
| WO2017223473A1 (en) * | 2016-06-24 | 2017-12-28 | Ohio University | Glucose transport inhibitors and methods of using same |
| RU2662153C1 (ru) * | 2017-04-20 | 2018-07-24 | Общество С Ограниченной Ответственностью "Дермавитал Групп" | Гибридные эфиры на основе производных тиазолидин-2,4-диона и азолов (1н-1,3-имидазола и 1н-1,3,4-триазола) и их применение |
| RU2690161C1 (ru) * | 2018-06-28 | 2019-05-31 | Общество С Ограниченной Ответственностью "Дермавитал Групп" | 3,5-Замещенные производные тиазолидин-2,4-диона, обладающие противомикробной активностью |
| RU2703997C1 (ru) * | 2018-12-13 | 2019-10-23 | Общество с ограниченной ответственностью "Л-Био" | Гибридные амиды на основе триазола и тиазолидина, обладающие антимикробной активностью |
| CN112521382A (zh) * | 2020-12-14 | 2021-03-19 | 西南大学 | 芦荟大黄素噻唑烷二酮类化合物及其制备方法和应用 |
| WO2024258316A1 (ru) * | 2023-06-16 | 2024-12-19 | Общество с ограниченной ответственностью "Л-Био" | Новые потенциальные противогрибковые средства на основе тиазолидин-2,4-диона и триазола |
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| JPS6156175A (ja) * | 1984-08-24 | 1986-03-20 | Yamanouchi Pharmaceut Co Ltd | ロダニン誘導体およびその製造法 |
| JPH06192091A (ja) * | 1992-09-10 | 1994-07-12 | Eli Lilly & Co | 血糖低下用およびアルツハイマー病治療用化合物 |
| WO1994029287A1 (de) * | 1993-06-04 | 1994-12-22 | Boehringer Mannheim Gmbh | Aryliden-4-oxo-2-thioxo-3-thiazolidincarbonsäuren, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| JPH08109175A (ja) * | 1994-10-07 | 1996-04-30 | Torii Yakuhin Kk | チアゾリジン−２−オンエステル誘導体 |
| JPH08109174A (ja) * | 1994-10-07 | 1996-04-30 | Torii Yakuhin Kk | チアゾリジン−２−オン誘導体 |
| WO2000018746A1 (en) * | 1998-09-30 | 2000-04-06 | Roche Diagnostics Gmbh | Thiazolidine derivatives for the treatment and prevention of metabolic bone disorders |
| WO2000018747A1 (en) * | 1998-09-30 | 2000-04-06 | Roche Diagnostics Gmbh | Rhodanine carboxylic acid derivatives for the treatment and prevention of metabolic bone disorders |
| WO2001057006A1 (en) * | 2000-02-03 | 2001-08-09 | F. Hoffmann-La Roche Ag | Thiazolidine carboxylic acid derivatives and their use in the treatment of cancer |
-
2000
- 2000-08-31 GB GBGB0021421.3A patent/GB0021421D0/en not_active Ceased
-
2001
- 2001-08-30 EP EP01963157A patent/EP1313471B1/en not_active Expired - Lifetime
- 2001-08-30 DE DE60127845T patent/DE60127845T2/de not_active Expired - Lifetime
- 2001-08-30 AT AT01963157T patent/ATE359073T1/de not_active IP Right Cessation
- 2001-08-30 WO PCT/GB2001/003862 patent/WO2002017915A1/en not_active Ceased
- 2001-08-30 ES ES01963157T patent/ES2282283T3/es not_active Expired - Lifetime
- 2001-08-30 JP JP2002522888A patent/JP2004507501A/ja active Pending
- 2001-08-30 AU AU2001284190A patent/AU2001284190A1/en not_active Abandoned
-
2003
- 2003-02-21 US US10/371,964 patent/US7105554B2/en not_active Expired - Fee Related
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS6156175A (ja) * | 1984-08-24 | 1986-03-20 | Yamanouchi Pharmaceut Co Ltd | ロダニン誘導体およびその製造法 |
| JPH06192091A (ja) * | 1992-09-10 | 1994-07-12 | Eli Lilly & Co | 血糖低下用およびアルツハイマー病治療用化合物 |
| WO1994029287A1 (de) * | 1993-06-04 | 1994-12-22 | Boehringer Mannheim Gmbh | Aryliden-4-oxo-2-thioxo-3-thiazolidincarbonsäuren, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| JPH08109175A (ja) * | 1994-10-07 | 1996-04-30 | Torii Yakuhin Kk | チアゾリジン−２−オンエステル誘導体 |
| JPH08109174A (ja) * | 1994-10-07 | 1996-04-30 | Torii Yakuhin Kk | チアゾリジン−２−オン誘導体 |
| WO2000018746A1 (en) * | 1998-09-30 | 2000-04-06 | Roche Diagnostics Gmbh | Thiazolidine derivatives for the treatment and prevention of metabolic bone disorders |
| WO2000018747A1 (en) * | 1998-09-30 | 2000-04-06 | Roche Diagnostics Gmbh | Rhodanine carboxylic acid derivatives for the treatment and prevention of metabolic bone disorders |
| WO2001057006A1 (en) * | 2000-02-03 | 2001-08-09 | F. Hoffmann-La Roche Ag | Thiazolidine carboxylic acid derivatives and their use in the treatment of cancer |
| JP2003521542A (ja) * | 2000-02-03 | 2003-07-15 | エフ．ホフマン−ラ ロシュ アーゲー | チアゾリジンカルボン酸誘導体及び癌の治療におけるその利用 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011520968A (ja) * | 2008-05-20 | 2011-07-21 | メルク・シャープ・エンド・ドーム・コーポレイション | マンノシルトランスフェラーゼ阻害剤を使用した異種蛋白質の効率的生産 |
| WO2014024897A1 (ja) * | 2012-08-06 | 2014-02-13 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | チアゾリジンジオンおよびピロリジンジオン誘導体、並びにそれらを有効成分としてなる殺菌剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001284190A1 (en) | 2002-03-13 |
| DE60127845T2 (de) | 2007-12-20 |
| GB0021421D0 (en) | 2000-10-18 |
| WO2002017915A1 (en) | 2002-03-07 |
| US20040006112A1 (en) | 2004-01-08 |
| ES2282283T3 (es) | 2007-10-16 |
| EP1313471B1 (en) | 2007-04-11 |
| US7105554B2 (en) | 2006-09-12 |
| ATE359073T1 (de) | 2007-05-15 |
| EP1313471A1 (en) | 2003-05-28 |
| DE60127845D1 (de) | 2007-05-24 |
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