JPH11504647A - 抗生物質 - Google Patents

抗生物質

Info

Publication number: JPH11504647A
Authority: JP; Japan
Prior art keywords: alkyl; polyene macrolide; glycosyl; methyl; glucose
Prior art date: 1995-05-13
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

Application number

JP8533895A

Other languages

English (en)

Japanese (ja)

Inventor

ボロフスキ，エドヴァルト

グジボフスカ，ヨランタ

ソヴィンスキ，パヴェウ

グミエニアク，イェジ

チェルヴィンスキ，アンヂュジェイ

Original Assignee

ブリティッシュ・テクノロジー・グループ・リミテッド

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.)

1995-05-13

Filing date

1996-05-10

Publication date

1999-04-27

1996-05-10 Application filed by ブリティッシュ・テクノロジー・グループ・リミテッド filed Critical ブリティッシュ・テクノロジー・グループ・リミテッド

1999-04-27 Publication of JPH11504647A publication Critical patent/JPH11504647A/ja

Status Pending legal-status Critical Current

Links

239000003242 anti bacterial agent Substances 0.000 title claims abstract description 21
229940088710 antibiotic agent Drugs 0.000 title claims abstract description 20
150000004291 polyenes Chemical class 0.000 claims abstract description 72
239000003120 macrolide antibiotic agent Substances 0.000 claims abstract description 71
150000001875 compounds Chemical class 0.000 claims abstract description 68
238000000034 method Methods 0.000 claims abstract description 55
235000000346 sugar Nutrition 0.000 claims abstract description 27
239000000203 mixture Substances 0.000 claims abstract description 17
206010017533 Fungal infection Diseases 0.000 claims abstract description 16
208000031888 Mycoses Diseases 0.000 claims abstract description 16
241001465754 Metazoa Species 0.000 claims abstract description 11
150000001450 anions Chemical class 0.000 claims abstract description 11
150000007522 mineralic acids Chemical class 0.000 claims abstract description 11
150000007524 organic acids Chemical class 0.000 claims abstract description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 9
125000005907 alkyl ester group Chemical group 0.000 claims abstract description 8
229940121375 antifungal agent Drugs 0.000 claims abstract description 6
238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 108
150000003839 salts Chemical class 0.000 claims description 51
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 48
150000004702 methyl esters Chemical class 0.000 claims description 47
230000003115 biocidal effect Effects 0.000 claims description 36
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 35
239000000047 product Substances 0.000 claims description 33
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 32
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 32
WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 claims description 28
238000003691 Amadori rearrangement reaction Methods 0.000 claims description 28
239000002904 solvent Substances 0.000 claims description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 20
150000002772 monosaccharides Chemical class 0.000 claims description 18
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical group O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 17
239000000725 suspension Substances 0.000 claims description 17
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 16
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 15
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 15
DXENDDMPDZMHSQ-UHFFFAOYSA-N Candinine Chemical group C12=NC3=CC=CC=C3C(=O)N1C1=CC=CC=C1C2=C1C(=O)C2=CC=CC=C2N1 DXENDDMPDZMHSQ-UHFFFAOYSA-N 0.000 claims description 15
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 15
239000008101 lactose Substances 0.000 claims description 15
229920001542 oligosaccharide Polymers 0.000 claims description 15
150000002482 oligosaccharides Chemical class 0.000 claims description 15
239000007787 solid Substances 0.000 claims description 15
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 14
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 14
WQZGKKKJIJFFOK-ZZWDRFIYSA-N L-glucose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-ZZWDRFIYSA-N 0.000 claims description 14
229960003942 amphotericin b Drugs 0.000 claims description 14
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 12
239000012043 crude product Substances 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 11
208000015181 infectious disease Diseases 0.000 claims description 10
229960004348 candicidin Drugs 0.000 claims description 9
239000002552 dosage form Substances 0.000 claims description 9
239000003960 organic solvent Substances 0.000 claims description 9
YKSVGLFNJPQDJE-YDMQLZBCSA-N (19E,21E,23E,25E,27E,29E,31E)-33-[(2R,3S,4R,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-17-[7-(4-aminophenyl)-5-hydroxy-4-methyl-7-oxoheptan-2-yl]-1,3,5,7,37-pentahydroxy-18-methyl-9,13,15-trioxo-16,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid Chemical compound CC(CC(C)C1OC(=O)CC(=O)CCCC(=O)CC(O)CC(O)CC(O)CC2(O)CC(O)C(C(CC(O[C@@H]3O[C@H](C)[C@@H](O)[C@@H](N)[C@@H]3O)\C=C\C=C\C=C\C=C\C=C\C=C\C=C\C1C)O2)C(O)=O)C(O)CC(=O)C1=CC=C(N)C=C1 YKSVGLFNJPQDJE-YDMQLZBCSA-N 0.000 claims description 8
-1 polyene macrocycle Chemical class 0.000 claims description 8
DXENDDMPDZMHSQ-FMQUCBEESA-N Candidine Chemical group C12=NC3=CC=CC=C3C(=O)N1C1=CC=CC=C1/C2=C1/C(=O)C2=CC=CC=C2N1 DXENDDMPDZMHSQ-FMQUCBEESA-N 0.000 claims description 7
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 7
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 7
125000003147 glycosyl group Chemical group 0.000 claims description 7
229960005261 aspartic acid Drugs 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
229960000988 nystatin Drugs 0.000 claims description 6
VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 claims description 6
238000001556 precipitation Methods 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
238000003756 stirring Methods 0.000 claims description 6
CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 5
CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 5
238000005406 washing Methods 0.000 claims description 5
GXLOOVOKGBOVIH-YPBFURFVSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,29r,32r,33r,35s,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,29,32,33,35,37-heptahydroxy-18,20,21-trimethyl-23,27-dioxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10, Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)CC(=O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 GXLOOVOKGBOVIH-YPBFURFVSA-N 0.000 claims description 4
GXLOOVOKGBOVIH-UHFFFAOYSA-N Mycoheptin Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CC=CC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(=O)CC(O)CCC(O)C(O)CC(O)(CC(O)C2C(O)=O)OC2C1 GXLOOVOKGBOVIH-UHFFFAOYSA-N 0.000 claims description 4
239000002168 alkylating agent Substances 0.000 claims description 4
229940100198 alkylating agent Drugs 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
238000001035 drying Methods 0.000 claims description 4
239000003429 antifungal agent Substances 0.000 claims description 3
238000001704 evaporation Methods 0.000 claims description 3
239000002244 precipitate Substances 0.000 claims description 3
230000008020 evaporation Effects 0.000 claims description 2
238000007912 intraperitoneal administration Methods 0.000 claims description 2
238000001990 intravenous administration Methods 0.000 claims description 2
238000002955 isolation Methods 0.000 claims description 2
238000007920 subcutaneous administration Methods 0.000 claims description 2
230000000699 topical effect Effects 0.000 claims description 2
DPAGRPSAFDXQDN-UHFFFAOYSA-N 5-methoxy-8,8-dimethyl-2-phenyl-4H,8H-pyrano[2,3-h]chromen-4-one Chemical compound C=1C(=O)C=2C(OC)=CC=3OC(C)(C)C=CC=3C=2OC=1C1=CC=CC=C1 DPAGRPSAFDXQDN-UHFFFAOYSA-N 0.000 claims 2
230000029936 alkylation Effects 0.000 claims 2
238000005804 alkylation reaction Methods 0.000 claims 2
230000001376 precipitating effect Effects 0.000 claims 2
CYGXFHUZSVKTBA-MOAKSMKPSA-N Candidin Natural products C[C@H]1OC(=O)C[C@@H](O)C[C@@H](O)CC(=O)CC[C@@H](O)[C@H](O)CC(=O)C[C@@H](O)[C@H]([C@H](O)C[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N)[C@@H]2O)C=CC=CC=CC=CC=CC=CC=C[C@@H](C)[C@H](O)[C@@H]1C)C(=O)O CYGXFHUZSVKTBA-MOAKSMKPSA-N 0.000 claims 1
208000035473 Communicable disease Diseases 0.000 claims 1
230000002152 alkylating effect Effects 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
125000001033 ether group Chemical group 0.000 claims 1
230000008707 rearrangement Effects 0.000 claims 1
239000013589 supplement Substances 0.000 claims 1
230000000843 anti-fungal effect Effects 0.000 abstract description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
239000000243 solution Substances 0.000 description 22
241000699670 Mus sp. Species 0.000 description 11
231100000419 toxicity Toxicity 0.000 description 9
230000001988 toxicity Effects 0.000 description 9
239000008103 glucose Substances 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
125000003277 amino group Chemical group 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
230000000694 effects Effects 0.000 description 5
210000003743 erythrocyte Anatomy 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
229960001866 silicon dioxide Drugs 0.000 description 5
239000002253 acid Substances 0.000 description 4
239000012634 fragment Substances 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
229940041033 macrolides Drugs 0.000 description 4
231100000682 maximum tolerated dose Toxicity 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
241000222120 Candida <Saccharomycetales> Species 0.000 description 3
241000222122 Candida albicans Species 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
229940095731 candida albicans Drugs 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
239000004020 conductor Substances 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
150000002016 disaccharides Chemical group 0.000 description 3
231100000086 high toxicity Toxicity 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
230000011987 methylation Effects 0.000 description 3
238000007069 methylation reaction Methods 0.000 description 3
239000002994 raw material Substances 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
229930183010 Amphotericin Natural products 0.000 description 2
QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 2
SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
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241000282412 Homo Species 0.000 description 2
PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
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PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 2
229940009444 amphotericin Drugs 0.000 description 2
UAZIZEMIKKIBCA-TYVGYKFWSA-N amphotericin B methyl ester Chemical compound O([C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@]2(O)C[C@H](O)[C@H]([C@H](C1)O2)C(=O)OC)[C@@H]1O[C@H](C)[C@@H](O)[C@H](N)[C@@H]1O UAZIZEMIKKIBCA-TYVGYKFWSA-N 0.000 description 2
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SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 2
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DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
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OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
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GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical group Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 1
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102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
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PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
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241000255925 Diptera Species 0.000 description 1
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229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
102000001554 Hemoglobins Human genes 0.000 description 1
108010054147 Hemoglobins Proteins 0.000 description 1
238000006845 Michael addition reaction Methods 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
229930182474 N-glycoside Natural products 0.000 description 1
206010067482 No adverse event Diseases 0.000 description 1
206010042938 Systemic candida Diseases 0.000 description 1
210000001015 abdomen Anatomy 0.000 description 1
238000000862 absorption spectrum Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
201000003984 candidiasis Diseases 0.000 description 1
TWFZGCMQGLPBSX-UHFFFAOYSA-N carbendazim Chemical compound C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
OZECDDHOAMNMQI-UHFFFAOYSA-H cerium(3+);trisulfate Chemical compound [Ce+3].[Ce+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O OZECDDHOAMNMQI-UHFFFAOYSA-H 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
230000000973 chemotherapeutic effect Effects 0.000 description 1
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
238000005094 computer simulation Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
229940109239 creatinine Drugs 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000012581 double quantum filtered COSY Methods 0.000 description 1
238000002265 electronic spectrum Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
230000009036 growth inhibition Effects 0.000 description 1
230000002949 hemolytic effect Effects 0.000 description 1
PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
238000000691 measurement method Methods 0.000 description 1
125000004492 methyl ester group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
230000037081 physical activity Effects 0.000 description 1
239000002243 precursor Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000005588 protonation Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
RYVMUASDIZQXAA-UHFFFAOYSA-N pyranoside Natural products O1C2(OCC(C)C(OC3C(C(O)C(O)C(CO)O3)O)C2)C(C)C(C2(CCC3C4(C)CC5O)C)C1CC2C3CC=C4CC5OC(C(C1O)O)OC(CO)C1OC(C1OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OCC(O)C(O)C1O RYVMUASDIZQXAA-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001896 rotating frame Overhauser effect spectroscopy Methods 0.000 description 1
239000012449 sabouraud dextrose agar Substances 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
230000000153 supplemental effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000003325 tomography Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
231100000925 very toxic Toxicity 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Genetics & Genomics (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Epidemiology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

JP8533895A 1995-05-13 1996-05-10 抗生物質 Pending JPH11504647A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
PL95308583A PL180253B1 (pl)	1995-05-13	1995-05-13	Pochodne N-metylo-N-glikozylowe estrów metylowych antybiotyków z grupy makrolidów polienowych i ich sole oraz sposób ich otrzymywania PL PL PL PL PL PL
PL308583		1995-05-13
PCT/GB1996/001144 WO1996035701A1 (en)	1995-05-13	1996-05-10	Antibiotics

Publications (1)

Publication Number	Publication Date
JPH11504647A true JPH11504647A (ja)	1999-04-27

Family

ID=20065009

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP8533895A Pending JPH11504647A (ja)	1995-05-13	1996-05-10	抗生物質

Country Status (11)

Country	Link
EP (1)	EP0825995A1 (pl)
JP (1)	JPH11504647A (pl)
KR (1)	KR19990014843A (pl)
AU (1)	AU716883B2 (pl)
CA (1)	CA2220771A1 (pl)
IL (1)	IL118233A0 (pl)
MX (1)	MX9708637A (pl)
NZ (1)	NZ307592A (pl)
PL (1)	PL180253B1 (pl)
WO (1)	WO1996035701A1 (pl)
ZA (1)	ZA963787B (pl)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2015519389A (ja) *	2012-06-15	2015-07-09	ブリートスポルカアクシヤ	抗真菌性抗生物質アンフォテリシンｂのｎ−置換第二世代誘導体ならびにそれらの調製および塗布方法
JP2023030103A (ja) *	2015-04-15	2023-03-07	スファンガセラピューティクスインコーポレイテッド	アムホテリシンｂの誘導体

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5981721A (en) *	1997-10-23	1999-11-09	Karykion Corporation	Polyene macrolide schiff bases, their alkyl esters and processes for preparing polyene macrolide alkyl ester salts thereof
JP2003519662A (ja)	2000-01-14	2003-06-24	イントラバイオティクスファーマシューティカルズ，インコーポレイテッド	ポリエン・マクロライド誘導体並びにその製法及び使用
KR100687748B1 (ko) *	2005-06-23	2007-02-27	한국전자통신연구원	이동 단말에 독립적인 빠른 핸드오버 수행을 위한 방법 및그 시스템
GB0712881D0 (en)	2007-07-03	2007-08-15	Biosergen As	Compounds
WO2013132014A1 (en)	2012-03-09	2013-09-12	Blirt S.A.	Semisynthetic derivatives of nystatin a1
BR112016028890A8 (pt)	2014-06-12	2021-03-23	Shionogi & Co	composto derivado de macrolídeo de polieno, composição farmacêutica compreendendo o referido composto e processo para a preparação do mesmo
CN112920238B (zh) *	2021-01-27	2022-09-30	河南农业大学	一种糖胺类Amadori衍生物及其制备方法和应用

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FI60877C (fi) *	1971-08-13	1982-04-13	Politechnika Gdanska	Foerfarande foer framstaellning av terapeutiskt aktiva i vatten laett dispergerbara polyenmakrolidantibiot-n-glykosylderivat
US4002741A (en) *	1974-04-24	1977-01-11	Valter Osvaldovich Kulbakh	Meglumine complex fungicidal polyene macrolide antibiotic compositions and treatment method
US4195172A (en) *	1976-04-22	1980-03-25	Politechnika Gdanska	Salts of N-glycosyl derivatives of polyene macrolides, especially N-methylglucamine salts as well as the method of their preparation
US4144328A (en) *	1977-02-28	1979-03-13	Vainshtein Viktor A	N,N,N-Trimethyl derivatives of polyene amphoteric antibiotics, process of producing same and pharmaceutical composition
FR2654339B1 (fr) *	1989-11-14	1994-10-28	Mayoly Spindler Laboratoires	Nouveaux derives solubles et non toxiques des macrolides polyeniques basiques, leur preparation et leurs applications.

1995
- 1995-05-13 PL PL95308583A patent/PL180253B1/pl not_active IP Right Cessation
1996
- 1996-05-10 WO PCT/GB1996/001144 patent/WO1996035701A1/en not_active Ceased
- 1996-05-10 MX MX9708637A patent/MX9708637A/es unknown
- 1996-05-10 EP EP96915094A patent/EP0825995A1/en not_active Withdrawn
- 1996-05-10 AU AU56983/96A patent/AU716883B2/en not_active Ceased
- 1996-05-10 CA CA002220771A patent/CA2220771A1/en not_active Abandoned
- 1996-05-10 KR KR1019970708187A patent/KR19990014843A/ko not_active Withdrawn
- 1996-05-10 NZ NZ307592A patent/NZ307592A/xx unknown
- 1996-05-10 JP JP8533895A patent/JPH11504647A/ja active Pending
- 1996-05-13 IL IL11823396A patent/IL118233A0/xx unknown
- 1996-05-13 ZA ZA9603787A patent/ZA963787B/xx unknown

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2015519389A (ja) *	2012-06-15	2015-07-09	ブリートスポルカアクシヤ	抗真菌性抗生物質アンフォテリシンｂのｎ−置換第二世代誘導体ならびにそれらの調製および塗布方法
JP2023030103A (ja) *	2015-04-15	2023-03-07	スファンガセラピューティクスインコーポレイテッド	アムホテリシンｂの誘導体

Also Published As

Publication number	Publication date
IL118233A0 (en)	1996-09-12
PL308583A1 (en)	1996-11-25
NZ307592A (en)	1999-01-28
KR19990014843A (ko)	1999-02-25
AU716883B2 (en)	2000-03-09
AU5698396A (en)	1996-11-29
ZA963787B (en)	1997-11-13
EP0825995A1 (en)	1998-03-04
PL180253B1 (pl)	2001-01-31
WO1996035701A1 (en)	1996-11-14
CA2220771A1 (en)	1996-11-14
MX9708637A (es)	1998-02-28

Publication	Publication Date	Title
KR100486053B1 (ko)	2005-06-16	신규에리트로마이신유도체,그의제조방법및약제로서의그의용도
CZ38393A3 (en)	1994-01-19	Mometasonfuroate monohydrate, process for preparing such substance and process for preparing medicaments therefrom
KR100567695B1 (ko)	2006-04-05	에리쓰로마이신의 신규 유도체, 그의 제조 방법 및의약으로서 그의 용도
CZ97599A3 (cs)	1999-08-11	Cefemový derivát a způsob jeho výroby
Grzybowska et al.	1997	N-methyl-ND-fructopyranosylamphotericin B methyl ester, new amphotericin B derivative of low toxicity
CN110724209A (zh)	2020-01-24	岩藻糖基化硫酸软骨素寡糖及其制备方法、组合物和用途
FR2470134A1 (fr)	1981-05-29	Nouveaux antibiotiques, leur preparation et leur utilisation
AU716883B2 (en)	2000-03-09	Antibiotics
CA2146475C (en)	1999-06-29	Process for the preparation of azithromycin dihydrochloride
WO2017186110A1 (zh)	2017-11-02	一类万古霉素衍生物、其制备方法、药物组合物和用途
MXPA97008637A (en)	1998-02-01	Antibioti
CN102086219A (zh)	2011-06-08	具有抗癌活性的蒽环类抗生素简单结构类似物及制备方法
US5942495A (en)	1999-08-24	Antibiotics
Saksena et al.	2005	Immunogens from a synthetic hexasaccharide fragment of the O-SP of Vibrio cholerae O: 1, serotype Ogawa
JP2003514925A (ja)	2003-04-22	ベータ−シクロデキストリン及び関連化合物の部分メチルエーテルの結晶性混合物
PL201891B1 (pl)	2009-05-29	Dwie odmiany polimorficzne difosforanu (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[[2,6-dideoksy-3-C-metylo-3-O-metylo-4-C-[(propyloamino)metylo]-α-L-rybo-heksopiranozylo]oksy]-2-etylo-3,4,10-trihydroksy-3,5,8,10,12,14-heksametylo-11-[[3,4,6-trideoksy-3-(dimetyloamino)-ß-D-ksylo-heksapiranozylo]oksy]-1-oksa-6-azacyklopentadekan-15-onu, sposób ich wytwarzania, sposób przeprowadzania ciekłokrystalicznego lub krystalicznego difosforanu w wolną od zanieczyszczeń wolną zasadę, środek farmaceutyczny i zastosowanie wolnej zasady ciekłokrystalicznego lub krystalicznego difosforanu
EP0873347A2 (fr)	1998-10-28	Nouveaux derives amines de 2", 3" didesoxyglycosides d'epipodophyllotoxine, leur procede de preparation, leur utilisation comme medicament et leur utilisation destinee aux traitements anticancereux
FR2500837A1 (fr)	1982-09-03	Nouveaux derives a, b-(d)-n-glucosides ou a, b-(l)-n-glucosides d'aminoacridine, sels de ceux-ci, procede pour la preparation de composes de ce genre, et medicaments contenant ces composes
CN1189835A (zh)	1998-08-05	抗菌素
GRZYBOWSKA et al.	1990	Hydrazides-a novel type of derivatives of polyene macrolide antifungal antibiotics
JP2001518475A (ja)	2001-10-16	環状亜リン酸およびリン酸塩
CA2176893A1 (en)	1997-11-18	Antibiotics
JP3156135B2 (ja)	2001-04-16	免疫賦活用活性物質及びその製造法
CN103443114A (zh)	2013-12-11	激活fgf受体的3-o-烷基寡糖、其制备及其治疗用途
JP2843695B2 (ja)	1999-01-06	１０，１１，１２，１３−テトラヒドロ−デスマイコシン誘導体、その製造法及びその医薬としての用途

JPH11504647A - 抗生物質 - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (3)

Publications (1)

Family

ID=20065009

Family Applications (1)

Country Status (11)

Cited By (2)

Families Citing this family (7)

Family Cites Families (5)

Cited By (2)

Also Published As

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