UA77210C2 - Macrolids, process for their manufacture (variants), pharmaceutical composition, method for treatment of bacterial infections - Google Patents

Macrolids, process for their manufacture (variants), pharmaceutical composition, method for treatment of bacterial infections Download PDF

Info

Publication number: UA77210C2
Authority: UA; Ukraine
Prior art keywords: amino; dihydro; oxo; compound; cyclopropyl
Prior art date: 2001-11-14

Application number

UA20040503313A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Glaxo Group Ltd

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.)

2001-11-14

Filing date

2002-11-13

Publication date

2006-11-15

2002-11-13 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2006-11-15 Publication of UA77210C2 publication Critical patent/UA77210C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 24
208000035143 Bacterial infection Diseases 0.000 title claims abstract description 8
208000022362 bacterial infectious disease Diseases 0.000 title claims abstract description 8
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
238000004519 manufacturing process Methods 0.000 title abstract description 3
150000003839 salts Chemical class 0.000 claims abstract description 19
239000012453 solvate Substances 0.000 claims abstract description 12
230000009885 systemic effect Effects 0.000 claims abstract description 5
230000002265 prevention Effects 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 439
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 147
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 124
229960002626 clarithromycin Drugs 0.000 claims description 73
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 56
238000006243 chemical reaction Methods 0.000 claims description 42
239000001257 hydrogen Substances 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 35
229960004099 azithromycin Drugs 0.000 claims description 31
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 27
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 18
239000003814 drug Substances 0.000 claims description 15
125000004429 atom Chemical group 0.000 claims description 12
125000004122 cyclic group Chemical group 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 9
239000011737 fluorine Substances 0.000 claims description 9
241001465754 Metazoa Species 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 6
241000282414 Homo sapiens Species 0.000 claims description 5
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
235000010469 Glycine max Nutrition 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
244000068988 Glycine max Species 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
239000003120 macrolide antibiotic agent Substances 0.000 claims description 3
229940041033 macrolides Drugs 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
229940079593 drug Drugs 0.000 claims description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims 2
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims 1
208000027697 autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency Diseases 0.000 claims 1
244000309466 calf Species 0.000 claims 1
239000000571 coke Substances 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 379
239000000543 intermediate Substances 0.000 description 303
239000000243 solution Substances 0.000 description 218
239000000203 mixture Substances 0.000 description 162
239000002904 solvent Substances 0.000 description 144
239000011541 reaction mixture Substances 0.000 description 124
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 101
239000003480 eluent Substances 0.000 description 83
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 79
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
238000003818 flash chromatography Methods 0.000 description 69
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 63
239000012043 crude product Substances 0.000 description 61
238000005481 NMR spectroscopy Methods 0.000 description 56
239000012074 organic phase Substances 0.000 description 49
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
239000000725 suspension Substances 0.000 description 47
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
239000008346 aqueous phase Substances 0.000 description 37
239000012267 brine Substances 0.000 description 37
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 35
235000019439 ethyl acetate Nutrition 0.000 description 34
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 33
229960003276 erythromycin Drugs 0.000 description 32
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
239000000706 filtrate Substances 0.000 description 29
-1 for example Chemical group 0.000 description 28
229920006395 saturated elastomer Polymers 0.000 description 28
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 27
239000007864 aqueous solution Substances 0.000 description 26
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 25
239000012044 organic layer Substances 0.000 description 25
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
239000013058 crude material Substances 0.000 description 19
238000001704 evaporation Methods 0.000 description 19
230000008020 evaporation Effects 0.000 description 19
239000007787 solid Substances 0.000 description 19
INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
239000011347 resin Substances 0.000 description 18
229920005989 resin Polymers 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 17
239000000284 extract Substances 0.000 description 17
239000002244 precipitate Substances 0.000 description 17
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
238000005160 1H NMR spectroscopy Methods 0.000 description 16
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 16
229920000642 polymer Polymers 0.000 description 16
239000012300 argon atmosphere Substances 0.000 description 14
239000010410 layer Substances 0.000 description 14
238000011068 loading method Methods 0.000 description 14
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
239000012948 isocyanate Substances 0.000 description 12
150000002513 isocyanates Chemical class 0.000 description 12
OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 11
239000000047 product Substances 0.000 description 11
239000012047 saturated solution Substances 0.000 description 11
VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
230000003993 interaction Effects 0.000 description 9
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
239000012071 phase Substances 0.000 description 9
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 8
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
229910002092 carbon dioxide Inorganic materials 0.000 description 8
238000004440 column chromatography Methods 0.000 description 8
150000002431 hydrogen Chemical class 0.000 description 8
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
229940125846 compound 25 Drugs 0.000 description 7
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
229910052740 iodine Inorganic materials 0.000 description 7
238000001556 precipitation Methods 0.000 description 7
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 6
DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 6
229940127113 compound 57 Drugs 0.000 description 6
150000002367 halogens Chemical class 0.000 description 6
230000014759 maintenance of location Effects 0.000 description 6
239000012452 mother liquor Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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239000011780 sodium chloride Substances 0.000 description 6
MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 5
DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
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QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 4
150000001804 chlorine Chemical class 0.000 description 4
229940125773 compound 10 Drugs 0.000 description 4
229940125898 compound 5 Drugs 0.000 description 4
229940125900 compound 59 Drugs 0.000 description 4
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UXKUODQYLDZXDL-UHFFFAOYSA-N fulminic acid Chemical compound [O-][N+]#C UXKUODQYLDZXDL-UHFFFAOYSA-N 0.000 description 4
239000012535 impurity Substances 0.000 description 4
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 4
239000007788 liquid Substances 0.000 description 4
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
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239000001569 carbon dioxide Substances 0.000 description 1
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MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 1
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230000002951 depilatory effect Effects 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
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229940042935 dichlorodifluoromethane Drugs 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
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IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
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CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
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239000000975 dye Substances 0.000 description 1
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VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
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238000001802 infusion Methods 0.000 description 1
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
RGDXATQMQZIAAX-UHFFFAOYSA-N iron;propan-2-ol Chemical compound [Fe].CC(C)O RGDXATQMQZIAAX-UHFFFAOYSA-N 0.000 description 1
230000002262 irrigation Effects 0.000 description 1
238000003973 irrigation Methods 0.000 description 1
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239000006210 lotion Substances 0.000 description 1
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238000001819 mass spectrum Methods 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
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244000000010 microbial pathogen Species 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
239000010413 mother solution Substances 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
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OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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239000002674 ointment Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
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XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
208000026435 phlegm Diseases 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
239000006187 pill Substances 0.000 description 1
235000021018 plums Nutrition 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920000767 polyaniline Polymers 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
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000011435 rock Substances 0.000 description 1
239000013049 sediment Substances 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
239000002453 shampoo Substances 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
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239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents

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

UA20040503313A 2001-11-14 2002-11-13 Macrolids, process for their manufacture (variants), pharmaceutical composition, method for treatment of bacterial infections UA77210C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0127349.9A GB0127349D0 (en)	2001-11-14	2001-11-14	Macrolides
PCT/GB2002/005101 WO2003042228A1 (en)	2001-11-14	2002-11-13	Macrolides

Publications (1)

Publication Number	Publication Date
UA77210C2 true UA77210C2 (en)	2006-11-15

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UA20040503313A UA77210C2 (en)	2001-11-14	2002-11-13	Macrolids, process for their manufacture (variants), pharmaceutical composition, method for treatment of bacterial infections

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US (1)	US7202221B2 (sr)
EP (1)	EP1453846B1 (sr)
JP (1)	JP2005515978A (sr)
CN (1)	CN1307194C (sr)
AR (1)	AR037371A1 (sr)
AT (1)	ATE362479T1 (sr)
BR (1)	BR0214132A (sr)
CA (1)	CA2466975A1 (sr)
DE (1)	DE60220180T2 (sr)
EA (1)	EA007433B1 (sr)
ES (1)	ES2287332T3 (sr)
GB (1)	GB0127349D0 (sr)
HR (1)	HRP20040433A2 (sr)
HU (1)	HUP0402225A3 (sr)
IL (1)	IL161710A0 (sr)
PL (1)	PL371472A1 (sr)
RS (1)	RS41904A (sr)
UA (1)	UA77210C2 (sr)
WO (1)	WO2003042228A1 (sr)
ZA (1)	ZA200403684B (sr)

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DK1503759T3 (da) *	2002-05-14	2009-04-14	Univ California	Substituerede quinoloncarboxylsyrer, deres derivater, virkningssted og anvendelser heraf
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GB0225384D0 (en) *	2002-10-31	2002-12-11	Glaxo Group Ltd	Novel compounds
US6645941B1 (en)	2003-03-26	2003-11-11	Enanta Pharmaceuticals, Inc.	6,11-3C-bicyclic 9a-azalide derivatives
GB0310980D0 (en) *	2003-05-13	2003-06-18	Glaxo Group Ltd	Novel compounds
GB0310979D0 (en) *	2003-05-13	2003-06-18	Glaxo Group Ltd	Novel compounds
ES2278319T3 (es) *	2003-05-13	2007-08-01	Glaxo Group Limited	Nuevos compuestos con 14 y 15 miembros en el anillo.
GB0310986D0 (en)	2003-05-13	2003-06-18	Glaxo Group Ltd	Novel compounds
GB0310984D0 (en) *	2003-05-13	2003-06-18	Glaxo Group Ltd	Novel compounds
WO2005030227A1 (en)	2003-09-23	2005-04-07	Enanta Pharmaceuticals, Inc.	9a, 11-3C-BICYCLIC 9a-AZALIDE DERIVATIVES
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WO2005108412A1 (en) *	2004-05-06	2005-11-17	Glaxosmithkline Istrazivacki Centar Zagreb D.O.O.	Ester linked macrolides useful for the treatment of microbial infections
JP2007536372A (ja) *	2004-05-06	2007-12-13	グラクソスミスクライン・イストラジヴァッキ・センタル・ザグレブ・ドルズバ・ゼー・オメイェノ・オドゴヴォルノスティオ	微生物感染症の治療に有用なカルバミン酸エステル結合マクロライド
WO2006047167A2 (en) *	2004-10-21	2006-05-04	Janssen Pharmaceutica, N.V.	9 alkyl and 9 alkylidenyl 6-0 alkyl-11, 12 carbamate ketolide antimicrobials
GB0424961D0 (en) *	2004-11-11	2004-12-15	Glaxo Group Ltd	Novel compounds
GB0424959D0 (en)	2004-11-11	2004-12-15	Glaxo Group Ltd	Novel compounds
GB0424951D0 (en) *	2004-11-11	2004-12-15	Glaxo Group Ltd	Novel compounds
GB0424958D0 (en) *	2004-11-11	2004-12-15	Glaxo Group Ltd	Novel compounds
BRPI0716408A2 (pt)	2006-08-09	2013-09-24	Basilea Pharmaceutica Ag	macrolÍdeos éteis doenÇa inflamatària e alÉrgica
CA2661538A1 (en)	2006-08-24	2008-02-28	Wockhardt Research Centre	Novel macrolides and ketolides having antimicrobial activity
WO2009106419A1 (en)	2008-02-08	2009-09-03	Basilea Pharmaceutica Ag	New macrolides and their use
ES2561332T3 (es)	2009-05-27	2016-02-25	Wockhardt Limited	Compuestos cetólidos que tienen actividad antimicrobiana
PT2673285T (pt)	2010-12-09	2017-10-19	Wockhardt Ltd	Resumo
BR112013019283A2 (pt) *	2011-01-31	2016-09-13	Meiji Seika Pharma Co Ltd	composto, fármaco, composição farmacêutica e uso
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2001
- 2001-11-14 GB GBGB0127349.9A patent/GB0127349D0/en not_active Ceased
2002
- 2002-11-13 BR BR0214132-9A patent/BR0214132A/pt not_active IP Right Cessation
- 2002-11-13 US US10/495,413 patent/US7202221B2/en not_active Expired - Fee Related
- 2002-11-13 DE DE60220180T patent/DE60220180T2/de not_active Expired - Fee Related
- 2002-11-13 IL IL16171002A patent/IL161710A0/xx unknown
- 2002-11-13 AR ARP020104364A patent/AR037371A1/es unknown
- 2002-11-13 JP JP2003544063A patent/JP2005515978A/ja active Pending
- 2002-11-13 CN CNB028270452A patent/CN1307194C/zh not_active Expired - Fee Related
- 2002-11-13 HU HU0402225A patent/HUP0402225A3/hu unknown
- 2002-11-13 UA UA20040503313A patent/UA77210C2/uk unknown
- 2002-11-13 PL PL02371472A patent/PL371472A1/xx not_active Application Discontinuation
- 2002-11-13 CA CA002466975A patent/CA2466975A1/en not_active Abandoned
- 2002-11-13 EA EA200400536A patent/EA007433B1/ru not_active IP Right Cessation
- 2002-11-13 WO PCT/GB2002/005101 patent/WO2003042228A1/en not_active Ceased
- 2002-11-13 HR HR20040433A patent/HRP20040433A2/hr not_active Application Discontinuation
- 2002-11-13 RS YU41904A patent/RS41904A/sr unknown
- 2002-11-13 EP EP02779670A patent/EP1453846B1/en not_active Expired - Lifetime
- 2002-11-13 AT AT02779670T patent/ATE362479T1/de not_active IP Right Cessation
- 2002-11-13 ES ES02779670T patent/ES2287332T3/es not_active Expired - Lifetime
2004
- 2004-05-13 ZA ZA200403684A patent/ZA200403684B/xx unknown

Also Published As

Publication number	Publication date
CN1612888A (zh)	2005-05-04
RS41904A (sr)	2006-10-27
WO2003042228A1 (en)	2003-05-22
PL371472A1 (en)	2005-06-13
DE60220180T2 (de)	2008-01-17
HUP0402225A2 (hu)	2005-02-28
HRP20040433A2 (en)	2005-04-30
ES2287332T3 (es)	2007-12-16
ZA200403684B (en)	2005-09-13
EP1453846A1 (en)	2004-09-08
BR0214132A (pt)	2004-09-14
CA2466975A1 (en)	2003-05-22
GB0127349D0 (en)	2002-01-02
EA007433B1 (ru)	2006-10-27
CN1307194C (zh)	2007-03-28
ATE362479T1 (de)	2007-06-15
HUP0402225A3 (en)	2006-01-30
AR037371A1 (es)	2004-11-03
JP2005515978A (ja)	2005-06-02
US7202221B2 (en)	2007-04-10
EA200400536A1 (ru)	2004-12-30
EP1453846B1 (en)	2007-05-16
US20050080025A1 (en)	2005-04-14
DE60220180D1 (de)	2007-06-28
IL161710A0 (en)	2004-09-27

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