ZA200703603B - Macrolones - amino substituted quinolones - Google Patents

Macrolones - amino substituted quinolones Download PDF

Info

Publication number: ZA200703603B
Authority: ZA; South Africa
Prior art keywords: dihydro; oxo; carboxy; dimethylamino; erythromycin
Prior art date: 2004-11-11

Application number

ZA200703603A

Other languages

English (en)

Inventor

Best Desmond John

Elder John Stephen

Fajdetic Andrea

Forrest Andrew Keith

Sheppard Robert John

Original Assignee

Glaxo Group Ltd

Glaxosmithkline Zagreb

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.)

2004-11-11

Filing date

2007-05-04

Publication date

2008-07-30

2007-05-04 Application filed by Glaxo Group Ltd, Glaxosmithkline Zagreb filed Critical Glaxo Group Ltd

2008-07-30 Publication of ZA200703603B publication Critical patent/ZA200703603B/en

Links

229920004011 Macrolon® Polymers 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 413
229960003276 erythromycin Drugs 0.000 claims description 171
229960002626 clarithromycin Drugs 0.000 claims description 107
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Natural products 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 claims description 86
238000006243 chemical reaction Methods 0.000 claims description 78
-1 -OR'TM Inorganic materials 0.000 claims description 73
229910052739 hydrogen Inorganic materials 0.000 claims description 71
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 71
239000001257 hydrogen Substances 0.000 claims description 70
238000000034 method Methods 0.000 claims description 65
125000006308 propyl amino group Chemical group 0.000 claims description 52
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 45
125000000623 heterocyclic group Chemical group 0.000 claims description 44
229910052799 carbon Inorganic materials 0.000 claims description 39
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 37
229910052757 nitrogen Inorganic materials 0.000 claims description 32
229960004099 azithromycin Drugs 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 28
125000004122 cyclic group Chemical group 0.000 claims description 27
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
150000002431 hydrogen Chemical class 0.000 claims description 21
229930006677 Erythromycin A Natural products 0.000 claims description 20
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 19
238000002360 preparation method Methods 0.000 claims description 19
238000011282 treatment Methods 0.000 claims description 19
241000282414 Homo sapiens Species 0.000 claims description 18
239000003814 drug Substances 0.000 claims description 18
239000000546 pharmaceutical excipient Substances 0.000 claims description 18
125000006239 protecting group Chemical group 0.000 claims description 18
239000008194 pharmaceutical composition Substances 0.000 claims description 17
125000003118 aryl group Chemical group 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical class 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
230000008569 process Effects 0.000 claims description 15
125000004429 atom Chemical group 0.000 claims description 14
229910052760 oxygen Inorganic materials 0.000 claims description 14
239000001301 oxygen Substances 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 11
239000003085 diluting agent Substances 0.000 claims description 11
125000001072 heteroaryl group Chemical group 0.000 claims description 11
125000005842 heteroatom Chemical group 0.000 claims description 11
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
239000003054 catalyst Substances 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
239000011593 sulfur Chemical group 0.000 claims description 10
150000002923 oximes Chemical class 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 7
NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical group NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 claims description 6
241001465754 Metazoa Species 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 5
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
208000015181 infectious disease Diseases 0.000 claims description 5
230000000813 microbial effect Effects 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
238000011321 prophylaxis Methods 0.000 claims description 5
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 5
238000002560 therapeutic procedure Methods 0.000 claims description 5
230000000699 topical effect Effects 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
125000002619 bicyclic group Chemical group 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
230000009885 systemic effect Effects 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
239000003638 chemical reducing agent Substances 0.000 claims description 2
TYQXKHPOXXXCTP-CSLYCKPJSA-N erythromycin A 2'-propanoate 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)OC(=O)CC)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 TYQXKHPOXXXCTP-CSLYCKPJSA-N 0.000 claims description 2
229950001028 erythromycin propionate Drugs 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 1
101150065749 Churc1 gene Proteins 0.000 claims 1
102100038239 Protein Churchill Human genes 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 657
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 426
239000000543 intermediate Substances 0.000 description 244
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239000000203 mixture Substances 0.000 description 197
230000002829 reductive effect Effects 0.000 description 191
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 190
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 173
239000007787 solid Substances 0.000 description 162
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 146
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 141
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 127
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 124
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 118
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 116
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 99
239000000741 silica gel Substances 0.000 description 95
229910002027 silica gel Inorganic materials 0.000 description 95
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 78
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 68
235000019439 ethyl acetate Nutrition 0.000 description 64
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
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229910021529 ammonia Inorganic materials 0.000 description 54
238000004587 chromatography analysis Methods 0.000 description 52
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 51
239000002904 solvent Substances 0.000 description 51
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
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239000006260 foam Substances 0.000 description 41
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 39
229910052786 argon Inorganic materials 0.000 description 39
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
239000003480 eluent Substances 0.000 description 35
235000019253 formic acid Nutrition 0.000 description 34
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 33
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
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239000012044 organic layer Substances 0.000 description 26
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239000002585 base Substances 0.000 description 11
125000004432 carbon atom Chemical group C* 0.000 description 11
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
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229910000073 phosphorus hydride Inorganic materials 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
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125000003386 piperidinyl group Chemical group 0.000 description 1
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239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000011591 potassium Substances 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
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
YVZVETBYUFHWDL-UHFFFAOYSA-N quinoline-3-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=CC2=CC(C(=O)O)=CN=C21 YVZVETBYUFHWDL-UHFFFAOYSA-N 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
XSCSSBJLKZEACJ-UHFFFAOYSA-N s-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethyl] ethanethioate Chemical compound CC(=O)SCCOCCNC(=O)OC(C)(C)C XSCSSBJLKZEACJ-UHFFFAOYSA-N 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
239000002453 shampoo Substances 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
239000002195 soluble material Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000001587 sorbitan monostearate Substances 0.000 description 1
235000011076 sorbitan monostearate Nutrition 0.000 description 1
229940035048 sorbitan monostearate Drugs 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
229960000391 sorbitan trioleate Drugs 0.000 description 1
230000003019 stabilising effect Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
229940031000 streptococcus pneumoniae Drugs 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
POPGBGYTSRQYLK-UHFFFAOYSA-N tert-butyl n-(2-prop-2-ynoxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCOCC#C POPGBGYTSRQYLK-UHFFFAOYSA-N 0.000 description 1
XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 1
KSFVNEXYCULLEJ-UHFFFAOYSA-N tert-butyl n-[2-(2-hydroxyethoxy)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOCCO KSFVNEXYCULLEJ-UHFFFAOYSA-N 0.000 description 1
QVMLIHFGUIRVKU-UHFFFAOYSA-N tert-butyl n-methyl-n-prop-2-ynylcarbamate Chemical compound C#CCN(C)C(=O)OC(C)(C)C QVMLIHFGUIRVKU-UHFFFAOYSA-N 0.000 description 1
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 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
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
229930195735 unsaturated hydrocarbon Chemical group 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000001238 wet grinding Methods 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

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

ZA200703603A 2004-11-11 2007-05-04 Macrolones - amino substituted quinolones ZA200703603B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB0424959A GB0424959D0 (en)	2004-11-11	2004-11-11	Novel compounds

Publications (1)

Publication Number	Publication Date
ZA200703603B true ZA200703603B (en)	2008-07-30

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ID=33523587

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200703603A ZA200703603B (en)	2004-11-11	2007-05-04	Macrolones - amino substituted quinolones

Country Status (19)

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US (2)	US7718621B2 (es)
EP (1)	EP1824870A1 (es)
JP (1)	JP2008519788A (es)
KR (1)	KR20070085919A (es)
CN (1)	CN101098881A (es)
AR (1)	AR053311A1 (es)
AU (1)	AU2005303961A1 (es)
BR (1)	BRPI0517792A (es)
CA (1)	CA2587413A1 (es)
GB (1)	GB0424959D0 (es)
IL (1)	IL182978A0 (es)
MA (1)	MA29213B1 (es)
MX (1)	MX2007005776A (es)
NO (1)	NO20072939L (es)
PE (1)	PE20061137A1 (es)
RU (1)	RU2007121581A (es)
TW (1)	TW200630378A (es)
WO (1)	WO2006050942A1 (es)
ZA (1)	ZA200703603B (es)

Families Citing this family (17)

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Publication number	Priority date	Publication date	Assignee	Title
EP3738591A3 (en)	2003-03-10	2021-03-24	Merck Sharp & Dohme Corp.	Novel antibacterial agents
WO2007054295A1 (en) *	2005-11-09	2007-05-18	Glaxo Group Limited	New 4*-substituted erythromycin derivative
EP1879904A1 (en) *	2005-05-10	2008-01-23	GlaxoSmithKline istrazivacki centar Zagreb d.o.o.	4" amino linked macrolides useful for the treatment of microbial infections
WO2007054296A1 (en) *	2005-11-09	2007-05-18	Glaxo Group Limited	Macrolones
AU2008298545B2 (en)	2007-09-14	2013-12-12	Vertex Pharmaceuticals Incorporated	Modulators of cystic fibrosis transmembrane conductance regulator
WO2009055557A1 (en)	2007-10-25	2009-04-30	Cempra Pharmaceuticals, Inc.	Process for the preparation of macrolide antibacterial agents
TW200946109A (en) *	2008-05-09	2009-11-16	Enanta Pharm Inc	Anti-bacterial activity of 9-hydroxy derivatives 6, 11-bicyclolides
HRP20160222T1 (hr)	2008-10-24	2016-04-08	Cempra Pharmaceuticals, Inc.	Biozaštite uporabom makrolida koji sadrže triazol
US9937194B1 (en)	2009-06-12	2018-04-10	Cempra Pharmaceuticals, Inc.	Compounds and methods for treating inflammatory diseases
AU2010292010B2 (en)	2009-09-10	2016-01-07	Cempra Pharmaceuticals, Inc.	Methods for treating malaria, tuberculosis and MAC diseases
RU2608390C2 (ru) *	2010-05-20	2017-01-18	Семпра Фармасьютикалз, Инк.	Способы получения макролидов и кетолидов, и промежуточных соединений для их получения
JP6042334B2 (ja)	2010-09-10	2016-12-14	センプラファーマシューティカルズ，インコーポレイテッド	疾患治療のための水素結合形成フルオロケトライド
HK1205939A1 (en)	2012-03-27	2015-12-31	Cempra Pharmaceuticals, Inc.	Parenteral formulations for administering macrolide antibiotics
HK1217665A1 (zh)	2013-03-14	2017-01-20	森普拉制药公司	用於治療呼吸道疾病的方法及其製劑
AU2014233240B2 (en)	2013-03-15	2018-08-09	Cempra Pharmaceuticals, Inc.	Convergent processes for preparing macrolide antibacterial agents
CN106589023A (zh) *	2016-11-22	2017-04-26	宜昌东阳光药业股份有限公司	一种罗红霉素杂质及其合成方法
EP3601282B1 (en)	2017-03-30	2021-07-21	F. Hoffmann-La Roche AG	Novel pyrido[2,3-b]indole compounds for the treatment and prophylaxis of bacterial infection

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Publication number	Priority date	Publication date	Assignee	Title
DE2808070A1 (de) *	1978-02-24	1979-08-30	Bayer Ag	Verfahren zur herstellung von 4-pyridon-3-carbonsaeuren und/oder deren derivaten
GB0127349D0 (en)	2001-11-14	2002-01-02	Glaxo Group Ltd	Macrolides
GB0225384D0 (en) *	2002-10-31	2002-12-11	Glaxo Group Ltd	Novel compounds

2004
- 2004-11-11 GB GB0424959A patent/GB0424959D0/en not_active Ceased
2005
- 2005-11-09 BR BRPI0517792-8A patent/BRPI0517792A/pt not_active IP Right Cessation
- 2005-11-09 CN CNA2005800463765A patent/CN101098881A/zh active Pending
- 2005-11-09 TW TW094139277A patent/TW200630378A/zh unknown
- 2005-11-09 EP EP05801894A patent/EP1824870A1/en not_active Withdrawn
- 2005-11-09 JP JP2007540573A patent/JP2008519788A/ja not_active Withdrawn
- 2005-11-09 AU AU2005303961A patent/AU2005303961A1/en not_active Abandoned
- 2005-11-09 KR KR1020077012942A patent/KR20070085919A/ko not_active Withdrawn
- 2005-11-09 US US11/719,004 patent/US7718621B2/en not_active Expired - Fee Related
- 2005-11-09 PE PE2005001311A patent/PE20061137A1/es not_active Application Discontinuation
- 2005-11-09 WO PCT/EP2005/012038 patent/WO2006050942A1/en not_active Ceased
- 2005-11-09 RU RU2007121581/04A patent/RU2007121581A/ru not_active Application Discontinuation
- 2005-11-09 MX MX2007005776A patent/MX2007005776A/es unknown
- 2005-11-09 CA CA002587413A patent/CA2587413A1/en not_active Abandoned
- 2005-11-09 AR ARP050104704A patent/AR053311A1/es not_active Application Discontinuation
2006
- 2006-11-07 US US12/093,145 patent/US20080269146A1/en not_active Abandoned
2007
- 2007-05-03 IL IL182978A patent/IL182978A0/en unknown
- 2007-05-04 ZA ZA200703603A patent/ZA200703603B/en unknown
- 2007-05-22 MA MA29930A patent/MA29213B1/fr unknown
- 2007-06-08 NO NO20072939A patent/NO20072939L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
BRPI0517792A (pt)	2008-10-21
PE20061137A1 (es)	2006-12-13
US7718621B2 (en)	2010-05-18
CA2587413A1 (en)	2006-05-18
WO2006050942A1 (en)	2006-05-18
MA29213B1 (fr)	2008-02-01
US20080269146A1 (en)	2008-10-30
US20080090773A1 (en)	2008-04-17
GB0424959D0 (en)	2004-12-15
KR20070085919A (ko)	2007-08-27
TW200630378A (en)	2006-09-01
MX2007005776A (es)	2007-07-16
JP2008519788A (ja)	2008-06-12
RU2007121581A (ru)	2008-12-20
EP1824870A1 (en)	2007-08-29
NO20072939L (no)	2007-08-08
AR053311A1 (es)	2007-05-02
AU2005303961A1 (en)	2006-05-18
CN101098881A (zh)	2008-01-02
IL182978A0 (en)	2007-08-19

Publication	Publication Date	Title
ZA200703603B (en)	2008-07-30	Macrolones - amino substituted quinolones
EP1628989B1 (en)	2006-12-20	Novel 14 and 15 membered-ring compounds
EP1756135B1 (en)	2009-08-12	Ester linked macrolides useful for the treatment of microbial infections
US20090111760A1 (en)	2009-04-30	Macrolone compounds
EP1628988B1 (en)	2006-10-04	Novel 14 and 15 membered-ring compounds
CA2525449A1 (en)	2004-11-25	Macrolides substituded at the 4"-position
EP1628990B1 (en)	2009-12-02	Novel 14 and 15 membered ring compounds
WO2004101589A1 (en)	2004-11-25	Novel 14 and 15 membered-ring compounds
US20090062218A1 (en)	2009-03-05	Macrolone compounds
EP1633765B1 (en)	2007-11-14	Novel 14 and 15 membered-ring compounds
US20080096829A1 (en)	2008-04-24	Macrolone Compounds
WO2004101584A1 (en)	2004-11-25	Macrolides substituted at the 3-position having antimicrobial activity
EP1879904A1 (en)	2008-01-23	4" amino linked macrolides useful for the treatment of microbial infections
EP1756134A1 (en)	2007-02-28	Carbamate linked macrolides useful for the treatment of microbial infections
WO2007054295A1 (en)	2007-05-18	New 4*-substituted erythromycin derivative