NO315560B1 - C-4"-substituerte makrolidderivater og fremgangsmåte for fremstilling derav, samt farmasöytisk blanding - Google Patents

C-4"-substituerte makrolidderivater og fremgangsmåte for fremstilling derav, samt farmasöytisk blanding Download PDF

Info

Publication number: NO315560B1
Authority: NO; Norway
Prior art keywords: formula; compound; groups; alkyl; hydroxy
Prior art date: 1997-06-11

Application number

NO19996107A

Other languages

English (en)

Norwegian (no)

Other versions

NO996107L (no

NO996107D0 (no

Inventor

Brian Scott Bronk

Takushi Kaneko

Michael Anthony Letavic

Hengmiao Cheng

Edward Alan Glazer

Bingwei Vera Yang

Original Assignee

Pfizer Prod Inc

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.)

1997-06-11

Filing date

1999-12-10

Publication date

2003-09-22

1999-12-10 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

1999-12-10 Publication of NO996107D0 publication Critical patent/NO996107D0/no

2000-02-10 Publication of NO996107L publication Critical patent/NO996107L/no

2003-09-22 Publication of NO315560B1 publication Critical patent/NO315560B1/no

Links

238000000034 method Methods 0.000 title claims description 47
238000002360 preparation method Methods 0.000 title description 19
239000003120 macrolide antibiotic agent Substances 0.000 title description 18
239000008194 pharmaceutical composition Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 250
-1 cyano, triazolyl Chemical group 0.000 claims description 60
150000003839 salts Chemical class 0.000 claims description 39
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
239000000203 mixture Substances 0.000 claims description 27
229910052799 carbon Inorganic materials 0.000 claims description 26
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 19
150000002367 halogens Chemical class 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 19
125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 13
208000035143 Bacterial infection Diseases 0.000 claims description 12
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 12
208000022362 bacterial infectious disease Diseases 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 11
208000010362 Protozoan Infections Diseases 0.000 claims description 11
125000002883 imidazolyl group Chemical group 0.000 claims description 11
125000000168 pyrrolyl group Chemical group 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
241000124008 Mammalia Species 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
241000251468 Actinopterygii Species 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
125000002971 oxazolyl group Chemical group 0.000 claims description 6
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims description 6
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 5
241000271566 Aves Species 0.000 claims description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
125000003386 piperidinyl group Chemical group 0.000 claims description 5
239000012312 sodium hydride Substances 0.000 claims description 5
229910000104 sodium hydride Inorganic materials 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
125000001425 triazolyl group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 claims description 3
SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 claims description 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
125000006725 C1-C10 alkenyl group Chemical group 0.000 claims description 3
LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 claims description 3
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 3
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
229920002554 vinyl polymer Polymers 0.000 claims description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
125000006019 1-methyl-1-propenyl group Chemical group 0.000 claims description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
229960005235 piperonyl butoxide Drugs 0.000 claims description 2
125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 claims description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 claims 1
HFRYYTUQIYTHCH-UHFFFAOYSA-N tetrasodium butan-1-olate Chemical compound [O-]CCCC.[O-]CCCC.[O-]CCCC.[O-]CCCC.[Na+].[Na+].[Na+].[Na+] HFRYYTUQIYTHCH-UHFFFAOYSA-N 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
239000000243 solution Substances 0.000 description 79
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
239000000460 chlorine Substances 0.000 description 40
208000015181 infectious disease Diseases 0.000 description 34
239000011541 reaction mixture Substances 0.000 description 34
239000012267 brine Substances 0.000 description 30
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
235000019439 ethyl acetate Nutrition 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
239000011734 sodium Substances 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 21
229920006395 saturated elastomer Polymers 0.000 description 21
239000002904 solvent Substances 0.000 description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 20
229910052727 yttrium Inorganic materials 0.000 description 19
239000007864 aqueous solution Substances 0.000 description 18
239000002585 base Substances 0.000 description 17
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 16
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
239000010410 layer Substances 0.000 description 14
239000000047 product Substances 0.000 description 14
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
239000008186 active pharmaceutical agent Substances 0.000 description 13
239000000284 extract Substances 0.000 description 13
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 13
238000000926 separation method Methods 0.000 description 13
238000003756 stirring Methods 0.000 description 13
125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
238000012360 testing method Methods 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
239000002253 acid Substances 0.000 description 11
239000012044 organic layer Substances 0.000 description 11
230000002829 reductive effect Effects 0.000 description 11
238000010898 silica gel chromatography Methods 0.000 description 11
241001465754 Metazoa Species 0.000 description 10
235000011114 ammonium hydroxide Nutrition 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
230000001580 bacterial effect Effects 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
239000012043 crude product Substances 0.000 description 9
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
239000003960 organic solvent Substances 0.000 description 8
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical class 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 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
241000606856 Pasteurella multocida Species 0.000 description 7
229910004298 SiO 2 Inorganic materials 0.000 description 7
125000003277 amino group Chemical group 0.000 description 7
238000003556 assay Methods 0.000 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
238000001035 drying Methods 0.000 description 7
230000000694 effects Effects 0.000 description 7
229910052717 sulfur Inorganic materials 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
PKSROMPNLONTJT-UHFFFAOYSA-N azanium;chloroform;methanol;hydroxide Chemical compound N.O.OC.ClC(Cl)Cl PKSROMPNLONTJT-UHFFFAOYSA-N 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
239000001257 hydrogen Substances 0.000 description 6
230000004048 modification Effects 0.000 description 6
238000012986 modification Methods 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
238000000746 purification Methods 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N CHCl3 Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
239000003242 anti bacterial agent Substances 0.000 description 5
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000001632 sodium acetate Substances 0.000 description 5
235000017281 sodium acetate Nutrition 0.000 description 5
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 4
PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 4
241000193403 Clostridium Species 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
229940088710 antibiotic agent Drugs 0.000 description 4
229960004099 azithromycin Drugs 0.000 description 4
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 description 4
230000003197 catalytic effect Effects 0.000 description 4
150000001768 cations Chemical class 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000012467 final product Substances 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
150000007522 mineralic acids Chemical class 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 4
229910003446 platinum oxide Inorganic materials 0.000 description 4
239000002002 slurry Substances 0.000 description 4
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
229920001817 Agar Polymers 0.000 description 3
241000283690 Bos taurus Species 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
241000282326 Felis catus Species 0.000 description 3
241000606768 Haemophilus influenzae Species 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
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 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
241001293418 Mannheimia haemolytica Species 0.000 description 3
241000193996 Streptococcus pyogenes Species 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000008272 agar Substances 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
229960001760 dimethyl sulfoxide Drugs 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
125000003700 epoxy group Chemical group 0.000 description 3
229960003276 erythromycin Drugs 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000012458 free base Substances 0.000 description 3
239000000499 gel Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
229940041033 macrolides Drugs 0.000 description 3
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 3
239000002674 ointment Substances 0.000 description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
238000003752 polymerase chain reaction Methods 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
238000010992 reflux Methods 0.000 description 3
230000008261 resistance mechanism Effects 0.000 description 3
238000013207 serial dilution Methods 0.000 description 3
239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
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238000001514 detection method Methods 0.000 description 1
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229940038472 dicalcium phosphate Drugs 0.000 description 1
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238000010790 dilution Methods 0.000 description 1
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NISYDOWSZJJYCA-UHFFFAOYSA-N ethyl thiophene-2-carboximidate;hydrochloride Chemical compound Cl.CCOC(=N)C1=CC=CS1 NISYDOWSZJJYCA-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
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238000001640 fractional crystallisation Methods 0.000 description 1
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238000005469 granulation Methods 0.000 description 1
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230000009036 growth inhibition Effects 0.000 description 1
150000003278 haem Chemical class 0.000 description 1
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238000005984 hydrogenation reaction Methods 0.000 description 1
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
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235000015110 jellies Nutrition 0.000 description 1
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150000002596 lactones Chemical class 0.000 description 1
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229910052744 lithium Inorganic materials 0.000 description 1
229910001496 lithium tetrafluoroborate Inorganic materials 0.000 description 1
ATKCLEUSJFRRKA-UHFFFAOYSA-N lithium;prop-1-yne Chemical compound [Li+].CC#[C-] ATKCLEUSJFRRKA-UHFFFAOYSA-N 0.000 description 1
244000144972 livestock Species 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-UHFFFAOYSA-M 0.000 description 1
SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
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229940013390 mycoplasma pneumoniae Drugs 0.000 description 1
ILBIXZPOMJFOJP-UHFFFAOYSA-N n,n-dimethylprop-2-yn-1-amine Chemical compound CN(C)CC#C ILBIXZPOMJFOJP-UHFFFAOYSA-N 0.000 description 1
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125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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235000019161 pantothenic acid Nutrition 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
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239000000312 peanut oil Substances 0.000 description 1
208000031232 peroneal neuropathy Diseases 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
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YGXCETJZBDTKRY-DZCVGBHJSA-N pristinamycin IA Chemical compound N([C@@H]1C(=O)N[C@@H](C(N2CCC[C@H]2C(=O)N(C)[C@@H](CC=2C=CC(=CC=2)N(C)C)C(=O)N2CCC(=O)C[C@H]2C(=O)N[C@H](C(=O)O[C@@H]1C)C=1C=CC=CC=1)=O)CC)C(=O)C1=NC=CC=C1O YGXCETJZBDTKRY-DZCVGBHJSA-N 0.000 description 1
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201000003068 rheumatic fever Diseases 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
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150000004760 silicates Chemical class 0.000 description 1
201000009890 sinusitis Diseases 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
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
229940041030 streptogramins Drugs 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000004354 sulfur functional group Chemical group 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
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239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 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
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
206010044008 tonsillitis Diseases 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108091005703 transmembrane proteins Proteins 0.000 description 1
102000035160 transmembrane proteins Human genes 0.000 description 1
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
208000000143 urethritis Diseases 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- 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
- A61P33/00—Antiparasitic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

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

NO19996107A 1997-06-11 1999-12-10 C-4"-substituerte makrolidderivater og fremgangsmåte for fremstilling derav, samt farmasöytisk blanding NO315560B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US4998097P	1997-06-11	1997-06-11
PCT/IB1998/000799 WO1998056801A1 (fr)	1997-06-11	1998-05-25	Derives de macrolide substitue en c-4''

Publications (3)

Publication Number	Publication Date
NO996107D0 NO996107D0 (no)	1999-12-10
NO996107L NO996107L (no)	2000-02-10
NO315560B1 true NO315560B1 (no)	2003-09-22

Family

ID=21962765

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19996107A NO315560B1 (no)	1997-06-11	1999-12-10	C-4"-substituerte makrolidderivater og fremgangsmåte for fremstilling derav, samt farmasöytisk blanding

Country Status (39)

Country	Link
EP (1)	EP0988309B1 (fr)
JP (1)	JP3262806B2 (fr)
KR (1)	KR100369959B1 (fr)
CN (1)	CN1145636C (fr)
AP (1)	AP1189A (fr)
AR (1)	AR013085A1 (fr)
AT (1)	ATE310742T1 (fr)
AU (1)	AU745006C (fr)
BG (1)	BG64357B1 (fr)
BR (1)	BR9810097A (fr)
CA (1)	CA2293397C (fr)
CO (1)	CO4950584A1 (fr)
DE (1)	DE69832486T2 (fr)
DZ (1)	DZ2515A1 (fr)
EA (1)	EA002440B1 (fr)
ES (1)	ES2251081T3 (fr)
GT (1)	GT199800075A (fr)
HN (1)	HN1998000074A (fr)
HR (1)	HRP980315A2 (fr)
HU (1)	HUP0004076A3 (fr)
ID (1)	ID24530A (fr)
IL (1)	IL132808A (fr)
IS (1)	IS1979B (fr)
MA (1)	MA24563A1 (fr)
MY (1)	MY133027A (fr)
NO (1)	NO315560B1 (fr)
NZ (1)	NZ500652A (fr)
OA (1)	OA11226A (fr)
PA (1)	PA8452001A1 (fr)
PE (1)	PE79999A1 (fr)
PL (1)	PL337497A1 (fr)
SK (1)	SK168299A3 (fr)
TN (1)	TNSN98084A1 (fr)
TW (2)	TW200418871A (fr)
UA (1)	UA70298A (fr)
UY (1)	UY25041A1 (fr)
WO (1)	WO1998056801A1 (fr)
YU (1)	YU62999A (fr)
ZA (1)	ZA985016B (fr)

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* Cited by examiner, † Cited by third party
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ATE353014T1 (de) *	1997-09-10	2007-02-15	Merial Ltd	Verwendung von 9a-azaliden als antimikrobielle mittel für tiere
EP1779853A3 (fr) *	1997-09-10	2010-01-27	Merial Ltd.	9a-azalides en tant qu'agents anti-microbiens à usage vétérinaire
US6339063B1 (en)	1997-09-10	2002-01-15	Merck & Co., Inc.	9a-azalides as veterinary antimicrobial agents
AP9801420A0 (en) *	1998-01-02	1998-12-31	Pfizer Prod Inc	Novel macrolides.
EP1437360A3 (fr) *	1998-08-19	2005-04-06	Pfizer Products Inc.	C11-carbamates des macrolides antibactériens
US6043227A (en) *	1998-08-19	2000-03-28	Pfizer Inc.	C11 carbamates of macrolide antibacterials
US6100240A (en) *	1998-10-09	2000-08-08	Pfizer Inc	Macrolide derivatives
TR200200436T2 (tr)	1998-11-03	2002-06-21	Pfizer Inc.	Yeni makrolit antibiyotikler
CA2292359C (fr) *	1999-01-28	2004-09-28	Pfizer Products Inc.	Nouveaux azalides et procede de fabrication
ATE315042T1 (de) *	1999-08-24	2006-02-15	Abbott Lab	9a-azalide mit antibakterieller wirkung
US6764996B1 (en)	1999-08-24	2004-07-20	Abbott Laboratories	9a-azalides with antibacterial activity
BRPI0017013B1 (pt)	2000-01-27	2015-07-14	Zoetis P Llc	Composição de antibiótico azalídeo e método para sua obtenção
WO2002088158A1 (fr) *	2001-04-27	2002-11-07	Pfizer Products Inc.	Procede de preparation de derives de 9-deoxo-9a-aza-9a-homoerythromycine a substitues en 4''
JP2003040782A (ja) *	2001-05-31	2003-02-13	Pfizer Prod Inc	アザリド抗生物質組成物
AU2003255851B2 (en)	2002-07-08	2009-07-23	Glaxosmithkline Istrazivacki Centar Zagreb D.O.O.	New compounds, compositions and methods for treatment of inflammatory diseases and conditions
EP1551865B1 (fr)	2002-07-08	2009-04-22	GlaxoSmithKline istrazivacki centar Zagreb d.o.o.	Molecules hybrides de macrolides avec des molecules anti-inflammatoires steroidiennes/non-steroidiennes
NZ537716A (en) *	2002-07-08	2007-05-31	Glaxosmithkline Zagreb	Novel nonsteroidal anti-inflammatory substances, compositions and methods for their use
AR043050A1 (es)	2002-09-26	2005-07-13	Rib X Pharmaceuticals Inc	Compuestos heterociclicos bifuncionales y metodos para preparar y usar los mismos
EP1638549A4 (fr) *	2003-03-10	2011-06-15	Optimer Pharmaceuticals Inc	Nouveaux agents antibacteriens
WO2005030227A1 (fr)	2003-09-23	2005-04-07	Enanta Pharmaceuticals, Inc.	Derives 9a-azalide 11-3c-bicycliques
EP2716647A3 (fr)	2004-02-27	2014-08-20	Rib-X Pharmaceuticals, Inc.	Composes Macrocycliques Et Leurs Procedes De Fabrication Et D'utilisation
WO2009019868A1 (fr)	2007-08-06	2009-02-12	Taisho Pharmaceutical Co., Ltd.	Composé 10a-azalide réticulé en position 10a et en position 12
CA2703475A1 (fr)	2007-10-25	2009-04-30	Cempra Pharmaceuticals, Inc.	Procede pour la preparation d'agents antibacteriens macrolides
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1998
- 1998-05-20 HN HN1998000074A patent/HN1998000074A/es unknown
- 1998-05-22 PA PA19988452001A patent/PA8452001A1/es unknown
- 1998-05-25 KR KR10-1999-7011643A patent/KR100369959B1/ko not_active Expired - Fee Related
- 1998-05-25 JP JP50192999A patent/JP3262806B2/ja not_active Expired - Fee Related
- 1998-05-25 AT AT98919414T patent/ATE310742T1/de not_active IP Right Cessation
- 1998-05-25 CA CA002293397A patent/CA2293397C/fr not_active Expired - Fee Related
- 1998-05-25 WO PCT/IB1998/000799 patent/WO1998056801A1/fr not_active Ceased
- 1998-05-25 AU AU72281/98A patent/AU745006C/en not_active Ceased
- 1998-05-25 EA EA199901014A patent/EA002440B1/ru not_active IP Right Cessation
- 1998-05-25 NZ NZ500652A patent/NZ500652A/en unknown
- 1998-05-25 IL IL13280898A patent/IL132808A/en not_active IP Right Cessation
- 1998-05-25 ES ES98919414T patent/ES2251081T3/es not_active Expired - Lifetime
- 1998-05-25 BR BR9810097-1A patent/BR9810097A/pt not_active IP Right Cessation
- 1998-05-25 ID IDW991565A patent/ID24530A/id unknown
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- 1998-05-25 HU HU0004076A patent/HUP0004076A3/hu unknown
- 1998-05-25 YU YU62999A patent/YU62999A/sh unknown
- 1998-05-25 UA UA99126737A patent/UA70298A/uk unknown
- 1998-05-25 SK SK1682-99A patent/SK168299A3/sk unknown
- 1998-05-25 DE DE69832486T patent/DE69832486T2/de not_active Expired - Fee Related
- 1998-05-25 CN CNB988060493A patent/CN1145636C/zh not_active Expired - Fee Related
- 1998-05-25 EP EP98919414A patent/EP0988309B1/fr not_active Expired - Lifetime
- 1998-06-04 AP APAP/P/1998/001254A patent/AP1189A/en active
- 1998-06-08 PE PE1998000469A patent/PE79999A1/es not_active Application Discontinuation
- 1998-06-08 GT GT199800075A patent/GT199800075A/es unknown
- 1998-06-08 TW TW093111859A patent/TW200418871A/zh unknown
- 1998-06-08 TW TW087109085A patent/TWI224106B/zh active
- 1998-06-09 AR ARP980102704A patent/AR013085A1/es active IP Right Grant
- 1998-06-09 MY MYPI98002563A patent/MY133027A/en unknown
- 1998-06-10 DZ DZ980125A patent/DZ2515A1/fr active
- 1998-06-10 TN TNTNSN98084A patent/TNSN98084A1/fr unknown
- 1998-06-10 ZA ZA9805016A patent/ZA985016B/xx unknown
- 1998-06-10 CO CO98033231A patent/CO4950584A1/es unknown
- 1998-06-10 MA MA25106A patent/MA24563A1/fr unknown
- 1998-06-11 UY UY25041A patent/UY25041A1/es not_active IP Right Cessation
- 1998-06-11 HR HR60/049,980A patent/HRP980315A2/hr not_active Application Discontinuation
1999
- 1999-11-16 IS IS5250A patent/IS1979B/is unknown
- 1999-12-03 OA OA9900270A patent/OA11226A/en unknown
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Also Published As

Publication number	Publication date
MA24563A1 (fr)	1998-12-31
DZ2515A1 (fr)	2003-02-01
BG64357B1 (bg)	2004-11-30
ES2251081T3 (es)	2006-04-16
ID24530A (id)	2000-07-20
NO996107L (no)	2000-02-10
MY133027A (en)	2007-10-31
TWI224106B (en)	2004-11-21
CN1259955A (zh)	2000-07-12
OA11226A (en)	2003-07-16
EP0988309B1 (fr)	2005-11-23
AR013085A1 (es)	2000-12-13
DE69832486D1 (de)	2005-12-29
CA2293397C (fr)	2004-08-31
BR9810097A (pt)	2000-08-08
SK168299A3 (en)	2000-09-12
AP1189A (en)	2003-07-16
KR100369959B1 (ko)	2003-02-12
UA70298C2 (uk)	2004-10-15
AU7228198A (en)	1998-12-30
EA002440B1 (ru)	2002-04-25
UY25041A1 (es)	2000-09-29
EA199901014A1 (ru)	2000-06-26
PE79999A1 (es)	1999-08-25
CO4950584A1 (es)	2000-09-01
YU62999A (sh)	2002-10-18
WO1998056801A1 (fr)	1998-12-17
AP9801254A0 (en)	1998-06-30
EP0988309A1 (fr)	2000-03-29
PA8452001A1 (es)	2000-05-24
HUP0004076A2 (hu)	2001-04-28
HN1998000074A (es)	1999-01-08
CA2293397A1 (fr)	1998-12-17
NO996107D0 (no)	1999-12-10
UA70298A (uk)	2004-10-15
IL132808A0 (en)	2001-03-19
TW200418871A (en)	2004-10-01
KR20010013633A (ko)	2001-02-26
HUP0004076A3 (en)	2003-05-28
CN1145636C (zh)	2004-04-14
AU745006B2 (en)	2002-03-07
DE69832486T2 (de)	2006-07-27
ATE310742T1 (de)	2005-12-15
GT199800075A (es)	1999-11-30
ZA985016B (en)	1999-12-10
IL132808A (en)	2004-08-31
HRP980315A2 (en)	1999-04-30
IS5250A (is)	1999-11-16
NZ500652A (en)	2001-10-26
JP3262806B2 (ja)	2002-03-04
TNSN98084A1 (fr)	2005-03-15
HK1025974A1 (en)	2000-12-01
BG103969A (en)	2000-07-31
PL337497A1 (en)	2000-08-28
JP2000514097A (ja)	2000-10-24
IS1979B (is)	2005-01-14
AU745006C (en)	2006-02-23

Publication	Publication Date	Title
EP0988309B1 (fr)	2005-11-23	Derives de macrolide substitue en c-4''
US6420536B1 (en)	2002-07-16	4″-substituted-9-deoxo-9a-aza-9a-homoerythromycin a derivatives
US6407074B1 (en)	2002-06-18	C-4″-substituted macrolide derivatives
RS58699B1 (sr)	2019-06-28	Formulacije apiksabana
NO319796B1 (no)	2005-09-19	13-leddete azalider, fremgangsmåte for fremstilling og anvendelse derav samt farmasøytisk sammensetning.
MXPA99011496A (en)	2000-07-01	C-4''-substituted macrolide derivatives
CZ438999A3 (cs)	2000-05-17	C-4"- substituované makrolidové deriváty
MXPA99011495A (en)	2001-05-17	4"-substituted-9-deoxo-9a-aza-9a-homoerythromycin a derivatives