KR20060026407A - 14원 및 15원 고리 화합물 - Google Patents
14원 및 15원 고리 화합물 Download PDFInfo
- Publication number
- KR20060026407A KR20060026407A KR1020057021593A KR20057021593A KR20060026407A KR 20060026407 A KR20060026407 A KR 20060026407A KR 1020057021593 A KR1020057021593 A KR 1020057021593A KR 20057021593 A KR20057021593 A KR 20057021593A KR 20060026407 A KR20060026407 A KR 20060026407A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- substituted
- hydrogen
- unsubstituted
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 title claims description 242
- 238000000034 method Methods 0.000 claims abstract description 48
- 238000011282 treatment Methods 0.000 claims abstract description 15
- 241001465754 Metazoa Species 0.000 claims abstract description 10
- 208000015181 infectious disease Diseases 0.000 claims abstract description 8
- 230000000813 microbial effect Effects 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 230000009885 systemic effect Effects 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 308
- 125000000217 alkyl group Chemical group 0.000 claims description 142
- -1 cyano, phenyl Chemical group 0.000 claims description 138
- 229910052739 hydrogen Inorganic materials 0.000 claims description 108
- 239000001257 hydrogen Substances 0.000 claims description 101
- 125000000623 heterocyclic group Chemical group 0.000 claims description 77
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 70
- 238000006243 chemical reaction Methods 0.000 claims description 52
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 229960003276 erythromycin Drugs 0.000 claims description 38
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 229960002626 clarithromycin Drugs 0.000 claims description 35
- 229960004099 azithromycin Drugs 0.000 claims description 31
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000003342 alkenyl group Chemical group 0.000 claims description 25
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 14
- 229950010035 davercin Drugs 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 12
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
- 229910052770 Uranium Inorganic materials 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004001 thioalkyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 abstract description 9
- 229940041033 macrolides Drugs 0.000 abstract description 4
- 238000011321 prophylaxis Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 208
- 239000000203 mixture Substances 0.000 description 129
- 239000000543 intermediate Substances 0.000 description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 88
- 239000000243 solution Substances 0.000 description 78
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
- 239000007787 solid Substances 0.000 description 59
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
- 239000000741 silica gel Substances 0.000 description 50
- 229910002027 silica gel Inorganic materials 0.000 description 50
- 239000003480 eluent Substances 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
- 238000004587 chromatography analysis Methods 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 150000003839 salts Chemical class 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 25
- 239000000047 product Substances 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 150000003254 radicals Chemical class 0.000 description 22
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 19
- 239000000706 filtrate Substances 0.000 description 19
- 239000000843 powder Substances 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 239000006260 foam Substances 0.000 description 17
- 238000009472 formulation Methods 0.000 description 17
- 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 16
- 239000002253 acid Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 229960004132 diethyl ether Drugs 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 229910052786 argon Inorganic materials 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000012300 argon atmosphere Substances 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 238000004007 reversed phase HPLC Methods 0.000 description 11
- 239000008259 solid foam Substances 0.000 description 11
- 0 CC(C)(*1)C(C)(C)OC1=O Chemical compound CC(C)(*1)C(C)(C)OC1=O 0.000 description 10
- 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 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 239000012453 solvate Substances 0.000 description 10
- 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 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 9
- 239000000969 carrier Substances 0.000 description 9
- 235000019253 formic acid Nutrition 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000001632 sodium acetate Substances 0.000 description 9
- 235000017281 sodium acetate Nutrition 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000001569 carbon dioxide Substances 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 6
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000008351 acetate buffer Substances 0.000 description 6
- 230000000845 anti-microbial effect Effects 0.000 description 6
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 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 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
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- 125000002950 monocyclic group Chemical group 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- 241000606768 Haemophilus influenzae Species 0.000 description 4
- 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 4
- 241000193996 Streptococcus pyogenes Species 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 238000007429 general method Methods 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
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- 150000004760 silicates Chemical class 0.000 description 1
- XREXLURSIQKXMJ-UHFFFAOYSA-M sodium 7-[2-(dibenzylamino)ethoxy]-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylate Chemical compound [Na+].C=1C(=C23)C(=O)C(C(=O)[O-])=CN2CCCC3=CC=1OCCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 XREXLURSIQKXMJ-UHFFFAOYSA-M 0.000 description 1
- JCFUHNSBZXRKNF-UHFFFAOYSA-M sodium 7-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylate Chemical compound [Na+].C1=C(C([O-])=O)C(=O)C2=CC(CCCNC(=O)OC(C)(C)C)=CC3=C2N1CCC3 JCFUHNSBZXRKNF-UHFFFAOYSA-M 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 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
- 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
- VILMUCRZVVVJCA-UHFFFAOYSA-M sodium glycolate Chemical compound [Na+].OCC([O-])=O VILMUCRZVVVJCA-UHFFFAOYSA-M 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- RNTNZUJPGMYBFI-UHFFFAOYSA-M sodium;1-ethyl-6-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethylsulfanyl]-4-oxoquinoline-3-carboxylate Chemical compound [Na+].CC(C)(C)OC(=O)NCCSC1=CC=C2N(CC)C=C(C([O-])=O)C(=O)C2=C1 RNTNZUJPGMYBFI-UHFFFAOYSA-M 0.000 description 1
- ZRYHDDAVZVFTJU-UHFFFAOYSA-M sodium;6-(3-aminopropyl)-1-ethyl-4-oxoquinoline-3-carboxylate Chemical compound [Na+].NCCCC1=CC=C2N(CC)C=C(C([O-])=O)C(=O)C2=C1 ZRYHDDAVZVFTJU-UHFFFAOYSA-M 0.000 description 1
- QTNIGDSAOBIWEZ-UHFFFAOYSA-M sodium;6-[2-(dibenzylamino)ethoxy]-1-ethyl-4-oxoquinoline-3-carboxylate Chemical compound [Na+].C=1C=C2N(CC)C=C(C([O-])=O)C(=O)C2=CC=1OCCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 QTNIGDSAOBIWEZ-UHFFFAOYSA-M 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 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
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940071117 starch glycolate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000012258 stirred mixture 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
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000002459 sustained effect Effects 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
- 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
- 229940095064 tartrate Drugs 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 238000004448 titration Methods 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
- 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
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 229930195735 unsaturated hydrocarbon Chemical group 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000001238 wet grinding Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0310986.5A GB0310986D0 (en) | 2003-05-13 | 2003-05-13 | Novel compounds |
| GB0310986.5 | 2003-05-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20060026407A true KR20060026407A (ko) | 2006-03-23 |
Family
ID=9957984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020057021593A Withdrawn KR20060026407A (ko) | 2003-05-13 | 2004-05-11 | 14원 및 15원 고리 화합물 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US7569550B2 (enExample) |
| EP (1) | EP1628988B1 (enExample) |
| JP (1) | JP2007502313A (enExample) |
| KR (1) | KR20060026407A (enExample) |
| CN (1) | CN1849328A (enExample) |
| AR (1) | AR044309A1 (enExample) |
| AT (1) | ATE341560T1 (enExample) |
| AU (1) | AU2004238528A1 (enExample) |
| BR (1) | BRPI0410246A (enExample) |
| CA (1) | CA2525452A1 (enExample) |
| CL (1) | CL2004001010A1 (enExample) |
| DE (1) | DE602004002696T2 (enExample) |
| DK (1) | DK1628988T3 (enExample) |
| ES (1) | ES2273255T3 (enExample) |
| GB (1) | GB0310986D0 (enExample) |
| HR (1) | HRP20060448T3 (enExample) |
| MX (1) | MXPA05012163A (enExample) |
| PL (1) | PL1628988T3 (enExample) |
| PT (1) | PT1628988E (enExample) |
| RU (1) | RU2005134908A (enExample) |
| WO (1) | WO2004101586A1 (enExample) |
| ZA (1) | ZA200509079B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0424961D0 (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 |
| EP1851236B1 (en) * | 2005-01-13 | 2010-08-04 | GlaxoSmithKline istrazivacki centar Zagreb d.o.o. | Macrolides with anti-inflammatory activity |
| WO2006120541A1 (en) * | 2005-05-10 | 2006-11-16 | Glaxosmithkline Istrazivacki Centar Zagreb D.O.O. | Ether linked macrolides useful for the treatment of microbial infections |
| PE20070802A1 (es) * | 2005-11-09 | 2007-10-19 | Glaxo Group Ltd | Derivados de eritromicina 4''-sustituidos como agentes antimicrobianos |
| EP1945652A1 (en) * | 2005-11-09 | 2008-07-23 | Glaxo Group Limited | Macrolones |
| EP2384333B1 (en) | 2009-01-30 | 2013-04-17 | Glaxo Group Limited | Anti-inflammatory macrolide |
| CN111574575B (zh) * | 2020-04-29 | 2022-05-17 | 北京理工大学 | 一种含有大环内酯基的喹喏酮衍生物、制备方法及应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE128714T1 (de) * | 1989-03-28 | 1995-10-15 | Abbott Lab | Erythromycinderivate. |
| WO1996034007A1 (es) * | 1995-04-27 | 1996-10-31 | Laboratorios Aranda, S.A. De C.V. | Derivados de quinolonilcarboxieritromicina y composiciones farmaceuticas que los contienen |
| CA2253451A1 (en) * | 1996-05-07 | 1997-11-13 | Abbott Laboratories | 3-descladinose-2,3-anhydroerythromycin derivatives |
| GB0025688D0 (en) * | 2000-10-19 | 2000-12-06 | Glaxo Group Ltd | Macrolides |
| WO2003014136A1 (en) * | 2001-08-08 | 2003-02-20 | Taisho Pharmaceutical Co., Ltd. | 11a-AZALIDE COMPOUNDS AND PROCESS FOR PRODUCING THE SAME |
| GB0127349D0 (en) * | 2001-11-14 | 2002-01-02 | Glaxo Group Ltd | Macrolides |
-
2003
- 2003-05-13 GB GBGB0310986.5A patent/GB0310986D0/en not_active Ceased
-
2004
- 2004-05-11 RU RU2005134908/04A patent/RU2005134908A/ru not_active Application Discontinuation
- 2004-05-11 CL CL200401010A patent/CL2004001010A1/es unknown
- 2004-05-11 AT AT04732102T patent/ATE341560T1/de not_active IP Right Cessation
- 2004-05-11 HR HR20060448T patent/HRP20060448T3/xx unknown
- 2004-05-11 BR BRPI0410246-0A patent/BRPI0410246A/pt not_active IP Right Cessation
- 2004-05-11 DE DE602004002696T patent/DE602004002696T2/de not_active Expired - Lifetime
- 2004-05-11 CA CA002525452A patent/CA2525452A1/en not_active Abandoned
- 2004-05-11 US US10/556,645 patent/US7569550B2/en not_active Expired - Fee Related
- 2004-05-11 PL PL04732102T patent/PL1628988T3/pl unknown
- 2004-05-11 EP EP04732102A patent/EP1628988B1/en not_active Expired - Lifetime
- 2004-05-11 JP JP2006529794A patent/JP2007502313A/ja active Pending
- 2004-05-11 PT PT04732102T patent/PT1628988E/pt unknown
- 2004-05-11 AU AU2004238528A patent/AU2004238528A1/en not_active Abandoned
- 2004-05-11 DK DK04732102T patent/DK1628988T3/da active
- 2004-05-11 CN CNA2004800192646A patent/CN1849328A/zh active Pending
- 2004-05-11 AR ARP040101614A patent/AR044309A1/es not_active Application Discontinuation
- 2004-05-11 KR KR1020057021593A patent/KR20060026407A/ko not_active Withdrawn
- 2004-05-11 WO PCT/EP2004/005082 patent/WO2004101586A1/en not_active Ceased
- 2004-05-11 ES ES04732102T patent/ES2273255T3/es not_active Expired - Lifetime
- 2004-05-11 MX MXPA05012163A patent/MXPA05012163A/es active IP Right Grant
-
2005
- 2005-11-09 ZA ZA200509079A patent/ZA200509079B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20070185117A1 (en) | 2007-08-09 |
| ATE341560T1 (de) | 2006-10-15 |
| AR044309A1 (es) | 2005-09-07 |
| CA2525452A1 (en) | 2004-11-25 |
| HRP20060448T3 (hr) | 2007-03-31 |
| GB0310986D0 (en) | 2003-06-18 |
| EP1628988A1 (en) | 2006-03-01 |
| MXPA05012163A (es) | 2006-05-19 |
| CL2004001010A1 (es) | 2005-03-18 |
| CN1849328A (zh) | 2006-10-18 |
| RU2005134908A (ru) | 2006-06-27 |
| DE602004002696T2 (de) | 2007-08-16 |
| PL1628988T3 (pl) | 2007-03-30 |
| ES2273255T3 (es) | 2007-05-01 |
| AU2004238528A1 (en) | 2004-11-25 |
| DK1628988T3 (da) | 2007-02-05 |
| ZA200509079B (en) | 2007-02-28 |
| DE602004002696D1 (de) | 2006-11-16 |
| WO2004101586A1 (en) | 2004-11-25 |
| EP1628988B1 (en) | 2006-10-04 |
| BRPI0410246A (pt) | 2006-05-16 |
| JP2007502313A (ja) | 2007-02-08 |
| US7569550B2 (en) | 2009-08-04 |
| PT1628988E (pt) | 2007-01-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20051112 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |