EA007433B1 - Макролиды - Google Patents
Макролиды Download PDFInfo
- Publication number
- EA007433B1 EA007433B1 EA200400536A EA200400536A EA007433B1 EA 007433 B1 EA007433 B1 EA 007433B1 EA 200400536 A EA200400536 A EA 200400536A EA 200400536 A EA200400536 A EA 200400536A EA 007433 B1 EA007433 B1 EA 007433B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- amino
- ethyl
- dihydro
- oxo
- cyclopropyl
- Prior art date
Links
- 239000003120 macrolide antibiotic agent Substances 0.000 title abstract description 6
- 229940041033 macrolides Drugs 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 239000012453 solvate Substances 0.000 claims abstract description 11
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 7
- 241001465754 Metazoa Species 0.000 claims abstract description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 230000009885 systemic effect Effects 0.000 claims abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 374
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 296
- -1 nitro, cyano, amino Chemical group 0.000 claims description 270
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 178
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 139
- 229960002626 clarithromycin Drugs 0.000 claims description 94
- 229960004099 azithromycin Drugs 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 229960003276 erythromycin Drugs 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 25
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 22
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 229960005224 roxithromycin Drugs 0.000 claims description 11
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- RXZBMPWDPOLZGW-XMRMVWPWSA-N (E)-roxithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[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 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 558
- 239000000543 intermediate Substances 0.000 description 319
- 239000000243 solution Substances 0.000 description 226
- 239000000203 mixture Substances 0.000 description 157
- 239000002904 solvent Substances 0.000 description 144
- 239000011541 reaction mixture Substances 0.000 description 127
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- 239000003480 eluent Substances 0.000 description 82
- 238000003818 flash chromatography Methods 0.000 description 69
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 61
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 239000012074 organic phase Substances 0.000 description 50
- 238000005160 1H NMR spectroscopy Methods 0.000 description 49
- 239000000047 product Substances 0.000 description 49
- 239000000725 suspension Substances 0.000 description 49
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 47
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- 239000012267 brine Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 239000008346 aqueous phase Substances 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 34
- 239000000706 filtrate Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 229920006395 saturated elastomer Polymers 0.000 description 26
- PGTLJOKITYXKEN-UHFFFAOYSA-N 6-(2-aminoethylamino)-7-chloro-1-cyclopropyl-4-oxoquinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.C1=C(Cl)C(NCCN)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 PGTLJOKITYXKEN-UHFFFAOYSA-N 0.000 description 25
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 25
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 23
- 239000007864 aqueous solution Substances 0.000 description 23
- 239000012043 crude product Substances 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 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 19
- 238000001704 evaporation Methods 0.000 description 19
- 230000008020 evaporation Effects 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- 239000011347 resin Substances 0.000 description 18
- 229920005989 resin Polymers 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000002994 raw material Substances 0.000 description 17
- 229920000642 polymer Polymers 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 229930006677 Erythromycin A Natural products 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 239000012948 isocyanate Substances 0.000 description 12
- 150000002513 isocyanates Chemical class 0.000 description 12
- 238000011068 loading method Methods 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 239000012047 saturated solution Substances 0.000 description 12
- 235000019253 formic acid Nutrition 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000012300 argon atmosphere Substances 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 239000012071 phase Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 125000004193 piperazinyl group Chemical group 0.000 description 8
- 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 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 239000012452 mother liquor Substances 0.000 description 7
- 235000015320 potassium carbonate Nutrition 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 150000005826 halohydrocarbons Chemical class 0.000 description 5
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 4
- ISPVACVJFUIDPD-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 ISPVACVJFUIDPD-UHFFFAOYSA-N 0.000 description 4
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- IDYZIJYBMGIQMJ-UHFFFAOYSA-N enoxacin Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 IDYZIJYBMGIQMJ-UHFFFAOYSA-N 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 3
- IYOCSFWBGHFAHD-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propylamino]-4-oxoquinoline-3-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)NCCCNC=1C=C2C(C(=CN(C2=CC=1Cl)C1CC1)C(=O)O)=O IYOCSFWBGHFAHD-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 150000001804 chlorine Chemical class 0.000 description 3
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 229940113088 dimethylacetamide Drugs 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 2
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- 244000005700 microbiome Species 0.000 description 1
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- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
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- 238000012545 processing Methods 0.000 description 1
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- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
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- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- HIWQTAGEUYPYPP-UHFFFAOYSA-N tert-butyl n-[2-[(3-carbamoyl-1-cyclopropyl-6-fluoro-4-oxoquinolin-7-yl)amino]ethyl]carbamate Chemical compound C1=C(C(N)=O)C(=O)C=2C=C(F)C(NCCNC(=O)OC(C)(C)C)=CC=2N1C1CC1 HIWQTAGEUYPYPP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0127349.9A GB0127349D0 (en) | 2001-11-14 | 2001-11-14 | Macrolides |
| PCT/GB2002/005101 WO2003042228A1 (en) | 2001-11-14 | 2002-11-13 | Macrolides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200400536A1 EA200400536A1 (ru) | 2004-12-30 |
| EA007433B1 true EA007433B1 (ru) | 2006-10-27 |
Family
ID=9925777
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200400536A EA007433B1 (ru) | 2001-11-14 | 2002-11-13 | Макролиды |
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|---|---|
| US (1) | US7202221B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1453846B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2005515978A (cg-RX-API-DMAC7.html) |
| CN (1) | CN1307194C (cg-RX-API-DMAC7.html) |
| AR (1) | AR037371A1 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE362479T1 (cg-RX-API-DMAC7.html) |
| BR (1) | BR0214132A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2466975A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE60220180T2 (cg-RX-API-DMAC7.html) |
| EA (1) | EA007433B1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2287332T3 (cg-RX-API-DMAC7.html) |
| GB (1) | GB0127349D0 (cg-RX-API-DMAC7.html) |
| HR (1) | HRP20040433A2 (cg-RX-API-DMAC7.html) |
| HU (1) | HUP0402225A3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL161710A0 (cg-RX-API-DMAC7.html) |
| PL (1) | PL371472A1 (cg-RX-API-DMAC7.html) |
| RS (1) | RS41904A (cg-RX-API-DMAC7.html) |
| UA (1) | UA77210C2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2003042228A1 (cg-RX-API-DMAC7.html) |
| ZA (1) | ZA200403684B (cg-RX-API-DMAC7.html) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6995143B2 (en) * | 2002-02-28 | 2006-02-07 | Basilea Pharmaceutica Ag | Macrolides with antibacterial activity |
| US7135573B2 (en) | 2002-05-13 | 2006-11-14 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of O-(6-Pyrazol-1-yl-pyridin-3-ylmethyl)-hydroxylamine |
| US7910558B2 (en) | 2002-05-13 | 2011-03-22 | Enanta Pharmaceuticals, Inc. | Bridged macrocyclic compounds and processes for the preparation thereof |
| US7022679B2 (en) | 2002-05-13 | 2006-04-04 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of 6-11 bicyclic erythromycin derivatives |
| US6764998B1 (en) | 2003-06-18 | 2004-07-20 | Enanta Pharmaceuticals, Inc. | 6,11-4C-bicyclic 9a-azalide derivatives |
| KR20040107525A (ko) * | 2002-05-14 | 2004-12-20 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 치환된 퀴놀론 카르복실산, 이들의 유도체, 그의 작용부위 및 용도 |
| AR043050A1 (es) | 2002-09-26 | 2005-07-13 | Rib X Pharmaceuticals Inc | Compuestos heterociclicos bifuncionales y metodos para preparar y usar los mismos |
| GB0225384D0 (en) | 2002-10-31 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| US6645941B1 (en) | 2003-03-26 | 2003-11-11 | Enanta Pharmaceuticals, Inc. | 6,11-3C-bicyclic 9a-azalide derivatives |
| ATE348837T1 (de) * | 2003-05-13 | 2007-01-15 | Glaxo Group Ltd | Neue 14- und 15-gliedrige ringverbindungen |
| GB0310980D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| GB0310984D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| GB0310979D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| GB0310986D0 (en) * | 2003-05-13 | 2003-06-18 | Glaxo Group Ltd | Novel compounds |
| WO2005030227A1 (en) | 2003-09-23 | 2005-04-07 | Enanta Pharmaceuticals, Inc. | 9a, 11-3C-BICYCLIC 9a-AZALIDE DERIVATIVES |
| WO2005070113A2 (en) | 2004-01-09 | 2005-08-04 | Enanta Pharmaceuticals, Inc. | 9n-substituted 6-11 bicyclic erythromycin derivatives |
| US8202843B2 (en) | 2004-02-27 | 2012-06-19 | Rib-X Pharmaceuticals, Inc. | Macrocyclic compounds and methods of making and using the same |
| EP1756134A1 (en) * | 2004-05-06 | 2007-02-28 | GlaxoSmithKline istrazivacki centar Zagreb d.o.o. | Carbamate linked macrolides useful for the treatment of microbial infections |
| JP2007536371A (ja) * | 2004-05-06 | 2007-12-13 | グラクソスミスクライン・イストラジヴァッキ・センタル・ザグレブ・ドルズバ・ゼー・オメイェノ・オドゴヴォルノスティオ | 微生物感染症の治療に有用なエステル結合マクロライド |
| WO2006047167A2 (en) * | 2004-10-21 | 2006-05-04 | Janssen Pharmaceutica, N.V. | 9 alkyl and 9 alkylidenyl 6-0 alkyl-11, 12 carbamate ketolide antimicrobials |
| GB0424959D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| GB0424951D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| GB0424958D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| GB0424961D0 (en) * | 2004-11-11 | 2004-12-15 | Glaxo Group Ltd | Novel compounds |
| WO2008017696A1 (en) * | 2006-08-09 | 2008-02-14 | Basilea Pharmaceutica Ag | New macrolides useful against inflammatory and allergic disseases |
| CN101541331A (zh) | 2006-08-24 | 2009-09-23 | 沃克哈特研究中心 | 具有抗微生物活性的新颖大环内酯和酮内酯 |
| KR101617897B1 (ko) | 2008-02-08 | 2016-05-03 | 바실리어 파마슈티카 아게 | 신규 마크로라이드 및 그의 용도 |
| EP2435460B1 (en) | 2009-05-27 | 2015-01-07 | Wockhardt Limited | Ketolide compounds having antimicrobial activity |
| CN103384676B (zh) | 2010-12-09 | 2016-02-03 | 沃克哈特有限公司 | 酮内酯化合物 |
| CA2826174A1 (en) * | 2011-01-31 | 2012-08-09 | Meiji Seika Pharma Co., Ltd. | Novel macrolide derivative |
| CN103619849B (zh) | 2011-03-01 | 2016-05-25 | 沃克哈特有限公司 | 酮内酯中间体的制备方法 |
| CN119060110A (zh) * | 2023-05-30 | 2024-12-03 | 北京理工大学 | 一种红霉素衍生物及其制备方法和应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0248279A2 (en) * | 1986-06-04 | 1987-12-09 | Abbott Laboratories | Semisynthetic erythromycin antibiotics |
| EP0508699A1 (en) * | 1991-04-04 | 1992-10-14 | Merck & Co. Inc. | 9-Deoxo-8a-aza-8a-homoerythromycin a derivatives modified at the 4"- and 8a-positions |
| EP0895999A1 (en) * | 1997-08-06 | 1999-02-10 | Pfizer Products Inc. | C-4" substituted macrolide antibiotics |
| WO2002032917A1 (en) * | 2000-10-19 | 2002-04-25 | Glaxo Group Limited | Macrolides |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0126344A2 (en) | 1983-05-20 | 1984-11-28 | Abbott Laboratories | Tripeptide esters of therapeutic agents |
| AU623764B2 (en) * | 1989-03-28 | 1992-05-21 | Abbott Laboratories | Erythromycin derivatives |
| BR9708929A (pt) | 1996-05-07 | 1999-08-03 | Abbott Lab | Composto composição farmacêutica e processos para controlar uma infecção bacteriana em um mamífero e para preparar compostos de macrólidos |
| US6262030B1 (en) * | 1998-11-03 | 2001-07-17 | Pfizer Inc. | Erythromycin derivatives |
| EP1180110A1 (en) | 1999-05-24 | 2002-02-20 | Pfizer Products Inc. | 13-methyl-erythromycin derivatives |
| WO2001014397A1 (en) | 1999-08-24 | 2001-03-01 | Abbott Laboratories | 9a-azalides with antibacterial activity |
| US6946446B2 (en) * | 2000-02-24 | 2005-09-20 | Abbott Laboratories | Anti-infective agents useful against multidrug-resistant strains of bacteria |
| WO2001063539A2 (en) | 2000-02-24 | 2001-08-30 | Abbott Laboratories | Anti-infective agents useful against multidrug-resistant strains of bacteria |
| JP2002173498A (ja) | 2000-09-27 | 2002-06-21 | Hokuriku Seiyaku Co Ltd | エリスロマイシン誘導体 |
-
2001
- 2001-11-14 GB GBGB0127349.9A patent/GB0127349D0/en not_active Ceased
-
2002
- 2002-11-13 EA EA200400536A patent/EA007433B1/ru not_active IP Right Cessation
- 2002-11-13 US US10/495,413 patent/US7202221B2/en not_active Expired - Fee Related
- 2002-11-13 AR ARP020104364A patent/AR037371A1/es unknown
- 2002-11-13 PL PL02371472A patent/PL371472A1/xx not_active Application Discontinuation
- 2002-11-13 BR BR0214132-9A patent/BR0214132A/pt not_active IP Right Cessation
- 2002-11-13 RS YU41904A patent/RS41904A/sr unknown
- 2002-11-13 CN CNB028270452A patent/CN1307194C/zh not_active Expired - Fee Related
- 2002-11-13 DE DE60220180T patent/DE60220180T2/de not_active Expired - Fee Related
- 2002-11-13 IL IL16171002A patent/IL161710A0/xx unknown
- 2002-11-13 HU HU0402225A patent/HUP0402225A3/hu unknown
- 2002-11-13 HR HR20040433A patent/HRP20040433A2/hr not_active Application Discontinuation
- 2002-11-13 CA CA002466975A patent/CA2466975A1/en not_active Abandoned
- 2002-11-13 ES ES02779670T patent/ES2287332T3/es not_active Expired - Lifetime
- 2002-11-13 WO PCT/GB2002/005101 patent/WO2003042228A1/en not_active Ceased
- 2002-11-13 JP JP2003544063A patent/JP2005515978A/ja active Pending
- 2002-11-13 EP EP02779670A patent/EP1453846B1/en not_active Expired - Lifetime
- 2002-11-13 UA UA20040503313A patent/UA77210C2/uk unknown
- 2002-11-13 AT AT02779670T patent/ATE362479T1/de not_active IP Right Cessation
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2004
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0248279A2 (en) * | 1986-06-04 | 1987-12-09 | Abbott Laboratories | Semisynthetic erythromycin antibiotics |
| EP0508699A1 (en) * | 1991-04-04 | 1992-10-14 | Merck & Co. Inc. | 9-Deoxo-8a-aza-8a-homoerythromycin a derivatives modified at the 4"- and 8a-positions |
| EP0895999A1 (en) * | 1997-08-06 | 1999-02-10 | Pfizer Products Inc. | C-4" substituted macrolide antibiotics |
| WO2002032917A1 (en) * | 2000-10-19 | 2002-04-25 | Glaxo Group Limited | Macrolides |
Non-Patent Citations (1)
| Title |
|---|
| BAKER W.R. ET AL.: "MODIFICATION OF MACROLIDE ANTIBIOTICS. SYNTHESIS OF 11-DEOXY-11-(CARBOXYAMINO)-6-OMICRON-METHYLERYTHROMYCIN A 11,12-(CYCLIC ESTERS)VIA AN INTRAMOLECULAR MICHAEL REACTION OF OMICRON-CARBAMATES WITH AN ALPHA, BETA-UNSATURATED KETONE" JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 53, no. 10, 1988, pages 2340-2345, XP002026111 ISSN: 0022-3263 the whole document * |
Also Published As
| Publication number | Publication date |
|---|---|
| IL161710A0 (en) | 2004-09-27 |
| UA77210C2 (en) | 2006-11-15 |
| RS41904A (sr) | 2006-10-27 |
| GB0127349D0 (en) | 2002-01-02 |
| CA2466975A1 (en) | 2003-05-22 |
| AR037371A1 (es) | 2004-11-03 |
| ZA200403684B (en) | 2005-09-13 |
| ES2287332T3 (es) | 2007-12-16 |
| EP1453846A1 (en) | 2004-09-08 |
| DE60220180D1 (de) | 2007-06-28 |
| HUP0402225A3 (en) | 2006-01-30 |
| HUP0402225A2 (hu) | 2005-02-28 |
| EA200400536A1 (ru) | 2004-12-30 |
| JP2005515978A (ja) | 2005-06-02 |
| CN1612888A (zh) | 2005-05-04 |
| CN1307194C (zh) | 2007-03-28 |
| PL371472A1 (en) | 2005-06-13 |
| HRP20040433A2 (en) | 2005-04-30 |
| DE60220180T2 (de) | 2008-01-17 |
| BR0214132A (pt) | 2004-09-14 |
| ATE362479T1 (de) | 2007-06-15 |
| US7202221B2 (en) | 2007-04-10 |
| US20050080025A1 (en) | 2005-04-14 |
| EP1453846B1 (en) | 2007-05-16 |
| WO2003042228A1 (en) | 2003-05-22 |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |