AU2001282105A1 - New macrolides with antibacterial activity - Google Patents
New macrolides with antibacterial activityInfo
- Publication number
- AU2001282105A1 AU2001282105A1 AU2001282105A AU8210501A AU2001282105A1 AU 2001282105 A1 AU2001282105 A1 AU 2001282105A1 AU 2001282105 A AU2001282105 A AU 2001282105A AU 8210501 A AU8210501 A AU 8210501A AU 2001282105 A1 AU2001282105 A1 AU 2001282105A1
- Authority
- AU
- Australia
- Prior art keywords
- thio
- hexopyranosyl
- oxy
- ethyl
- dimethylamino
- 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.)
- Abandoned
Links
- 239000003120 macrolide antibiotic agent Substances 0.000 title claims abstract description 14
- 229940041033 macrolides Drugs 0.000 title abstract description 4
- 230000000844 anti-bacterial effect Effects 0.000 title description 4
- 150000002148 esters Chemical class 0.000 claims abstract description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 238000001727 in vivo Methods 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 191
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 140
- 150000001875 compounds Chemical class 0.000 claims description 109
- KTSNTUOKEHVPGX-UHFFFAOYSA-N 1-oxacyclotetradeca-7,9-diene-2,5,11,13-tetrone Chemical compound O=C1CCC(=O)OCC(=O)CC(=O)C=CC=CC1 KTSNTUOKEHVPGX-UHFFFAOYSA-N 0.000 claims description 99
- -1 pyridinyl-lH-pyrazol-1-yl Chemical group 0.000 claims description 83
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 17
- 208000035473 Communicable disease Diseases 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
- 239000003814 drug Substances 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000000848 adenin-9-yl group Chemical group [H]N([H])C1=C2N=C([H])N(*)C2=NC([H])=N1 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000013160 medical therapy Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000004071 biological effect Effects 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 229940088710 antibiotic agent Drugs 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 219
- 238000005160 1H NMR spectroscopy Methods 0.000 description 126
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 98
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 93
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 90
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 82
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 77
- 239000000203 mixture Substances 0.000 description 73
- 239000000047 product Substances 0.000 description 66
- NWRKWMZOIHCCHM-UHFFFAOYSA-N 1-oxacyclotetradeca-7,9,11-triene-2,5,13-trione Chemical compound O=C1CCC(=O)OCC(=O)C=CC=CC=CC1 NWRKWMZOIHCCHM-UHFFFAOYSA-N 0.000 description 62
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 49
- 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 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 44
- 238000002360 preparation method Methods 0.000 description 42
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 34
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 28
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
- 239000003835 ketolide antibiotic agent Substances 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 19
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography 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
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 229910001868 water Inorganic materials 0.000 description 16
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 15
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000012043 crude product Substances 0.000 description 14
- 238000006140 methanolysis reaction Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000010511 deprotection reaction Methods 0.000 description 13
- 235000002639 sodium chloride Nutrition 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 238000007363 ring formation reaction Methods 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 229940093495 ethanethiol Drugs 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 8
- 229940089960 chloroacetate Drugs 0.000 description 8
- FOCAUTSVDIKZOP-UHFFFAOYSA-M chloroacetate Chemical compound [O-]C(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-M 0.000 description 8
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 8
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 7
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 7
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000000829 suppository Substances 0.000 description 7
- UCPSXSQPMODSIB-UHFFFAOYSA-N 1-oxacyclotetradeca-3,5,7,9,11,13-hexaene-3-carbonitrile Chemical compound N#CC1=CC=CC=CC=CC=CC=COC1 UCPSXSQPMODSIB-UHFFFAOYSA-N 0.000 description 6
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- BDUPRNVPXOHWIL-UHFFFAOYSA-N dimethyl sulfite Chemical compound COS(=O)OC BDUPRNVPXOHWIL-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 5
- 101150041968 CDC13 gene Proteins 0.000 description 5
- 229920002261 Corn starch Polymers 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
- 229910006124 SOCl2 Inorganic materials 0.000 description 5
- 239000012876 carrier material Substances 0.000 description 5
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 5
- 229940106681 chloroacetic acid Drugs 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- 241000606768 Haemophilus influenzae Species 0.000 description 4
- BVIAOQMSVZHOJM-UHFFFAOYSA-N N(6),N(6)-dimethyladenine Chemical compound CN(C)C1=NC=NC2=C1N=CN2 BVIAOQMSVZHOJM-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- LJVAJPDWBABPEJ-PNUFFHFMSA-N telithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)[C@@H](C)C(=O)O[C@@H]([C@]2(OC(=O)N(CCCCN3C=C(N=C3)C=3C=NC=CC=3)[C@@H]2[C@@H](C)C(=O)[C@H](C)C[C@@]1(C)OC)C)CC)[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O LJVAJPDWBABPEJ-PNUFFHFMSA-N 0.000 description 4
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 4
- 229940113082 thymine Drugs 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- JJLMOUMOJSUSSX-UHFFFAOYSA-N 3-(1h-pyrazol-5-yl)pyridine Chemical compound N1N=CC=C1C1=CC=CN=C1 JJLMOUMOJSUSSX-UHFFFAOYSA-N 0.000 description 3
- 101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 3
- 101001053395 Arabidopsis thaliana Acid beta-fructofuranosidase 4, vacuolar Proteins 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 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 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 229960004132 diethyl ether Drugs 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000005179 haloacetyl group Chemical group 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 2
- HGTBAIVLETUVCG-UHFFFAOYSA-M (methylthio)acetate Chemical compound CSCC([O-])=O HGTBAIVLETUVCG-UHFFFAOYSA-M 0.000 description 2
- OYRPGAOCKYUDMU-UHFFFAOYSA-N 1-[4-[1-(3-chloropropyl)pyrazol-4-yl]phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1=CN(CCCCl)N=C1 OYRPGAOCKYUDMU-UHFFFAOYSA-N 0.000 description 2
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00117971 | 2000-08-22 | ||
| EP00117971 | 2000-08-22 | ||
| PCT/EP2001/009560 WO2002016380A1 (en) | 2000-08-22 | 2001-08-20 | New macrolides with antibacterial activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2001282105A1 true AU2001282105A1 (en) | 2002-03-04 |
Family
ID=8169600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2001282105A Abandoned AU2001282105A1 (en) | 2000-08-22 | 2001-08-20 | New macrolides with antibacterial activity |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6740642B2 (enExample) |
| EP (1) | EP1313751B1 (enExample) |
| JP (1) | JP4162992B2 (enExample) |
| KR (1) | KR100502031B1 (enExample) |
| CN (1) | CN1234718C (enExample) |
| AT (1) | ATE408614T1 (enExample) |
| AU (1) | AU2001282105A1 (enExample) |
| BR (1) | BR0113472A (enExample) |
| CA (1) | CA2419296C (enExample) |
| DE (1) | DE60135859D1 (enExample) |
| ES (1) | ES2313975T3 (enExample) |
| MX (1) | MXPA03001607A (enExample) |
| WO (1) | WO2002016380A1 (enExample) |
| ZA (1) | ZA200301047B (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2275621T3 (es) * | 2000-12-21 | 2007-06-16 | Glaxo Group Limited | Antibioticos macrolidos. |
| FR2826274B1 (fr) * | 2001-06-21 | 2003-09-26 | Aventis Pharma Sa | Formulation pharmaceutique au gout masque et son procede de preparation |
| CN1589277A (zh) * | 2001-09-17 | 2005-03-02 | 奥索-麦克尼尔药品公司 | 6－o－氨基甲酸酯－11,12－内酯－酮内酯抗菌剂 |
| US6995143B2 (en) * | 2002-02-28 | 2006-02-07 | Basilea Pharmaceutica Ag | Macrolides with antibacterial activity |
| US6727229B2 (en) * | 2002-08-19 | 2004-04-27 | Enanta Pharmaceuticals, Inc. | 11,12-substituted lactone ketolide derivatives having antibacterial activity |
| US6720308B1 (en) | 2002-11-07 | 2004-04-13 | Enanta Pharmaceuticals, Inc. | Anhydrolide derivatives having antibacterial activity |
| US6716820B1 (en) | 2003-06-05 | 2004-04-06 | Enanta Pharmaceuticals, Inc. | 6-O-substituted bicyclic macrolides |
| US20040254126A1 (en) * | 2003-06-05 | 2004-12-16 | Yao-Ling Qiu | 11-12 Bicyclic erythromycin derivatives |
| US6790835B1 (en) | 2003-06-05 | 2004-09-14 | Enanta Pharmaceuticals, Inc. | Bicyclic macrolide derivatives |
| US6774115B1 (en) | 2003-06-05 | 2004-08-10 | Enanta Pharmaceuticals, Inc. | 6-O-substituted bicyclic ketolides |
| WO2004108745A2 (en) * | 2003-06-05 | 2004-12-16 | Enanta Pharmaceuticals, Inc. | 11-12 bicyclic erythromycin derivatives |
| US6765016B1 (en) | 2003-06-05 | 2004-07-20 | Enanta Pharmaceuticals, Inc. | Bicyclic ketolide derivatives |
| WO2006065721A2 (en) * | 2004-12-13 | 2006-06-22 | Enanta Pharmaceuticals, Inc. | 11, 12-lactone bicyclolides |
| DE602006006030D1 (de) * | 2005-02-09 | 2009-05-14 | Basilea Pharmaceutica Ag | Neue makrolide |
| CN101115764B (zh) * | 2005-02-09 | 2012-09-26 | 巴斯利尔药物股份公司 | 大环内酯类化合物 |
| US7517859B2 (en) * | 2005-05-04 | 2009-04-14 | Enanta Pharmaceuticals, Inc. | Spirocyclic bicyclolides |
| JP2009506066A (ja) | 2005-08-24 | 2009-02-12 | リブ−エックス ファーマシューティカルズ，インコーポレイテッド | トリアゾール化合物ならびにこれを作製する方法および使用する方法 |
| PT2049556E (pt) * | 2006-08-09 | 2013-08-22 | Basilea Pharmaceutica Ag | Novos macrólidos úteis contra doenças inflamatórias e alérgicas |
| EP2056844A4 (en) * | 2006-08-24 | 2010-11-24 | Wockhardt Research Center | NEW MACROLIDS AND KETOLIDS WITH ANTIMICROBIAL EFFECT |
| CN101939327B (zh) * | 2008-02-08 | 2015-03-11 | 巴斯利尔药物股份公司 | 新的大环内酯类及其用途 |
| JP5769972B2 (ja) * | 2008-02-08 | 2015-08-26 | バジリア ファルマスーチカ アーゲーＢａｓｉｌｅａ Ｐｈａｒｍａｃｅｕｔｉｃａ ＡＧ | Ｐｄｅ阻害により仲介される疾患を処置するためのマクロライド |
| RU2011153353A (ru) * | 2009-05-27 | 2013-07-10 | Вокхардт Рисерч Сентер | Кетолидные соединения, обладающие противомикробной активностью |
| US8796474B1 (en) | 2010-08-23 | 2014-08-05 | Rutgers, The State University Of New Jersey | Macrolide compounds and methods and intermediates useful for their preparation |
| CN102417530A (zh) * | 2010-09-26 | 2012-04-18 | 中国医学科学院药物研究所 | 广谱抗菌素红霉素a大环酮内酯类衍生物的合成方法和用途 |
| EP3216798A3 (en) | 2010-12-09 | 2017-10-25 | Wockhardt Limited | Ketolide compounds |
| US9206214B2 (en) | 2011-03-01 | 2015-12-08 | Wockhardt Ltd. | Process for preparation of ketolide intermediates |
| PL2938623T3 (pl) * | 2012-12-31 | 2017-03-31 | Basilea Pharmaceutica Ag | Wybrane makrolidy o działaniu hamującym pde4 |
| US10857171B2 (en) | 2016-01-12 | 2020-12-08 | Wockhardt Limited | Pharmaceutical compositions |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2719587B1 (fr) * | 1994-05-03 | 1996-07-12 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments. |
-
2001
- 2001-08-20 EP EP01960680A patent/EP1313751B1/en not_active Expired - Lifetime
- 2001-08-20 US US10/362,526 patent/US6740642B2/en not_active Expired - Lifetime
- 2001-08-20 AU AU2001282105A patent/AU2001282105A1/en not_active Abandoned
- 2001-08-20 JP JP2002521477A patent/JP4162992B2/ja not_active Expired - Fee Related
- 2001-08-20 BR BR0113472-8A patent/BR0113472A/pt not_active Application Discontinuation
- 2001-08-20 KR KR10-2003-7002616A patent/KR100502031B1/ko not_active Expired - Fee Related
- 2001-08-20 CN CNB018160891A patent/CN1234718C/zh not_active Expired - Fee Related
- 2001-08-20 AT AT01960680T patent/ATE408614T1/de not_active IP Right Cessation
- 2001-08-20 MX MXPA03001607A patent/MXPA03001607A/es active IP Right Grant
- 2001-08-20 DE DE60135859T patent/DE60135859D1/de not_active Expired - Lifetime
- 2001-08-20 WO PCT/EP2001/009560 patent/WO2002016380A1/en not_active Ceased
- 2001-08-20 CA CA002419296A patent/CA2419296C/en not_active Expired - Fee Related
- 2001-08-20 ES ES01960680T patent/ES2313975T3/es not_active Expired - Lifetime
-
2003
- 2003-02-06 ZA ZA200301047A patent/ZA200301047B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE60135859D1 (de) | 2008-10-30 |
| MXPA03001607A (es) | 2003-06-04 |
| EP1313751A1 (en) | 2003-05-28 |
| CN1234718C (zh) | 2006-01-04 |
| CA2419296C (en) | 2008-12-09 |
| ES2313975T3 (es) | 2009-03-16 |
| JP2004506740A (ja) | 2004-03-04 |
| ATE408614T1 (de) | 2008-10-15 |
| CA2419296A1 (en) | 2002-02-28 |
| KR20030029839A (ko) | 2003-04-16 |
| KR100502031B1 (ko) | 2005-07-25 |
| WO2002016380A1 (en) | 2002-02-28 |
| US20030199459A1 (en) | 2003-10-23 |
| JP4162992B2 (ja) | 2008-10-08 |
| BR0113472A (pt) | 2003-07-01 |
| ZA200301047B (en) | 2004-05-06 |
| US6740642B2 (en) | 2004-05-25 |
| EP1313751B1 (en) | 2008-09-17 |
| CN1464880A (zh) | 2003-12-31 |
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