专利号:WO-2012095438-A1 优先权日:2011-01-12 标 题 :Particles and suspensions of cephalosporin antibiotics 发明人:NIEDERMANN HANS PETER; BOTHE HEIKO 权利人:INTERVET INT BV; NIEDERMANN HANS PETER; BOTHE HEIKO 摘要:Disclosed is a method of making particles of a cephalosporin antibiotic, particularly cefquinome, wherein use is made of diafiltration. The diafiltration can be with anti- solvent, in which case a precipitate is obtained of particles as such. The diafiltration can also be with a pharmaceutically acceptable suspension medium. In that case several process steps of isolating, drying, transporting of particles can be avoided, because the suspension resulting from the synthesis of the particles is directly turned into a final drug product formulation.
专利号:US-9066864-B2 优先权日:2011-01-12 标 题:Use of liquid medium exchange by cross flow filtration in the preparation of drug suspensions 发明人:NIEDERMANN HANS PETER; BOTHE HEIKO 权利人:NIEDERMANN HANS PETER; BOTHE HEIKO; INTERVET INC 摘要:Disclosed is a method of making particles of a drug wherein use is made of diafiltration. The diafiltration can be with anti-solvent, in which case a precipitate is obtained of particles as such. The diafiltration can also be with a pharmaceutically acceptable suspension medium. In that case several process steps of isolating, drying, transporting of particles can be avoided, because the suspension resulting from the synthesis of the particles is directly turned into a final drug product formulation.
专利号:US-7452990-B2 优先权日:2002-12-26 标题 :Intermediates for synthesis of cephalosporins and process for preparation of such intermediates 发明人:DATTA DEBASHISH; DANTU MURALIKRISHNA; MISHRA BRIJKISHORE; SHARMA POLLEPEDDI LAKSHMI NARAYANA 权利人:LUPIN LTD 摘要:A novel 4-halo-2-oxyimino-3-oxo butyric acid-N,N-dimethyl formiminium chloride chlorosulfate of formula (I) useful in the preparation of cephalosporin antibiotics n nwhereinn n X is chlorine or bromine; R is hydrogen, C 1-4 alkyl group, an easily removable hydroxyl protective group, —CH 2 COOR 5 , or —C(CH 3 ) 2 COOR 5 , wherein R 5 is hydrogen or an easily hydrolysable ester group. The compound of formula (I) is prepared by reacting 4-halo-2-oxyimino-3-oxobutyric acid of formula (IV 1 ), n nwherein X, R and R 5 are as defined above, with N,N-dimethylformiminium chloride chlorosulphate of formula (VII)n n nin an organic solvent at a temperature ranging from −30° C. to −15° C. The cephalosporins that may be prepared from the intermediate include cefdinir, cefditoren pivoxil, cefepime, cefetamet pivoxil, cefixime, cefmenoxime, cefodizime, cefoselis, cefotaxime, cefpirome, cefpodoxime proxetil, cefquinome, ceftazidime, cefteram pivoxil, ceftiofur, ceftizoxime, ceftriaxone and cefuzonam.
专利号:US-2009111737-A1 优先权日:1999-05-24 标题:Novel antibacterial agents 发明人:CHRISTENSEN BURTON G; MORAN EDMUND J; GRIFFIN JOHN H; JUDICE J KEVIN; MU YONGQI; PACE JOHN L; MAMMEN MATHAI; AGGEN JAMES 权利人:CHRISTENSEN BURTON G; MORAN EDMUND J; GRIFFIN JOHN H; JUDICE J KEVIN; MU YONGQI; PACE JOHN L; MAMMEN MATHAI; AGGEN JAMES 摘要:This invention relates to novel multibinding compounds (agents) that are antibacterial agents. The multibinding compounds of the invention comprise from 2-10 ligands covalently connected by a linker or linkers, wherein each of said ligands in their monovalent (i.e., unlinked) state have the ability to bind to a an enzyme involved in cell wall biosynthesis and metabolism, a precursor used in the synthesis of the bacterial cell wall and/or the bacterial cell surface thereby interfere with the synthesis and/or metabolism of the cell wall. In particular the multibinding compounds of the invention comprise from 2-10 ligands covalently connected by a linker or linkers, wherein each of said ligands hasn a ligand domain capable of binding to penicillin binding proteins, a transpeptidase enzyme, a substrate of a transpeptidase enzyme, a beta-lactamase enzyme, pencillinase enzyme, cephalosporinase enzyme, a transglycoslase enzyme, or a transglycosylase enzyme substrate; Preferably, the ligands are selected from the beta lactam or glycopeptide class of antibacterial agents.
专利号:US-2006135761-A1 优先权日:2002-12-26 标 题 :Novel intermediates for synthesis of cephalosporins and process for preparation of such intermediates
专利号:WO-2004058695-A1 优先权日:2002-12-26 标 题 :Novel intermediates for synthesis of cephalosporins and process for preparation of such intermediates
1: Ohtaki K, Matsubara K, Fujimaru S, Shimizu K, Awaya T, Suno M, Chiba K, Hayase N, Shiono H. Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release. J Neural Transm (Vienna). 2004 Dec;111(12):1523-35. doi: 10.1007/s00702-004-0177-0. Epub 2004 Jul 7. 114:222-6. doi: 10.1016/j.jpba.2015.05.033. Epub 2015 Jun 1. 18(14):2006-12. 74(1):53-9. doi: 10.1016/s0091-3057(02)00947-4. 24(9):1049-52. doi: 10.1248/bpb.24.1049. 135(2):427-32. doi: 10.1038/sj.bjp.0704496. 7: Cheng JW, Su JR, Xiao M, Yu SY, Zhang G, Zhang JJ, Yang Y, Duan SM, Kudinha T, Yang QW, Xu YC. In vitro Activity of a New Fourth-Generation Cephalosporin, Cefoselis, Against Clinically Important Bacterial Pathogens in China. Front Microbiol. 2020 Feb 28;11:180. doi: 10.3389/fmicb.2020.00180.
合成参考文献
参考文献:10.1371/journal.pone.0175573 摘要:Wu J, Zhou C, Wu P, Xu J, Guo Y, Xue F, Getachew A, Xu S. Brain metabolomic profiling of eastern honey bee (Apis cerana) infested with the mite Varroa destructor. PLoS ONE. 2017 Apr 12;12(4):e0175573. doi: 10.1371/journal.pone.0175573.