Approximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite. The desacetyl metabolite has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M2 and M3) account for about 20-25%. They lack bactericidal activity.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
Approximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite.
Synthesis and biological evaluation of a series of parenteral 3'-quaternary ammonium cephalosporins
摘要：
The preparation and biological evaluation of a series of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoximinoacetamido]cep halosporins, substituted at the 3'-position with monocyclic or bicyclic nitrogen-containing heterocycles are described. The resulting family of parenteral compounds displays a broad spectrum of antibacterial activity. Some compounds exhibit a similar level of Gram-negative activity to that of the "third-generation" cephalosporins with increased staphylococcal activity. The in vitro and in vivo antimicrobial activity, structure-activity relationships, beta-lactamase stability, and in vitro and in vivo pharmacological evaluations are presented.
A method for producing cephalosporins 7-substituted with an amino-thiazolylacetic group by reacting 7-ACA or its derivatives having the amino group and the carboxyl protected with reactive derivatives of amino-thiazolylacetic acid.
[EN] NOVEL INTERMEDIATES FOR SYNTHESIS OF CEPHALOSPORINS AND PROCESS FOR PREPARATION OF SUCH INTERMEDIATES<br/>[FR] NOUVEAUX INTERMEDIAIRES POUR LA SYNTHESE DE CEPHALOSPORINES ET LEUR PROCEDE DE PREPARATION
申请人：LUPIN LTD
公开号：WO2004058695A1
公开（公告）日：2004-07-15
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, wherein X is chlorine or bromine; R is hydrogen, C1-4 alkyl group, an easily removable hydroxyl protective group, -CH2COOR5, or -C(CH3)2COOR5, wherein R5 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 (IV1), wherein X, R and R5 are as defined above, with N, N-dimethylformiminium chloride chlorosulphate of formula (VII), in 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.
Method for preparation of ceftiofur and salts thereof
申请人：LUPIN LIMITED
公开号：US20040132996A1
公开（公告）日：2004-07-08
A process for preparation of ceftiofur sodium of formula (Ib)
1
possessing high stability and having purity of more than 97% and substantially free of impurities, is disclosed. The process comprises:
i) reacting cefotaxime or its salts or its esters of formula (VI)
2
wherein R
3
is hydrogen, an alkali or alkaline earth metal, or an easily hydrolysable ester, with thiofuroic acid, employed in a molar proportion of 1.5 to 3.0 moles per mole of compound (VI), in the presence of acetonitrile as solvent and in the presence of large excess of methanesulfonic acid, employed in molar proportions of 12 to 18 moles per mole of compound (VI), and at a temperature of between −5° C. to 30° C. to give after necessary neutralisation of the alkali or alkaline earth metal or removal of the ester group of the 4-carboxylic acid function, wherever applicable, ceftiofur of formula (Ia), possessing high stability and having purity of more than 97% and substantially free of impurities;
3
ii) converting the ceftiofur of formula (Ia) thus obtained to its salt with an organic amine by treating a solution of ceftiofur in a mixture of water and a water-miscible organic solvent with an organic amine, at a temperature ranging from −10° C. to 10° C.;
iii) reacting of the amine salt thus obtained with a sodium metal carrier in a mixture of water and water-miscible organic solvent and in presence of sodium hydrogen sulfite to give ceftiofur sodium of formula (Ib)
Process for the preparation of cephalosporin intermediate and its use for the manufacture of cephalosporin compounds
申请人：Orchid Chemicals and Pharmaceuticals Limited
公开号：US20030199712A1
公开（公告）日：2003-10-23
The present invention relates to a process for the preparation of 4-halogeno-2-substitutedimino-3-oxo-butyric acid of formula (I)
1
wherein R
1
represents CH
3
, CR
a
R
b
COOR
c
where R
a
and R
b
independently represent hydrogen or methyl and R
c
represents hydrogen or (C
1
-C
6
)alkyl, X represents halogen such as chlorine or bromine, also discloses the activation of this acid and its further use in the preparation of cephalosporanic antibiotics (II) in excellent yields and purity
Ratiometric Fluorescence Detection of Pathogenic Bacteria Resistant to Broad-Spectrum β-Lactam Antibiotics
作者：Junxiang Zhang、Yang Shen、Sarah L. May、Daniel C. Nelson、Shuwei Li
DOI：10.1002/anie.201107810
日期：2012.2.20
Identification of bacteria: A methoxyimino cephalosporin derivative containing a pair of fluorescence resonance energy transfer (FRET) fluorophores was synthesized. This probe displays selective cleavage toward different types of β‐lactamases, thereby providing a rapid assay to distinguish bacterial cells that are either sensitive or resistant to broad‐spectrum β‐lactam antibiotics (see picture).
