专利号:US-8017776-B2 优先权日:2003-07-15 标题 :Methods for synthesis of acyloxyalkyl compounds 发明人:BHAT LAXMINARAYAN; GALLOP MARK A 权利人:XENOPORT INC 摘要:Disclosed herein are methods for synthesizing 1-(acyloxy)-alkyl prodrug derivatives of drugs through oxidation of 1-acyl-alkyl derivatives of drugs under anhydrous reaction conditions. The methods typically proceed stereospecifically, in high yield, do not require the use of activated intermediates and/or toxic compounds and are readily amenable to scale-up.
专利号:US-8143437-B2 优先权日:2002-02-19 标题:Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof 发明人:GALLOP MARK A; XIANG JIA-NING; YAO FENMEI; BHAT LAXMINARAYAN; ZHOU CINDY X 权利人:GALLOP MARK A; XIANG JIA-NING; YAO FENMEI; BHAT LAXMINARAYAN; ZHOU CINDY X; XENOPORT INC 摘要:The present invention provides a method for synthesizing 1-(acyloxy)-alkyl derivatives from 1-acyl-alkyl derivatives, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and/or toxic compounds and is readily amendable to scale-up. The current invention also provides 1-acyl-alkyl derivatives of known drug components and methods for synthesizing these 1-acyl-alkyl derivatives.
专利号:US-4927964-A 优先权日:1988-01-18 标 题:Method for production of 2-oxyimino-3-oxobutyric acids 发明人:NAITO KENZO; ISHIBASHI YUKIO; SHINBO HARUO 权利人:TAKEDA CHEMICAL INDUSTRIES LTD 摘要:An advantageous method of producing in large amounts on a commercial scale 2-substituted oxyimino-3-oxobutyric acids, which are useful as intermediates in the synthesis of e.g. aminothiazole cephalosporins, is characterized by reacting a tert-butyl 2-substituted oxyimino-3-oxobutyrate with a hydrogen halide in an anhydrous organic solvent.
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-9006421-B2 优先权日:2013-03-14 标题 :Cephalosporin compositions and methods of manufacture 发明人:LAI JAN-JI; PATHARE PRADIP M; KOLLA LAXMA; SORET ADRIEN F 权利人:CUBIST PHARM INC 摘要:Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising the conversion of a protected 7-amino group into a 7-carboxamide moiety in a single step.
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
1: Eicken A, Schöber JG, Roos R, Machka K. Cerebrospinal fluid penetration of cefmenoxime in children with bacterial meningitis. Infection. 1991 Nov-Dec;19(6):406-8. Japanese. 4: Kita Y, Itakura K, Tsuchiya K, Imada A. Pharmacokinetics of SCE-1141, a stereoisomer of cefmenoxime, in rats. J Antimicrob Chemother. 1986 Feb;17(2):205-13. 6: Sennello LT, Quinn D, Rollins DE, Tolman KG, Sonders RC. Effect of probenecid on the pharmacokinetics of cefmenoxime. Antimicrob Agents Chemother. 1983 Jun;23(6):803-7.
合成参考文献
参考文献:10.1177/106002809603000919 摘要:Dalla Costa T, Derendorf H. AUIC--a general target for the optimization of dosing regimens of antibiotics Ann Pharmacother. 1996 Sep;30(9):1024–8. doi: 10.1177/106002809603000919. 参考文献:10.1007/s00134-002-1212-y 摘要:Lipman J, Gous AG, Mathivha LR, Tshukutsoane S, Scribante J, Hon H, Pinder M, Riera-Fanego JF, Verhoef L, Stass H. Ciprofloxacin pharmacokinetic profiles in paediatric sepsis: how much ciprofloxacin is enough Intensive Care Med. 2002 Apr;28(4):493–500. doi: 10.1007/s00134-002-1212-y. 参考文献:10.2165/00044011-199815060-00010 摘要:Owens CA, Ambrose PG, Quintiliani R, Nightingale CH, Nicolau DP. Infusion phlebitis: relative incidence associated with cefuroxime administered by intermittent and continuous infusion. Clin Drug Investig. 1998;15(6):531–5. doi: 10.2165/00044011-199815060-00010. 参考文献:10.2165/00044011-199816040-00008 摘要:Cazzola M, Matera MG, Donner CF. Pharmacokinetics and pharmacodynamics of newer oral cephalosporins: implications for treatment of community-acquired lower respiratory tract infections. Clin Drug Investig. 1998;16(4):335–46. doi: 10.2165/00044011-199816040-00008.