公开(公告)号：EP0831093A1

公开(公告)日：1998-03-25

申请号：EP97116236.7

申请日：1997-09-18

申请人： F. HOFFMANN-LA ROCHE AG

发明人： Angehrn, Peter ,  Hebeisen, Paul ,  Heinze-Krauss, Ingrid ,  Page, Malcolm

IPC分类号： C07D463/00 ,  A61K31/545

CPC分类号： C07D463/22 ,  Y02P20/55

摘要： 1-carba-(dethia)-cephalosporin derivatives of the general formula I
wherein

R 1 is hydrogen, optionally fluoro substituted lower alkyl, aralkyl, cycloalkyl, -COR 4 or -C(R 5 R 6 )CO 2 R 7 -C(R 5 R 6 )CONHR 7 ; where R 5 and R 6 are each independently hydrogen or lower alkyl, or R 5 and R 6 taken together form a cycloalkyl group; R 4 is hydrogen or lower alkyl and R 7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group;
R 2 is hydrogen, hydroxy, lower alkyl-Q m , cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl-Q m , aryl-Q m , aryloxy, aralkoxy, a heterocyclic ring or heterocyclyl lower alkyl, the lower alkyl, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl, aryl, aryloxy, aralkoxy and the heterocyclic ring being unsubstituted or substituted with at least one group selected from carboxy, amino, nitro, cyano, optionally fluoro substituted lower alkyl, lower alkoxy, hydroxy, halogen, -COR 6 , -C(R 5 R 6 )CO 2 R 7 , -C(R 5 R 6 )CONR 5 R 8 , -CONR 5 R 6 , -N(R 6 )COOR 10 , R 6 OCO- or R 6 COO- where R 5 and R 6 are hydrogen or lower alkyl; R 7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group; R 8 is hydrogen, lower alkyl or optionally substituted phenyl; R 10 is lower alkyl, lower alkenyl or a carboxylic acid protecting group;
Q is -CHR-, -CO- or -SO 2 -;
R is hydrogen or lower alkyl
R 3 is hydroxy, lower-alkoxy, or -O - , when R 2 has a positive charge, or -OM and M represents an alkali metal;
m is 0 or 1;
n is 0, 1 or 2;
X is CH or N
as well as readily hydrolysable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts.

摘要翻译： 其中R 1为氢，任选氟取代的低碳烷基，芳烷基，环烷基，-COR 4或-C（R 5 R 6）CO 2 R 7 -C（R 5 R 6）CONHR 7的通式I的1-碳 - （dethia） - 头孢菌素衍生物; 其中R5和R6各自独立地为氢或低级烷基，或者R5和R6一起形成环烷基; R4是氢或低级烷基，R7是氢，低级烷基，低级链烯基或羧酸保护基; R2为氢，羟基，低级烷基-Qm，环烷基，低级烷氧基，低级链烯基，环烯基，低级炔基，芳烷基-Qm，芳基-Qm，芳氧基，芳烷氧基，杂环或杂环基低级烷基， 低级链烯基，环烯基，低级炔基，芳烷基，芳基，芳氧基，芳烷氧基和杂环未被取代或被选自羧基，氨基，硝基，氰基，任选氟取代的低碳烷基，低碳烷氧基， 羟基，卤素，-COR6，-C（R5R6）CO2R7，-C（R5R6）CONR5R8，-CONR5R6，-N（R6）COOR10，R6OCO-或R6COO-，其中R5和R6为氢或低级烷基; R7是氢，低级烷基，低级链烯基或羧酸保护基; R8是氢，低级烷基或任选取代的苯基; R10是低级烷基，低级链烯基或羧酸保护基; Q是-CHR - ， - CO-或-SO2-; 当R2具有正电荷时，R是氢或低级烷基，R3是羟基，低级烷氧基或-O-，或者-OM和M表示碱金属; m是0或1; n是0,1或2; X是CH或N以及其易水解的酯，所述化合物的药学上可接受的盐和式I化合物的水合物以及它们的酯和盐。

公开(公告)号：EP0460881B1

公开(公告)日：1995-11-22

申请号：EP91304975.5

申请日：1991-06-03

申请人： THE UNIVERSITY OF NOTRE DAME DU LAC

发明人： Miller, Marvin Joseph ,  Williams, Matthew Alan

IPC分类号： C07D463/00 ,  C07D477/00 ,  C07D205/08 ,  C07D205/085

CPC分类号： C07D477/04 ,  C07D463/04

公开(公告)号：EP0627429A1

公开(公告)日：1994-12-07

申请号：EP94303942.0

申请日：1994-06-01

申请人： ELI LILLY AND COMPANY

发明人： Henning, William Carl ,  O'Dea, Michael Eugene

IPC分类号： C07D463/00

CPC分类号： C07D471/04 ,  C07D463/22

摘要： The invention is directed to the crystalline isopropyl alcohol solvate of loracarbef, and also is directed to a process for the preparation of the crystalline monohydrate form of the compound of formula (I)

which includes exposing the crystalline isopropyl solvate form of the compound of formula (I) to a temperature of between about 50° and 90°C and a relative humidity of between about 60 to about 100%.

摘要翻译： 本发明涉及劳拉卡贝的结晶异丙醇溶剂化物，还涉及制备式（I）化合物的结晶一水合物形式的方法，其包括将化合物的结晶异丙基溶剂合物形式 （I）的温度至约50-90℃的温度和约60至约100％之间的相对湿度。

公开(公告)号：EP0504612A3

公开(公告)日：1993-01-27

申请号：EP92102925.2

申请日：1992-02-21

申请人： AMERICAN CYANAMID COMPANY

发明人： Feigelson, Gregg Brian ,  Curran, William V. ,  Ziegler, Carl Bernard

IPC分类号： C07D205/08 ,  C07F7/18 ,  C07D477/00 ,  C07D463/00

CPC分类号： C07D477/04 ,  C07D205/08 ,  C07F7/1856 ,  C07F7/186 ,  C07F9/568

摘要： 4-substituted azetidinones having the formulae I and II:

with R¹, R², R³, R⁴, R⁵ and X defined hereafter, which are intermediates for the preparation of carbapenem and carbacephem antibacterials and processes for producing such antibacterials through the utilization of an acid mediated ring closure reaction. R¹is hydrogen, hydroxy (lower) alkyl or protected hydroxy (lower) alkyl; R²is selected from the group consisting of hydrogen and (C₁-C₆) alkyl; R³is hydrogen, or an organic group; R⁴is hydrogen or a suitable removable protecting group for an amide nitrogen; R⁵is hydrogen or a suitable removable protecting group for a carboxylic acid; Xis oxygen, sulfur, a moiety of the formula NR⁶.

公开(公告)号：EP0512813A3

公开(公告)日：1993-01-13

申请号：EP92304075.2

申请日：1992-05-06

申请人： ELI LILLY AND COMPANY

发明人： Berglund, Richard Alan

IPC分类号： C07D463/00

CPC分类号： C07D463/22

摘要： A process is provided for producing 7-protected-amino-4-protected carboxy-3-halo-1-carbacephalosporins which includes the steps of mixing the hydrochloride salt of the carbacephalosporin with a polar organic aprotic solvent having a dielectric constant of at least about 20 and a base selected from a group consisting of 5- or 6-membered tertiary cyclic amine containing 0-1 oxygen atoms, and dimethylbenzamine to form the free amine of a carbacephalosporin and thereafter without isolating the free amine mixing it with an acylating agent to result in the doubly blocked carbacephalosporin.

公开(公告)号：EP0511001A2

公开(公告)日：1992-10-28

申请号：EP92303714.7

申请日：1992-04-24

申请人： ELI LILLY AND COMPANY

发明人： Ternansky, Robert John

IPC分类号： C07D463/00 ,  C07D405/06

CPC分类号： C07D463/04

摘要： The invention provides a process for preparing 7-protected amino-4-protected carboxy-1-carbacephalosporins which includes subjecting a 3-protected-amino-4-(1-propylene oxide)-methyl(protected carboxy)-azetidin-2-one to a strong base to form a 2-hydroxycepham and thereafter dehydrating the 2-hydroxycepham to form the desired 1-carbacephalosporin. Also included in the invention are novel intermediates.

摘要翻译： 本发明提供了制备7-保护的氨基-4-保护的羧基-1-碳头孢菌素的方法，其包括使3-保护的氨基-4-（1-环氧丙烷） - 甲基（被保护的羧基） - 氮杂环丁烷-2-酮 到强碱以形成2-羟基头孢，然后使2-羟基头孢脱水以形成所需的1-碳孢霉素。 本发明还包括新型中间体。

公开(公告)号：EP0222022B1

公开(公告)日：1992-09-23

申请号：EP86903558.4

申请日：1986-05-17

申请人： Otsuka Kagaku Kabushiki Kaisha

发明人： SASAOKA, Michio ,  SAITO, Norio ,  SHIROI, Takashi ,  NAGAO, Shigemitsu ,  KIKUCHI, Ryo ,  KAMEYAMA, Yutaka

IPC分类号： C07D463/00 ,  C07D498/053 ,  C07D499/08 ,  C07D501/02

CPC分类号： C07D505/00 ,  C07D499/00 ,  Y02P20/55

摘要： A process for producing beta-lactam derivatives, which comprises reacting a beta-lactam derivative wherein the carboxyl group is protected and which is represented by the general formula: A-COO-X (wherein A represents a beta-lactam derivative residue, and X represents a benzyl group having an electron-donating group in the phenyl group, a diphenylmethyl group optionally having an electron-donating group in the phenyl group, or a tert-butyl group) with a phenol to obtain a beta-lactam derivative represented by the general formula: A-COOH (wherein A is the same as defined above).

公开(公告)号：EP0495585A1

公开(公告)日：1992-07-22

申请号：EP92300182.0

申请日：1992-01-09

申请人： ELI LILLY AND COMPANY

发明人： Ternansky, Robert John

IPC分类号： C07D463/00 ,  A61K31/435

CPC分类号： C07D463/22

摘要： Various 3-substituted 1-carba(1-dethia)-3-cephems, useful as antibacterial agents are provided. Also provided are pharmaceutical compositions comprising same and methods for treating bacterial infections in man and other animals.
An antibacterial compound of the formula

wherein R is hydrogen, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, or C₁-C₆ haloalkyl;
   A and A′ are independently hydrogen, C₁-C₆ alkyl, nitro, amino, a 5-6 membered organic heterocycle containing 1, 2 or 3 hetero atoms selected from nitrogen or sulfur, C₁-C₆ alkoxy or phenyl; or A and A′ taken together from a group of the formulae

wherein X is hydrogen, halo, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, amino, nitro, or carboxy; and Y is nitrogen or carbon; or a pharmaceutically acceptable salt thereof.

摘要翻译： 提供了可用作抗菌剂的各种3-取代的1- carb（1-脱硫）-3-头孢烯。 还提供了包含其的药物组合物和用于治疗人和其它动物细菌感染的方法。 式CHEM的抗菌化合物，其中R是氢，C 1 -C 6烷基，C 2 -C 6烯基，C 2 -C 6炔基，C 3 -C 6环烷基或C 1 -C 6卤代烷基; A和A min独立地是氢，C 1 -C 6烷基，硝基，氨基，含有1,2或3个选自氮或硫的杂原子的5-6元有机杂环，C 1 -C 6烷氧基或苯基; 或者A和A分别为一个式（CHEM），其中X为氢，卤素，C 1 -C 6烷基，C 1 -C 6烷氧基，C 1 -C 6烷氧基羰基，氨基，硝基或羧基; Y为氮或碳; 或其药学上可接受的盐。

公开(公告)号：EP0484030A2

公开(公告)日：1992-05-06

申请号：EP91309725.9

申请日：1991-10-21

申请人： Bristol-Myers Squibb Company

发明人： Hudyma, Thomas W. ,  Partyka, Richard A.

IPC分类号： C07D501/20 ,  C07D501/18 ,  C07D463/00 ,  A61K31/545 ,  A61K31/435

CPC分类号： C07D501/00 ,  Y02P20/55

摘要： A compound of formula I

wherein

X is sulfur or CH2;
R 1 is hydrogen, hydroxy, amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl optionally substituted with one to three C 1-6 alkyl, C 1-6 alkyloxy or hydroxy, C 1-6 alkylthio, phenylthio optionally substituted with one to three C 1-6 alkyl or C 1-6 alkyloxy on the phenyl ring, phenylmethyloxy optionally substituted with one to three C 1-6 alkyl or C 1-6 alkyloxy on the phenyl ring, 1-morpholino, C 1-6 alkyloxy, C 2-6 alkenylmethyloxy, C 3-6 alkynylmethyloxy, C 1-6 alkylamino, C 1-6 dialkylamino or a radical selected from the group consisting of
and

in which n is 0 to 3, R 5 is C 1-6 alkyl or hydrogen, and R 3 and R 4 are independently C 1-6 alkyl ;
R 2 is hydrogen, a conventional amino protecting group or an acyl group ;
R° is hydrogen or a conventional carboxy protecting group, or -CO Z R° taken together forms a physiologically hydrolyzable ester; or
pharmaceutically acceptable salts or solvates thereof.

摘要翻译： 式I化合物其中X是硫或CH2; R 1是氢，羟基，氨基，C 1-6烷基，C 2-6烯基，C 2-6炔基，任选地被一至三个C 1-6烷基，C 1-6烷氧基或羟基，C 1-6烷硫基， 任选被苯基环上一至三个C 1-6烷基或C 1-6烷氧基取代的苯硫基，苯基环上任选被一至三个C 1-6烷基或C 1-6烷氧基取代的苯基甲氧基，1-吗啉代，C 1-6烷氧基 ，C 2-6烯基甲氧基，C 3-6炔基甲氧基，C 1-6烷基氨基，C 1-6二烷基氨基或选自下组的基团，其中n为0至3，R 5为C 1-6烷基或 氢，R 3和R 4独立地是C 1-6烷基; R 2是氢，常规的氨基保护基或酰基; R DEG是氢或常规的羧基保护基，或-CO 2 R 2一起形成生理上可水解的酯; 或其药学上可接受的盐或溶剂化物。 婷

公开(公告)号：EP0416810A3

公开(公告)日：1992-04-01

申请号：EP90309483.7

申请日：1990-08-30

申请人： Beecham Group p.l.c.

发明人： Branch, Clive Leslie ,  Guest, Angela Wendy ,  Finch, Stephen Christopher

IPC分类号： C07D501/57 ,  A61K31/545 ,  C07D505/00 ,  C07D463/00

CPC分类号： C07D501/00

摘要： 7 α-formamido cephalosporin derivatives having a 3[N-(optionally substituted)aminothiopyridinium thiomethyl] substituent have anti-bacterial activity and are of use in anti-bacterial therapy. Processes for the preparation thereof and intermediates for use in these processes are also disclosed.