公开(公告)号：US4307230A

公开(公告)日：1981-12-22

申请号：US152084

申请日：1980-05-21

申请人： Daniel Farge ,  Claude Moutonnier ,  Pierre Le Roy ,  Jean-Francois Peyronel

发明人： Daniel Farge ,  Claude Moutonnier ,  Pierre Le Roy ,  Jean-Francois Peyronel

IPC分类号： C07D501/04 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D253/075 ,  C07D257/04 ,  C07D317/28 ,  C07D501/00 ,  C07D501/06 ,  C07D501/14 ,  C07D501/20 ,  C07D501/24 ,  C07D501/26 ,  C07D501/60

CPC分类号： C07D253/075 ,  C07D257/04 ,  C07D317/28 ,  C07D501/00 ,  C07D501/24

摘要： Novel 3-vinyl-cephalosporins of the formula ##STR1## in which n is 0 or 1, R.sub.1 is hydrogen, a radical of the formula ##STR2## [in which R.sub.4 is hydrogen or a protective radical and R.sub.5 is hydrogen, alkyl, vinyl or cyanomethyl or is a protective radical], or a protective radical, and R.sub.2 is hydrogen, a protective radical or an enzymatically removable radical, or R.sub.1 is hydrogen or an acyl radical which may carry various substituents and R.sub.2 is hydrogen or a protective radical, and R.sub.3 is a radical of the general formula R'.sub.3 --SO.sub.2 --O-- or R".sub.3 --CO--O--, in which R'.sub.3 is alkyl, trifluoromethyl, trichloromethyl or phenyl which is substituted by a halogen atom or by an alkyl or nitro radical, and R".sub.3 is defined like R'.sub.3 or represents methyl which is substituted by acyl or alkoxycarbonyl, or represents ethyl or propyl substituted in the 2-position by acyl or alkoxycarbonyl. These compounds are useful as intermediates for the preparation of antibiotic 3-thiovinyl-cephalosporins.

摘要翻译： 式（I）的新型3-乙烯基头孢菌素其中n为0或1，R 1为氢，式（II）的基团[其中R 4为氢或保护基，R 5为 是氢，烷基，乙烯基或氰基甲基，或是保护基]或保护基，R2是氢，保护基或酶可除去的基团，或R 1是氢或可以带有各种取代基的酰基，R 2是 氢或保护基，R3是通式为R'3-SO2-O-或R'3-CO-O-的基团，其中R'3是烷基，三氟甲基，三氯甲基或被取代的苯基 卤素原子或烷基或硝基，R“3定义为R'3，或表示被酰基或烷氧基羰基取代的甲基，或代表在2-位被酰基或烷氧基羰基取代的乙基或丙基。 这些化合物可用作制备抗生素3-硫代乙烯基 - 头孢菌素的中间体。

公开(公告)号：US4304717A

公开(公告)日：1981-12-08

申请号：US36756

申请日：1979-05-07

申请人： Magda Huhn ,  Gabor Szabo ,  Gabor Resofszki ,  Eva Somfai

发明人： Magda Huhn ,  Gabor Szabo ,  Gabor Resofszki ,  Eva Somfai

IPC分类号： C07C69/353 ,  A61K31/43 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D333/24 ,  C07D499/00 ,  C07D499/12 ,  C07D499/72 ,  C07D501/06 ,  C07D501/20 ,  C07D501/22 ,  C07D501/26 ,  C07D501/28 ,  C07D501/32 ,  C07D501/34 ,  C07D501/60

CPC分类号： C07D499/00

摘要： This invention relates to a process for the preparation of acid amides having the formula (I) or their salts ##STR1## wherein R.sup.1 is hydrogen or an easily removable ester-forming or salt-forming group, preferably a trialkylamine, trialkylsilyl, trichloroethyl, acetoxymethyl, phenacyl, substituted phenacyl, substituted phenyl or benzyl group,R.sup.2 is hydrogen, alkyl group, alkenyl group, alkyl group having an aryl or heterocyclic (preferably furyl or thienyl) - substituent, an aryl group having an alkyl substituent (preferably xylyl), or an aryl, aralkyl or heterocyclic group (preferably a phenyl, thienyl, or furyl group) which can have one or more substituents,R.sup.3 is hydrogen, or substituted or unsubstituted aryl, alkyl, cycloalkyl or aralkyl group, andX is a group of one of the formulae ##STR2## according to the invention an amine of the formula (II), ##STR3## wherein R.sup.4 is an easily removable ester-forming group, preferably a trialkylamino, trialkylsilyl, trichloroethyl, acetoxymethyl, phenacyl, substituted phenacyl, substituted phenyl or benzyl group, or a salt formed preferably with an alkali metal or a trialkylamine, is acylated with an ester of the formula (III), ##STR4## wherein R.sup.5 is a substituted or unsubstituted aryl, alkyl, cycloalkyl or aralkyl group, and, if desired, substituents R.sup.4 and/or R.sup.5 of the obtained product can be split off, and/or, if desired, the obtained product is converted into its salt or a salt is converted into the free acid.

摘要翻译： 本发明涉及一种制备具有式（I）的酸酰胺或其盐（Ⅰ）的方法，其中R1是氢或易于除去的形成酯或成盐基团，优选三烷基胺，三烷基甲硅烷基， 三氯乙基，乙酰氧基甲基，苯甲酰甲基，取代的苯甲酰甲基，取代的苯基或苄基，R2是氢，烷基，烯基，具有芳基或杂环（优选呋喃基或噻吩基） - 取代基的烷基，具有烷基取代基的芳基 二甲苯基）或可具有一个或多个取代基的芳基，芳烷基或杂环基（优选苯基，噻吩基或呋喃基），R 3为氢或取代或未取代的芳基，烷基，环烷基或芳烷基，X为 根据本发明的一组式（IMAGE），式（II）的胺，其中R 4是易于除去的酯形成基团，优选三烷基氨基，三烷基甲硅烷基，三氯乙基，乙酰氧基 乙基，苯甲酰甲基，取代的苯甲酰甲基，取代的苯基或苄基，或优选与碱金属或三烷基胺形成的盐，用式（III）的酯，其中R5是取代或 未取代的芳基，烷基，环烷基或芳烷基，并且如果需要，所得产物的取代基R 4和/或R 5可以被分离，和/或如果需要，将得到的产物转化为其盐或盐被转化 进入游离酸。

公开(公告)号：US4299955A

公开(公告)日：1981-11-10

申请号：US132761

申请日：1980-03-24

申请人： Marco Falciani ,  Renato Broggi

发明人： Marco Falciani ,  Renato Broggi

IPC分类号： A61K20060101 ,  A61K31/545 ,  C07D501/00 ,  C07D501/04 ,  C07D501/06 ,  C07D501/20 ,  C07D501/22

CPC分类号： C07D501/22

摘要： Process for preparing cephalexine monohydrate and cephadroxyl monohydrate, according to which a reaction is carried out of a mixed anhydride prepared from a Dane salt of phenylglycine or p-hydroxyphenyl-glycine with a chloroformiate, with an aqueous solution of 7-ADCA in a solvent selected from the group comprising dimethyl sulphoxide, dimethylacetamide, formamide, dimethylformamide and dioxane.

摘要翻译： 制备头孢氨苄一水合物和甲肾上腺素一水合物的方法，根据该方法，将由苯基甘氨酸或对羟基苯基 - 甘氨酸的丹烷盐与氯甲酸酯制备的混合酸酐与选自下列溶剂的7-ADCA水溶液进行反应 由二甲基亚砜，二甲基乙酰胺，甲酰胺，二甲基甲酰胺和二恶烷组成。

公开(公告)号：US4281117A

公开(公告)日：1981-07-28

申请号：US183918

申请日：1980-09-04

申请人： Pamela A. Chauvette ,  Robert R. Chauvette

发明人： Pamela A. Chauvette ,  Robert R. Chauvette

IPC分类号： C07D501/06 ,  C07D501/04 ,  C07D501/59 ,  C07D501/60

CPC分类号： C07D501/04

摘要： 7-Amino-3-hydroxy-3-cephem esters react with a chlorinating agent, e.g. phosgene, thionyl chloride and preferably PCl.sub.3 -DMF to provide 7.beta.-[(dimethylaminomethylene)amino]-3-chloro-3-cephem esters which on reaction with a carboxylic acid, a percarboxylic acid, or a phenol, having a pH in water of about 2-5, afford 7.beta.-formamido-3-chloro-3-cephem esters, and corresponding 2-cephem esters. Percarboxylic acids provide 7.beta.-formamido-3-chloro-3-cephem ester 1-oxides. The 7-formamido derivatives provide the 7-amino-3-chloro-3-cephem ester on acid hydrolysis. The 7-amino-3-chloro esters are useful for preparing antibiotics.

摘要翻译： 7-氨基-3-羟基-3-头孢烯酯与氯化剂反应，例如， 光气，亚硫酰氯，优选PCl 3-DMF，得到7β-[（二甲基氨基亚甲基）氨基] -3-氯-3-头孢烯酯，其与羧酸，过羧酸或苯酚反应，其具有在水中的pH 约2-5，得到7β-甲酰胺基-3-氯-3-头孢烯酯和相应的2-头孢烯酯。 过羧酸提供7β-甲酰胺基-3-氯-3-头孢烯酯1-氧化物。 7-甲酰氨基衍生物在酸水解时提供7-氨基-3-氯-3-头孢烯酯。 7-氨基-3-氯酯可用于制备抗生素。

公开(公告)号：US4248868A

公开(公告)日：1981-02-03

申请号：US14454

申请日：1979-02-23

申请人： Riccardo Scartazzini ,  Hans Bickel

发明人： Riccardo Scartazzini ,  Hans Bickel

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D20060101 ,  C07D501/04 ,  C07D501/06 ,  C07D501/14 ,  C07D501/16 ,  C07D501/20 ,  C07D501/22 ,  C07D501/24 ,  C07D501/26 ,  C07D501/60

CPC分类号： C07D501/04 ,  C07D501/14

摘要： The invention comprises carbonylmethyl derivatives of the formula IA and corresponding carbonylmethylene derivatives of the formula IB ##STR1## in which R.sub.1.sup.a represents a member of the group comrising hydrogen and an acyl radical of the formula AR.sub.a --C(R.sub.b)(R.sub.c)--C(.dbd.O)-- (A)in which R.sub.a represents a member of the group comprising optionally substituted phenyl, thienyl, furyl, cyclohexadienyl and cyclohexenyl, R.sub.b represents hydrogen and R.sub.c represents a member of the group comprising hydrogen, optionally protected hydroxyl, optionally protected amino and phenyl-lower protected sulpho, or in which R.sub.a represents a member of the group comprising cyano, optionally substituted phenoxy, pyridylthio, and tetrazolyl, and R.sub.b and R.sub.c each represent hydrogen, or in which R.sub.a represents a member of the group comprising phenyl, thienyl, furyl, and R.sub.b and R.sub.c together denote a member of the group comprising lower alkoxyimino, cycloalkoxyimino and phenyl-lower alkoxyimino in the syn-configuration, and such a group of the formula (A) contains at most one free amino group, R.sub.1.sup.b represents hydrogen, R.sub.2 represents a member of the group comprising hydroxyl, .alpha.-poly-branched lower alkoxy and 2-halogeno-lower alkoxy, which can easily be converted into the latter, and also phenacyloxy, 1-phenyl-lower alkoxy which has 1-3 phenyl radicals which are optionally substituted by lower alkoxy or nitro, lower alkanoyloxymethoxy, .alpha.-amino-lower alkanoyloxymethoxy, or 2-phthalidyloxy, and also tris-lower alkylsilyloxy, and R.sub.3 represents a member of the group comprising hydrogen, lower alkyl, cycloalkyl, phenyl which is optionally substituted by lower alkyl, lower alkoxy or halogen, phenyllower alkyl which is optionally substituted by nitro, lower alkyl, lower alkoxy or halogen, hydroxyl, etherified hydroxyl, especially lower alkoxy, above all methoxy, amino, lower alkylamino, di-lower alkylamino, lower alkyleneamino, oxa-lower alkylenamino, phenylamino, hydroxylamino, lower alkoxyamino, hydrazino, 2-lower alkylhydrazino, 2-phenylhydrazino, 4-lower alkylpiperazin-1-ylamino, lower alkylamino which is substituted by amino and/or carboxyl, and heterocyclylamino which is optionally substituted by lower alkyl, and wherein the heterocyclyl radical preferably contains 5-6 rings members and contains, as hetero-atoms, nitrogen, which is optionally also in the N-oxidized form, oxygen or sulphur and 1-oxides and salts of such compounds, which compounds are active against microorganisms, such as Gram-positive and Gram-negative bacteria, and pharmaceutical preparations containing these compounds.

公开(公告)号：US4172892A

公开(公告)日：1979-10-30

申请号：US868665

申请日：1978-01-11

申请人： Giuliano Nannini ,  Ettore Perrone ,  Dino Severino ,  Giuseppe Meinardi ,  Gisella Monti ,  Alberta Bianchi ,  Angelo Forgione ,  Carlo Confalonieri

发明人： Giuliano Nannini ,  Ettore Perrone ,  Dino Severino ,  Giuseppe Meinardi ,  Gisella Monti ,  Alberta Bianchi ,  Angelo Forgione ,  Carlo Confalonieri

IPC分类号： C07D501/04 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07C20060101 ,  C07D20060101 ,  C07D499/00 ,  C07D501/00 ,  C07D501/06 ,  C07D501/20 ,  C07D501/24 ,  C07D501/26 ,  C07D501/28 ,  C07D501/36 ,  C07D501/40 ,  C07D501/50 ,  C07D501/60

CPC分类号： C07C323/60

摘要： Heteromonocyclic and heterobicyclic derivatives of unsaturated 7-acylamido-3-cephem-4-carboxylic acid are disclosed which exhibit antibacterial activity against Gram-positive and Gram-negative microorganisms and can be used to treat infections caused by such microorganisms.

摘要翻译： 公开了不饱和7-酰基氨基-3-头孢烯-4-羧酸的杂环和杂双环衍生物，其表现出对革兰氏阳性和革兰氏阴性微生物的抗菌活性，并且可用于治疗由这种微生物引起的感染。

公开(公告)号：US4125611A

公开(公告)日：1978-11-14

申请号：US745749

申请日：1976-11-29

申请人： Hirotada Yamade ,  Takenari Nakagome ,  Toshiaki Komatsu

发明人： Hirotada Yamade ,  Takenari Nakagome ,  Toshiaki Komatsu

IPC分类号： A61K20060101 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D20060101 ,  C07D501/04 ,  C07D501/06 ,  C07D501/20 ,  C07D501/24 ,  C07D501/28 ,  C07D501/32 ,  C07D501/34 ,  C07D501/36 ,  C07D501/40 ,  C07D501/44 ,  C07D501/46 ,  C07D501/56 ,  C07D501/57 ,  C07D501/60 ,  C07D519/06

CPC分类号： C07D501/57 ,  Y02P20/55

摘要： A cephalosporin of the formula (I): ##STR1## wherein A is a mono- or polycyclic heteroaromatic ring containing at least one nitrogen atom as a hetero atom, which may be unsubstituted or substituted; R is a phenyl group which may be unsubstituted or substituted, a thienyl group, a furyl group, a cyclohexadienyl group or a cyclohexenyl group; X is an acetoxy group, a pyridinium group which may be unsubstituted or substituted with a methyl or carbamoyl group, a group of the formula: ##STR2## in which R.sub.1 and R.sub.2, which may be the same or different, each is a hydrogen atom or a (C.sub.1 - C.sub.4) alkyl group, or a group of the formula:-S-Hetin which Het is a heterocyclic ring containing 1 to 5 oxygen, nitrogen and sulfur atoms as a hetero atom, in which the heterocyclic ring system may be either polycyclic or 5- or 6-membered monocyclic and may be unsubstituted or substituted; and M is a hydrogen atom or a biologically active carboxyl-protecting group, or is an anionic charge only when X is a pyridinium group; and the pharmaceutically acceptable salts thereof, which are useful as antimicrobial agents and prepared by the reaction of a compound of the formula (II):ho--a--cooh (ii)wherein A is as defined above, or a reactive derivative thereof, with a compound of the formula (III): ##STR3## wherein R, M and X are as defined above, or a derivative thereof.

摘要翻译： 式（I）的头孢菌素：其中A是含有至少一个氮原子作为杂原子的单环或多环杂芳环，其可以是未取代的或取代的; R是可以是未取代或取代的苯基，噻吩基，呋喃基，环己二烯基或环己烯基; X是乙酰氧基，可以是未取代的或被甲基或氨基甲酰基取代的吡啶鎓基，下式的基团：其中R 1和R 2可以相同或不同，各自为氢原子 或（C 1 -C 4）烷基，或下式的基团：

公开(公告)号：US4073687A

公开(公告)日：1978-02-14

申请号：US686219

申请日：1976-05-12

申请人： Eiji Kondo ,  Takashi Mitsugi

发明人： Eiji Kondo ,  Takashi Mitsugi

IPC分类号： C07D499/12 ,  C07D499/64 ,  C07D501/06 ,  C07D501/22 ,  C07D501/32 ,  C12P35/04 ,  C12P37/04 ,  C12D1/02

CPC分类号： C12P35/04 ,  Y10S435/911 ,  Y10S435/925

摘要： Penicillin or cephalosporin antibiotics represented by following formula: ##STR1## where ##STR2## is an acyl group derived from an .alpha.-amino acid, N-ammonium salt of .alpha.-amino acid, or N--(C.sub.1 to C.sub.10) acyl-.alpha.-amino acid; COOM is carboxy or carboxylate salt group!Are prepared by treating an amino compound selected from a group consisting of 6-aminopenicillanic acid, 7-aminocephalosporanic acid, 7-aminodeacetoxycephalosporanic acid, and their salts with an ester represented by following formula:RCOOR.sup.1 where ##STR3## is as defined above and R.sup.1 is a (C.sub.1 to C.sub.10) alkyl group! BY ENZYMATIC ACYLATION EFFECTED WITH MYCELIUM OR MYCELIUM PREPARATION FROM A MICROORGANISM BELONGING TO GENUS Aphanocladium or Cephalosporium.

摘要翻译： 由下列化学式表示的青霉素或头孢菌素抗生素： 其中是衍生自α-氨基酸，α-氨基酸N-铵盐或N-（C1 至C10）酰基-α-氨基酸; COOM是羧基或羧酸盐基团]通过处理由含有6-氨基苯甲酸，7-氨基戊酸，4-氨基乙酰氧基苯甲酸的组合选择的氨基化合物及其与以下公式表示的酯的盐：

公开(公告)号：US4051129A

公开(公告)日：1977-09-27

申请号：US630816

申请日：1975-11-11

申请人： Bunji Shimizu ,  Akio Saito ,  Masakatsu Kaneko ,  Hiroaki Yanagisawa ,  Hideo Nakao

发明人： Bunji Shimizu ,  Akio Saito ,  Masakatsu Kaneko ,  Hiroaki Yanagisawa ,  Hideo Nakao

IPC分类号： C07D501/04 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/06 ,  C07D501/16 ,  C07D501/18 ,  C07D501/22 ,  C07D501/24 ,  C07D501/26 ,  C07D501/28 ,  C07D501/34 ,  C07D501/36 ,  C07D501/40 ,  C07D501/46 ,  C07D501/57 ,  C07D501/60

CPC分类号： C07D501/57 ,  Y02P20/55

摘要： A process for preparing 7.alpha.-methoxycephalosporin compounds which comprises reacting a salt of a 7.beta.-benzylideneamino-7.alpha.-methoxy-3-cephem-4-carboxylic acid with a hydrazine compound to give a salt of a 7.beta.-amino-7.alpha.-methoxy-3-cephem-4-carboxylic acid and reacting the latter compound with a carboxylic acid or its reactive derivative. The products are useful as antibacterial agents.

摘要翻译： 一种制备7α-甲氧头孢菌素化合物的方法，其包括使7β-亚苄基氨基-7α-甲氧基-3-头孢烯-4-羧酸的盐与肼化合物反应，得到7β-氨基-7 α-甲氧基-3-头孢烯-4-羧酸，并使后一化合物与羧酸或其反应性衍生物反应。 该产品可用作抗菌剂。

公开(公告)号：US4034088A

公开(公告)日：1977-07-05

申请号：US573110

申请日：1975-04-30

申请人： Christian Berger ,  Daniel Farge ,  Georges Gros ,  Mayer Naoum Messer ,  Claude Moutonnier

发明人： Christian Berger ,  Daniel Farge ,  Georges Gros ,  Mayer Naoum Messer ,  Claude Moutonnier

IPC分类号： C07D501/06 ,  A61K20060101 ,  A61K31/545 ,  A61K31/546 ,  C07D20060101 ,  C07D501/04 ,  C07D501/16 ,  C07D501/20 ,  C07D501/22 ,  C07D501/24 ,  C07D501/26 ,  C07D501/34 ,  C07D501/36 ,  C07D501/46 ,  C07D501/60

CPC分类号： C07D501/20

摘要： New cephalosporin derivatives of the general formula: ##STR1## in which R represents a straight or branched chain C.sub.1-4 alkyl radical, or a phenyl (straight or branched chain C.sub.1-4 alkyl) radical, n is 0, 1 or 2, and either R.sub.1 is a pyridinio ion and R.sub.2 is a carboxylato ion, or R.sub.1 represents a hydrogen atom, or an acetoxy, (5-methyl-1,3,4-thiadiazol-2-yl)-thio or (1-methyl-1,2,3,4-tetrazol-5-yl)-thio radical and R.sub.2 represents a carboxy radical or a radical of the formula; ##STR2## in which the radical: ##STR3## is a radical which can be removed easily by enzymatic means and in which R.sub.3 represents a hydrogen atom or a straight or branched chain C.sub.1-4 alkyl radical, a phenyl radical or a phenyl (C.sub.1-2 alkyl) radical and R.sub.4 represents a straight or branched chain C.sub.1-4 alkyl radical, a straight or branched chain C.sub.1-4 alkoxy radical, a cyclohexyl radical, a phenyl radical or a phenyl (C.sub.1-2 alkyl) radical;With the proviso that when R is an alkyl radical and either R.sub.1 is a hydrogen atom or an acetoxy radical and R.sub.2 is a carboxy radical or R.sub.1 is a pyridinio ion and R.sub.2 is a carboxylato ion, n is 1 or 2, and metal salts thereof and addition salts thereof with nitrogen-containing bases are new compounds; they possess valuable antibacterial properties, showing activity against both Gram-positive and Gram-negative bacteria.

摘要翻译： 新的头孢菌素衍生物，其通式为：其中R表示直链或支链C 1-4烷基或苯基（直链或支链C 1-4烷基）基团，n为0,1或2，以及 R1是吡啶鎓离子，R2是羧基离子，或R1代表氢原子，或乙酰氧基，（5-甲基-1,3,4-噻二唑-2-基） - 硫代或（1-甲基-1 ，2,3,4-四唑-5-基） - 硫基，R 2表示下式的羧基或基团： ，其中基团：是可以通过酶学方法容易地除去的基团，其中R 3表示氢原子或直链或支链C 1-4烷基，苯基或苯基（C 1 -2烷基）基，R 4表示直链或支链C 1-4烷基，直链或支链C 1-4烷氧基，环己基，苯基或苯基（C 1-2烷基）基; 当R为烷基且R 1为氢原子或乙酰氧基且R 2为羧基或R 1为吡啶并且R 2为羧基离子时，n为1或2，其金属盐为 其与含氮碱的加成盐是新化合物; 它们具有有价值的抗菌性能，显示出对革兰氏阳性菌和革兰氏阴性菌的活性。