公开(公告)号：US4359473A

公开(公告)日：1982-11-16

申请号：US72234

申请日：1979-09-04

Applicant: Irene Stirling ,  Brian P. Clarke

Inventor： Irene Stirling ,  Brian P. Clarke

IPC: A61K31/42 ,  C07D503/00 ,  C07D498/04

CPC classification number: C07D503/00 ,  A61K31/42

Abstract: The compounds of the formula (XVII) ##STR1## and their esters wherein R.sub.2 is a hydrogen, fluorine, chlorine or bromine atom or an alkyl group of 1-3 carbon atoms, an alkoxyl group of 1-3 carbon atoms, an acyloxyl group of 1-3 atoms, a hydroxyl group, an alkoxycarbonyl group containing 1-3 carbon atoms in the alkoxy part, or a group --N(R.sub.5)CO.R.sub.6, --N(R.sub.5)SO.sub.2 R.sub.6 or --CO-NR.sub.5 R.sub.6 where R.sub.5 is a hydrogen atom or an alkyl group of 1-3 carbon atoms or a phenyl or benzyl group and R.sub.6 is an alkyl group of 1-3 carbon atoms or a phenyl or benzyl group; R.sub.3 is a hydrogen, fluorine or chlorine atom or an alkyl group of 1-3 carbon atoms, an alkoxyl group of 1-3 carbon atoms; or an acyloxyl group of 1-3 carbon atoms R.sub.4 is a hydrogen fluorine or chlorine atom or an alkyl group of 1-3 atoms or an alkoxyl group of 1-3 carbon atoms; and X is a bond or alkylene group of 1-4 carbon atoms; have been found to be .beta.-lactamase inhibitors and antibacterial agents. Their preparation and use is described.

Abstract translation: 式（XVII）化合物（XVII）及其酯，其中R2是氢，氟，氯或溴原子或1-3个碳原子的烷基，1-3个碳原子的烷氧基， 1-3个原子的酰氧基，羟基，烷氧基部分含有1-3个碳原子的烷氧基羰基，或基团-N（R5）CO.R6，-N（R5）SO2R6或-CO-NR5R6 其中R5是氢原子或1-3个碳原子的烷基或苯基或苄基，R6是1-3个碳原子的烷基或苯基或苄基; R3是氢，氟或氯原子或1-3个碳原子的烷基，1-3个碳原子的烷氧基; 或1-3个碳原子的酰氧基R 4是氢或氯原子或1-3个原子的烷基或1-3个碳原子的烷氧基; X为1-4个碳原子的键或亚烷基; 已被发现是β-内酰胺酶抑制剂和抗菌剂。 描述了它们的制备和使用。

公开(公告)号：US4293555A

公开(公告)日：1981-10-06

申请号：US83721

申请日：1979-10-10

Applicant: Burton G. Christensen ,  Frank P. DiNinno

Inventor： Burton G. Christensen ,  Frank P. DiNinno

IPC: C07D205/08 ,  C07D213/70 ,  C07D249/02 ,  C07D257/04 ,  C07D307/64 ,  C07D333/34 ,  C07D409/06 ,  C07D498/04 ,  C07D499/00 ,  C07D503/00 ,  A61K31/42

CPC classification number: C07D213/70 ,  C07C327/00 ,  C07D205/08 ,  C07D249/02 ,  C07D257/04 ,  C07D307/64 ,  C07D333/34 ,  C07D499/00 ,  C07D503/00

Abstract: Disclosed are 6- and 6,6-disubstituted-2-substituted-oxapen-2-em-3-carboxylic acids of the following structure: ##STR1## wherein: R.sup.1 and R.sup.2 are independently selected from hydrogen, alkyl, alkoxyl, aralkyl, aryl, heterocyclyl and heterocyclylalkyl; R is selected from hydrogen, --OR, --SR, --NR.sub.2, alkyl, aryl, aralkyl, heterocyclyl, or heterocyclylalkyl. Such compounds and their pharmaceutically acceptable salt, and ester derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

Abstract translation: 公开了以下结构的6-和6,6-二取代-2-取代 - 氧杂-2-烯-3-羧酸：其中：R 1和R 2独立地选自氢，烷基，烷氧基，芳烷基， 芳基，杂环基和杂环基烷基; R选自氢，-OR，-SR，-NR 2，烷基，芳基，芳烷基，杂环基或杂环基烷基。 这些化合物及其药学上可接受的盐和酯衍生物可用作抗生素。 还公开了制备这些化合物的方法，包含这些化合物的药物组合物和治疗方法，包括当指出抗生素作用时施用这些化合物和组合物。

公开(公告)号：US4275067A

公开(公告)日：1981-06-23

申请号：US932489

申请日：1978-08-10

Applicant: Eric Hunt

Inventor： Eric Hunt

IPC: A61K31/42 ,  A61P31/04 ,  A61P31/10 ,  C07D503/00 ,  C07D498/04

CPC classification number: C07D503/00

Abstract: Compounds of the formula (II): ##STR1## wherein X is S, SO or SO.sub.2 ; and R is (a) an alkyl group of up to 4 carbon atoms, (b) an alkyl group of up to 4 carbon atoms substituted by an OR.sup.1, NHR.sup.1, NH.CO.R.sup.1 or CO.sub.2 R.sup.2 group wherein R.sup.1 is a hydrogen atoms, an alkyl group of up to 4 carbon atoms or benzyl group, and R.sup.2 is a moiety such that CO.sub.2 R.sup.2 is a carboxyl, salted carboxyl or esterified carboxyl group, (c) an aryl group or (d) an aralkyl group are useful for their anti-fungal and .beta.-lactamase inhibitory properties.

Abstract translation: 式（II）的化合物：其中X是S，SO或SO 2; 并且R是（a）至多4个碳原子的烷基，（b）由OR 1，NHR 1，NH.CO.R 1或CO 2 R 2基团取代的至多4个碳原子的烷基，其中R 1是氢原子， 最多4个碳原子的烷基或苄基，R2是CO 2R2是羧基，盐化羧基或酯化羧基的部分，（c）芳基或（d）芳烷基可用于其抗 - 真菌和β-内酰胺酶抑制性质。

公开(公告)号：US4255332A

公开(公告)日：1981-03-10

申请号：US935887

申请日：1978-08-23

Applicant: Richard V. Davies

Inventor： Richard V. Davies

IPC: C07D503/00 ,  C07D498/04

CPC classification number: C07D503/00

Abstract: The present invention provides a process for the preparation of potassium clavulanate which process comprises contacting a concentrated solution of lithium clavulanate with a concentrated solution of potassium fluoride, potassium orthophosphate, potassium metaphosphate potassium carbonate or potassium bicarbonate, separating off the resulting precipitated lithium fluoride, lithium orthophosphate, lithium metaphosphate or lithium carbonate and thereafter recovering the potassium clavulanate from solution.

Abstract translation: 本发明提供了一种制备克拉维酸钾的方法，该方法包括将克拉维酸钾的浓溶液与氟化钾，正磷酸钾，偏磷酸钾钾或碳酸氢钾的浓溶液接触，分离所得沉淀的氟化锂，锂 正磷酸盐，偏磷酸锂或碳酸锂，然后从溶液中回收克拉维酸钾。

公开(公告)号：US4208325A

公开(公告)日：1980-06-17

申请号：US856121

申请日：1977-11-30

Applicant: Saul Wolfe

Inventor： Saul Wolfe

IPC: C07D205/085 ,  C07D263/58 ,  C07D265/06 ,  C07D265/36 ,  C07D503/00 ,  C07D205/08 ,  C07D403/12 ,  C07D407/12 ,  C07D409/12

CPC classification number: C07D263/58 ,  C07D205/085 ,  C07D265/06 ,  C07D265/36 ,  C07D503/00

Abstract: The invention provides a novel process for opening the ring of 2-R-6-(1'-R.sup.1 -oxycarbonyl-2'-methyl-prop-1'-enyl)-1-oxa-3,6-diaza-4S,5R-bicyclo[3,2,0]hept-2-en-7-one by treatment with a sulfonic acid salt thereby forming R.sup.1 2-(2'R-R-oxy-3'S-amino-4'-oxo)azetidinyl-3-methyl-2-butenoate sulfonic acid salts which can provide oxapenicillins by two different routes depending on the substituent desired on the carboxamido group of the 1-oxapenicillins. In the alternate processes, new intermediates are also provided.

Abstract translation: 本发明提供了一种用于打开2-R-6-（1'-R1-氧羰基-2'-甲基 - 丙-1'-烯基）-1-氧杂-3,6-二氮杂-4,4的环的新方法， 5R-双环[3,2,0]庚-2-烯-7-酮，由此形成R1-2-（2'RR-氧基-3'-氨基-4'-氧代）氮杂环丁烷基-3 2-甲基-2-丁烯酸磺酸盐，其可以根据1-氧杂青霉素的羧酰胺基上所需的取代基通过两种不同的途径提供oxapenicillins。 在替代过程中，还提供了新的中间体。

公开(公告)号：US4187228A

公开(公告)日：1980-02-05

申请号：US880949

申请日：1978-02-24

Applicant: Kong Luk

Inventor： Kong Luk

IPC: C07D503/00 ,  C07D263/14 ,  A61K31/42

CPC classification number: C07D503/00

Abstract: Compounds of the formula (II): ##STR1## wherein R is hydrogen, is useful for its antibacterial activity and as a synergist for penicillins and cephalosporins.

Abstract translation: 式（II）化合物：其中R为氢的化合物可用于其抗菌活性和作为青霉素和头孢菌素的增效剂。

公开(公告)号：US4167630A

公开(公告)日：1979-09-11

申请号：US798287

申请日：1977-05-19

Applicant: Raymond A. Firestone

Inventor： Raymond A. Firestone

IPC: C07D463/00 ,  C07D503/00 ,  C07D505/00 ,  C07D263/52 ,  C07D221/02 ,  C07D239/70 ,  C07D265/12

CPC classification number: C07D505/00 ,  C07D463/06 ,  C07D463/16 ,  C07D503/00

Abstract: Through total synthesis methods developed in the assignee's laboratories, new as well as old penicillin and cephalosporin compounds (all containing the beta-lactam functional group) have been prepared. One of the key intermediates prepared by total synthesis has the 7-amino (6-amino in the case of a penicillin derivative) group in the alpha configuration. The instant invention provides a general route for preparing the 7.beta.-amino (or 6.beta.-amino) compound, through the formation of an imino-containing intermediate, followed by hydrolysis to the desired epimer. Novel intermediate products are provided. The compounds having the desired beta epimer can be converted to acylaminoantibiotics.

Abstract translation: 通过受让人实验室开发的全合成方法，制备了新的以及老青霉素和头孢菌素化合物（均含有β-内酰胺官能团）。 通过全合成制备的关键中间体之一是α构型中的7-氨基（在青霉素衍生物的情况下为6-氨基）。 本发明提供通过形成含亚氨基的中间体然后水解成所需的差向异构体来制备7β-氨基（或6β-氨基）化合物的一般途径。 提供新的中间产品。 具有所需β-差向异构体的化合物可以转化为酰基氨基抗生素。

公开(公告)号：US4166904A

公开(公告)日：1979-09-04

申请号：US880948

申请日：1978-02-24

Applicant: Eric Hunt

Inventor： Eric Hunt

IPC: C07D503/00 ,  C07D263/52

CPC classification number: C07D503/00

Abstract: Compounds of the formula (II) ##STR1## wherein R.sub.1 is CH.sub.3, CH.sub.2 OH, CHO or CH.sub.2 OCOR.sub.4 wherein R.sub.4 is a hydrocarbon of 1-7 carbon atoms andR.sub.2 is a group of the formula R.sub.3 or COR.sub.3 wherein R.sub.3 is a hydrocarbon of 1-7 carbon atoms optionally inertly substituted by halogen are useful as antibacterial agents and .beta.-lactamase inhibitory agents.

Abstract translation: 式（II）化合物其中R1是CH3，CH2OH，CHO或CH2OCOR4，其中R4是1-7个碳原子的烃基，R2是式R3或COR3的基团，其中R3是烃 任选被卤素惰性取代的1-7个碳原子可用作抗菌剂和β-内酰胺酶抑制剂。

公开(公告)号：US4145430A

公开(公告)日：1979-03-20

申请号：US921738

申请日：1978-07-03

Applicant: Eric Hunt

Inventor： Eric Hunt

IPC: A61K31/42 ,  A61P31/04 ,  C07D498/14 ,  C07D503/00 ,  C07D498/04

CPC classification number: C07D503/00

Abstract: The compounds of the formula (I): ##STR1## wherein X represents a moiety of the sub-formula (a) or (b): ##STR2## HAVE BEEN FOUND TO BE .beta.-LACTAMASE INHIBITORS WHICH MAY BE USED IN PHARMACEUTICAL COMPOSITIONS TO ENHANCE THE EFFECTIVENESS OF PENICILLINS OR CEPHALOSPORINS. The diene of the formula (I) may be produced by the decarboxylation of clavulanic acid or a derivative thereof and the monoene of the formula (I) may be produced by the 1,4 addition of hydrogen to the diene of the formula (I). The diene is thus also useful as a chemical intermediate and other such uses are demonstrated.

Abstract translation: 已经发现式（I）化合物：其中X代表子式（a）或（b）的部分：是β-内酰胺酶抑制剂，其可以用于药物组合物中 提高青霉素或头孢菌素的有效性。 式（I）的二烯可以通过克拉维酸或其衍生物的脱羧产生，式（I）的单烯可以通过向式（I）的二烯加1,4氢来制备， 。 因此，二烯也可用作化学中间体，并且证明了其它此类用途。

公开(公告)号：US4140764A

公开(公告)日：1979-02-20

申请号：US809995

申请日：1977-06-27

Applicant: Thomas T. Howarth

Inventor： Thomas T. Howarth

IPC: A61K31/42 ,  A61K31/43 ,  A61K31/545 ,  C07D503/00 ,  C12P17/18

CPC classification number: C07D503/00 ,  A61K31/42 ,  A61K31/43 ,  A61K31/545 ,  C12P17/188

Abstract: .beta.-Lactamase inhibitory and antibacterial compounds of the formula: ##STR1## wherein R is a hydrogen atom or an acyl group and salts and esters thereof, are produced and pharmaceutical compositions containing the same.

Abstract translation: 制备下式的β-内酰胺酶抑制剂和抗菌化合物：其中R是氢原子或酰基及其盐和酯，其中含有它们的药物组合物。