公开(公告)号：US4290949A

公开(公告)日：1981-09-22

申请号：US809915

申请日：1977-06-24

申请人： Peter C. Cherry ,  Christopher E. Newall ,  Nigel S. Watson ,  Gordon I. Gregory ,  Peter Ward

发明人： Peter C. Cherry ,  Christopher E. Newall ,  Nigel S. Watson ,  Gordon I. Gregory ,  Peter Ward

IPC分类号： C07D503/00 ,  C07D498/04

CPC分类号： C07D503/00

摘要： 2-Vinylclavem compounds are disclosed which have been found of value in the synthesis of thio-derivatives of clavulanic acid which possess antibiotic and .beta.-lactamase inhibitory activity. Methods for preparing the vinylclavem compounds are disclosed and processes for preparing the thio-derivatives are given.

摘要翻译： 公开了已经发现在合成具有抗生素和β-内酰胺酶抑制活性的克拉维酸硫代衍生物中有价值的2-乙烯基化合物。 公开了制备乙烯基化合物的方法，并给出了制备硫代衍生物的方法。

公开(公告)号：US4228074A

公开(公告)日：1980-10-14

申请号：US831549

申请日：1977-09-08

申请人： Peter C. Cherry ,  Christopher E. Newall ,  Nigel S. Watson

发明人： Peter C. Cherry ,  Christopher E. Newall ,  Nigel S. Watson

IPC分类号： C07D205/08 ,  C07D503/00 ,  C07F7/18 ,  C07D405/12 ,  C07D413/04 ,  C07D417/04

CPC分类号： C07F7/186 ,  C07D205/08 ,  C07D503/00

摘要： .beta.-Lactam compounds of the formula (I) ##STR1## (wherein R represents an esterified carboxyl group, --NR.sup.1 R.sup.2 R.sup.3 represents the residue of a nitrogen base, and R.sup.4 represents a hydrogen atom, a hydroxyl group or acylated or etherified hydroxyl group or the residue of a sulphur nucleophile) are disclosed, together with processes for their preparation. The compounds are valuable intermediates for the preparation or purification of further .beta.-lactam compounds having .beta.-lactamase inhibitory activity.

摘要翻译： 式（I）的β-内酰胺化合物（I）（其中R表示酯化的羧基，-NR 1 R 2 R 3表示氮基的残基，R 4表示氢原子，羟基或酰化或醚化的羟基 基团或硫亲核试剂的残基）及其制备方法。 该化合物是制备或纯化具有β-内酰胺酶抑制活性的其它β-内酰胺化合物的有价值的中间体。

公开(公告)号：US4427675A

公开(公告)日：1984-01-24

申请号：US306729

申请日：1981-09-29

申请人： Barry E. Ayres ,  Cynthia H. O'Callaghan ,  David G. H. Livermore ,  Christopher E. Newall

发明人： Barry E. Ayres ,  Cynthia H. O'Callaghan ,  David G. H. Livermore ,  Christopher E. Newall

IPC分类号： A61K20060101 ,  A61K31/545 ,  A61K31/55 ,  C07D20060101 ,  C07D501/38 ,  C07D501/46 ,  C07D501/56

CPC分类号： C07D501/46

摘要： Cephalosporin antibiotics of general formula ##STR1## (wherein R.sup.a and R.sup.b, which may be the same or different, each represent a C.sub.1-4 alkyl group, or together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene group). These compounds exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms.Particularly effective compounds of formula (I) are (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamio]-3-(pyridazinium-1-ylmethyl)ceph-3-em-4-carboxylate and (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(t-carboxycyclobut-1-oxyimino)acetamido]-3-(pyridazinium-1-ylmethyl)ceph-3-em-4-carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I), compositions containing the antibiotic compounds of the invention and a method of combatting bacterial infection utilizing the antibiotics.

摘要翻译： 通式（I）（I）的头孢菌素抗生素（其中可以相同或不同的R a和R b各自表示C 1-4烷基，或与它们所连接的碳原子一起形成C3-7 环亚烷基）。 这些化合物表现出广谱抗生素活性，对于革兰氏阴性生物体如假单胞菌属生物菌株，其活性异常高。 特别有效的式（I）化合物是（6R，7R）-7 - [（Z）-2-（2-氨基噻唑-4-基）-2-（2-羧基-2-氧亚氨基）乙酰胺] -3 - （哒嗪鎓-1-基甲基）头孢-3-烯-4-羧酸酯和（6R，7R）-7 - [（Z）-2-（2-氨基噻唑-4-基）-2-（叔 - 羧基环 - -1-乙酰氨基）乙酰氨基] -3-（哒嗪鎓-1-基甲基）头孢-3-烯-4-羧酸酯。 本发明还包括式（I）化合物的无毒盐和无毒代谢不稳定酯，含有本发明抗生素化合物的组合物和利用抗生素对抗细菌感染的方法。

公开(公告)号：US4464368A

公开(公告)日：1984-08-07

申请号：US285966

申请日：1981-07-23

申请人： Cynthia H. O'Callaghan ,  Barry E. Ayres ,  Christopher E. Newall ,  David G. H. Livermore ,  Derek R. Sutherland

发明人： Cynthia H. O'Callaghan ,  Barry E. Ayres ,  Christopher E. Newall ,  David G. H. Livermore ,  Derek R. Sutherland

IPC分类号： C07D277/20 ,  C07D501/46 ,  C07D501/38 ,  A61K31/425

CPC分类号： C07D277/587

摘要： Cephalosporin antibiotics of general formula ##STR1## (wherein R.sup.a and R.sup.b, which may be the same or different, each represent a C.sub.1-4 alkyl group, or together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene group and R.sup.1 represents a C.sub.1-4 alkyl group) exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms.Particularly effective compounds of formula (I) are (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(2-methylpyrazolium-1-ylmethyl)ceph-3-em-4-carboxylate and (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-carboxycyclobut-1-oxyimino)acetamido]-3-(2-methylpyrazolium-1-ylmethyl)]ceph-3-em-4-carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I), compositions containing the antibiotic compounds of the invention, and methods for combatting bacterial infections utilizing the antibiotics.

摘要翻译： 通式（I）（I）的头孢菌素抗生素（其中可以相同或不同的R a和R b各自表示C 1-4烷基，或与它们所连接的碳原子一起形成C3-7 环烷叉基，R 1表示C 1-4烷基）表现出广谱抗生素活性，对革兰氏阴性生物如假单胞菌属生物体的活性异常高。 特别有效的式（I）化合物是（6R，7R）-7 - [（Z）-2-（2-氨基噻唑-4-基）-2-（2-羧基-2-氧亚氨基）乙酰氨基] -3 - （2-甲基吡唑-1-基甲基）头孢-3-烯-4-羧酸酯和（6R，7R）-7 - [（Z）-2-（2-氨基噻唑-4-基）-2 - [（1 - 羧基环丁-1-氧基咪唑o）乙酰氨基] -3-（2-甲基吡唑鎓-1-基甲基）]头孢-3-烯-4-羧酸乙酯。 本发明还包括式（I）化合物的无毒盐和无毒代谢不稳定的酯，含有本发明的抗生素化合物的组合物，以及利用抗生素对抗细菌感染的方法。

公开(公告)号：US4504477A

公开(公告)日：1985-03-12

申请号：US285492

申请日：1981-07-21

申请人： Cynthia H. O'Callaghan ,  Barry E. Ayres ,  David G. H. Livermore ,  Christopher E. Newall ,  Niall G. Weir

发明人： Cynthia H. O'Callaghan ,  Barry E. Ayres ,  David G. H. Livermore ,  Christopher E. Newall ,  Niall G. Weir

IPC分类号： C07D501/56 ,  A61K20060101 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D20060101 ,  C07D501/36 ,  C07D501/46

CPC分类号： C07D501/36

摘要： Cephalosporin antibiotics of general formula ##STR1## (wherein Y.sup..sym. represents a C-attached 1-C.sub.1-4 alkylpyridinium group) exhibit broad spectrum antibiotic activity with unusually high activity against strains of Pseudomonas organisms as well as high activity against various members of the Enterobacteriaceae. The invention also includes the non-toxic salts, non-toxic metabolically labile esters and 1-oxides of compounds of formula (I). Also described are compositions containing the antibiotics of the invention and processes for the preparation of the antibiotics.

摘要翻译： 具有通式（I）（其中Y（+）表示C-连接的1-C 1-4烷基吡啶基）的头孢菌素抗生素表现出广谱抗生素活性，对假单胞菌生物体的菌株具有异常高的活性，以及​​对各种 肠杆菌科的成员。 本发明还包括式（I）化合物的无毒盐，无毒代谢不稳定的酯和1-氧化物。 还描述了含有本发明的抗生素和制备抗生素的方法的组合物。

公开(公告)号：US4600772A

公开(公告)日：1986-07-15

申请号：US417656

申请日：1982-09-13

申请人： Cynthia H. O'Callaghan ,  David G. H. Livermore ,  Christopher E. Newall

发明人： Cynthia H. O'Callaghan ,  David G. H. Livermore ,  Christopher E. Newall

IPC分类号： C07D501/06 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D20060101 ,  C07D277/20 ,  C07D501/04 ,  C07D501/46 ,  C07D501/56 ,  C07D501/60 ,  C07D501/38

CPC分类号： C07D277/20 ,  C07D277/587

摘要： Cephalosporin antibiotics of the general formula ##STR1## (wherein R.sup.a and R.sup.b, which may be the same or different, each represent a C.sub.1-4 alkyl group or R.sup.a and R.sup.b together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene group; and R.sup.4 represents hydrogen or a 3- or 4-carbamoyl group) exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms. A particular antibiotic compound of formula (I) possessing excellent antibacterial activity against strains of Pseudomonas organisms, as well as other valuable therapeutic properties, is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino) acetamido]-3-(1-pyridiniummethyl)-ceph-3-em-4 carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I). Also described are compositions containing the antibiotics of the invention and processes for the preparation of such antibiotics.

摘要翻译： 通式（Ⅰ）（Ⅰ）的头孢菌素抗生素（其中Ra和Rb可以相同或不同，分别代表C1-4烷基或Ra和Rb与它们所连接的碳原子一起形成 C3-7亚环烷基; R4代表氢或3-或4-氨基甲酰基）表现出广谱抗生素活性，对革兰氏阴性生物如假单胞菌属生物体的活性异常高。 （6R，7R）-7 - [（Z）-2-（2-氨基噻唑-4-基） - 苯并噻唑-4-基] - 对于具有优异的抗假单胞菌菌株抗菌活性的其它有价值的治疗性质的式（I） 吡啶-3-基）-2-（2-羧基丙-2-炔亚氨基）乙酰氨基] -3-（1-吡啶鎓甲基） - 头孢-3-烯-4-羧酸酯。 本发明还包括式（I）化合物的无毒盐和无毒代谢不稳定的酯。 还描述了含有本发明的抗生素的组合物和制备这些抗生素的方法。

公开(公告)号：US4621081A

公开(公告)日：1986-11-04

申请号：US423555

申请日：1982-09-27

申请人： Cynthia H. O'Callaghan ,  Barry E. Ayres ,  David G. H. Livermore ,  Christopher E. Newall ,  Niall G. Weir

发明人： Cynthia H. O'Callaghan ,  Barry E. Ayres ,  David G. H. Livermore ,  Christopher E. Newall ,  Niall G. Weir

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D277/20 ,  C07D501/24 ,  C07D501/36

CPC分类号： C07D277/20 ,  C07D277/587

摘要： Cephalosporin antibiotics of general formula: ##STR1## (wherein R.sup.a and R.sup.b, which may be the same or different, each represent a C.sub.1-4 alkyl group or R.sup.a and R.sup.b together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene group, and Y.sup..sym. represents a C-linked 5- or 6-membered heterocyclic ring containing at least one C.sub.1-4 alkyl-substituted quaternary nitrogen atom, which ring may also contain one or more sulphur atoms) exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms.A particular antibiotic compound of formula (I) possessing excellent antibacterial activity against strains of Pseudomonas organisms, as well as other valuable therapeutic properties, is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxycyclobut-1-oxyimino)acetamido]-3-[(1-methylpyridinium-4-yl)-thiomethyl]ceph-3-em-4-carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I). Also described are compositions containing the antibiotics of the invention and processes for the preparation of the antibiotics.

摘要翻译： 具有以下通式的头孢菌素抗生素：其中可以相同或不同的R a和R b各自代表C 1-4烷基或R a和R b与它们所连接的碳原子一起形成 C 3-7亚环烷基，Y（+）表示含有至少一个C 1-4烷基取代的季氮原子的C连接的5-或6-元杂环，该环也可含有一个或多个硫原子） 广谱抗生素活性，对革兰氏阴性生物体（如假单胞菌属生物菌株）的活性异常高。 （6R，7R）-7 - [（Z）-2-（2-氨基噻唑-4-基） - 苯并噻唑-4-基] - 对于具有优异的抗假单胞菌菌株抗菌活性的其它有价值的治疗性质的式（I） 吡啶-4-基）-2-（1-羧基环丁-1-氧亚氨基）乙酰氨基] -3 - [（1-甲基吡啶鎓-4-基） - 硫代甲基]环丙-3-烯-4-羧酸甲酯。 本发明还包括式（I）化合物的无毒盐和无毒代谢不稳定的酯。 还描述了含有本发明的抗生素和制备抗生素的方法的组合物。

公开(公告)号：US4258041A

公开(公告)日：1981-03-24

申请号：US042594

申请日：1979-05-25

申请人： Cynthia H. O'Callaghan ,  David G. H. Livermore ,  Christopher E. Newall

发明人： Cynthia H. O'Callaghan ,  David G. H. Livermore ,  Christopher E. Newall

IPC分类号： C07D501/06 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D20060101 ,  C07D277/20 ,  C07D501/04 ,  C07D501/46 ,  C07D501/56 ,  C07D501/60 ,  C07D499/44

CPC分类号： C07D277/20 ,  C07D277/587

摘要： Cephalosporin antibiotics of the general formula ##STR1## (wherein R.sup.a and R.sup.b, which may be the same or different, each represent a C.sub.1-4 alkyl group or R.sup.a and R.sup.b together with the carbon atom to which they are attached form a C.sub.3-7 cycloalkylidene group; and R.sup.4 represents hydrogen or a 3- or 4-carbamoyl group) exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms. A particular antibiotic compound of formula (I) possessing excellent antibacterial activity against strains of Pseudomonas organisms, as well as other valuable therapeutic properties, is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimono) acetamido]-3-(1-pyridiniummethyl)-ceph-3-em-4 carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I). Also described are compositions containing the antibiotics of the invention and processes for the preparation of such antibiotics.

摘要翻译： 通式（Ⅰ）（Ⅰ）的头孢菌素抗生素（其中Ra和Rb可以相同或不同，分别代表C1-4烷基或Ra和Rb与它们所连接的碳原子一起形成 C3-7亚环烷基; R4代表氢或3-或4-氨基甲酰基）表现出广谱抗生素活性，对革兰氏阴性生物如假单胞菌属生物体的活性异常高。 （6R，7R）-7 - [（Z）-2-（2-氨基噻唑-4-基） - 苯并噻唑-4-基] - 对于具有优异的抗假单胞菌菌株抗菌活性的其它有价值的治疗性质的式（I） （2-羧基-2-丙炔基）乙酰氨基] -3-（1-吡啶鎓甲基） - 头孢-3-烯-4-羧酸酯。 本发明还包括式（I）化合物的无毒盐和无毒代谢不稳定的酯。 还描述了含有本发明的抗生素的组合物和制备这些抗生素的方法。