公开(公告)号：US4017515A

公开(公告)日：1977-04-12

申请号：US618167

申请日：1975-09-30

申请人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

发明人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

IPC分类号： C07C271/14 ,  C07D207/32 ,  C07D207/325 ,  C07D209/48 ,  C07D213/55 ,  C07D307/42 ,  C07D307/54 ,  C07D307/79 ,  C07D333/16 ,  C07D333/24 ,  C07D333/60 ,  C07D499/00

CPC分类号： C07D207/325 ,  C07C271/14 ,  C07D209/48 ,  C07D213/55 ,  C07D307/42 ,  C07D307/54 ,  C07D307/79 ,  C07D333/16 ,  C07D333/24 ,  C07D333/60 ,  C07D499/00

摘要： .alpha.-(Etherified oximino)carboxylic acids, represented by the formula:- ##STR1## where R is hydrogen or an organic group having 1-20 carbon atoms and R.sup.a is an etherifying monovalent organic group having 1-16 carbon atoms linked to the oxygen atom through a carbon atom, and the corresponding acid chlorides, are useful intermediates in the preparation of highly active, highly .beta.-lactamase-stable 7.beta.-[.alpha.-(etherified oximino)acylamido]-ceph-3-em-4-carboxylic acid antibiotics. The compounds are syn isomers or exist as mixtures of syn and anti isomers containing at least 75% of the syn isomer.

摘要翻译： α-（醚化的肟基）羧酸，由下式表示： -

公开(公告)号：US4200746A

公开(公告)日：1980-04-29

申请号：US888242

申请日：1978-03-20

申请人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

发明人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

IPC分类号： C07D501/20 ,  C07D501/46

CPC分类号： C07D501/46

摘要： Cephalosporin antibiotics in which the 7.beta.-acylamido group has the formula ##STR1## (where R.sup.1 is furyl or thienyl and R.sup.2 is C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, furylmethyl or thienylmethyl) and in which the 3-position substituent is a pyridiniummethyl group wherein the pyridine ring is optionally substituted by carbamoyl, carboxy, carboxymethyl, sulpho or methyl exhibit high antibacterial activity against a broad range of gram-positive and gram-negative organisms, coupled with particularly high stability to .beta.-lactamases produced by various gram-negative organisms and good stability in vivo, particularly to esterases.

摘要翻译： 头孢菌素抗生素，其中7β-酰胺基具有式（IMAGE）（其中R 1为呋喃基或噻吩并且R 2为C 1-4烷基，C 3-7环烷基，呋喃基甲基或噻吩基甲基），其中3位取代基为 吡啶甲基，其中吡啶环任选被氨基甲酰基，羧基，羧甲基，磺基或甲基取代，对广泛的革兰氏阳性和革兰氏阴性生物表现出高抗菌活性，加上由各种克产生的β-内酰胺酶具有特别高的稳定性 - 阴性生物体和良好的体内稳定性，特别是酯酶。

公开(公告)号：US4144393A

公开(公告)日：1979-03-13

申请号：US668245

申请日：1976-03-18

申请人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

发明人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

IPC分类号： C07D307/54 ,  C07D333/24 ,  C07D501/20 ,  C07D501/34 ,  A61K31/545

CPC分类号： C07D307/54 ,  C07D333/24

摘要： 3-Acetoxymethyl cephalosporin antibiotics in which the 7.beta.-acylamido group has the structure ##STR1## where R is thienyl, furyl or phenyl; R.sup.a is C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl or phenyl, and R.sup.b is hydrogen, carboxy, C.sub.2 -C.sub.5 carbalkoxy or any of the groups designated for R.sup.a, 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 or cycloalkenylidene group; exhibit broad spectrum antibiotic activity characterized by particularly high activity against gram negative microorganisms, including those which produce .beta.-lactamases. The compounds, which are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer, have particularly high in vitro activity against strains of Escherichia coli. Haemophilus influenzae and Proteus organisms; and also shown unusually high activity against Pseudomonas organisms.

摘要翻译： 3-乙酰氧基甲基头孢菌素抗生素，其中7β-酰胺基具有结构

公开(公告)号：US4138555A

公开(公告)日：1979-02-06

申请号：US852808

申请日：1977-11-18

申请人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

发明人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

IPC分类号： C07C271/14 ,  C07D213/55 ,  C07D307/42 ,  C07D307/54 ,  C07D307/79 ,  C07D333/16 ,  C07D333/24 ,  C07D333/60 ,  C07D499/00 ,  C07D501/26 ,  C07D501/20

CPC分类号： C07D307/42 ,  C07C271/14 ,  C07D213/55 ,  C07D307/54 ,  C07D307/79 ,  C07D333/16 ,  C07D333/24 ,  C07D333/60 ,  C07D499/00 ,  C07D501/26

摘要： Cephalosporin antibiotics in which the 7.beta.-acylamido group has the structure ##STR1## where R.sup.1 is a furyl, thienyl or phenyl group and R.sup.2 is a C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl or phenyl group and in which the 3-position substituent is a carbamoyloxymethyl group possess a particularly valuable combination of properties, exhibiting high antibacterial activity against a broad range of gram positive and gram negative organisms, paticularly high stablity to .beta.-lactamases produced by various organisms, and stability in vivo. The compounds are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer. Particularly important compounds of this type are (6R,7R)-3-carbamoyloxymethyl-7-[2-(fur-2-yl)-2-methoxyiminoacetamido]ceph-3-em-4-carboxylic acid (syn isomer) and its non-toxic derivatives, e.g. the sodium salt.

摘要翻译： 头孢菌素抗生素，其中7β-酰氨基具有结构，其中R 1是呋喃基，噻吩基或苯基，R 2是C 1 -C 4烷基，C 3 -C 7环烷基或苯基，其中3位取代基 是具有特别有价值的性质组合的氨基甲酰氧基甲基，对广泛的革兰氏阳性和革兰氏阴性生物表现出高抗菌活性，对各种生物体产生的β-内酰胺酶具有高度的稳定性和在体内的稳定性。 这些化合物是顺式异构体，或作为含有至少90％的顺式异构体的顺式和反异构体的混合物存在。 特别重要的这种类型的化合物是（6R，7R）-3-氨基甲酰氧基甲基-7- [2-（呋喃-2-基）-2-甲氧基亚氨基乙酰氨基] c eph-3-em-4-羧酸（顺式异构体）和 其无毒衍生物，例如 钠盐。

公开(公告)号：US4011215A

公开(公告)日：1977-03-08

申请号：US601397

申请日：1975-08-01

申请人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

发明人： Martin C. Cook ,  Gordon I. Gregory ,  Janice Bradshaw

IPC分类号： A61K20060101 ,  A61K31/545 ,  C07D20060101 ,  C07D501/06 ,  C07D501/20 ,  C07D501/26 ,  C07D501/34 ,  C07D501/60

CPC分类号： C07D501/34

摘要： Cephalosporin antibiotics in which the 7.beta.-acylamido group is syn 2-furyl-2-methoxyiminoacetamido and in which the 3-position substituent is a chloroalkylcarbamoyloxymethyl group exhibit high antibacterial activity against a broad range of gram positive and gram negative organisms, particularly high stability to .beta.-lactamases produced by various organisms, and stability in vivo. The compounds are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer.

公开(公告)号：US4165430A

公开(公告)日：1979-08-21

申请号：US696276

申请日：1976-06-15

申请人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

发明人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

IPC分类号： C07D307/54 ,  C07D333/24 ,  C07D501/38 ,  C07D501/46 ,  A61K31/545

CPC分类号： C07D307/54 ,  C07D333/24

摘要： Cephalosporin antibiotics having the formula: ##STR1## (where R is thienyl, furyl or phenyl; R.sup.a is hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl or phenyl, and R.sup.b is hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl, phenyl, carboxy or C.sub.2-5 alkoxycarbonyl, 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 or cycloalkenylidene group: and Y is the residue of a nitrogen nucleophile and their physiologically acceptable derivatives exhibit broad spectrum antibiotic activity characterized by particularly high activity against gram negative microorganisms, including those which produce .beta.-lactamases. The compounds, which are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer, have particularly high in vitro activity against strains of Escherichia coli, Haemophilus influenzae and Proteus organisms; and unusually high activity against Pseudomonas organisms.

摘要翻译： 具有下式的头孢菌素抗生素：其中R是噻吩基，呋喃基或苯基; R a是氢，C 1-4烷基，C 2-4烯基，C 3-7环烷基或苯基，R b是氢，C 1-4烷基， C 2-4烯基，C 3-7环烷基，苯基，羧基或C 2-5烷氧基羰基，或者R a和R b与它们所连接的碳原子一起形成C 3-7亚环烷基或亚环烯基：Y是 氮亲核试剂及其生理上可接受的衍生物表现出广谱抗生素活性，其特征在于对革兰氏阴性微生物特别高的活性，包括产生β-内酰胺酶的那些活性，这些化合物是顺式异构体或作为含有至少90个 顺式异构体的％具有对大肠杆菌，流感嗜血杆菌和变形杆菌生物体的菌株特别高的体外活性;以及对假单胞菌生物体的异常高的活性。

公开(公告)号：US4162360A

公开(公告)日：1979-07-24

申请号：US832956

申请日：1977-09-13

申请人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

发明人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

IPC分类号： C07D307/54 ,  C07D333/24 ,  C07D501/26 ,  C07D501/32 ,  C07D501/34

CPC分类号： C07D333/24 ,  C07D307/54

摘要： 3-Carbamoyloxymethyl and 3-N-methylcarbamoyloxymethyl cephalosporin antibiotics in which the 7.beta.-acylamido group has the structure ##STR1## where R is thienyl, furyl or phenyl; R.sup.a is C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl or phenyl, and R.sup.b is hydrogen, carboxy, C.sub.2 -C.sub.5 carbalkoxy or any of the groups designated for R.sup.a, 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 or cycloalkenylidene group; exhibit broad spectrum antibiotic activity characterized by particularly high activity against gram negative microorganisms, including those which produce .beta.-lactamases. The compounds, which are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer, have particularly high in vitro activity against strains of Escherichia coli, Haemophilus influenzae and Proteus organisms; and also shown unusually high activity against Pseudomonas organisms.

摘要翻译： 3-羧甲酰氧基甲基和3-N-甲基氨基甲酰氧甲基头孢菌素抗生素，其中7β-酰胺基具有结构

公开(公告)号：US4144392A

公开(公告)日：1979-03-13

申请号：US696438

申请日：1976-06-15

申请人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

发明人： Janice Bradshaw ,  Martin C. Cook ,  Gordon I. Gregory

IPC分类号： C07D307/54 ,  C07D333/24 ,  C07D501/36 ,  C07D501/56 ,  A61K31/545

CPC分类号： C07D307/54 ,  C07D333/24

摘要： Cephalosporin antibiotics having the formula: ##STR1## (where R is thienyl, furyl or phenyl; R.sup.a is hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl or phenyl, and R.sup.b is hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-7 cycloalkyl, phenyl, carboxy or C.sub.2-5 alkoxycarbonyl, 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 or cycloalkenylidene group; R.sup.13 is C.sub.1 -C.sub.6 alkyl, C.sub.3-7 cycloalkyl, phenylalkyl, phenyl or naphthyl, thiadiazolyl, diazolyl, triazolyl, tetrazolyl, thiazolyl, thiatriazolyl, oxazolyl, oxadiazolyl, pyridyl, pyrimidyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, triazolopyridyl or purinyl, and n is 0, 1 or 2 and their physiologically acceptable derivatives exhibit broad spectrum antibiotic activity characterized by particularly high activity against gram negative microorganisms, including those which produce .beta.-lactamases. The compounds, which are syn isomers or exist as mixtures of syn and anti isomers containing at least 90% of the syn isomer, have particularly high in vitro activity against strains of Escherichia coli, Haemophilus influenzae and Proteus organisms; and unusually high activity against Pseudomonas organisms.

摘要翻译： 具有下式的头孢菌素抗生素：其中R是噻吩基，呋喃基或苯基; R a是氢，C 1-4烷基，C 2-4烯基，C 3-7环烷基或苯基，R b是氢，C 1-4烷基，C 2 -4-烯基，C 3-7环烷基，苯基，羧基或C 2-5烷氧基羰基，或者R a和R b与它们所连接的碳原子一起形成C 3-7亚环烷基或亚环烯基; R 13是C 1 -C 6烷基，C 3 -7个环烷基，苯基烷基，苯基或萘基，噻二唑基，二唑基，三唑基，四唑基，噻唑基，三唑基，恶唑基，恶二唑基，吡啶基，嘧啶基，苯并咪唑基，苯并恶唑基，苯并噻唑基，三唑并吡啶基或嘌呤基，n为0,1或2 生理上可接受的衍生物表现出广谱抗生素活性，其特征在于对革兰氏阴性微生物特别高的活性，包括产生β-内酰胺酶的那些活性。这些化合物是顺式异构体或以含有至少90％t 他的顺式异构体对大肠杆菌，流感嗜血杆菌和变形杆菌生物体的菌株具有特别高的体外活性; 并且对假单胞菌有机体具有异常高的活性。

公开(公告)号：US4209616A

公开(公告)日：1980-06-24

申请号：US951761

申请日：1978-10-16

申请人： Michael Gregson ,  Martin C. Cook ,  Gordon I. Gregory

发明人： Michael Gregson ,  Martin C. Cook ,  Gordon I. Gregory

IPC分类号： C07C259/02 ,  C07D307/54 ,  C07D333/24 ,  C07D501/26 ,  C07D501/20

CPC分类号： C07D307/54 ,  C07C259/02 ,  C07D333/24

摘要： The invention provides novel antibiotic compounds which are 7.beta.-acylamidoceph-3-em-4-carboxylic acids, and non-toxic derivatives thereof, and 6.beta.-acylamidopenam-3-carboxylic acids, and non-toxic derivatives thereof, characterized in that the acylamido group has the structure ##STR1## where R is a hydrogen atom or an organic group and R.sup.a is a hydrogen atom or an acyl group. The compounds are syn isomers or exist as mixtures containing at least 75% of the syn isomer. These antibiotic compounds possess high antibacterial activity against a range of gram positive and gram negative organisms coupled with particularly high stability to .beta.-lactamases produced by various gram negative organisms. The invention is also concerned with the administration of the compounds.

摘要翻译： 本发明提供了新的抗生素化合物，它们是7β-酰基酰胺基头孢-3-烯-4-羧酸及其无毒衍生物，和6β-酰基氨基青蒿素-3-羧酸及其无毒衍生物，其特征在于 酰胺基具有结构

公开(公告)号：USD514125S1

公开(公告)日：2006-01-31

申请号：US29212610

申请日：2004-09-03

申请人： Martin C. Cook

设计人： Martin C. Cook