公开(公告)号：US5189157A

公开(公告)日：1993-02-23

申请号：US189936

申请日：1988-05-03

Applicant: Chung-Chen Wei ,  Kevin F. West

Inventor： Chung-Chen Wei ,  Kevin F. West

IPC: C07D501/22 ,  A61K31/545 ,  C07D501/18 ,  C07D501/26 ,  C07D501/34 ,  C07D501/36 ,  C07D501/38 ,  C07D501/46 ,  C07D501/57

CPC classification number: C07D501/36 ,  C07D501/26 ,  C07D501/34 ,  C07D501/38 ,  C07D501/46 ,  Y02P20/55

Abstract: There are presented antibacterial cephalosporins having broad antimicrobial activity as well as intermediates for their formation, such compounds having the formula ##STR1## wherein X is ##STR2## R is hydrogen or a carboxylic acid protecting group; R.sub.1 is hydrogen or an acyl group;R.sub.2 is hydrogen or lower alkoxy; andR.sub.3 is carbocyclic aryl or alkyl carbocyclic aryl substituted on the ring with two or more of hydroxy and/or lower alkanoyl ester groups, with halogen being an optional additional ring substituent;as well as the corresponding readily hydrolyzable esters, pharmaceutically acceptable salts and hydrates of these compounds where R is hydrogen.

Abstract translation: 呈现具有广谱抗微生物活性的抗菌头孢菌素及其形成中间体，具有下式的化合物，其中X为氢或羧酸保护基; R1是氢或酰基; R2是氢或低级烷氧基; 并且R 3是在具有两个或多个羟基和/或低级烷酰基酯基团的环上被取代的碳环芳基或烷基碳环基，其中卤素是任选的另外的环取代基; 以及其中R是氢的这些化合物的相应的易水解的酯，药学上可接受的盐和水合物。

公开(公告)号：US4783443A

公开(公告)日：1988-11-08

申请号：US835280

申请日：1986-03-03

Applicant: Michael A. Johnston ,  Shahrair Mobashery

Inventor： Michael A. Johnston ,  Shahrair Mobashery

IPC: A61K31/545 ,  C07D501/26 ,  C07D501/28 ,  C07D501/30 ,  C07D501/34 ,  C07D501/36 ,  C07D501/46

CPC classification number: C07D501/36 ,  C07D501/26 ,  C07D501/34 ,  Y02P20/55

Abstract: Antibacterial cephalosporin compounds of the Formula (I): ##STR1## wherein W is a pharmaceutically acceptable salt or a carboxyl-protecting group; n is an integer from 1 to 2; --X-- is --X.sup.1 -- where the X.sup.1 moieties are the same or different and selected from the group consisting of (D) or (L) ##STR2## Y is --O--; wherein R.sup.1 is selected from the group consisting of: ##STR3## R.sup.2 is H, --CH.sub.2 R.sup.4, --CHR.sup.5.sub.2 or --CR.sup.5.sub.3, wherein R.sup.4 is H, F, Cl, Br, --OH, --CN, ##STR4## --CH(CH.sub.3).sub.2, --CH.sub.2 (OH), ##STR5## or --C.tbd.CH, where Q.sup.1, Q.sup.2 and Q.sup.3 are the same or different and selected from the group consisting of H, F, Cl or Br; R.sup.5 is F, Cl or Br; and Z.sup.1 is H or an amino protecting group.

Abstract translation: 式（I）的抗菌头孢菌素化合物：其中W是药学上可接受的盐或羧基保护基; n是1至2的整数; -X-是-X1-，其中X1部分相同或不同，并且选自（D）或（L）Y是-O-; 其中R 1选自：R 2是H，-CH 2 R 4，-CHR 52或-CR 53，其中R 4是H，F，Cl，Br，-OH，-CN， ）2，-CH 2（OH），或-C 3 CH 3，其中Q 1，Q 2和Q 3相同或不同，并选自H，F，Cl或Br; R5是F，Cl或Br; Z1为H或氨基保护基。

公开(公告)号：US4166178A

公开(公告)日：1979-08-28

申请号：US897157

申请日：1978-04-17

Applicant: Susumu Tsushima ,  Michiyuki Sendai ,  Mitsuru Shiraishi ,  Norichika Matsumoto

Inventor： Susumu Tsushima ,  Michiyuki Sendai ,  Mitsuru Shiraishi ,  Norichika Matsumoto

IPC: A61K31/545 ,  C07D501/20 ,  C07D501/26

CPC classification number: C07D501/18 ,  C07D501/26

Abstract: Novel 3-acyloxymethyl-cephem compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen or an acyl group; X is a divalent group consisting of a carbon chain having 2 to 3 carbon atoms and a carbonyl or sulfonyl group at one terminal end thereof, said divalent group being either substituted or unsubstituted on the carbon chain; and Z is an organic acid residue, and salts thereof were found to be useful as starting materials for preparing cephalosporins of the formula: ##STR2## wherein R.sup.2 stands for a residue of a nucleophilic compound and R.sup.1 has the same meaning as above.

公开(公告)号：US3974153A

公开(公告)日：1976-08-10

申请号：US497113

申请日：1974-08-13

Applicant: Martin Christopher Cook ,  Gordon Ian Gregory ,  Janice Bradshaw

Inventor： Martin Christopher Cook ,  Gordon Ian Gregory ,  Janice Bradshaw

IPC: C07D307/42 ,  C07D307/54 ,  C07D307/79 ,  C07D501/26 ,  C07D501/60

CPC classification number: C07D307/42 ,  C07D307/54 ,  C07D307/79 ,  C07D501/26

Abstract: Cephalosporin antibiotics in which the 7.beta.-acylamido group has the structure ##EQU1## 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, 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. 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.

Abstract translation: 头孢菌素抗生素，其中7个β-酰基酰氨基具有结构R1.C.CO.NH-并环N | OR2，其中R1是呋喃基，噻吩基或苯基，R2是C1-C4烷基，C3C7环烷基或苯基， 其中3-位取代基是氨基甲酰氧基甲基具有特别有价值的性质组合，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，特别是对各种生物体产生的β-内酰胺酶具有高稳定性，并且稳定性 体内。 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。 这种类型的特别重要的化合物是（6R，7R）-3-氨基甲酰氧基甲基-7- [2-（呋喃-2-基）-2-甲氧基亚氨基乙酰胺基]环庚-3-烯-4-羧酸（顺式异构体）及其 无毒的衍生物，例如 钠盐。

公开(公告)号：US3966717A

公开(公告)日：1976-06-29

申请号：US413970

申请日：1973-11-08

Applicant: Martin Christopher Cook ,  Gordon Ian Gregory ,  Janice Bradshaw

Inventor： Martin Christopher Cook ,  Gordon Ian Gregory ,  Janice Bradshaw

IPC: C07D307/42 ,  C07D307/54 ,  C07D307/79 ,  C07D501/34 ,  C07D501/20

CPC classification number: C07D307/42 ,  C07D307/54 ,  C07D307/79 ,  C07D501/26

Abstract: The invention provides novel antibiotic compounds comprising 7.beta.-acylamido-3-carbamoyloxymethylceph-3-em-4-carboxylic acids and non-toxic derivatives thereof wherein the acylamido group has the structure ##EQU1## IN WHICH R is a carbocyclic or heterocyclic aryl group and R.sup.a is a lower alkyl, cycloalkyl or phenyl 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 organisms and stability in the presence of human serum. The invention is also concerned with the administration of the compounds.

Abstract translation: 本发明提供了包含7个β-酰氨基-3-氨基甲酰氧基甲基头孢-3-烯-4-羧酸及其无毒衍生物的新型抗生素化合物，其中酰氨基具有RCCO结构.N-和 碳环或杂环芳基，Ra是低级烷基，环烷基或苯基。 这些化合物是顺式异构体，或作为含有至少75％的顺式异构体的混合物存在。 这些抗生素化合物对一系列革兰氏阳性和革兰氏阴性生物具有高抗菌活性，与各种生物体产生的β-内酰胺酶具有特别高的稳定性，并在人血清存在下具有稳定性。 本发明还涉及化合物的给药。

公开(公告)号：US3875153A

公开(公告)日：1975-04-01

申请号：US36581673

申请日：1973-05-31

Applicant: SQUIBB & SONS INC

Inventor： TREUNER UWE D ,  BREUER HERMANN

IPC: C07D501/20 ,  C07D99/24

CPC classification number: C07D501/22 ,  C07D501/26

Abstract: New cephalosporin derivatives of the formula

WHEREIN R is hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)silyl, alkali metal, alkaline earth metal or amine group or the group

R1 is cyano; R2 is cyano or phenylsulfonyl; R3 is hydrogen, lower alkyl, phenyl or thienyl; R4 is hydrogen or lower alkyl; R5 is lower alkyl, phenyl or phenyl-lower alkyl; and X is hydrogen, hydroxy or lower alkanoyloxy; are useful as antibacterial agents.

Abstract translation: 式WHEREIN R的新型头孢菌素衍生物为氢，低级烷基，苯基 - 低级烷基，三（低级烷基）甲硅烷基，碱金属，碱土金属或胺基，或R1为氰基; R2是氰基或苯基磺酰基; R3是氢，低级烷基，苯基或噻吩基; R4是氢或低级烷基; R5是低级烷基，苯基或苯基 - 低级烷基; X为氢，羟基或低级烷酰氧基; 作为抗菌剂是有用的。

公开(公告)号：US3445463A

公开(公告)日：1969-05-20

申请号：US3445463D

申请日：1965-06-17

Applicant: LILLY CO ELI

Inventor： HEYNINGEN EARLE M VAN

IPC: A61K31/545 ,  C07D501/26 ,  C07D99/24 ,  A61K21/00

CPC classification number: C07D501/26 ,  A61K31/545

公开(公告)号：US3422103A

公开(公告)日：1969-01-14

申请号：US3422103D

申请日：1967-08-11

Applicant: GLAXO LAB LTD

Inventor： WALL WILFRED FRANK ,  FATHERLEY MICHAEL ,  BOOTHROYD BRIAN

IPC: C07D501/26 ,  C07D501/32 ,  C07D99/24 ,  A61K21/00

CPC classification number: C07D501/26 ,  C07D501/32

公开(公告)号：US5336768A

公开(公告)日：1994-08-09

申请号：US197943

申请日：1988-05-24

Applicant: Harry A. Albrecht ,  Dennis D. Keith ,  Frederick M. Konzelmann ,  Pamela L. Rossman ,  Manfred Weigele

Inventor： Harry A. Albrecht ,  Dennis D. Keith ,  Frederick M. Konzelmann ,  Pamela L. Rossman ,  Manfred Weigele

IPC: C07D501/18 ,  C07D501/34 ,  C07D519/00 ,  A61K31/545

CPC classification number: C07D501/46 ,  C07D501/18 ,  C07D501/26 ,  C07D501/32 ,  C07D501/34 ,  C07D501/38 ,  C07D501/44 ,  C07D519/00 ,  Y02P20/55

Abstract: There are presented antibacterial cephalosporine having broad antimicrobial activity, having the formula ##STR1## wherein R is hydrogen or a carboxylic acid-protecting group: R.sub.1 represents a substituted piperazinyl group of formula ##STR2## or a substituted pyrrolidinylamino group of formula ##STR3## or a substituted pyrrolidinylmethylamino group of formula ##STR4## where the piperazinyl or pyrrolidinyl group may be optionally substituted with one or more lower alkyl groups, and where Q represents a substituted quinolinyl or naphthyridinyl group: R.sub.2 is selected from the group consisting of hydrogen, lower alkoxy, lower alkylthio and amido; R.sub.3 is hydrogen or an acyl group: and m is 0, 1 or 2, but preferably 0; as well as the corresponding readily hydrolyzable esters. pharmaceutically acceptable salts and hydrates of these compounds.

Abstract translation: 提供具有广泛抗微生物活性的抗菌头孢菌素，其具有式Ⅰ的化合物，其中R是氢或羧酸保护基团：R1代表通式为“IMAGE”的取代的哌嗪基或式IMAMA的取代的吡咯烷基氨基， 或取代的吡咯烷基甲基氨基，其中哌嗪基或吡咯烷基可以任选被一个或多个低级烷基取代，并且其中Q表示取代的喹啉基或萘啶基：R2选自氢，低级 烷氧基，低级烷硫基和酰氨基; R3为氢或酰基，m为0,1或2，但优选为0; 以及相应的易水解酯。 这些化合物的药学上可接受的盐和水合物。

公开(公告)号：US5162522A

公开(公告)日：1992-11-10

申请号：US691307

申请日：1991-04-25

Applicant: Kenzo Naito ,  Yukio Ishibashi ,  Toshihiko Fujitani

Inventor： Kenzo Naito ,  Yukio Ishibashi ,  Toshihiko Fujitani

IPC: A61K31/545 ,  C07D501/04 ,  C07D501/18 ,  C07D501/24 ,  C07D501/26

CPC classification number: C07D501/04 ,  C07D501/18 ,  C07D501/26

Abstract: A method for producing 3-(3-oxobutyryloxymethyl)-3-cepham-4-carboxylic acids which are antibiotics or intermediates for the synthesis of antibiotics, at a low temperature in a very short period of time and in good yield, characterized by reacting a 3-hydroxylmethyl-3-cephem-4-carboxylic acid with diketene in the presence of a 4-(tertiary-amino)pyridine and if necessary, when a 7-acylamino-3-(3-oxobutyryloxymethyl)-3-cephem-4-carboxylic acid is obtained, subjecting it to deacylation at the 7-position thereof.

Abstract translation: 一种生产3-（3-氧代丁酰氧基甲基）-3-头孢烯-4-羧酸的方法，它是抗生素或用于合成抗生素的中间体，在非常短的时间内以低的温度和良好的产率，其特征在于反应 3-羟基甲基-3-头孢烯-4-羧酸与4-（叔 - 氨基）吡啶存在下的双烯酮，如果需要，当7-酰基氨基-3-（3-氧代丁酰氧基甲基）-3-头孢烯-4-羧酸 得到4-羧酸，使其在其7-位脱羟基。