Additional Hetero Ring Containing Patents (Class 540/222)
  • Patent number: 4820833
    Abstract: There is described a product which is a highly pure substantially amorphous form of cefuroxime axetil (cefuroxime 1-acetoxyethyl ester) which is stable, which has increased absorption via the gastro-intestinal tract and has a correspondingly high level of bioavailability on oral or rectal administration.Methods of preparing the product are also described which involve the recovery of the product from a solution thereof. A preferred method is the use of spray drying techniques, though roller drying, solvent precipitation or freeze-drying are also described.Also disclosed are pharmaceutical compositions containing the product and methods for its use in medicine.
    Type: Grant
    Filed: December 4, 1986
    Date of Patent: April 11, 1989
    Assignee: Glaxo Group Limited
    Inventors: Harold A. Crisp, John C. Clayton, Leonard G. Elliott, Edward M. Wilson
  • Patent number: 4820832
    Abstract: A process for preparing 7.beta.-acylamino (or 7.beta.-protected amino)-3-H-1-carba(1-dethia)-3-cephem-4-carboxylic acid esters and the corresponding cephalosporins is provided. 7.beta.-Acylamino (or 7.beta.-protected amino)-3-halo (or 3-sulfonyl ester)-1-carba(dethia)-3-cephem carboxylic acid esters and the corresponding cephalosporins are reduced with Pd(O) and a tetra-C.sub.2 -C.sub.6 alkyl stannane and, when a 3-sulfonyloxy ester is reduced, the process is carried out in the presence of an alkali metal halide. 3-Sulfonyloxy-3-cephem esters such as 3-mesylate, 3-tosylate and 3-triflate are employed.
    Type: Grant
    Filed: March 23, 1988
    Date of Patent: April 11, 1989
    Assignee: Eli Lilly and Company
    Inventors: Gwendolyn K. Cook, John H. McDonald, III
  • Patent number: 4814328
    Abstract: The compound having the formula: ##STR1## wherein R is a straight chain, branched chain or cyclic lower alkyl, a lower alkenyl or a lower alkynyl group which may be substituted by a carboxyl group, and R.sup.1 is hydrogen atom or an acetyl group; or a pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof.
    Type: Grant
    Filed: September 26, 1986
    Date of Patent: March 21, 1989
    Assignee: Banyu Pharmaceutical Co., Ltd.
    Inventors: Susumu Nakagawa, Norikazu Otake, Ryosuke Ushizima
  • Patent number: 4812561
    Abstract: An antibacterial, 7.beta.-[(Z)-2-(2-aminothiazol-4-yl)-4-carboxybut-2-enoylamino]-3-cephem-4 -carboxylic acid is stable in a (di or tri)-hydrate crystal form. A pharmacologically effective amount of this hydrate is filled in a gelatin hard capsule sealed by a band of gelatin to make a stable composition for clinical use after storage for a long time.
    Type: Grant
    Filed: July 1, 1987
    Date of Patent: March 14, 1989
    Assignee: Shionogi & Co., Ltd.
    Inventors: Yoshio Hamashima, Kyoji Minami, Kyozo Kawata, Teruo Sakamoto, Toyohiko Takeda, Yusuke Suzuki, Masanori Tujikawa
  • Patent number: 4808617
    Abstract: Amorphous solid formed by lyophilization or cosolvent precipitation of an aqueous solution of 7-[.alpha.-(2-aminothiazol-4-yl)-.alpha.-(Z)-methoximinoacetamido]-3-[(1-m ethyl-1-pyrrolidinio)-methyl[-3-cephem-4-carboxylate zwitterion and a salt or mixture of salts from a selected particular group is a broad spectrum antibiotic composition and has better temperature stability at least up to 45.degree. C. than the zwitterion. The salt is one wherein the cation is selected from the group consisting of sodium, lithium, calcium, and magnesium and the anion is selected from the group consisting of chloride, bromide, and iodide. The molar ratio of zwitterion to salt ranges from about 0.5:1 to about 2:l.
    Type: Grant
    Filed: January 9, 1987
    Date of Patent: February 28, 1989
    Assignee: Bristol-Myers Company
    Inventors: Murray A. Kaplan, Nageswara R. Palepu, Joseph B. Bogardus
  • Patent number: 4808712
    Abstract: A process for preparing cephalosporin compounds represented by the formula ##STR1## wherein R.sup.1 represents an alkyl group, alkenyl group, substituted or unsubstituted aryl group, substituted or unsubstituted arylmethyl group or substituted or unsubstituted phenoxymethyl group, R.sup.2 represents a carboxyl group or protected carboxyl group, and Y represents the residue of a nucleophilic reagent.
    Type: Grant
    Filed: October 14, 1986
    Date of Patent: February 28, 1989
    Assignee: Otsuka Kagaku Kabushiki Kaisha
    Inventor: Shigeru Torii
  • Patent number: 4808711
    Abstract: There is disclosed a novel .beta.-lactam antibiotics represented by the formula: ##STR1## wherein A is a group represented by the formulae -NHCO--, --NHCONHCO--, --NHCOCH.dbd.CH-- or ##STR2## where R.sub.6 is a hydrogen atom or a lower alkyl group; R.sub.1 and R.sub.2 are independently a hydrogen atom or a protective group; R.sub.3 is a hydrogen atom or a methoxy group; X is a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a halogen atom, a lower alkoxy group or a nitro group; n is an integer of 1 or 2; Y is a group represented by the formulae: ##STR3## provided that a carbon atom which is bonded by a carboxyl group being bonded to nitrogen atom; M is a hydrogen atom, a protective group or an easily hydrolyzable group in a human body; R.sub.7 is a hydrogen atom, a methyl group a lower alkoxy-methyl group or a group represented by the formula: --CH.sub.
    Type: Grant
    Filed: January 17, 1986
    Date of Patent: February 28, 1989
    Assignees: Sankei Pharmaceutical Co., Ltd., Nippon Pharmaceutical Development Institute Co.
    Inventors: Shigeo Shimizu, Hiroyuki Takano, Fujio Yagihashi
  • Patent number: 4801703
    Abstract: A novel method of producing a cephalosporin compound of the formula ##STR1## wherein R.sup.1 is a hydrogen atom or an acyl group; R is a hydrogen atom or an ester residue; the dotted line means a double bond in 2- or 3-position of the cephem ring; and R.sup.4 is a nucleophilic compound residue, or a salt thereof, directedly in one step from a compound of the formula ##STR2## wherein R.sup.1, R and the dotted line have the meanings defined above, or a salt thereof, by reacting in the presence of an organic solvent the compound [II] or a salt thereof, a nucleophilic compound or a salt thereof, and (1) a trivalent or pentavalent cyclic phosphorus compound having a partial structure of the formula ##STR3## wherein W is an oxygen atom, a sulfur atom or NR.sup.2 ; W.sup.1 is an oxygen atom, a sulfur atom or NR.sup.3 ; and R.sup.2 and R.sup.
    Type: Grant
    Filed: August 18, 1986
    Date of Patent: January 31, 1989
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Kenzo Naito, Masayasu Kato, Kazuo Tsukamura
  • Patent number: 4800199
    Abstract: Cephalosporins active as antibacterial agents, and processes for synthesis of such agents, are disclosed.
    Type: Grant
    Filed: October 20, 1986
    Date of Patent: January 24, 1989
    Assignee: American Cyanamid Company
    Inventors: Robert Babine, Ving J. Lee
  • Patent number: 4791196
    Abstract: A storage stable form of the crystalline sulfate of 7-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[5-(2-hydroxyeth yl)-4-methylthiazoliomethyl]-3-cephem-4-carboxylate has a specified X-ray diffraction pattern and is prepared by adding aqueous sulfuric acid to an aqueous solution of the compound under controlled conditions.
    Type: Grant
    Filed: September 23, 1987
    Date of Patent: December 13, 1988
    Assignee: Sankyo Company Limited
    Inventors: Junya Ide, Koichi Fujimoto
  • Patent number: 4788185
    Abstract: A compound of the formula; ##STR1## wherein R.sup.0 stands for hydrogen atom, nitrogen-containing heterocyclic group, acyl group or esterified carboxyl group, Z stands for S, S.fwdarw.O, O or CH.sub.2, R.sup.4 stands for hydrogen atom, methoxy group or formamido group, R.sup.13 stands for hydrogen atom, methyl group, hydroxyl group or halogen atom and A stands for an optionally substituted imidazol-1-yl group forming a condensed ring at the 2,3- or 3,4-position or a physiologically or pharmaceutically acceptable salt or ester thereof.This compound is novel and has excellent antibacterial activity.
    Type: Grant
    Filed: April 23, 1985
    Date of Patent: November 29, 1988
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Akio Miyake, Masahiro Kondo, Masahiko Fujino
  • Patent number: 4783443
    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.
    Type: Grant
    Filed: March 3, 1986
    Date of Patent: November 8, 1988
    Assignee: The University of Chicago
    Inventors: Michael A. Johnston, Shahrair Mobashery
  • Patent number: 4775750
    Abstract: There is disclosed a process for preparing sodium cefuroxime in very high purity. The process comprises reacting (6R,7R)-7-[Z-2-(fur-2-yl)-2-methoxyimino-acetamido]-3-hydroxymethylceph-3- em-4-carboxylic acid with a halosulphonyl isocyanate in an alkyl acetate solvent, hydrolyzing the resulting intermediate product, forming sodium cefuroxime by the addition of the sodium salt of a weak acid and isolating the sodium cefuroxime in high purity. The use of methyl acetate is particularly preferred and reaction can be carried out at from -25.degree. to +25.degree. C. The hydrolysis, generally in situ, may be carried out at from 10.degree. to 30.degree. C. Fewer steps are required than in previous processes and the product is of higher purity.
    Type: Grant
    Filed: December 1, 1986
    Date of Patent: October 4, 1988
    Assignee: Glaxo Group Limited
    Inventors: Herbert J. White, David T. Eastlick, John F. Oughton
  • Patent number: 4767754
    Abstract: Antibacterially effective cephalosporins of the formula ##STR1## in which R.sup.1 denotes C.sub.1 -C.sub.6 -alkyl, phenyl or halogen-substituted phenyl andA represents a nitrogen-containing, positively charged heterocyclic 5-membered to 7-membered ring which is bonded via N and can contain a total of up to 4 hetero-atoms from the group comprising N, O and S, and onto which up to two further rings can be fused, and which can optionally be substituted, with the proviso that, if the ring is a 6-membered ring, A does not represent an unsubstituted pyridine ring or a pyridine ring which is mono- or di-substituted by identical or different substituents from the group comprising C.sub.1 -C.sub.4 -alkyl, chlorine, bromine, carbamoyl or N-C.sub.1 -C.sub.4 -alkylcarbamoyl, or pharmaceutically acceptable salts thereof or esters thereof which can be split under physiological conditions.
    Type: Grant
    Filed: October 30, 1986
    Date of Patent: August 30, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Rolf Angerbauer, Michael Boberg, Karl G. Metzger, Hans-Joachim Zeiler
  • Patent number: 4767852
    Abstract: Process for the production of known 2-oximinoacetamido-3-cephem-4-carboxylic derivatives comprising acylation of 7-amino-3-cephem-4-carboxylic acid derivatives with novel 2-oximinoacetic acid thio esters, as well as such thioesters and their production.
    Type: Grant
    Filed: November 19, 1986
    Date of Patent: August 30, 1988
    Assignee: Biochemie
    Inventor: Gerd Ascher
  • Patent number: 4758556
    Abstract: Cephem derivatives of the general formula ##STR1## in which the R.sub.2 O group is in the syn-position, a process for their manufacture and pharmaceutical formulations which are active against bacterial infections and contain these compounds.
    Type: Grant
    Filed: March 30, 1978
    Date of Patent: July 19, 1988
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Walter Durckheimer, Dieter Bormann, Eberhard Ehlers, Elmar Schrinner, Rene Heymes
  • Patent number: 4757065
    Abstract: Antibacterially effective cephalosporins of the formula ##STR1## in which R.sup.1 denotes C.sub.1 -C.sub.6 -alkyl, phenyl or halogen-substituted phenyl andA represents a nitrogen-containing, positively charged heterocyclic 5-membered to 7-membered ring which is bonded via N and can contain a total of up to 4 hetero-atoms from the group comprising N, O and S, and onto which up to two further rings can be fused, and which can optionally be substituted, with the proviso that, if the ring is a 6-membered ring, A does not represent an unsubstituted pyridine ring or a pyridine ring which is mono- or di-substituted by identical or different substituents from the group comprising C.sub.1 -C.sub.4 -alkyl, chlorine, bromine, carbamoyl or N--C.sub.1 -C.sub.4 -alkylcarbamoyl,or pharmaceutically acceptable salts thereof or esters thereof which can be split under physiological conditions.
    Type: Grant
    Filed: November 20, 1984
    Date of Patent: July 12, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Rolf Angerbauer, Michael Boberg, Karl G. Metzger, Hans-Joachim Zeiler
  • Patent number: 4754031
    Abstract: A process for the preparation of a cephalosporin of the formula ##STR1## in which R.sup.1 is an aliphatic or cycloaliphatic radical with up to 6 carbon atoms, andA is a pyridinium radical or a radical of the formula ##STR2## comprising reacting an acid of the formula ##STR3## with methanesulphonyl chloride to form an anhydride of the formula ##STR4## and reacting the anhydride with a 7-aminocephalosporanate of the formula ##STR5## The reaction proceeds smoothly and in high yield.
    Type: Grant
    Filed: May 6, 1985
    Date of Patent: June 28, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Rolf Angerbauer, Gunther Kinast
  • Patent number: 4751295
    Abstract: 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(substituted)-iminoacetamido]-3-[3-( quaternaryammonio)-1-propen-1-yl]-3-cephem-4-carboxylates of the formula ##STR1## in which R.sup.1 and R.sup.2 are defined herein and --.sup..sym. N.tbd.Q is a quaternary ammonio group as defined herein, and salts, solvates, hydrates and esters thereof, are potent antibacterial agents. Processes for their preparation and intermediates in such processes are described.
    Type: Grant
    Filed: October 17, 1986
    Date of Patent: June 14, 1988
    Assignee: Bristol-Myers Company
    Inventors: Masahisa Oka, Haruhiro Yamashita, Jun Okumura, Takayuki Naito
  • Patent number: 4748171
    Abstract: Described herein is a cephem derivative represented by the general formula: ##STR1## wherein n stands for 1 or 2, Y stands for CH or nitrogen atoms, R.sub.1 represents a lower hydrocarbon group or a carboxyl-substituted, a carbamoyl-substituted, or a cyclopropyl-substituted lower alkyl group, and R.sub.2 denotes hydroxyl group, a lower alkyl group, a hydroxy-substituted lower alkyl group, or carbamoyl group. The derivative is useful as an antibacterial agent. Also described herein are processes for the production of the derivative, antibacterial composition, intermediate of the derivative and process for the production thereof.
    Type: Grant
    Filed: January 14, 1986
    Date of Patent: May 31, 1988
    Assignee: Eisai Co., Ltd.
    Inventors: Hiroshi Yamauchi, Isao Sugiyama, Isao Saito, Seiichiro Nomoto, Takashi Kamiya, Yoshimasa Machida, Shigeto Negi
  • Patent number: 4748163
    Abstract: Antibacterially active and animal growth-promoting novel .beta.-lactam compounds of the formula ##STR1## in which R.sup.1 represents the radical ##STR2## Y representing N or CR.sup.9, or Y--R.sup.7 representing >C.dbd.O or >C.dbd.N--R.sup.7,Z representing O, S, or NR.sup.10, andR.sup.2 represents hydrogen or a protective group.
    Type: Grant
    Filed: February 21, 1986
    Date of Patent: May 31, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Gunter Schmidt, Hans-Joachim Zeiler, Karl G. Metzger
  • Patent number: 4748170
    Abstract: An antibacterial 7beta-(carboxyalkenoyl)amino-3-cephem-4-carboxylic acid represented by the following formula: ##STR1## (wherein R is aryl or a heterocyclic group; R.sup.1 is hydrogen or halogen;R.sup.2 is a single bond, alkylene, or thiaalkylene;R.sup.3 is a hydrogen atom or carboxy modifying group;R.sup.4 is hydrogen or methoxy;R.sup.5 is hydrogen or a 3-substituent of cephalosporins;R.sup.6 is a hydrogen atom or carboxy modifying group; andX is oxygen, sulfur, or sulfinyl)a pharmaceutical composition containing the same, and a method for treating a bacterial infection with the same.
    Type: Grant
    Filed: February 20, 1986
    Date of Patent: May 31, 1988
    Assignee: Shionogi & Co., Ltd.
    Inventor: Yoshio Hamashima
  • Patent number: 4748172
    Abstract: Cephalosporin compounds substituted in the 7-position by a 2-(5- or 6-membered heterocyclic)-2-oximinoacetylamino group and in the 3-position with an imidazolo, oxazolo or thiazolopyridinium-methyl group are broad spectrum antibiotics highly effective in combating bacterial infections of gram-negative and gram-positive microorganisms. The cephalosporins are best prepared by reacting a silylated 7-[2-(heterocyclic)-2-oximinoacetylamino-3-iodomethyl-3-cephem-4-carboxyli c acid with an imidazolopyridine, an oxazolopyridine or a thiazolopyridine. Pharmaceutical formulations comprising a compound of the invention and a method for treating bacterial infections comprising their use are also provided.
    Type: Grant
    Filed: January 12, 1987
    Date of Patent: May 31, 1988
    Assignee: Eli Lilly and Company
    Inventor: Allen S. Katner
  • Patent number: 4742053
    Abstract: The invention relates to an antibiotic comprising a compound having the formula: ##STR1## wherein R.sup.1 is a straight chain, branched chain, or cyclic lower alkyl group which may be substituted by a carboxyl group, and R.sup.2 designates vicinal dihydroxyl groups or diacetoxy groups; or a pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof.
    Type: Grant
    Filed: November 8, 1985
    Date of Patent: May 3, 1988
    Assignee: Banyu Pharmaceutical Co., Ltd.
    Inventors: Susumu Nakagawa, Ryosuke Ushijima, Eiichi Mano, Norikazu Ban, Minoru Sanada
  • Patent number: 4735937
    Abstract: The invention concerns 7-amino-ceph-3-em-4-carboxylic acid compounds of the formula ##STR1## wherein R.sub.1.sup.a represents hydrogen or an amino protective group R.sub.1.sup.A and R.sub.1.sup.b represent hydrogen or an acyl group AC, or R.sub.1.sup.A and R.sub.1.sup.b together denote a bivalent amino protective group, and R.sub.2 represents hydrogen or an organic radical R.sub.2.sup.A which together with the --C(.dbd.O)--O-- grouping forms a protected carboxyl group, or salts such compounds which possess salt-forming groups; these compounds have antibiotic properties.
    Type: Grant
    Filed: March 28, 1986
    Date of Patent: April 5, 1988
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Karl Heusler, Hans Bickel, Bruno Fechtig, Heinrich Peter, Riccardo Scartazzini
  • Patent number: 4736026
    Abstract: The invention relates to a process for producing a cephalosporin of the formula ##STR1## by reacting the compound ##STR2## with the compound ##STR3## in the presence of boron trifluoride or a complex thereof.
    Type: Grant
    Filed: June 24, 1986
    Date of Patent: April 5, 1988
    Assignee: Toyama Chemical Co., Ltd.
    Inventors: Hiroyuki Imaizumi, Takihiro Inaba, Seishi Morita, Ryuko Takeno, Yoshiharu Murotani, Hirohiko Fukuda, Junichi Yoshida, Kiyoshi Tanaka, Shuntaro Takano, Isamu Saikawa
  • Patent number: 4734407
    Abstract: Antibacterially active and animal growth-regulating novel .beta.-lactam compounds of the formula ##STR1## in which R.sup.1 represents an optionally substituted radical of the formula ##STR2## Z represents oxygen, sulphur or --N--R.sup.
    Type: Grant
    Filed: March 10, 1986
    Date of Patent: March 29, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Gunter Schmidt, Hans-Joachim Zeiler, Karl G. Metzger
  • Patent number: 4731361
    Abstract: An oral antibacterial, 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-alkenoylamino]-3-cephem-4-carboxylic acid pharmaceutically acceptable ester represented by the following formula: ##STR1## (wherein R is amino or protected amino,R.sup.1 is straight, branched, or cyclic alkyl optionally substituted by alkoxy,R.sup.2 is hydrogen or a 3-substitutent of cephalosporins,R.sup.3 is a pharmaceutically acceptable ester group, andX is sulfur or sulfinyl).
    Type: Grant
    Filed: March 27, 1986
    Date of Patent: March 15, 1988
    Assignee: Shionogi & Co., Ltd.
    Inventors: Yoshio Hamashima, Koji Ishikura, Kyoji Minami, Tadatoshi Kubota, Tadashi Yoshida
  • Patent number: 4731362
    Abstract: An antibacterial 3-(alkylcarbamoyloxymethyl)-3-cephem-4-carboxylic acid or its derivatives represented by the following formula ##STR1## (wherein R is hydrogen or an amino-protecting group,R.sup.1 and R.sup.2 each is the same or different 1C to 8C alkyl,R.sup.3 is hydrogen, a salt or ester forming atom or group, andX is sulfur or sulfinyl),a pharmaceutical composition containing the same, a method for treating a bacterial infection with the same, and a method for preparing the same are disclosed.
    Type: Grant
    Filed: July 23, 1986
    Date of Patent: March 15, 1988
    Assignee: Shionogi & Co., Ltd.
    Inventors: Yoshio Hamashima, Teruji Tsuji, Tetsuo Okada, Kyoji Minami, Hiroyuki Ishitobi, Koji Ishikura
  • Patent number: 4729991
    Abstract: The invention relates to novel cephem compounds of high antimicrobial activity of the formula: ##STR1## wherein R.sup.1 is amino or protected amino,R.sup.2 is halogen,R.sup.3 is hydrogen or lower alkyl,R.sup.4 is hydrogen, lower alkyl or lower alkoxy,R.sup.5 is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxymethyl or unsaturated heterocyclicthiomethyl in which the heterocyclic moiety may be substituted with lower alkyl or lower alkenyl, andR.sup.6 is carboxy or functionally modified carboxy, and its pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: September 24, 1982
    Date of Patent: March 8, 1988
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Ikuo Ueda, Masakazu Kobayashi, Tadashi Kitaguchi
  • Patent number: 4727070
    Abstract: The antibiotic 7-[D-2-amino-2-(4-hydroxyphenyl)acetamido]-3-[(Z)-1-propenyl]ceph-3-em-4-c arboxylic acid (BMY-28100) forms imidazolidinone derivatives on reaction with ketones. These derivatives are useful in pharmaceutical dosage forms and as intermediates for separation thereof from mixtures containing the [(E)-1-propenyl]isomer of the antibiotic.
    Type: Grant
    Filed: November 25, 1985
    Date of Patent: February 23, 1988
    Assignee: Bristol-Myers Company
    Inventors: Murray A. Kaplan, Michael W. Lovell, Joseph B. Bogardus
  • Patent number: 4719206
    Abstract: The invention relates to novel cephem compounds, of high antimicrobial activity, of the formula: ##STR1## wherein R.sup.1 and R.sup.9 are amino or acylamino; andR.sup.9 is a group of the formula: ##STR2## where R.sup.2 is organic group,X is CH or N,Z is acid residueY is CH or N and n is O; orY is N.sup..sym. --R.sup.2 wherein R.sup.2 is as defined above and n is 1,or a group of the formula:--A--N.sup..sym. (R.sup.10).sub.3whereinR.sup.10 is lower alkyl andA is lower alkylene.
    Type: Grant
    Filed: January 31, 1986
    Date of Patent: January 12, 1988
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Takao Takaya, Takashi Masugi, Takashi Ogino, Hisashi Takasugi, Hideaki Yamanaka
  • Patent number: 4717768
    Abstract: A process for the separation of a mixture of syn and anti oxime isomers one from the other which comprises adsorbing said mixed oxime isomers onto a non-functional macroreticular adsorption resin, and eluting said resin to yield at least one eluate fraction containing one of said isomers while being substantially free of the other of said isomers.The application of this process to the separation of syn and anti isomers of cephalosporin compounds possessing an oxime grouping in a side-chain in the 7.beta.-position, and of acids corresponding to this 7.beta.-side chain, is described.
    Type: Grant
    Filed: September 7, 1984
    Date of Patent: January 5, 1988
    Assignee: Glaxo Group Limited
    Inventors: Colin Robinson, David T. Eastlick, Audrey J. Bownass
  • Patent number: 4717767
    Abstract: This invention relates to a 7-amino-3-(pyrazinylmethyl)- or (pyridazinylmethyl)-cephalosporins of the formula: ##STR1## wherein R.sup.1 represents a hydrogen atom or a carboxyl-protecting group; R.sup.2 represents a group of the formula: ##STR2## in which R.sup.6 represents a hydrogen atom, a C.sub.1-5 alkyl group or a di-C.sub.1-5 alkylamino group; R.sup.13 represents a C.sub.1-5 alkyl group; and R.sup.28 represents an amino group.
    Type: Grant
    Filed: July 22, 1986
    Date of Patent: January 5, 1988
    Assignee: Toyama Chemical Co., Ltd.
    Inventors: Hiroshi Sadaki, Hiroyuki Imaizumi, Takashi Nagai, Kenji Takeda, Isao Myokan, Takihiro Inaba, Yasuo Watanabe, Yoshikazu Fukuoka, Shinzaburo Minami, Isamu Saikawa
  • Patent number: 4716158
    Abstract: Compounds of formula (I): ##STR1## wherein: R.sup.1 represents a lower alkyl group selected from methyl groups and ethyl groups;R.sup.2 represents a hydrogen atom or a methyl group; andR.sup.3 represents a group selected from C.sub.1 --C.sub.5 alkoxy groups,and pharmaceutically acceptable acid addition salts thereof have valuable antibiotic activity and are suitable for oral administration. They may be prepared by a variety of synthetic routes.
    Type: Grant
    Filed: June 10, 1986
    Date of Patent: December 29, 1987
    Assignee: Sankyo Company Limited
    Inventors: Hideo Nakao, Koichi Fujimoto, Sadao Ishihara, Shinichi Sugawara, Isamu Igarashi
  • Patent number: 4714760
    Abstract: Stable, crystalline cephalosporin intermediates of the formula ##STR1## wherein X is HI or HCl and Nu and Nu.sup..sym. are certain N-containing heterocyclic rings attached via a sulfur atom or a ring nitrogen atom, respectively, which are substantially free of the .DELTA..sup.2 isomer; processes for, and intermediates in, the preparation of the above compounds; and processes for the preparation of broad-spectrum cephalosporin antibiotics.
    Type: Grant
    Filed: July 11, 1986
    Date of Patent: December 22, 1987
    Assignee: Bristol-Myers Company
    Inventors: Steven P. Brundidge, Paul R. Brodfuehrer, Chet Sapino, Jr., Kun M. Shih, Donald G. Walker
  • Patent number: 4708955
    Abstract: This invention provides novel cephalosporanic acids and esters thereof having the general formula ##STR1## wherein R.sup.2 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl or acyl, R.sup.3 is hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, andR.sup.4 is hydrogen, pivaloyloxymethyl, acetoxymethyl, 1-acetoxyethyl, 5-methyl-2-oxo-1, 3-dioxolen-4-ylmethyl or 4-glycyloxybenzoyloxymethyl. These compounds, especially esters, are useful as broad spectrum antibiotics in the treatment and prevention of infectious diseases of mammals, and for other purposes known in the art.
    Type: Grant
    Filed: June 24, 1985
    Date of Patent: November 24, 1987
    Assignee: Bristol-Myers Company
    Inventors: Seiji Iimura, Yoshio Abe, Jun Okumura, Takayuki Naito, Hajime Kamachi
  • Patent number: 4705784
    Abstract: A cephem compound represent by the general formula ##STR1## wherein, R.sup.1 represents hydrogen or lower alkyl, R.sup.2 and R.sup.3 are the same or different and each represents hydrogen or lower alkyl, R.sup.4 represents carboxyl or esterified carboxyl, and n represents 0 or 1, a salt of the cephem compound, and a process for producing the cephem compound or a salt thereof. Compounds of the above formula and salts thereof are valuable as antibacterial agents and are especially useful as oral drugs in the prevention or treatment of bacterial infectious diseases.
    Type: Grant
    Filed: December 17, 1984
    Date of Patent: November 10, 1987
    Assignee: Sumitomo Pharmaceuticals Company, Limited
    Inventors: Hirotada Yamada, Naruhito Masai, Sinji Ueda, Takao Okuda, Masatomo Fukasawa, Masuhiro Kato, Masataka Fukumura
  • Patent number: 4703046
    Abstract: This invention concerns antibiotic cephalosporins of the formula ##STR1## wherein R.sup.1 is amino or protected amino; R.sup.2 is halogen; R.sup.3 is alkyl; and R.sup.6 is carboxy or protected carboxy.
    Type: Grant
    Filed: September 6, 1979
    Date of Patent: October 27, 1987
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Ikuo Ueda, Masakazu Kobayashi, Tadashi Kitaguchi
  • Patent number: 4699904
    Abstract: Tetrazolyl derivatives of .beta.-lactams are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.
    Type: Grant
    Filed: July 1, 1985
    Date of Patent: October 13, 1987
    Assignee: Merck & Co., Inc.
    Inventors: James B. Doherty, Paul E. Finke, William K. Hagmann, Shrenik K. Shah
  • Patent number: 4699980
    Abstract: Various 7-amino-3-substituted-methyl-3-cephem-4-carboxylic acids and lower alkylsilyl derivatives such as 7-amino-3-(2,3-cyclopenteno-1-pyridiniomethyl)-3-cephem-4-carboxylic acid iodide and trimethylsilyl 7-trimethyl-silylamino-3-(5,6,7,8-tetrahydro-2-isoquinoliniomethyl)-3-ceph em-4-carboxylate iodide are valuable intermediates in the preparation of new and novel antibacterial agents. A new process for the preparation of these acids and the derivatives has been devised.
    Type: Grant
    Filed: February 8, 1985
    Date of Patent: October 13, 1987
    Assignee: Yamanouchi Pharmacutical Co., Ltd.
    Inventors: Tadao Shibanuma, Kohji Nakano, Noriaki Nagano, Yukiyasu Murakami, Ryuichiro Hara, Akio Koda, Atsuki Yamazaki
  • Patent number: 4698336
    Abstract: Described herein is 3-(pyrrolidinio)methyl-3-cephem derivative represented by the general formula: ##STR1## wherein Y stands for CH or nitrogen atom, R.sub.1 and R.sub.2 are the same or different, and represent a lower alkyl group, R.sub.3 denotes a hydroxy-substituted lower alkyl group, a lower alkyl group, or a carbamoyl group, and when Y stands for CH, R.sub.3 denotes a hydroxy-substituted lower alkyl group. The derivative is useful as antibacterial composition. Also described herein are process for the production of the derivative and antibacterial composition.
    Type: Grant
    Filed: January 23, 1986
    Date of Patent: October 6, 1987
    Assignee: Eisai Co., Ltd.
    Inventors: Isao Saito, Seiichiro Nomoto, Takashi Kamiya, Hiroshi Yamauchi, Isao Sugiyama, Yoshimasa Machida, Shigeto Negi
  • Patent number: 4698337
    Abstract: The invention relates to novel cephem compounds, of high antimicrobial activity, of the formula ##STR1## wherein R.sup.1 is amino or protected amino,R.sup.2 is lower alkyl substituted with 1 to 3 halogen atoms,R.sup.3 is thiadiazolylthiomethyl which may be substituted with lower alkyl, or tetrazolylthiomethyl which may be substituted with lower alkyl or lower alkenyl, andR.sup.4 is carboxy or protected carboxy, and a pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: September 25, 1986
    Date of Patent: October 6, 1987
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Takao Takaya, Hisashi Takasugi, Kiyoshi Tsuji, Toshiyuki Chiba
  • Patent number: 4695627
    Abstract: A process for the preparation of 7.beta.-acylamino-3-substituted-3-cephem-4-carboxylic acid compounds comprising reacting at -70.degree. C. to 0.degree. C. in an inert organic solvent phosphorus pentachloride with a cephalosporin compound in the presence of an olefinic compound having at least one carbon-carbon double bond having not more than three hydrogen atoms attached thereto capable of removing chlorine at least in part by addition to a carbon-carbon double bond.
    Type: Grant
    Filed: September 21, 1984
    Date of Patent: September 22, 1987
    Assignee: Gist-Brocades N.V.
    Inventors: Jan Verweij, Herman H. Grootveld, Henri G. J. Hirs, Gerardus J. Van Veen, Jan Kalter, Peter W. Henniger
  • Patent number: 4694001
    Abstract: .beta.-Lactam compounds represented by the general formula: ##STR1## (wherein X represents CH.sub.2, S or O; Y represents a hydroxyl group, a lower alkanoyloxy group or a lower alkoxycarbonyloxy group; W is a group represented by CH.sub.2, NH, ##STR2## A is a phenyl group, a naphthyl group, or a monocyclic or dicyclic heterocyclic group, respectively substituted by (Y).sub.n ; R.sub.4 and R.sub.5 each are a hydrogen atom, a lower alkyl group, or a cycloalkylidene group with a carbon atom combined therewith; l is 0 or an integer of 1, 2 or 3; m is 0 or 1; n is an integer of 1, 2, 3, 4 or 5; and R.sub.1, R.sub.2 and R.sub.3 are groups often used in the conventional .beta.-lactam compounds) have strong antimicrobial activities against a wide range of Gram positive and negative bacteria; particularly Gram negative bacteria including Pseudomonas aeruginosa, Pseudomonas sepatia and various Enterobacters.
    Type: Grant
    Filed: November 26, 1984
    Date of Patent: September 15, 1987
    Assignee: Kyowa Hakko Kogyo Co., Ltd.
    Inventors: Tadashi Hirata, Kenichi Mochida, Chihiro Shiraki, Kiyoshi Sato
  • Patent number: 4692516
    Abstract: Process for the preparation of cephem compounds of the formula ##STR1## wherein R is optionally substituted aminothiazolyl or amino-1,2,4-thiadiazolyl, A is optionally substituted pyridinium, R.sup.1 is hydrogen or methoxy and R.sup.2 are special aliphatic substituents, by a nucleophilic replacement in the substituent in 3-position in the presence of tri-C.sub.1 C.sub.4 -alkyl iodosilane.
    Type: Grant
    Filed: May 7, 1984
    Date of Patent: September 8, 1987
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Reiner Kirrstetter, Walter Durckheimer, Rudolf Lattrell, Wilfried Schwab
  • Patent number: 4692517
    Abstract: There are disclosed novel antibacterial compounds having the formula ##STR1## wherein R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclo lower alkyl, aryl of 6-12 carbon atoms, all the said foregoing groups being optionally substituted with carboxy, lower alkoxycarbonyl, phenoxycarbonyl, amino, mono- or di-lower alkyl substituted amino, hydroxy, lower alkoxy, phenoxy, carbamoyl, lower alkyl carbonyl, benzoyl, cyano, nitro, formamido, lower alkanoylamino or benzamido;R.sup.1 is hydrogen, lower alkyl or an alkali metal cation;A is lower alkoxy, lower alkenoxy, lower alkynoxy, aryloxy of 6-12 carbon atoms, di-lower alkyl substituted amino, di-lower alkenyl substituted amino, di-lower alkynyl substituted amino, di-aryl of 6-12 carbon atoms substituted amino, lower alkyl, lower alkenyl, lower alkynyl, aryl of 6-12 carbon atoms.
    Type: Grant
    Filed: March 20, 1986
    Date of Patent: September 8, 1987
    Assignee: American Home Products Corporation
    Inventors: Jerauld S. Skotnicki, Thomas J. Commons
  • Patent number: 4691014
    Abstract: A cephalosporin compound having the formula: ##STR1## wherein R.sub.1 is a hydroxy group, a lower alkanoyloxy group or a lower alkoxycarbonyloxy group, R.sub.2 is a hydrogen atom, a hydroxy group, a lower alkanoyloxy group or a lower alkoxycarbonyloxy group, R.sub.3 is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkenyl group, a lower alkoxy group or --CH.sub.2 R.sub.7 (wherein R.sub.7 is a hydrogen atom, an azido group, a lower alkanoyloxy group, a carbamoyloxy group, a substituted or unsubstituted pyridinium group or a substituted or unsubstituted heterocyclic thio group), R.sub.4 is a hydrogen atom or a carboxy-protecting group, each of R.sub.5 and R.sub.6 is a hydrogen atom or a lower alkyl group, or R.sub.5 and R.sub.6 form a cycloalkylidene group together with the carbon atom to which they are attached, and m is 0 to 1, or a pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: October 1, 1985
    Date of Patent: September 1, 1987
    Assignee: Kaken Pharmaceutical Co., Ltd.
    Inventors: Takanobu Naito, Masaaki Yokoyama, Kazuya Sasaki, Makoto Yamamoto, Kouji Amemiya
  • Patent number: 4687769
    Abstract: A class of new cephem compounds is now provided, which is useful as antibacterial agent and is represented by the general formula (I) ##STR1## wherein R.sup.1 is methyl group or carboxymethyl group and R.sup.2 is carboxyl group or a protected carboxyl group, and a pharmaceutically acceptable salt or ester thereof.
    Type: Grant
    Filed: December 16, 1985
    Date of Patent: August 18, 1987
    Assignee: Meiji Seika Kaisha, Ltd.
    Inventors: Yuichi Yamamoto, Takashi Yoshida, Shunzo Fukatsu, Toshiyasu Ishimaru
  • Patent number: 4686216
    Abstract: Novel cephalosporins of the formula ##STR1## in which R.sup.1 is an aliphatic or cycloaliphatic hydrocarbyl radical of up to 6 carbon atoms which is optionally substituted by a carboxyl group, ##STR2## R.sup.2 and R.sup.3 each independently is an optionally substituted aliphatic or cycloaliphatic hydrocarbyl radical of up to 6 carbon atoms, but is not unsubstituted methyl,or pharmaceutically acceptable salts thereof, are effective antibacterially and promote the growth of animals.
    Type: Grant
    Filed: May 6, 1985
    Date of Patent: August 11, 1987
    Assignee: Bayer Aktiengesellschaft
    Inventors: Rolf Angerbauer, Michael Boberg, Karl G. Metzger, Hans-Joachim Zeiler