Additional Hetero Ring Containing Patents (Class 540/222)
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Patent number: 5066797Abstract: There is described a process for producing exomethylene cepham intermediates useful in cephalosporin chemistry. The process comprises the preparation of a compound of the formula ##STR1## in which R.sup.1 is an amino group, a protected amino group, an acylamino group or a diacylamino group,R.sup.2 is hydrogen, C.sub.1-4 alkoxy or C.sub.1-4 alkylthio,R.sup.3 is hydrogen, a salt ion or an ester-forming group, andR.sup.4 is hydrogen or C.sub.1-3 alkyl,by reacting a compound of the formula ##STR2## in which Y is a bridging group of the formula ##STR3## Z is chloro, bromo or iodo, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the above defined values, with a reagent providing cobalt I, under reducing conditions.Type: GrantFiled: July 10, 1989Date of Patent: November 19, 1991Assignee: Lilly Industries LimitedInventor: Jack E. Baldwin
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Patent number: 5064824Abstract: Cephalosporin antibiotics having a 3-position substituent of the formula: ##STR1## are described; wherein R.sup.1 is hydrogen or certain substituted alkyl groups, Z is CH or N, R.sup.2 and R.sup.3 are hydroxy or in vivo hydrolysable esters thereof, (R.sup.12).sub.n represents various optional substituents and X=Y is an olefin, oxime, azo or related group. Processes for their preparation and use are described.Type: GrantFiled: May 5, 1989Date of Patent: November 12, 1991Assignee: Imperial Chemical Industries PLCInventors: David G. Acton, David H. Davies, Jeffrey P. Poyser
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Patent number: 5064649Abstract: .beta.-Lactam antibiotics of the formula (Ia) or a pharmaceutically acceptable salt or pharmaceutically acceptable in vivo hydrolysable ester thereof are disclosed: ##STR1## wherein R.sup.1 is hydrogen, methoxy or formamido; R.sup.2 is a acyl group, in particular that of an antibacterially active cephalosporin; CO.sub.2 R.sup.6 is carboxy group or a carboxylate anion; R.sup.4 is a butenolide or butanolide ring, optionally substituted by one or two alkyl, dialkylamino, alkoxy, hydroxy or aryl groups, which may be the same or different, or, wherein two adjacent carbon atoms which are available for substitution define the common bond of an aromatic fused bicyclic system; X is S, SO, SO.sub.2, O or CH.sub.2 ; and the dashed line adjacent to R.sup.4 represents an optional double bond. Processes for the preparation of compounds together with intermediates for use therein are disclosed.Type: GrantFiled: September 14, 1989Date of Patent: November 12, 1991Assignee: Beecham Group p.l.c.Inventors: George Burton, Stephen C. M. Fell, John H. Bateson
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Patent number: 5063224Abstract: R-Cefuroxime axetil which is substantially free of the S-isomer is readily absorbed from the stomach and gastro-intestinal track of animals, and is therefore ideally suited to oral therapy of bacterial infections.Type: GrantFiled: July 9, 1990Date of Patent: November 5, 1991Assignee: Eli Lilly and CompanyInventors: Gerold L. Mosher, Michael V. Mullen
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Patent number: 5061702Abstract: A novel cephem compound which has antimicrobial activity is disclosed. The cephem compound is represented by the formula: ##STR1## wherein R.sup.1 represents a hydrogen atom or a carboxyl group; R.sup.2 and R.sup.3, which may be the same or different, each represent a hydrogen atom or a lower alkyl group of 1-3 carbon atoms; and R.sup.4 and R.sup.5, which may be the same or different, each represent a hydrogen atom or an acyl group; and pharmaceutically acceptable salts thereof.Type: GrantFiled: September 5, 1989Date of Patent: October 29, 1991Assignee: Meiji Seika Kabushiki KaishaInventors: Kunio Atsumi, Katsuyoshi Iwamatsu, Kenji Sakagami, Takashi Yoshida, Haruo Yamamoto, Seiji Shibahara, Shigeharu Inouye
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Patent number: 5055462Abstract: Cephalosporin antibiotics having a 3-position substituent of the formula:--CH.sub.2 NR.sup.1 --Y--A--Z--Qare described, wherein R.sup.1 is hydrogen or certain optionally substituted alkyl groups; Y is --CO-- or --SO.sub.2 --; A is optionally substituted phenylene or heterocyclylene; Z is a linking group and Q is a catechol or related ring system. Processes for their preparation and use are described.Type: GrantFiled: May 10, 1989Date of Patent: October 8, 1991Assignees: Imperial Chemical Industries plc, ICI PharmaInventors: Gareth M. Davies, Colin J. Strawson, Jean J. Lohmann
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Patent number: 5049558Abstract: A cephalosporin derivative of the formula I: ##STR1## in which X is ##STR2## represents one of C-7 acyl groups known in the cephalosporin art, R3 is hydrogen or methoxy, R4 is hydrogen, optionally substituted alkyl or allyl, and R5 is an aromatic heterocyclic ring system which is linked via carbon, and which contains a quaternized nitrogen atom.Type: GrantFiled: September 19, 1989Date of Patent: September 17, 1991Assignees: Imperial Chemical Industries plc, ICI PharmaInventors: Robert H. Bradbury, Frederic H. Jung, Jean J. Lohmann, Peter R. Marsham, Georges Pasquet
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Patent number: 5049665Abstract: A cephalosporin derivative having the formula: ##STR1## wherein R.sup.1 is a substituted amino group, X is an alkylene group, R.sup.2 is an aryl or heterocyclic group which may be substituted and R.sup.3 is a hydrogen atom, a negative charge or a residue of an ester which can form a pharmaceutically acceptable ester hydrolyzable in a living body; or a pharmaceutically acceptable salt thereof.Type: GrantFiled: September 29, 1989Date of Patent: September 17, 1991Assignee: Banyu Pharmaceutical Co., Ltd.Inventors: Susumu Nakagawa, Hiroshi Fukatsu, Yoshiaki Katoh, Satoshi Murase
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Patent number: 5043439Abstract: Cephalosporin intermediates having a replacable organosulfonylyoxy or heterocyclothio group in the 3-position undergo a carbon alkylation process with organocopper reagents to provide 3-hydrocarbon substituted cephalosporin antibiotics.Type: GrantFiled: March 8, 1990Date of Patent: August 27, 1991Assignee: Bristol-Myers Squibb CompanyInventors: Joydeep Kant, Chester Sapino, Jr.
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Patent number: 5043334Abstract: Compounds of general formula (I) ##STR1## (where R.sup.1 is a carboxyl group, a group COO.sup..crclbar. or a blocked carboxyl group;R.sup.2 is an amino or protected amino group; andR is hydrogen or a group of the formula CH.sub.2 X, where X represents a halogen atom, a hydroxyl group, an acetoxy group; a group of the formula O.CO.NHR.sup.3, where R.sup.3 is hydrogen, a C.sub.1-4 alkyl group optionally substituted by 1 to 3 halogen atoms or an N-protecting group; a group of the formula OR.sup.4, where R.sup.4 is a C.sub.1-4 alkyl group optionally substituted by halogen or a C.sub.1-4 alkoxy group; or a pyridinium, 3-carbamoyl-pyridinium or 4-carbamoyl-pyridinium group;B is --S-- or --SO-- (.alpha.- or .beta.-); and the dotted line bridging the 2-, 3- and 4- positions indicates that the compound is a ceph-2-em or ceph-3-em compound) and salts thereof, the compounds of formula (I) being associated with an anion when X represents a pyridinium, 3-carbamoylpyridinium group or a 4-carbamoylpyridinium group and R.Type: GrantFiled: November 27, 1989Date of Patent: August 27, 1991Assignee: Glaxo Group LimitedInventors: Richard Bell, Michael W. Foxton, Brian E. Looker
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Patent number: 5037975Abstract: The invention provides a free radical process for preparing 1-carba(1-dethia)cephalosporin antibiotics with 2-substituted methylcephalosporin 1,1-dioxides wherein the substituent on the 2-methylene group is a free radical precursor group such as a phenyl or alkylseleno group. The latter dioxides are treated with a free radical initiator, e.g., a trialkyltin hydride or actinic radiation at 40.degree. C. to 150.degree. C. to provide the 1-carba-3-cephem and 1-carba-2-cephem products. The invention also provides free radical compounds formed as intermediates in the process.Type: GrantFiled: March 28, 1990Date of Patent: August 6, 1991Assignee: Eli Lilly and CompanyInventor: Larry C. Blaszczak
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Patent number: 5036064Abstract: Antibacterial compounds of the formula ##STR1## wherein R is a mononuclear carbocyclic aromatic group, a 5-membered aromatic heterocyclic group which contains as the hetero (non-carbon) ring member(s) an oxygen or sulphur atom or an imino or lower alkylimino group and, optionally, one or two nitrogen atoms, or a 6-membered aromatic heterocyclic group which contains one to three nitrogen atoms as the hetero ring member(s); R.sup.1 is hydrogen or a 3-substituent which is usable in cephalosporin chemistry; A is lower alkylene or C.sub.3-7 -cycloalkylene which is optionally substituted with carboxy, carbamoyl, lower alkylcarbamoyl or di(lower alkyl)carbamoyl; Q is lower alkylene or C.sub.3-7 -cycloalkylene which is optionally substituted with carboxy, carbamoyl, lower alkylcarbamoyl or di(lower alkyl)carbamoyl, or the group --NR.sup.2 -- or --NR.sup.2 NR.sup.3 --; R.sup.2 and R.sup.3 are independently hydrogen or lower alkyl; p and m are the zero or 1, n is zero, 1 or 2; R.sup.Type: GrantFiled: August 9, 1988Date of Patent: July 30, 1991Assignee: Hoffmann-La Roche Inc.Inventor: Erwin Gotschi
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Patent number: 5028601Abstract: Cephalosporin compounds of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different and are a hydrogen atom or a lower alkyl group of 1-5 carbon atoms and A is a hydrogen atom or a nucleophilic compound residue or pharmacologically acceptable salts thereof have excellent antibacterial activity against Gram positive and Gram negative microorganisms.Type: GrantFiled: April 21, 1988Date of Patent: July 2, 1991Assignees: Meiji Saika Kaisha, Ltd., Zaidanhojin Biseibutsu Kagaku KenkyukaiInventors: Shinichi Kondo, Takashi Tsuruoka, Katsuyoshi Iwamatsu, Kiyoaki Katano, Satoru Nakabayashi, Hiroko Ogino, Takashi Yoshida, Masaji Sezaki
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Patent number: 5026842Abstract: Reaction of a 7-aminocephalosporanic acid with a carboxylic acid in the presence of a dehydration condensing agent and an acid or acid complex provides the corresponding amide in high yield and high purity.Type: GrantFiled: June 28, 1989Date of Patent: June 25, 1991Assignees: Ajinomoto Co., Inc., Mochida Pharmaceutical Co., Ltd.Inventors: Kazuhiro Watanabe, Husayoshi Kakizaki, Isao Arai, Kimihiro Murakami, Kazuo Kato
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Patent number: 5026695Abstract: A compound of the formula ##STR1## in which R.sup.1 is a group of the formula: ##STR2## wherein R.sup.4 is lower alkyl and R.sup.5 is amino or a protected amino group, R.sup.2 lower alkoxymethyl, lower alkylthiomethyl or lower alkenylthiomethyl, R.sup.3 is carboxy or a protected carboxy group, and A is lower alkylene which may have a substituent selected from the groups consisting of amino, a protected amino group, hydroxy, oxo and a group of the formula:.dbd.N.about.OR.sup.6, wherein R.sup.6 is hydrogen, lower alkenyl, lower alkynyl, lower alkyl, or lower alkyl substituted by one or more substituent(s) selected from carboxy, a protected carboxy group, amino, a protected amino group and a heterocyclic group, and a pharmaceutically acceptable salt thereof, its preparation and its utility as an antimicrobial agent.Type: GrantFiled: January 5, 1990Date of Patent: June 25, 1991Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Takao Takaya, Hisashi Takasugi, Takashi Masugi, Hideaki Yamanaka, Kohji Kawabata
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Patent number: 5021564Abstract: An improvement in the process of preparing ceftazidime pentahydrate from ceftazidime dihydrobromide which comprises commingling a secondary-amine-type ion-exchange resin such as Amberlite LA-2 in a water-immiscible organic solvent with an aqueous solution of the dihydrobromide, stirring the mixture while maintaining a pH at or below about 6.0 and isolating ceftazidime pentahydrate from the aqueous layer. This process provides significantly higher yields of the pentahydrate than previously could be obtained from the dihydrobromide.Type: GrantFiled: November 26, 1990Date of Patent: June 4, 1991Assignee: Eli Lilly and CompanyInventor: David D. Wirth
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Patent number: 5019570Abstract: Cephalosporin derivatives having a 3-position substituent of the formula I are described: ##STR1## wherein R.sup.1 is hydrogen, alkenyl or optionally substituted alkyl, Het us a 5- or 6-membered heterocyclic ring bonded via a carbon atom to the amide linkage, wherein Het is selected from a group of the formulae II-III: ##STR2## wherein A is CH or a nitrogen atom; B is oxygen, sulphur or a group NR.sup.4 ; one or two of D, E, F and G are nitrogen atoms and the remainder are CH groups: or Het is a pyrazinone, pyridinone, pyridazinone or pyrimidinone ring, or is a thione equivalent of such a ring, said rings having a substituent R.sup.4 on one nitrogen atom, or is pyranone, or pyranthione; the ring Het being fused by any adjacent carbon atoms to the benzene ring; and Het being attached to the --CH.sub.2 NR.sup.1 CO-- group via a carbon atom;R.sup.2 is hydroxy or an in vivo hydrolyzable ester thereof;R.sup.3 is ortho to R.sup.2 and is hydroxy or an in vivo hydrolyzable ester thereof; and R.sup.Type: GrantFiled: July 25, 1988Date of Patent: May 28, 1991Assignees: Imperial Chemical Industries PLC, I.C.I. PharmaInventors: Jean C. Arnould, Dominique Boucherot, David H. Davies, Frederick H. Jung, Colin J. Strawson
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Patent number: 5017569Abstract: Cephalosporin compounds having a 3-position substituent of the formula (I) are described:--CH.sub.2 --Y--Q (I)wherein Y is a linking group --NR.sup.4 CO--Y'--, --NR.sup.4 SO.sub.2 --Y'--, --OCO--Y;-- or --SCO--Y'-- wherein R.sup.4 is hydrogen, various optionally substituted alkyl groups or alkenyl and Y' is a bond or various optionally substituted alkylene or alkenylene groups; and Q is a benzene ring (optionally fused to a further benzene ring so forming a naphthyl group or optionally fused to a 5 or 6 membered heterocyclic aromatic group containing 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur), said benzene ring (or in the case of naphthyl either benzene ring) being substituted by groups R.sup.1 and R.sup.2 which are ortho with respect to one another, wherein R.sup.1 is hydroxy or an in vivo hydrolyzable ester thereof and R.sup.Type: GrantFiled: November 6, 1987Date of Patent: May 21, 1991Assignee: ICI PharmaInventors: Alain M. Bertrandie, Thomas G. C. Bird, Frederic H. Jung, Jean-Jacques M. Lohmann
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Patent number: 5015736Abstract: A new compound called N,N'-carbonyl-bis-(4-ethyl-2,3-dioxo)-piperazine of Formula I ##STR1## A process for the preparation thereof based on the reaction of 4-ethyl-2,3-dioxo-piperazine or a trimethylsilyl derivative thereof with carbonyl chloride or a derivative thereof.The use of the compound of Formula I as an intermediate in the preparation of compounds of Formula II ##STR2## where R is a radical, substituted in alpha position, of a molecule of an acid selected from the group formed by phenylacetic acid, p-hydroxy phenylacetic acid, a 6-(phenylacetamido)-penicillanic acid and a 7-(phenylacetamido)-cephalosporanic acid.Type: GrantFiled: November 15, 1989Date of Patent: May 14, 1991Assignee: Gema, S.A.Inventors: Juan Cabre Castellvi, Jose Diago Meseguer, Asuncion Esteve Bianchini, Carlos E. Lenhardt Padro, Esteve Sans Pitarch
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Patent number: 5013730Abstract: Cephalosporins having a 3-position substituent of the formula: ##STR1## are described, wherein R.sup.5 is hydrogen, alkenyl, alkyl or substituted alkyl, Q is a mono- or bicyclic heterocyclic ring, variously substituted, Y is variously substituted alkylene, Y' represents various linking groups, m and n are independently zero or one, and P is a benzene ring with two ortho groups, one of which is hydroxy or an in-vivo hydrolysable ester thereof and the other is hydroxy, an in vivo hydrolysable ester thereof, carboxy, sulpho, hydroxymethyl, --NHSO.sub.2 CH.sub.3 or --NHCONH.sub.2 ; or P is a particularly substituted pyridone or pyranone. The use of such compounds as antibacterial agents is described, as are processes for their preparation.Type: GrantFiled: July 18, 1988Date of Patent: May 7, 1991Assignee: ICI-PHARMAInventors: Jean C. Arnould, Thomas G. C. Bird
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Patent number: 5013833Abstract: 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: GrantFiled: October 18, 1988Date of Patent: May 7, 1991Assignee: Glaxo Group LimitedInventors: Harold A. Crisp, John C. Clayton, Leonard G. Elliott, Edward M. Wilson
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Patent number: 5013731Abstract: A cephalosporin derivative of the formula I: ##STR1## in which X is S, O, CH.sub.2 or SO, ##STR2## represents one of the C-7 acyl groups known in the cephalosporin art, R3 is hydrogen or methoxy, R4 is hydrogen, optionally substituted alkyl, allyl, furfuryl or benzyl, and R5 is an aromatic heterocyclic ring system which is linked via carbon, and which contains a quaternized nitrogen atom.Type: GrantFiled: April 19, 1990Date of Patent: May 7, 1991Assignee: ICI PharmaInventors: Jean C. Arnould, Jean J. Lohmann, Georges Pasquet
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Patent number: 5010188Abstract: 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 atom, 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 composition. Also described herein are processes for the production of the derivative, antibacterial composition, intermediate of the derivative and process for the production thereof.Type: GrantFiled: March 16, 1988Date of Patent: April 23, 1991Assignee: Eisai Co., Ltd.Inventors: Hiroshi Yamauchi, Isao Sugiyama, Isao Saito, Seiichiro Nomoto, Takashi Kamiya, Yoshimasa Machida, Shigeto Negi
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Patent number: 5008257Abstract: The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are:(a) compounds of the formula[D-DHC] (I)wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine.revreaction.pyridinium salt redox carrier, with the proviso that when [DHC] is ##STR1## wherein R is a lower alkyl or benzyl and [D] is a drug species containing a single NH.sub.2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH.sub.Type: GrantFiled: January 11, 1989Date of Patent: April 16, 1991Assignee: University of FloridaInventor: Nicholas S. Bodor
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Patent number: 5008258Abstract: Cephalosporin compounds having as a 3-substituent the group: ##STR1## wherein Y represents a bond, optionally substituted alkylene or --CH.sub.2 CH.sub.2 NHCO--, P is a benzene ring substituted by groups W and Z ortho with respect to one another wherein W is hydroxy or an in vivo hydrolyzable ester thereof, Z is hydroxy, an in vivo hydrolyzable ester thereof, carboxy, sulpho, hydroxymethyl, --NHSO.sub.2 CH.sub.3 or NHCONH.sub.2, Q is a mono- or bicyclic ring system substituted by R.sup.7 wherein R.sup.7 is hydrogen or a range of groups and ring Q is optionally further substituted; are described as antibacterial agents. Processes for their preparation and their methods of use are described.Type: GrantFiled: July 18, 1988Date of Patent: April 16, 1991Assignee: I.C.I.-PharmaInventors: Thomas G. C. Bird, Frederick H. Jung
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Patent number: 5008260Abstract: 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 atom, 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: GrantFiled: March 16, 1988Date of Patent: April 16, 1991Assignee: Eisai Co., Ltd.Inventors: Hiroshi Yamauchi, Isao Sugiyama, Isao Saito, Seiichiro Nomoto, Takashi Kamiya, Yoshimasa Machida, Shigeto Negi
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Patent number: 5008259Abstract: Cephalosporin antibiotics having a 3-position substituent of the formula: ##STR1## are described, wherein R.sup.1 is hydrogen or certain optionally substituted alkyl groups; X is a benzene ring or certain 5 or 6-membered heterocyclic ring and is fused to ring Y which is a nitrogen containing heteroaryl group; R.sup.2 and R.sup.3 are independently hydroxy or an in vivo hydrolysable ester thereof, and ring system X-Y is optionally substituted. Processes for their preparation and use are described.Type: GrantFiled: May 10, 1989Date of Patent: April 16, 1991Assignees: Imperial Chemical Industries PLC, I.C.I.-PharmaInventors: Patrice J. Siret, Frederick H. Jung, William Bell
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Patent number: 5006649Abstract: A 3-propenylcephem derivative of the following formula: ##STR1## wherein R.sub.1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof, exhibiting excellent anti-bacterial activities against both Gram-positive bacteria and Gram-negative bacteria; Process for the preparation thereof; Anti-bacterial composition; Intermediate for the 3-propenylcephem derivative; and Process for the preparation of the intermediate.Type: GrantFiled: January 11, 1990Date of Patent: April 9, 1991Assignee: Eisai, Co.Inventors: Takashi Kamiya, Toshihiko Naito, Shigeto Negi, Yuuki Komatu, Yasunobu Kai, Takaharu Nakamura, Isao Sugiyama, Yoshimasa Machida, Seiichiro Nomoto, Kyosuke Kitoh, Kanemasa Katsu, Hiroshi Yamauchi
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Patent number: 4994567Abstract: 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: GrantFiled: October 18, 1988Date of Patent: February 19, 1991Assignee: Galaxo Group LimitedInventors: Harold A. Crisp, John C. Clayton, Edward M. Wilson
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Patent number: 4992431Abstract: Novel syn isomers of 3-alkoxymethyl or 3-alkylthiomethyl-7-[2-(2-amino-4-thiazolyl)-2-oximino-acetamido]-cephalos poranic acid compounds of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl and alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, acyl of an organic carboxylic acid of 1 to 18 carbon atoms and alkoxy carbonyl of 2 to 6 carbon atoms, A is selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, --NH.sub.Type: GrantFiled: June 30, 1982Date of Patent: February 12, 1991Assignee: RousselUclafInventors: Rene Heymes, Didier Pronine
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Patent number: 4992541Abstract: The present invention relates to an improved process for the preparation of the compounds of formula (I) ##STR1## which involve the direct oxidation without N-protection of the compound of the formula (II) ##STR2##Type: GrantFiled: August 1, 1989Date of Patent: February 12, 1991Assignee: Merck & Co., Inc.Inventors: Thomas J. Blacklock, John W. Butcher, Paul Sohar, Theresa Lamanec
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Patent number: 4988686Abstract: Disclosed is a novel cephem compound which is either one of a cis- or trans-isomer or a mixture of the cis-and trans-isomers, represented by the following general formula (I) and a pharmacologically acceptable salt thereof: ##STR1## wherein all of the substituents are as defined hereinbefore. Also disclosed are a process for producing the above compound and its use as an anti-bacterial agent comprising the same.Type: GrantFiled: June 28, 1989Date of Patent: January 29, 1991Assignee: Meiji Seika Kabushiki KaishaInventors: Kunio Atsumi, Katsuyoshi Iwamatsu, Kenji Sakagami, Hiroko Ogino, Takashi Yoshida
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Patent number: 4988685Abstract: Novel cephalosporins of the formula ##STR1## in which R.sup.1 represents hydrogen or an amino-protecting groupandR.sup.2 represents alkyl, cycloalkyl or alkenyl.Type: GrantFiled: January 11, 1990Date of Patent: January 29, 1991Assignee: Bayer AktiengesellschaftInventors: Jurgen Dornhagen, Rolf Angerbauer, Karl G. Metzger, Hans-Joachim Zeiler
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Patent number: 4983732Abstract: A method for preparing 2-amino-.beta.-lactams which are substituted by readily-removed protecting groups is provided. According to this invention, an acyl-2-amino-.beta.-lactam is further acylated with a different acyl group and is subsequently treated with base to provide a protected 2-amino .beta.-lactam with allyloxycarbonyl, t-butoxycarbonyl, naphthyloxycarbonyl, trichloroethyloxycarbonyl, p-nitrobenzyloxycarbonyl, benzhydryloxycarbonyl, p-methoxybenzyloxycarbonyl, or o-nitrobenzyloxycarbonyl.Type: GrantFiled: September 21, 1989Date of Patent: January 8, 1991Assignee: Eli Lilly and CompanyInventors: Larry C. Blaszczak, John E. Munroe, Douglas O. Spry
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Patent number: 4980464Abstract: A method for producing a compound of the formula; ##STR1## wherein R stands for a hydrogen atom, an acyl group or a protective group other than acyl groups, Q stands for a hydrogen atom or an ester residue, Y stands for the residue of a nucleophilic compound and the dotted line shows the double bond at 2- or 3- position of the cephem ring or a salt thereof, characterized by allowing a compound of the formula; ##STR2## [R, Q and the dotted line are of the same meaning as above] or a salt thereof to react with a nucleophilic compound or a salt thereof and a compound of the formula; ##STR3## wherein R.sup.1, R.sup.2, R.sup.3 independently stand for a hydrocarbon group having not more than 8 carbon atoms, or R.sup.1 and R.sup.2, R.sup.1 and R.sup.3 or R.sup.2 and R.sup.Type: GrantFiled: June 30, 1989Date of Patent: December 25, 1990Assignee: Takeda Chemical Industries, Ltd.Inventors: Kenzo Naito, Yukio Ishibashi
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Patent number: 4978752Abstract: Crystals of 7.beta.-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3- (1-imidazo[1,2-b]pyridazinium)methyl-3-cephem-4-carboxylate hydrochloride or a solvate thereof, which are stable and improved in solubility in water, are useable for an excellent antibacterial agent.Type: GrantFiled: November 22, 1988Date of Patent: December 18, 1990Assignee: Takeda Chemical Industries, Ltd.Inventors: Yoshiharu Maeda, Yukio Mizuno, Akira Nakatani, Mitsuhisa Yamano
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Patent number: 4973684Abstract: Broad spectrum antibiotics are provided which are compounds of the formula: ##STR1## wherein R.sup.4 is a residue of a nucleophilic compound and R.sup.5 is hydroxyl or protected hydroxyl; or a pharmaceutically acceptable salt or ester thereof.Type: GrantFiled: June 7, 1988Date of Patent: November 27, 1990Assignee: Takeda Chemical Industries, Ltd.Inventors: Michihiko Ochiai, Taiiti Okada, Osamu Aki, Akira Morimoto, Kenji Kawakita, Yoshihiro Matsushita
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Patent number: 4971961Abstract: This invention provides cephalosporin compounds represented by the following general formula: ##STR1## wherein R.sup.1 and R.sup.2 are same or different hydrogen atom or a lower alkyl group of 1 to 5 carbon atoms; R.sup.3 is a lower alkyl group which may optionally be substituted with a halogen atome (or atoms), an alkenyl group, or a cycloalkylmethyl group of 3 to 6 carbon atoms; and A is hydrogen atom or residue of a nucleophilic compound and pharmacologically acceptable salts thereof. These compounds have broad-spectrum antibacterial activity against Gram-positive and -negative bacteria including Pseudomonas aeruginosa, as well as against a great variety of .beta.-lactamase-producing strains.Type: GrantFiled: November 2, 1988Date of Patent: November 20, 1990Assignee: Meiji Seika Kaisha, Ltd.Inventors: Kaysuyoshi Iwamatsu, Kenji Sakagami, Kunio Atsumi, Takashi Yoshida, Seiji Shibahara, Takashi Tsuruoka, Shinichi Kondo
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Patent number: 4966900Abstract: There are disclosed a .beta.-lactam compound represented by the formula (I): ##STR1## wherein R.sub.1 and R.sub.2 are independently a hydrogen atom or a lower alkyl group; M is a hydrogen atom, a protective group or an eliminatable group which is easily hydrolyzable in a human body; R' and R" are independently a hydrogen atom or a protective group; A is a mercapto group substituted by a substituted or unsubstituted polycyclic nitrogen-containing heterocyclic ring or a group represented by the following formula (a):--OOCNR.sub.3 R.sub.4 (a)where R.sub.3 and R.sub.4 are independently a hydrogen atom or a lower alkyl group, provided that R.sub.1 and R.sub.2 are both hydrogen atoms, both R.sub.3 and R.sub.4 being hydrogen atoms are excluded,or its pharmaceutically acceptable salt, and a method for preparing the same , medicinal composition for microbism therapy containing the same and intermediates for synthesis of the same.Type: GrantFiled: July 20, 1987Date of Patent: October 30, 1990Assignees: Sankei Pharmaceutical Company Ltd., Nippon Pharmaceutical Development Institute Co., Ltd.Inventors: Shigeo Shimizu, Hiroyuki Takano
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Patent number: 4965358Abstract: A new compound called N,N'-carbonyl-bis-(4-ethyl-2,3-dioxo)-piperazine of Formula I ##STR1## A process for the preparation thereof based on the reaction of 4-ethyl-2,3-dioxo-piperazine or a trimethylsilyl derivative thereof with carbonyl chloride or a derivative thereof.The use of the compound of Formula I as an intermediate in the preparation of compounds of Formula II ##STR2## where R is a radical, substituted in alpha position, of a molecule of an acid selected from the group formed by phenylacetic acid, p-hydroxy phenylacetic acid, a 6-(phenylacetamido)-penicillanic acid and a 7-(phenylacetamido)-cephalosporanic acid.Type: GrantFiled: November 10, 1988Date of Patent: October 23, 1990Assignee: Gema, S. A.Inventors: Juan Cabre Castellvi, Jose Diago Meseguer, Asuncion Esteve Bianchini, Carlos E. Lenhardt Padro, Esteve Sans Pitarch
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Patent number: 4962100Abstract: A compound of the formula: ##STR1## wherein R.sup.1 is an amino group which may be protected, R.sup.3 is a hydrogen atom or an optionally substituted hydrocarbon residue; Z is S, S.fwdarw.O, O or CH.sub.2, R.sup.4 is a hydrogen atom, methoxy group or formamido group, R.sup.13 is a hydrogen atom, methyl group, hydroxyl group or halogen atom and A.sup..sym. is an optionally substituted imidazolium-1-yl group forming a condensed ring at the 2,3- or 3,4-position or a pharmaceutically acceptable salt or ester thereof is novel and has excellent antibacterial activity.Type: GrantFiled: March 28, 1989Date of Patent: October 9, 1990Assignee: Takeda Chemical Industries, Ltd.Inventors: Akio Miyake, Masahiro Kondo, Masahiko Fujino
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Patent number: 4960766Abstract: The invention relates to cephem compounds characterized by a substituted 2-pyrazoliomethyl group and a 7-(aminothiazolyl)(alkoxyimino)-acetamido group and certain derivatives thereof, to pharmaceutical compositions comprising the same and to use for treatment of infections diseases.Type: GrantFiled: November 14, 1986Date of Patent: October 2, 1990Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Takao Takaya, Kazuo Sakane, Kenzi Miyai, Kohji Kawabata
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Patent number: 4959469Abstract: The present invention relates to stable cyrstalline (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino)ac etamido]-3-(5,6-dihydroxy-2-methyl-2-isoindolinium)-3-cephem-4-carboxylate sulfate or its hydrate, a process for production of the compound and (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxyl-1-methylethoxyimino)a cetamido]-3-(5,6-dihydroxy-2-methyl-2-isoindolinium)methyl-3-cephem-4-carbo xylate hydrochloride or its hydrate which is a starting material useful for the production of the desired compound of the present invention.Type: GrantFiled: February 27, 1989Date of Patent: September 25, 1990Assignee: Banyu Pharmaceutical Company, Ltd.Inventors: Susumu Nakagawa, Ryosuke Ushijima, Fumio Nakano, Koji Yamada, Eiichi Mano
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Patent number: 4958018Abstract: Disclosed is a method of producing a 3-exomethylenecepham of the formula ##STR1## wherein R.sup.1 is amino or substituted amino and R.sup.2 is a carboxy-protecting group comprising reacting a cephem of the formula ##STR2## wherein R.sup.1 and R.sup.2 are as defined above and X is halogen with lead metal while maintaining the pH of the reaction system at about 0.1 to 8. The cephem (I) may be reacted with a catalytic amount of lead metal or a lead compound in the presence of a metal having a greater ionization tendency than lead.Type: GrantFiled: May 4, 1989Date of Patent: September 18, 1990Assignee: Otsuka Kagaku Kabushiki KaishaInventors: Sigeru Torii, Hideo Tanaka, Masatoshi Taniguchi, Michio Sasaoka, Norio Saito, Takashi Shiroi, Shigemitsu Nagao, Ryo Kikuchi, Yutaka Kameyama
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Patent number: 4956358Abstract: The compounds having a 4,11-dioxo-3-oxa-8(or 7)-thia-1-azatricyclo[7,2,0,0.sup.2,6 ]undecane-2-carboxylic acid skeleton as the base structures, their esters and their salts are useful antibacterial agents.Type: GrantFiled: July 10, 1987Date of Patent: September 11, 1990Assignee: Takeda Chemical Industries, Ltd.Inventors: Akira Morimoto, Noriyoshi Noguchi, Nobuo Choh
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Patent number: 4952578Abstract: The object of the invention is a new cephem compound with antimicrobial activity used for the treatment of infectious diseases of the general formula: ##STR1## wherein R1 is amino or a protected aminoR2 is lower alkyl which may have 1 to 3 halogensR3 is COO.sup..crclbar., carboxy or a protected carboxyR4 is hydroxy(lower)alkyl or protected hydroxy(lower)alkylR5 is amino or a protected aminoR6 is hydrogen or lower alkylX.sup..crclbar. is an anion, andn is 0 or 1with proviso that(i) when R3 is COO.sup..crclbar., then n is 0, and(ii) when R3 is carboxy or a protected carboxy, then n is 1,and pharmaceutically acceptable salt thereof.Type: GrantFiled: September 7, 1988Date of Patent: August 28, 1990Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Kazuo Sakane, Kohji Kawabata, Kenzi Miyai, Yoshiko Inamoto
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Patent number: 4950753Abstract: 3-Exomethylenecepham sulfoxide esters are obtained in improved yields via cyclization of 3-methyl-2-(4-chlorosulfinyl-2-oxo-3-acylamino-1-azetidinyl)-3-butenoic acid esters under anhydrous conditions with stannic chloride in the presence of both an oxo compound, e.g., an ether such as diethyl ether, a ketone such as acetone or methylethyl ketone, and an unsaturated compound, e.g., an alkene such as 1- or 2-hexene, a non-conjugated alkadiene such as 1,4-hexadiene, a cycloalkene such as cyclohexene, an allene, or a non-conjugated cycloalkadiene such as 1,4-cyclohexadiene.Type: GrantFiled: May 17, 1989Date of Patent: August 21, 1990Assignee: Eli Lilly and CompanyInventors: James D. Copp, Gregg A. Tharp
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Patent number: 4950661Abstract: The present invention relates to derivatives of the cephalosporin family, of formula: ##STR1## in which: X is an oxygen atom or a sulfur atomn is zero, 1 or 2.R.sub.1, R.sub.2 and R.sub.3 each designate, a hydrogen atom or else R.sub.1 and R.sub.2 designate a hydrogen atom or a methyl group, and R.sub.3 designates a carboxyl or cyclopropyl group, or elseR.sub.1 and R.sub.2 taken together with the carbon atom to which they are linked form a cyclobutyl or cyclopentyl group and R.sub.3 is a carboxyl group.B is the residue of a primary or secondary amine;their preparation process and application in therapeutics.Type: GrantFiled: April 28, 1988Date of Patent: August 21, 1990Assignee: SANOFIInventors: Dominique Olliero, Ali Salhi
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Patent number: 4943567Abstract: Cephalosporin compounds represented by the general formula (I): ##STR1## wherein R.sup.1 and R.sup.5 independently represent a hydrogen atom or a protective group for an amino group; R.sup.2 represents an alkyl group or a cycloalkyl group; R.sup.3 represents a hydrogen atom, a lower alkenyl group, an alkanoyloxymethyl group, a carbamoyloxymethyl group, a heterocyclic thiomethyl group or a heterocyclic methyl group; R.sup.4 represents a hydrogen atom or an ester residue; and X represents CH or a nitrogen atom and pharmacologically acceptable addition salts thereof, intermediate compounds used in the synthesis process of these compounds, production methods of these compounds and pharmaceutical compositions containing these compounds.Type: GrantFiled: May 27, 1988Date of Patent: July 24, 1990Assignee: Kyoto Pharmaceutical Industries, Ltd.Inventors: Susumu Nishizawa, Hiroyuki Muro, Masayasu Kasai, Satoru Hatano, Syouzi Kamiya, Nobuharu Kakeya, Kazuhiko Kitao
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Patent number: 4943568Abstract: Antibacterially active novel cephalosporins of the formula ##STR1## in which R.sup.1 represents alkyl, alkenyl, alkoxy, alkylthio, halogen, trifluoromethyl or trifluoromethoxy,R.sup.2 represents hydrogen or an organic radical,R.sup.3 represents hydrogen, alkyl, alkenyl, alkoxy, alkylthio, halogen, hydroxymethyl or ethers or esters thereof, or various organothiomethyl or substituted aminomethyl radicals, andR.sup.4 represents COO.sup.- or COOH, or salts thereof.Type: GrantFiled: November 21, 1986Date of Patent: July 24, 1990Assignee: Bayer AktiengesellschaftInventors: Michael Boberg, Rolf Angerbauer, Karl G. Metzger, Hans-Joachim Zeiler