Additional Hetero Ring Containing Patents (Class 540/222)
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Patent number: 6414140Abstract: A process for the production of a 3-vinylcephalosporin compound of formula I wherein R1 and R2 denote hydrogen or an organic group by a Wittig reaction reacting first a compound of formula II with a compound of formula P(R4)3 or P(OR4)3 to produce a compound of formula III and secondly reacting the compound of formula III with a weak base of formula or of formula R10—COO−W+ wherein R5 is hydrogen, alkly or aryl and R6 and R7 are each an activated group of formula —COOR8, —CN, —SO2R8, —COR8 or —CON(R8)2; or R5 and R8 are each aryl and R7 is an activated group of formula —COOR8, —CN, —SO2R8, —COR8 or —CON(R8)2, W+ is an alkali metal cation and R10 is alkyl or aryl to produce a compound of formula IV and finally reacting a compound of formula IV with a compound of formula V to produce a compound of formula I.Type: GrantFiled: February 23, 2001Date of Patent: July 2, 2002Assignee: Biochemie Gesellschaft m.b.H.Inventors: Josef Wieser, Gerd Ascher, Johannes Ludescher, Herbert Sturm
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Patent number: 6407091Abstract: The invention provides compounds of formula I and IV: wherein R1-R11 and A have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting &bgr;-lactamase enzymes, for enhancing the activity of &bgr;-lactam antibiotics, and for treating &bgr;-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula I and IV, and novel intermediates useful for the synthesis of compounds of formula I and IV. The A can be, for example, thio, sulfinyl, or sulfonyl.Type: GrantFiled: April 13, 2000Date of Patent: June 18, 2002Assignee: Research Corporation Technologies, Inc.Inventors: John D. Buynak, A. Srinivasa Rao, Greg C. Adam, Sirishkumar D. Nidamarthy, Venkata Ramana Doppalapudi
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Patent number: 6399770Abstract: A process for preparing a &bgr;-hydroxyester comprising reducing a &bgr;-keto ester in the presence of a salt of ammonium borohydride.Type: GrantFiled: June 6, 2000Date of Patent: June 4, 2002Assignee: Otsuka Kagaku Kabushiki KaishaInventor: Yutaka Kameyama
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Publication number: 20020065262Abstract: Crystalline 7-[2-(2-formylaminothiazol-4-yl)-2-(Z)-(methoxyimino)acetamido]-3-methoxymethyl-3-cephem-4-carboxylic acid-1-(isopropoxycarbonyloxy)ethyl ester and its use.Type: ApplicationFiled: October 31, 2001Publication date: May 30, 2002Inventors: Julia Greil, Johannes Ludescher, Klaus Totschnig, Siegfried Wolf
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Publication number: 20020058806Abstract: There is provided a process for the preparation of a compound according to Formula (II): 1Type: ApplicationFiled: July 30, 2001Publication date: May 16, 2002Inventors: Desmond John Best, George Burton, Brian Charles Gasson, Neal Frederick Osborne, Graham Walker
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Patent number: 6388070Abstract: The present invention provides novel thioester derivatives of thiazolyl acetic acid of the general formula (I), wherein, R1 represents H, trityl, CH3, or CRaRbCOOR3, in which Ra and Rb, independently of one another, represents hydrogen or methyl and R3 represents H or C1-C7 alkyl; and R2 represents C1-C4 alkyl or phenyl.Type: GrantFiled: January 5, 2001Date of Patent: May 14, 2002Assignee: Orchid Chemicals & Pharmaceuticals Ltd.Inventors: Pandurang Balwant Deshpande, Parven Kumar Luthra
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Patent number: 6384214Abstract: The present invention is concerned with a novel process for the manufacture of cephalosporin derivatives of the formula by converting a phosphonium salt into the corresponding ylide and reacting same with an aldehyde wherein R1 and R2 are as above.Type: GrantFiled: June 29, 2000Date of Patent: May 7, 2002Assignee: Basilea Pharmaceutica AGInventors: Paul Spurr, Georg Trickes
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Patent number: 6384212Abstract: The present invention relates to a new, simple, and easy process for preparing cephalosporin antibiotics of the following formula (I), such as ceftazidime and cefixime. The process comprises acylating a 7-amino cephalosporanic acid derivative of the following formula (III) with a crystalline aminothiazole compound of the following formula (II): wherein R1 and R2 are the same or different and independently represent H, a C1-4 alkyl or C3-5 cycloalkyl group, R4 represents acetoxymethyl, methylpyridine, or vinyl, X represents chlorine or bromine, and the acid in the acid addition salt represents an inorganic acid, such as hydrochloric acid, or an organic acid, such as formic acid or acetic acid.Type: GrantFiled: May 4, 2000Date of Patent: May 7, 2002Assignee: Hanmi Fine Chemicals Co., Ltd.Inventors: Dae-chul Yoon, Seung Won Yoo, Dong Gyun Shin, Myoung Ki Lee, Mi Soon Park, Yoon Seok Lee, Yoon Seok Song, Ju Cheol Lee, Sang Mi Oh
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Patent number: 6384213Abstract: There is described a process for the preparation of a pure amorphous form of cefuroxime axetil which involves dissolving crystalline cefuroxime axetil in acetic acid including at least 5% v/v water and recovering said amorphous form of cefuroxime axetil from the solution by the addition of additional water, the solution being added all at once to the additional water being present in a volume which is sufficient to precipitate said amorphous cefuroxime axetil.Type: GrantFiled: May 19, 2000Date of Patent: May 7, 2002Assignee: Ranbaxy Laboratories LimitedInventors: Vijay Kumar Handa, Om Dutt Tyagi, Uttam Kumar Ray
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Patent number: 6350869Abstract: Cefdinir in the form of a salt with dicyclohexylamine, a process for its production and its use in the purification of impure cefdinir.Type: GrantFiled: September 27, 1999Date of Patent: February 26, 2002Assignee: Biochemie Gesellschaft m.b.H.Inventors: Hubert Sturm, Siegfried Wolf, Johannes Ludescher
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Publication number: 20020016456Abstract: A process for the preparation of highly pure crystalline form of cefuroxime-1-acetoxyethyl ester (cefuroxime axetil) from cefuroxime by reacting an amine salt of cefuroxime with an esterifying reagent.Type: ApplicationFiled: July 16, 2001Publication date: February 7, 2002Inventors: Om Dutt Tyagi, Gyan Chand Yadav, Vijay Kumar Handa
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Patent number: 6333409Abstract: The invention relates to a new process for the depletion of 7-amino-3-[(E)-1-propen-1-yl]-3-cephem-4-carboxylic acid in mixtures of 7-amino-3-[(Z)-1-propen-1-yl]-3-cephem-4-carboxylic acid and 7-amino-3-[(E)-1-propen-1-yl]-3-cephem-4-carboxylic acid, by means of the crystalline hydrochloride or a metal or amine salt of 7-amino-3-[(z/E)-1-propen-1-yl]-3-cephem-4-carboxylic acid or by adsorption chromatography.Type: GrantFiled: May 4, 2000Date of Patent: December 25, 2001Assignee: Biochemie Gesellschaft m.b.H.Inventors: Johannes Ludescher, Bernhard Prager, Siegfried Wolf
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Patent number: 6313289Abstract: Crystalline 2-(amninothiazol-4-yl)-2-(tert.butoxycarbonylmethoxyimino)acetic acid-S-mercapto-benzo-thiazolylester in form of an N,N-dimethylacetamide solvate; a crystalline salt of a 7-[2-(aminothiazol-4-yl)-2-(carboxymethoxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid with an amine of formula N(R1)(R2)(R3), wherein R1, R2, and R3 have various meanings, a crystalline sulphuric acid addition salt of a 7-[2-(2-aminothiazol-4-yl)-2-carboxymethoxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid; and the use of these salts in the production of cefixime, e.g. in form of a trihydrate.Type: GrantFiled: August 4, 1999Date of Patent: November 6, 2001Assignee: Biochemie Gesellschaft m.b.H.Inventors: Johannes Ludescher, Ludwig Miller, Hubert Sturm, Werner Veit, Martin Decristoforo, Siegfried Wolf
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Patent number: 6303592Abstract: Derivatives of 7-alkylidene cephalosporanic acid sulfone and the pharmaceutically active salts thereof are found to be potent inhibitors of &bgr;-lactamase enzymes.Type: GrantFiled: March 14, 1997Date of Patent: October 16, 2001Assignee: Research Corporation Technologies, Inc.Inventors: John D. Buynak, Brian Bachmann
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Patent number: 6294668Abstract: The present invention relates to cephalosporin derivatives of the general formula where R1 is halogen, lower alkyl, phenyl, benzyl, styryl, naphthyl or heterocyclyl; the lower alkyl, phenyl, benzyl, styryl, naphthyl and heterocyclyl being optionally substituted by at least one of halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted phenyl, amino, lower alkylamino, di-lower alkylamino, carboxy, lower alkylcarboxy, carbamoyl or lower alkylcarbamoyl; R4, R5 independently are hydrogen, lower alkyl or phenyl; X is S, O, NH or CH2; n is 0,1 or 2; m is 0 or 1; s is 0 or 1; R2 is hydrogen, hydroxy, —CH2—CONHR6, lower alkyl-Qr, cycloalkyl-Qr, lower alkoxy, lower alkenyl, cycloalkenyl-Qr, lower alkynyl, aralkyl-Qr, aryl-Qr, aryloxy, aralkoxy, a heterocyclic ring or a heterocyclyl-Qr, the lower alkyl, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl, aryl, aryloxy, aralkoxy and the heterocyclicType: GrantFiled: November 5, 1997Date of Patent: September 25, 2001Assignee: Hoffman-La Roche Inc.Inventors: Peter Angehrn, Ingrid Heinze-Krauss, Hans G. F. Richter
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Patent number: 6255480Abstract: Aminothiazole derivatives having the carboxyl activated by means of thioesters, said derivatives being condensable with &bgr;-lactam nuclei to yield &bgr;-lactam antibioticsType: GrantFiled: June 24, 1999Date of Patent: July 3, 2001Assignee: Ortho-McNeil Pharmaceutical, Inc.Inventors: Maurizio Zenoni, Mario Leone, Maurizio Serra, Mauro Filippi
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Patent number: 6248881Abstract: A process for the production of a 3-vinylcephalosporin compound of formula I wherein R1 and R2 may be the same or different and denote hydrogen or an organic radical, which comprises subjecting a 3-iodomethyl-cephalosporin to a Wittig reaction in the presence of a weak base.Type: GrantFiled: March 31, 1997Date of Patent: June 19, 2001Assignee: Biochemie GmbHInventors: Josef Wieser, Gerd Ascher, Johannes Ludescher, Herbert Sturm
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Patent number: 6235896Abstract: There is described a process for the preparation of cefuroxime from predominantly S-cefuroxime axetil, R, S mixture of cefuroxime axetil or R-cefuroxime axetil not meeting the purity criteria. This comprises treating cefuroxime axetil with alkoxides in the presence of a suitable solvent or solvent mixture and isolating cefuroxime from the reaction mixture.Type: GrantFiled: March 9, 1999Date of Patent: May 22, 2001Assignee: Ranbaxy Laboratories LimitedInventors: Vijay Kumar Handa, Ramesh Dandala, Jag Mohan Khanna
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Substituted amino bicyclic-&bgr;-lactam penam and cepham derivatives as cysteine protease inhibitors
Patent number: 6232305Abstract: The present invention provides substituted amino bicyclic-&bgr;-lactam penam derivatives and substituted amino bicyclic-&bgr;-lactam cepham derivatives and their diastereoisomers of formula I, as well as compositions, methods of making, and methods of using, which exhibit excellent cysteine protease inhibitory activity and which may be used for treatment of different diseases such as cancer (including cancer metastasis), osteoporosis, rheumatoid arthritis.Type: GrantFiled: January 22, 1998Date of Patent: May 15, 2001Assignee: Naeja Pharmaceutical Inc.Inventors: Rajeshwar Singh, Nian Zhou, Deqi Guo, Ronald G. Micetich -
Patent number: 6232306Abstract: The present invention provides compounds of formula I wherein R1 is hydrogen, C1-6-alkyl, C1-6-alkyl substituted by fluoro, or C3-6-cycloalkyl; R2 is hydrogen or a substituent selected from the group consisting of —CH2C(═CHR)—COOR, —CH2OCOR, —CH(R)OCOR, —CH(R)OCOOR, —CH(OCOR)OCOR, —CH2COCH2OCOR and R3 is hydrogen or a substituent selected from the group consisting of —CH2C(═CH2)—COOR, —COOCH2C(═CHR)—COOR, —COOCH2OCOR, —COOCH(R)OCOR, —COOCH(R)OCOOR, —COOCH(OCOR)OCOR, —COOCH2COCH2OCOR, and with the proviso that one of R2 and R3 is hydrogen and the other is not hydrogen, R is hydrogen or C1-6-alkyl; R4 is hydrogen or hydroxy, R5 is hydrogen or &ohgr;-hydroxyalkyl; and X is CH or N, pharmaceutically acceptable salts of the compounds and hydrates of the compounds and of their salts.Type: GrantFiled: June 14, 1999Date of Patent: May 15, 2001Assignee: Hoffmann-La Roche Inc.Inventors: Paul Hebeisen, Christian Hubschwerlen, Jean-Luc Specklin
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Patent number: 6169180Abstract: The invention relates to a new economical and simple process, using a new intermediate compound, for the production of 3′-substituted 7-amino-3-propenyl-4-cephem-carboxylic acid derivatives of formula wherein R is hydrogen, a negative charge or a silyl protecting group, Ro is hydrogen or methoxy, R1 is hydrogen or a silyl protecting group and X is the radical of a nucleophile, and their acid addition salts.Type: GrantFiled: October 8, 1997Date of Patent: January 2, 2001Assignee: Biochemie GesellschaftInventors: Johannes Ludescher, Hubert Sturm, Josef Wieser
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Patent number: 6159706Abstract: The present invention provides a method for targeting toxic antimetabolites to gram negative infections. It provides a means of taking advantage of a key disease resistance mechanism to activate these drugs locally, and to overcome the resistance phenotype of the microbes. The invention further provides a method for selecting for antibiotic sensitivity, since a likely mechanism by which organisms are likely to gain resistance to the prodrugs is via loss of enzyme activity, which will make the bacteria sensitive to antibiotics once again.Type: GrantFiled: December 18, 1998Date of Patent: December 12, 2000Assignee: NewBiotics, Inc.Inventor: H. Michael Shepard
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Patent number: 6159961Abstract: A compound of the formula: ##STR1## wherein R.sup.1 is amino or protected amino,R.sup.2 is hydrogen or hydroxy protective group,R.sup.3 is carboxy or protected carboxy,R.sup.4 is hydrogen, lower alkenyl, acyloxy(lower)alkenyl, optionally substituted heterocyclic(lower)alkenyl, optionally substituted heterocyclic(lower)alkenylthio, optionally substituted heterocyclic(lower)alkylthio, or optionally substituted heterocyclic-thio(lower)alkylthio andR5 is halogen or lower alkyland pharmaceutically acceptable salts thereof, which is useful as a medicament for prophylactic and therapeutic treatment of infectious diseases.Type: GrantFiled: July 19, 1999Date of Patent: December 12, 2000Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Kohji Kawabata, Hirofumi Yamamoto, Yoshiteru Eikyu, Shinya Okuda, Hisashi Takasugi
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Patent number: 6156889Abstract: The subject matter of the present invention relates to a reagent and a process useful for cleaving a functional group protected by an alkoxycarbonyl group during an organic synthesis. This reagent comprises: a) an aqueous phase; b) a catalyst comprising at least one group VIII element in the periodic table of elements and at least one water-soluble ligand, wherein the group VIII element in the periodic table is maintained in the aqueous phase by the formation of a complex with at least one water-soluble ligand; and c) a nucleophilic compound soluble in the aqueous phase; and optionally d) an organic phase.Type: GrantFiled: October 9, 1998Date of Patent: December 5, 2000Assignee: Rhodia ChimieInventors: Jean-Marie Bernard, Errol Blart, Jean-Pierre Genet, Monique Savignac, Sandrine Lemaire-Audoire
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Patent number: 6150350Abstract: The invention relates to antimicrobial compositions comprising a combination of (1) a therapeutically effective amount of a compound of formula I ##STR1## with (2) a second ingredient selected from carbapenem antibiotics or with .beta.-lactamase inhibitors, to the use of the compositions for producing a medicament for the treatment and prophylaxis of infectious diseases, including MRSA infections, and to pharmaceutical compositions containing the combination.Type: GrantFiled: August 24, 1998Date of Patent: November 21, 2000Assignee: Hoffman-la Roche Inc.Inventors: Peter Angehrn, Ingrid Heinze-Krauss, Malcolm Page, Hans G. F. Richter
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Patent number: 6136967Abstract: The invention relates to a new process for the depletion of 7-amino-3-[(E)-1-propen-1-yl]-3-cephem-4-carboxylic acid in mixtures of 7-amino-3-[(Z)-1-propen-1-yl]-3-cephem-4-carboxylic acid and 7-amino-3-[(E)-1-propen-1-yl]-3-cephem-4-carboxylic acid, by means of the crystalline hydrochloride or a metal or amine salt of 7-amino-3-[(Z/E)-1-propen-1-yl]-3-cephem-4-carboxylic acid or by adsorption chromatography.Type: GrantFiled: November 12, 1998Date of Patent: October 24, 2000Assignee: Biochemie Gesellschaft m.b.H.Inventors: Johannes Ludescher, Bernhard Prager, Siegfried Wolf
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Patent number: 6107481Abstract: A process to prepare the E isomer of a 3-substituted (6R,7R)-7-phenyl-acetamido-ceph-3-em-4-carboxylic acid from a mixture of the E and Z-isomer of either the corresponding tert-butyl or the corresponding 4-methoxybenzyl ester of a 3-substituted (6R,7R)-7-phenylacetamido-ceph-3-em-4-carboxylate, characterized by the application of a compound selected from the group titanium tetrachloride, tin tetrachloride and tellurium tetrachloride.Type: GrantFiled: July 13, 1999Date of Patent: August 22, 2000Assignee: DSM N.V.Inventors: Erik De Vroom, Thomas Van Der Does
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Patent number: 6100393Abstract: Process for purifying 7-substituted aminodeacetoxycephalosporins through the use of filter membranes. A process for purification by ultrafiltration and/or nanofiltration with a cut-off for molecular weights over 10,000 Dalton and preferably over 2000 Dalton is described. For example cephalosporin-G of increased purity, represented by a 6-8% increase in the HPLC titre, with a reduction of 50% in absorbance, is obtained using this technique. The invention makes it possible for the purified products to be used directly in the synthesis of other antibiotic compounds without the need for intermediate isolation.Type: GrantFiled: February 25, 1998Date of Patent: August 8, 2000Assignee: Antibioticos, S.A.Inventors: Juan Francisco Lopez Ortiz, Oscar Ferrero Barruego, Emiliano Gonzalez de Prado, Alejandro Vitaller Alba, Francisco Salto Maldonado
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Patent number: 6093814Abstract: The present invention relates to a novel crystalline cefdinir intermediate having formula (II) which can be used very usefully for preparing a cephalosporin antibiotics, cefdinir, in which Ph represents phenyl, p-TsOH represents p-toluenesulfonic acid, and DMAC represents N,N-dimethylacetamide, to a process for preparation thereof and to a process for preparing cefdinir using the compound of formula (II). ##STR1## According to the present invention, cefdinir can be prepared in an excellent color and purity and with a good yield.Type: GrantFiled: May 18, 1998Date of Patent: July 25, 2000Assignee: Hanmi Pharmaceutical Co., Ltd.Inventors: Gwan Sun Lee, Young Kil Chang, Jong Pil Chun, Joon Hyung Koh
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Patent number: 6063778Abstract: The invention provides novel cephalosporin derivatives of the formula (I) ##STR1## and salts thereof for use in pharmaceutical compositions. Also novel precursors for synthesis of the cephalosporins are disclosed.Type: GrantFiled: June 26, 1998Date of Patent: May 16, 2000Assignee: Il-Dong Pharm. Co., Ltd.Inventors: Kee-Won Kim, Jae-Hoon Kang, Dong-Sik Yu, Moo-Soo Jang, Seung-Woo Yu
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Patent number: 6060599Abstract: A process for preparing cefuroxime axetil in substantially amorphous form comprises forming a mixture of crystalline cefuroxime axetil and at least one pharmaceutically acceptable excipient, and subjecting the mixture to milling for a period of time sufficient to convert the crystalline cefuroxime axetil to substantially amorphous form, i.e., the crystallinity is less than 5%. The amorphous cefuroxime axetil has a chemical purity of at least 95%. Desirably, the particles of the milled material are reduced to a size of less than 2 .mu.m. The amorphous cefuroxime axetil prepared by this method may consist of R isomer, S isomer, or a racemic mixture of the R and S isomers.Type: GrantFiled: June 17, 1998Date of Patent: May 9, 2000Assignee: Ranbaxy Laboratories LimitedInventors: Jitendra Krishan Somani, Sanjeev Sethi, Om Dutt Tyagi
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Patent number: 6034237Abstract: 3-Imino-cephalosporin derivatives of formula II ##STR1## wherein Y denotes alkyl, aryl or heterocyclyl; and R.sup.a and R.sup.d denote hydrogen or a silyl group; in free form or in salt form, and methods of preparation.Type: GrantFiled: September 30, 1998Date of Patent: March 7, 2000Assignee: Biochemie Gesellschaft m.b.H.Inventors: Gerd Ascher, Johannes Ludescher, Hubert Sturm, Josef Wieser
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Patent number: 6020329Abstract: .beta.-Lactam antibiotics of formula (I) or a salt thereof, wherein R.sup.1 is hydrogen, methoxy or formamido; R.sup.2 is an acy group; CO.sub.2 R.sup.3 is a carboxy group or a carboxylate anion, or R.sup.3 is a readily removable carboxy protecting group; R.sup.4 represents up to four substituents; X is S, SO, SO.sub.2, O or CH.sub.Type: GrantFiled: October 20, 1997Date of Patent: February 1, 2000Assignee: Pzifer Inc.Inventors: John Hargreaves Bateson, George Burton, Stephen Christopher Martin Fell
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Patent number: 6013647Abstract: This invention relates to new benzoxazinedione derivatives corresponding to the formula I: ##STR1## wherein R.sup.1 =H or carboxyalkyl, R.sup.2 =H, alkyl or phenyl, and R.sup.3 represents different acid groups derived from amino acids, dipeptides and hydrazones or conjugates thereof with active ingredients, e.g. antibiotics. The compounds may be present as free acids, in the form of their salts or as readily cleavable esters. The compounds according to the invention constitute heterocyclically protected catechol derivatives and are effective as siderophores against gram-negative bacterial strains, particularly against Pseudomonads and strains of E. coli and Salmonella. In the form of their conjugates with active ingredients, e.g. antibiotics (as "siderophore-antibiotic conjugates"), they can transport the latter into bacterial cells and can improve or extend the antibacterial effect thereof, sometimes even in relation to bacterial strains which are resistant to other .beta.-lactams.Type: GrantFiled: March 5, 1998Date of Patent: January 11, 2000Assignee: Gruenenthal GmbHInventors: Lothar Heinisch, Steffen Wittmann, Ute Moellmann, Rolf Reissbrodt
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Patent number: 6001997Abstract: .beta.-Lactam antibiotics of formula (I) or a salt thereof, wherein R.sup.1 is hydrogen, methoxy or formamido; R.sup.2 is an acyl group; CO.sub.2 R.sup.3 is a carboxy group or a carboxylate anion, or R.sup.3 is a readily removable carboxy protecting group; R.sup.4 represents up to four substituents; X is S, SO, SO.sub.2, O or CH.sub.2 ; m is 1 or 2; and n is 0, useful in the treatment of bacterial infections.Type: GrantFiled: January 11, 1999Date of Patent: December 14, 1999Inventors: John Hargreaves Bateson, George Burton, Stephen Christopher Martin Fell
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Patent number: 5998611Abstract: An industrially excellent, novel process for producing cephem compounds which are useful as medicines, particularly, antibiotics and represented by the following formula (III): ##STR1## wherein R.sup.1 means either group represented by the following formula: ##STR2## R.sup.2 denotes a carboxyl group or a carboxyl anion, and R.sup.3 stands for a lower alkyl group, a halogen atom, a lower alkyl group substituted by an aliphatic acyloxy group having 1-6 carbon atoms, or any one of the groups represented by the following formulae: ##STR3## which comprises reacting in water a 3-cephem-4-carboxylate represented by the following formula (I): ##STR4## or a salt thereof with an acid chloride represented by the formula (II), R.sup.1 COCl.Type: GrantFiled: September 25, 1997Date of Patent: December 7, 1999Assignee: Eisai Chemical Co., Ltd.Inventors: Homare Shinohara, Masato Kodama, Kimio Hamamura, Hirofumi Kuroda
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Patent number: 5981519Abstract: The present invention relates to compounds having the formula ##STR1## wherein X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are as defined herein as well as readily hydrolyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts. These compounds have valuable pharmacological activity for the treatment and prophylaxis of infectious diseases, especially those caused by methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.Type: GrantFiled: December 8, 1997Date of Patent: November 9, 1999Assignee: Hoffman-La Roche Inc.Inventors: Peter Angehrn, Paul Hebeisen, Ingrid Heinze-Krauss, Malcolm Page, Valerie Runtz
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Patent number: 5969131Abstract: A 3-[(E)-1-propenyl]cephem compound represented by formula (I): ##STR1## wherein R represents hydrogen, a protective group for an amino group, or the group shown by formula (II): ##STR2## in which R.sup.3 is a protective group for an amino group, R.sup.4 is a protective group for a hydroxyl group, and W is --CH.dbd. or --N.dbd.; R.sup.2 represents a protective group for a carboxyl group; and X represents hydrogen or chlorine. The compound is useful as an intermediate for producing cephem antibiotics and is prepared by isomerizing the corresponding 3-[(Z)-1-propenyl]cephem compound in an inert organic solvent in the presence of an aromatic thiol. The compound of formula (I) wherein X is chlorine can be converted into a 3-[(E)-3-ammonio-1-propenyl]cephem derivative through the reaction with a tertiary amine.Type: GrantFiled: September 18, 1997Date of Patent: October 19, 1999Assignee: Sumitomo Chemical Company, LimitedInventors: Mari Yuasa, Kazuyuki Yamagata, Hirokazu Murata, Masashi Komatsu, Isao Yoshida
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Patent number: 5955604Abstract: Substrates for .beta.-lactamase of the general formula I ##STR1## in which one of X and Y is a fluorescent donor moiety and the other is a quencher (which may or may not re-emit); R' is selected from the group consisting of H, lower (i.e., alkyl of 1 to about 5 carbon atoms) and (CH.sub.2).sub.n OH, in which n is 0 or an integer from 1 to 5; R" is selected from the group consisting of H, physiologically acceptable metal and ammonium cations, --CHR.sup.2 OCO(CH.sub.2).sub.n CH.sub.3, --CHR.sup.2 OCOC(CH.sub.3).sub.3, acylthiomethyl, acyloxy-alpha-benzyl, delta-butyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, beta-morpholinoethyl, dialkylaminoethyl, acyloxyalkyl, dialkylaminocarbonyloxymethyl and aliphatic, in which R.sup.2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO.sub.2 and CH.sub.2 ; and Z' and Z" are linkers for the fluorescent donor and quencher moieties. Methods of assaying .beta.Type: GrantFiled: October 21, 1997Date of Patent: September 21, 1999Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Gregor Zlokarnik
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Patent number: 5945532Abstract: This invention relates to reactive derivatives of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetic acid and 1H-tetrazol-1-acetic acid of the following general formula I, ##STR1## wherein ##STR2## as well as to use thereof in the manufacture of cephalosporin antibiotics such as cefotaxime, ceftriaxone and cefazolin.Type: GrantFiled: September 16, 1998Date of Patent: August 31, 1999Assignee: Lupin Laboratories LimitedInventors: Debashish Datta, Vinod George, Bishwa Prakash Rai
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Patent number: 5936083Abstract: A compound selected from the group consisting of a syn isomer of a compound of the formula ##STR1## in the R or S form or in the form of an R, S mixture wherein R us selected from the group consisting of ##STR2## R and R' are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, halogen, CO.sub.2 --Q, ##STR3## CH.sub.2 --SQ, Q and Q' are individually hydrogen or alkyl of 1 to 4 carbon atoms, P, P' and P" are individually alkyl of 1 to 4 carbon atoms optionally substituted by one of the substituents R and R' the dotted line indicating that P and P' can optionally form with the nitrogen atom to which they are linked a heterocycle with 5 or 6 links, R.sub.b and R.sub.c are individually selected from the group consisting of an equivalent of an alkali metal, an alkaline earth metal, magnesium, ammonium and an amine organic base or A and A' are the remainder of an easily cleavable ester group or CO.sub.2 A is CO.sub.Type: GrantFiled: April 1, 1996Date of Patent: August 10, 1999Assignee: Roussel UclafInventors: Jozsef Aszodi, Jean-Francois Chantot, Solange Gouin D'Ambrieres
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Patent number: 5929233Abstract: The invention provides a process for preparing an allenyl .beta.-lactam of formula (4), by reacting the hydroxyl group of a .beta.-lactam of formula (1) with a reactive derivative of sulfonic acid of formula (2) to convert the compound of formula (1) to a .beta.-lactam of formula (3), thereafter reacting the resulting .beta.-lactam with a basic anion exchange resin of the type having a tertiary organic base fixed to the resin and isolating the allenyl .beta.-lactam of formula (4) with stability and high purity in a high yield.The invention also provides a process for preparing an allenyl .beta.-lactam of formula (4), by reacting the hydroxyl group of a .beta.-lactam compound of formula (1) with a reactive derivative of sulfonic acid of formula (2) to convert the compound of the formula (1) to a .beta.-lactam compound of formula (3), thereafter reacting the resulting .beta.-lactam of formula (3) with a tertiary organic base to convert the compound (3) to the allenyl .beta.Type: GrantFiled: November 6, 1996Date of Patent: July 27, 1999Assignee: Otsuka Kagaku Kabushiki KaishaInventors: Sigeru Torii, Hideo Tanaka, Michio Sasaoka, Yutaka Kameyama, Isao Wada, Yasuhisa Amano
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Patent number: 5925632Abstract: Compounds of formula (I) ##STR1## wherein R.sup.1 is hydrogen, lower alkyl, aralkyl, cycloalkyl, R.sup.3 CO-- or --C(R.sup.4 R.sup.5)CO.sub.2 R.sup.6 ; where R.sup.4 and R.sup.5 are each independently hydrogen or lower alkyl, or R.sup.4 and R.sup.5 taken together with the carbon atom to which they are attached form a cycloalkyl group; R.sup.3 is hydrogen or lower alkyl and R.sup.6 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group;R.sup.2 is isobutyl, 2,2-dimethyl-propyl or cyclohexyl-methyl;n is 0, 1 or 2;X is CH or N;as well as readily hydrolyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts are disclosed. These compounds have valuable antibacterial activity.Type: GrantFiled: July 25, 1997Date of Patent: July 20, 1999Assignee: Hoffmann-La Roche Inc.Inventors: Ingrid Heinze-Krauss, Hans Richter
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Patent number: 5922861Abstract: An efficient process for de-esterification has been provided for by application of special tetrahalogenides. By applying this process a new compound, viz. cefesone, and especially the E-isomer thereof, has been prepared.Type: GrantFiled: April 1, 1998Date of Patent: July 13, 1999Assignee: Gist-Brocades B.V.Inventors: Erik De Vroom, Thomas Van Der Does
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Patent number: 5883248Abstract: Novel intermediates of the formula ##STR1## wherein the substituents are defined in the specification.Type: GrantFiled: July 30, 1997Date of Patent: March 16, 1999Assignee: Roussel UclafInventors: Jozsef Aszodi, Jean-Francois Chantot, Patrick Fauveau, Solange Gouin D'Ambrieres, Daniel Humbert, Christophe Dini
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Patent number: 5883247Abstract: The invention is concerned with a new process for the preparation of compounds of formula ##STR1## wherein R.sup.1 is trityl, acetyl, tetrahydropyranyl or cyclopentyl;R.sup.2 is hydrogen, hydroxy, lower alkyl, cycloalkyl, lower alkoxy, lower alkenyl, lower alkynyl, aryl, aryloxy, aryl-lower alkyl, aryl-lower alkoxy or heterocyclyl or heterocyclyl-lower alkyl; the lower alkyl, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aryl-lower alkyl, aryl, aryloxy, aryl-lower alkoxy, the heterocyclyl moieties being unsubstituted or substituted with at least one group selected from carboxy, amino, nitro, cyano, lower alkyl, lower alkoxy, hydroxy, halogen, --CONR.sup.21 R.sup.22, --N(R.sup.22)COOR.sup.23, R.sup.22 CO--, R.sup.22 OCO-- or R.sup.22 COO--, wherein R.sup.21 is hydrogen, lower alkyl, or cycloalkyl; R.sup.22 is hydrogen or lower alkyl; R.sup.23 is lower alkyl, lower alkenyl or a carboxylic acid protecting group;Y is --S-- and Z is --CH.sub.2 -- orY is --CH.sub.Type: GrantFiled: May 14, 1997Date of Patent: March 16, 1999Assignee: Hoffmann-La Roche Inc.Inventor: Thomas Oberhauser
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3-ammoniopropenyl cephalosporin compounds as antibacterial agents and process for preparing the same
Patent number: 5872249Abstract: A 3-ammoniopropenyl cephalosporin of the following formula (I): ##STR1## wherein P is hydroxylated alicyclic or aliphatic amines such as meso-3,4-dihydroxy-1-methylpyrrolidine, (3S,4S)-3,4-dihydroxy-1-methylpyrrolidine, (3R,4R)-3,4-dihydroxy-1-methylpyrrolidine, rac-3,4-trans-dihydroxy-1-methylpyrrlidine, (2S,4R)-4-hydroxy-1-methyl-2-pyrrolidinemethanol, N-methyl-bis(2-hydroxyethyl)amine, 3,4-cis-dihydroxy-1-methylpiperidine, 3,4-trans-dihydroxypiperidine, 4-hydroxy-1-methylpiperidine, 2-hydroxymethyl-1-methylpiperidine, or tropine, or a pharmaceutically acceptable salt thereof, exhibits good anti-bacterial activities against a wide variety of Gram-positive and Gram-negative bacteria; and a process for the preparation thereof.Type: GrantFiled: September 30, 1997Date of Patent: February 16, 1999Assignee: Korea Institute of Science and TechnologyInventors: Hokoon Park, Yong Sup Lee, Jae Yeol Lee, Dae Hwan Suk, Eun-Rhan Woo -
Patent number: 5861508Abstract: A p-toluenesulphonic acid salt of 7-?2-(2-aminothiazol-4-yl)-2-(Z)-hydroximino-acetamido!-3-N,N-dimethylcarb amoyloxymethyl-3-cephem-4-carboxylic acid (isopropoxycarbonyloxy)ethylester, e.g. of formula ##STR1## its use in the production of other salts and a pharmaceutical composition containing it.Type: GrantFiled: April 18, 1997Date of Patent: January 19, 1999Assignee: Biochemie Gesellschaft m.b.H.Inventors: Johannes Ludescher, Rainer Pucher, Siegfried Wolf
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Patent number: 5856474Abstract: Cephalosporin derivatives of formula ##STR1## wherein R.sub.1 signifies hydrogen or a silyl protecting group, processes for their production and their use as intermediate products.Type: GrantFiled: October 23, 1996Date of Patent: January 5, 1999Assignee: Biochemie Gesellschaft, m.b.H.Inventors: Gerd Ascher, Johannes Ludescher, Hubert Sturm, Josef Wieser
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Patent number: 5856320Abstract: Novel cephalosporin derivatives of formula (II): ##STR1## wherein R.sup.2 is hydrogen, methyl, or fluoromethyl; R.sup.3 is hydrogen, methyl or carboxyl; R.sup.4 is hydrogen or methyl; A is methylene or propenylene; Q is nitrogen or CH, and pharmaceutically acceptable salts, solvates, hydrates and esters thereof, a process for their preparation and an antimicrobial composition containing them.Type: GrantFiled: October 15, 1996Date of Patent: January 5, 1999Assignee: Katayama Seiyakusyo Co., Ltd.Inventors: Sadao Hayashi, Yasuyuki Kurita