7-position Substituent Contains Hetero Ring Patents (Class 540/225)
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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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Publication number: 20010011085Abstract: The present invention relates to cephem-derivatives and to a process for their preparation, having proper substituents at C-2 position, i.e. heterocyclylthio or acyloxy group. They are potent protease inhibitors, in particular human leucocyte elastase (HLE) inhibitors.Type: ApplicationFiled: August 14, 1997Publication date: August 2, 2001Inventors: MARCO ALPEGIANI, PIERLUIGI BISSOLINO, MASSIMILIANO PALLADINO, ETTORE PERRONE
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Patent number: 6265394Abstract: Provided by the present invention are cephem derivatives represented by the general formula wherein Ar is an optionally substituted lipophilic phenyl, naphthyl or pyridyl group; L1 and L2 are (C1-C6)alkylene optionally substituted with hydroxy or oxo and/or optionally interrupted with a vinylene group, S, O, aryl, heteroaryl, in which R1 is H or (C1-C6)alkyl; A is CO2H, PO3H, SO3H, tetrazolyl or x′{circle around (−)} is a pharmaceutically acceptable anion; and Q is an quaternized nitrogen group. The derivatives are gram-positive antibacterial agents especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus.Type: GrantFiled: August 4, 1999Date of Patent: July 24, 2001Assignee: Bristol-Myers Squibb CompanyInventors: Roman Z. Sterzycki, Oak K. Kim, Yasutsugu Ueda, Stanley V. D'Andrea, Dane M. Springer
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Patent number: 6214818Abstract: A cephem compound, wherein the cephem ring has a substituent at the 3-position, which substituent is shown by the formula II, wherein Het is a mono- or polycyclic heterocyclic group comprising one or more hetero atoms selected from the group consisting of N, O and S which may be the same or different from each other; R1 is hydrogen, an optionally substituted lower alkyl or an optionally substituted lower alkenyl; A is an optionally substituted lower alkylene, an optionally substituted lower alkenylene or a single bond; B is an optionally substituted imino or a single bond; or A and B taken together may form a single bond; and D is a single bond or a group of the formula (a): The cephem compounds of the present invention are useful as antibiotic agents.Type: GrantFiled: October 1, 1998Date of Patent: April 10, 2001Assignee: Shionogi & Co., Ltd.Inventors: Yasuhiro Nishitani, Koji Ishikura
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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: 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: 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: 6150351Abstract: This invention relates to new cephem compound represented by the following general formula (I): ##STR1## wherein each symbol is as defined in the specification or a salt thereof, which has antimicrobial activity against Helicobacter pylori, and are useful as anti-Helicobacter pylori agents, anti-gastritis agents, anti-ulcer agents and anti-cancer agents.Type: GrantFiled: August 12, 1998Date of Patent: November 21, 2000Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Yoshiki Yoshida, Shinya Okuda, Hiroshi Sasaki, Keiji Matsuda, Hisashi Takasugi
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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: 6093712Abstract: Provided are cephem derivatives represented by the general formula ##STR1## wherein Ar, R.sup.1, R.sup.2, R.sup.3, R.sup.9 and R.sup.10 are as defined in the application. The derivatives are gram-positive antibacterial agents especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus.Type: GrantFiled: December 10, 1998Date of Patent: July 25, 2000Assignee: Bristol-Meyers Squibb CompanyInventors: John D. Matiskella, Stanley V. D'Andrea, Thomas W. Hudyma, Yasutsugu Ueda, Oak K. Kim, Raymond F. Miller, Shelley E. Hoeft, Joanne J. Bronson
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Patent number: 6066630Abstract: The present invention includes novel compounds of formula ##STR1## where R.sup.99 is selected from the group consisting of sulfur, SO, SO.sub.2, NH, N-alkyl, oxygen, C.dbd.C (cis or trans), and C.tbd.C, and R.sup.12 is ##STR2## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.Type: GrantFiled: October 11, 1996Date of Patent: May 23, 2000Assignee: Microcide Pharmaceuticals, Inc.Inventors: In-Seop Cho, Scott J. Hecker, Tomaz W. Glinka, Ving J. Lee, Zhijia J. Zhang
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Patent number: 6057312Abstract: The present invention includes novel compounds of formula ##STR1## where G, H, J, L and M are carbon or nitrogen, R.sup.99 is selected from the group consisting of sulfur, SO, SO.sub.2, NH, N-alkyl, oxygen, C.dbd.C (cis or trans), and C.tbd.C, and R.sup.12 is NR.sup.13 R.sup.14, ##STR2## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.Type: GrantFiled: October 11, 1996Date of Patent: May 2, 2000Assignee: Microcide Pharmaceuticals, Inc.Inventors: In-Seop Cho, Scott J. Hecker, Tomasz W. Glinka, Ving J. Lee, Zhijia J. Zhang
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Patent number: 6034076Abstract: The cephalosporin compound [6R, 7R]-7-[2-(2-Amino-4-thiazolyl)-2-(Z)-(methoxyimino)acetamido]-3-[1-(methyl amino)pyridinium-4-thiomethyl]-ceph-3-em-4-carboxylic acid chloride hydrochloride is provided as a mono-, di- or tri-hydrate. The hydrates are produced by treating an aqueous solution of the corresponding carboxylate with hydrogen chloride and have been found to possess unexpectedly superior stability properties over other forms of the compound. The hydrates may be used in the treatment and/or prevention of bacterial infections in humans and animals.Type: GrantFiled: August 14, 1997Date of Patent: March 7, 2000Assignee: Pfizer Inc.Inventor: Richard Andrew Bentely Webster
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Patent number: 6025352Abstract: The present invention includes novel compounds of formula ##STR1## where G, H, J, L and M are carbon or nitrogen, R.sup.99 is selected from the group consisting of sulfur, SO, SO.sub.2, NH, N-alkyl, oxygen, C.tbd.C (cis or trans), and C.tbd.C, and R.sup.12 is NR.sup.13 R.sup.14, ##STR2## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.Type: GrantFiled: September 29, 1997Date of Patent: February 15, 2000Assignee: Microcide Pharmaceuticals, Inc.Inventors: In-Seop Cho, Scott J. Hecker, Tomasz W. Glinka, Ving J. Lee, Zhijia J. Zhang
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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: 5948774Abstract: Cephem compounds of the formula: ##STR1## wherein R.sup.1 is an optionally protected amino group; R.sup.2 is a fluoro-lower alkyl group; and the ring A may have further substituent(s), or their esters or salts, show broad and excellent antibacterial activities and are useful as antibacterial agents.Type: GrantFiled: July 29, 1997Date of Patent: September 7, 1999Assignee: Takeda Chemical Industries, Ltd.Inventors: Keiji Kamiyama, Kenji Okonogi, Akio Miyake
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Patent number: 5945414Abstract: Cefazolin, cefazedone, cefoperazone, cefamandole, cefatrizine or ceftriaxone is prepared by reacting glutaryl 7-ACA of the formula: ##STR1## with a compound of formula (II):R--SH (II)wherein R is 5-methyl-1,3,4-thiadiazol-2-yl, 1H-1,2,3-triazol-4-yl, 1-methyl-tetrazol-5-yl or1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl group, and R.sup.1 and R.sup.2 are both hydrogen and the other is an acyl group, in an aqueous solution in an amount of 3-5 mols per mol of glutaryl 7-ACA to about 90.degree. C. and for a time from about 2 to about 10 hours;optionally recovering the excess of the compound of formula (II), thereby preparing a compound of formula (III) in an aqueous solution: ##STR2## wherein R is as above defined and optionally deacylating said compound of formula (III); andconverting the resulting compound of formula (I) ##STR3## wherein R, R.sup.1 and R.sup.2 are as defined above in the presence of a non-chlorinated solvent into one of said cephalosporins.Type: GrantFiled: December 2, 1997Date of Patent: August 31, 1999Assignee: Antibioticos S.p.A.Inventors: Loris Sogli, Daniele Terrassan, Ermanno Bernasconi, Francisco Salto
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Patent number: 5935950Abstract: Compounds of formula I ##STR1## wherein R.sup.1 is hydrogen, lower alkyl, cycloalkyl or acetyl;x is CH or N;n is 0, 1 or 2;m is 0 or 1;R.sup.2 is hydrogen, lower alkyl, .omega.-hydroxy alkyl, benzyl or lower alkyl-heterocyclyl, the benzyl and the heterocyclyl group being unsubstituted or substituted with at least one of the groups amino, cyano, carboxy, halogen, hydroxy, lower alkyl, lower alkoxy or --CONR.sub.2, where R is hydrogen or lower alkyl; or R.sup.2 is --CH.sub.2 CONR.sup.4 R.sup.5 ; whereinR.sup.4, R.sup.5 are each independently hydrogen, .omega.-hydroxy-alkyl, phenyl, benzyl, naphthyl or heterocyclyl, the phenyl, benzyl, naphthyl or heterocyclyl groups being unsubstituted or substituted with at least one of the groups optionally protected hydroxy, halogen, optionally substituted lower alkyl, optionally substituted lower alkoxy, .omega.-hydroxyalkyl or cyano; or R.sup.4 and R.sup.Type: GrantFiled: September 5, 1997Date of Patent: August 10, 1999Assignee: Hoffmann-La Roche Inc.Inventors: Peter Angehrn, Ingrid Heinze-Krauss, Malcolm Page, Urs Weiss
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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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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: 5831085Abstract: This invention relates to reactive derivative of 2-(2-amino-4-thiazolyl)-(Z)-2-?(1-tert butoxycarbonyl-l-methylethoxy) imino!acetic acid of the following formula I ##STR1## as well as to the use thereof in the manufacture of cephalosporin antibiotic such as ceftazidime of formula II.Type: GrantFiled: April 25, 1997Date of Patent: November 3, 1998Assignee: Lupin Laboratories LimitedInventors: Debashish Datta, Bishwa Prakash Rai, Kishor Mehre
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Patent number: 5804577Abstract: The present invention relates to compounds of formula I ##STR1## wherein R.sup.1 is a group selected from 2-, 3-, and 4-hydroxyphenyl, 3-nitrophenyl, and 3-fluoro-4-hydroxyphenyl; as well as readily hydroyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts.Type: GrantFiled: August 27, 1996Date of Patent: September 8, 1998Assignee: Hoffmann-La Roche Inc.Inventors: Paul Hebeisen, Ingrid Heinze-Krauss, Hans Richter, Valeri Runtz, Henri Stalder, Urs Weiss, George Petros Yiannikouros
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Patent number: 5801242Abstract: The present invention provides processes for making compounds of the structure(Q--L.sup.1)--L--(L.sup.2 --B)wherein(I) Q is a quinolone moiety;(II) B is a lactam moiety; and(III) L, L.sup.1, and L.sup.2 together comprise a linking moiety;comprising the steps of:(1) coupling a compound of Formula (III) with a lactam-containing compound to form an intermediate compound; and(2) cyclizing the intermediate by reaction with an organosilicon compound to give a compound of the formula (Q--L.sup.1)--L--(L.sup.2 --B).Preferably, the process additionally comprises a step prior to the coupling step, wherein protected forms of the compound of Formula (III) and the lactam compound are formed; and deprotection steps after the cyclization step, wherein the protecting groups are removed. Preferred antimicrobial compounds made by these processes are those where the beta-lactam moiety is a penem, a carbapenem, a cephem, or a carbacephem. Also preferred are those compounds where L.sup.1, L, and L.sup.Type: GrantFiled: November 12, 1997Date of Patent: September 1, 1998Assignee: The Procter & Gamble CompanyInventors: Jared Lynn Randall, Jane Ellen Godlewski
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Patent number: 5789584Abstract: The present invention includes (7R)-7-(acylamino)-3-(substituted-pyridinyl)-3-cephem-4-carboxylic acids or their pharmacologically acceptable salts which exhibit antibiotic activity against methicillin-resistant bacteria and are therefore useful as antibacterial agents.Type: GrantFiled: March 29, 1995Date of Patent: August 4, 1998Assignee: Microcide Pharmaceuticals, Inc.Inventors: Burton G. Christensen, In-Seop Cho, Tomasz W. Glinka, Scott J. Hecker
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Patent number: 5777104Abstract: The present invention relates to the use of known cephem derivatives of the formula: ##STR1## wherein n is zero, one or two; R.sup.1 is hydrogen or an organic radical, R.sup.2 represents halo or an organic radical or R.sup.1 and R.sup.2 taken together with the C-2 carbon atom of the cephem nucleus constitute a carbocyclic or heterocyclyl group; R.sup.3 represents R.sup.2 as defined above or an organic radical, R.sup.4 is either R.sup.1 or an organic group, R.sup.5 is either R.sup.1 as defined above or halo or C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio or C.sub.1 -C.sub.6 acylamino;R.sup.6 is R.sup.2 as defined above or an organic group,or a pharmaceutically acceptable salts thereof.Type: GrantFiled: March 8, 1995Date of Patent: July 7, 1998Assignee: Pharmacia & Upjohn S.p.A.Inventors: Marco Alpegiani, Pierluigi Bissolino, Ettore Perrone, Enrico Pesenti
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Patent number: 5773435Abstract: The instant invention relates to a novel method for the delivery of antitumor drugs to tumor cells by the administration of a tumor-selective antibody-.beta.-lactamase conjugate that binds to tumor cells, and the additional administration of a cephalosporin prodrug that is converted at the tumor site, in the presence of the antibody-.beta.-lactamase, to an active cytotoxic drug. According to the preferred embodiment of this invention, a cephalosporin mustard has been constructed which when cleaved by .beta.-lactamase yields a cytotoxic nitrogen mustard. The methods, antibody-enzyme conjugate, prodrugs, pharmaceutical compositions, and combinations of this invention provide for enhanced selective killing of tumor cells and are thus useful in the treatment of cancers and other tumors.Type: GrantFiled: February 9, 1993Date of Patent: June 30, 1998Assignee: Bristol-Myers Squibb CompanyInventors: John Kadow, Takushi Kaneko, Peter D. Senter, Vivekanada M. Vrudhula
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Patent number: 5763617Abstract: A syn isomer in (R) or (S) form or a mixture thereof of a compound of the formula ##STR1## syn isomer, in the (R) or (S) form or in the form of an (R,S) mixture, in the form of an integral salt or their salts with organic or mineral acids wherein the substituents are as defined in the application and having antibacterial properties.Type: GrantFiled: December 18, 1996Date of Patent: June 9, 1998Assignee: Roussel UclafInventors: Jozsef Aszodi, Jean-Francois Chantot, Patrick Fauveau, Solange Gouin D'Ambrieres, Daniel Humbert, Christophe Dini
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Patent number: 5734047Abstract: Novel cephem derivatives represented by the general formula ##STR1## wherein Ar is an optionally substituted lipophilic phenyl, naphthyl, benzthiazolyl or pyridyl group; R.sup.1 represents a group of the formula ##STR2## in which R.sup.8 and R.sup.9 are each independently hydrogen, C.sub.1 -C.sub.6 alkyl or (C.sub.1 -C.sub.6)alkoxycarbonyl, said C.sub.1 -C.sub.6 alkyl group being optionally substituted by 1-5 hydroxy or C.sub.1 -C.sub.6 alkoxy groups; m is either 0 or 1; A is a C.sub.2 -C.sub.10 alkyl group optionally substituted by 1-5 hydroxy groups; and R.sup.2 and R.sup.3 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl. The derivatives are gram-positive antibacterial agents especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus.Type: GrantFiled: December 5, 1996Date of Patent: March 31, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Choung U. Kim, Muzammil M. Mansuri, Peter F. Misco, John A. Wichtowski
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Patent number: 5721359Abstract: Anhydrous and crystalline free acid form of the cephalosporin antiobiotic ceftiofur, processes for its manufacture, and pharmaceutical composition containing it are provided.Type: GrantFiled: September 11, 1995Date of Patent: February 24, 1998
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Patent number: 5710146Abstract: 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: GrantFiled: July 22, 1994Date of Patent: January 20, 1998Assignee: Hoechst AktiengesellschaftInventors: Walter Durckheimer, Dieter Bormann, Eberhard Ehlers, Elmar Schrinner, Rene Heymes
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Patent number: 5708165Abstract: 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: July 12, 1994Date of Patent: January 13, 1998Assignee: Sumitomo Chemical Company, LimitedInventors: Mari Yuasa, Kazuyuki Yamagata, Hirokazu Murata, Masashi Komatsu, Isao Yoshida
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Patent number: 5698547Abstract: The present invention includes novel (7R)-7-(acylamino)-3-(arylthio)-3-cephem-4-carboxylic acids or their pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.Type: GrantFiled: May 31, 1995Date of Patent: December 16, 1997Assignee: Microcide Pharmaceuticals, Inc.Inventors: Burton Christensen, In-Seop Cho, Tomasz Glinka, Scott Hecker, Ving J. Lee, Zhijia J. Zhang
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Patent number: 5698544Abstract: The present invention provides a cephem compound having a high antimicrobial activity against various pathogenic bacteria.The cephem compound of the invention is represented by the formula ##STR1## wherein Q represents CH or N, R.sup.1 represents a carboxylate or the like, R.sup.2 represents a hydrogen atom, and R represents ##STR2## wherein R.sup.3 represents a group --(CH.sub.2).sub.m --Y (wherein m is an integer of 1 to 5, and Y represents a quaternary ammonium group) or the like, n is an integer of 0 to 4, B.sup.- represents an anion, f is 0 or 1 when R.sup.1 represents a carboxylate, and 2 when R.sup.1 represents a carboxyl group, and the ring C represents a 5-membered heterocyclic group of not more than 4 nitrogen atoms, which may be substituted by a lower alkyl group.Type: GrantFiled: November 16, 1995Date of Patent: December 16, 1997Assignees: Otsuka Kagaku Kabushiki Kaisha, Taiho Pharmaceutical Co., Ltd.Inventors: Hiroshi Akagi, Masaru Yasui, Takae Yamada, Masahiro Ito, Akio Hyodo, Hideaki Hanaki
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Patent number: 5683996Abstract: A compound selected from the group consisting of a compound of the formula ##STR1## wherein R is selected from the group consisting of ##STR2## and R.sub.b --NH--, Ra is an organic radical, Ri and Rj are individually selected from the group consisting of hydrogen, aliphatic hydrocarbon, aromatic hydrocarbon and heterocycle or taken together with the nitrogen atom to which they are attached form an optionally substituted ring, Rb is selected from the group consisting of carbocyclic aryl and heterocyclic aryl, both optionally substituted, R.sub.1A is selected from the group consisting of ##STR3## and ##STR4## are individually selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, Z.sub.A is selected from the group consisting of a simple bond, --O-- and optionally oxidized sulfur, R.sub.Type: GrantFiled: November 7, 1994Date of Patent: November 4, 1997Assignee: Roussel UCLAFInventors: Jean-Georges Teutsch, Alain Bonnet, Jozsef Aszodi, Solange Gouin D'Ambrieres
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Patent number: 5675003Abstract: 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 1, 1995Date of Patent: October 7, 1997Assignee: Korea Institute of Science and TechnologyInventors: Hokoon Park, Yong Sup Lee, Jae Yeol Lee, Dae Hwan Suk, Eun-Rhan Woo
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Patent number: 5663331Abstract: The present invention relates to new cephalosporin compounds of the formula (I), particularly 3-position of cephem rings thereof substituted with new thione compounds and pharmaceutically acceptable salts thereof, which have broad antibacterial activities against both Gram-positive and Gram-negative bacteria, and the said compounds can be prepared by reacting the compounds of the formula (II) with the new thione compounds of the formula (III). ##STR1## wherein R.sub.1 is a C.sub.1-4 alkyl(preferably methyl or ethyl), C.sub.3-4 alkenyl(preferably allyl), C.sub.3-4 alkynyl (preferably propargyl) group or --C(R.sup.a) (R.sup.b)CO.sub.2 H(preferably --C(CH.sub.3).sub.2 CO.sub.2 H or --CH.sub.2 CO.sub.2 H), wherein R.sup.1 and R.sup.b, same or different, are a hydrogen atom or a C.sub.1-4 alkyl group;R.sub.2 is a C.sub.1-4 alkyl(preferably methyl or ethyl), C.sub.3-4 alkenyl(preferably allyl), C.sub.3-4 cycloalkyl(preferably cyclopropyl) group or carboxyalkyl(preferably --CH.sub.2 CO.sub.2 H) group;R.sub.Type: GrantFiled: January 23, 1995Date of Patent: September 2, 1997Assignee: Il-Dong Pharm. Co., Ltd.Inventors: Kee Won Kim, Jae Hoon Kang, Cheon Ho Park
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Patent number: 5661144Abstract: Compounds represented by the following formula (I), that is, cephem derivatives having substituted or unsubstituted 3-(imidazo[5,1-b]thiazolium-6-yl)-1-propenyl as a substituent at the 3-position of the cephem ring: ##STR1##Type: GrantFiled: June 28, 1996Date of Patent: August 26, 1997Assignee: Meiji Seika Kabushiki KaishaInventors: Masaki Tsushima, Kunio Atsumi, Katsuyoshi Iwamatsu, Atsushi Tamura
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Patent number: 5656754Abstract: The present invention provides a process for preparing a cephem compound represented by the general formula (3) characterized in that an allenyl-.beta.-lactam compound represented by the general formula (1) is reacted with an organotin compound represented by the general formula (2) in the presence of a monovalent copper salt ##STR1## wherein R.sup.1 is a hydrogen atom, halogen atom, amino or protected amino, R.sup.2 is a hydrogen atom, halogen atom, lower alkoxyl, lower acyl, lower alkyl, lower alkyl having hydroxyl or protected hydroxyl as a substituent, hydroxyl or protected hydroxyl, or R.sup.1 and R.sup.2 form=0 when taken together, R.sup.3 is a hydrogen atom or carboxylic acid protecting group, R.sup.4 is aryl, aryl having a substituent, nitrogen-containing aromatic heterocyclic group or nitrogen-containing aromatic heterocyclic group having a substituent, and m is 0 or 2,(R.sup.5).sub.n --Sn(R.sup.6).sub.4--n (2)wherein R.sup.Type: GrantFiled: March 22, 1994Date of Patent: August 12, 1997Assignee: Otsuka Kagaku Kabushiki KaishaInventors: Shigeru Torii, Hideo Tanaka, Michio Sasaoka, Takashi Shiroi, Yutaka Kameyama
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Patent number: 5654425Abstract: A method for the acylation of the 7-amino group of the cephalosporanic ring, according to which a 7-ACA amino thiazolyl protected adduct is prepared by acylating said amino group by an aminothiazolyl acetic acid whose amino group has been protected by a phenyl acetyl or a phenoxy acetyl group, the amino group being then deprotected by aqueous hydrolysis in the presence of penicillin G amidase or respectively penicillin V amidase.Type: GrantFiled: May 1, 1995Date of Patent: August 5, 1997Assignee: Finpael S.p.A.Inventors: Maurizio Zenoni, Claudio Fuganti
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Patent number: 5635500Abstract: The object of the present invention is to provide a cephem compound having high activity against various pathogenic microorganisms. The cephem compound of this invention is represented by the general formula ##STR1## wherein Q represents CH or N; R.sup.1 represents a carboxylate etc; and R represents ##STR2## or the group ##STR3## where R.sup.2 represents a lower alkyl group etc, n represents an integer of 0 or 1 through 3, B.sup.- represents an anion, f is equal to 0 when R.sup.1 represents a carboxylate and 1 where R.sup.1 represents a carboxyl group, and the ring C represents a 5-membered heterocyclic group of not more than 4 nitrogen atoms, which may be substituted by lower alkyls.Type: GrantFiled: May 16, 1994Date of Patent: June 3, 1997Assignees: Otsuka Kagaku Kabushiki Kaisha, Taiho Pharmaceutical Co., Ltd.Inventors: Hiroshi Akagi, Masaru Yasui, Yoshifumi Hara, Hideaki Hanaki, Akio Hyodo
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Patent number: 5620969Abstract: Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## wherein Ar is a lipophilic optionally substituted phenyl, naphthyl or pyridyl group; R.sup.1 represents either the residue of a heterocyclic amino acid or a C.sub.2 -C.sub.10 alkyl group substituted by both a carboxyl group and a group of the formula --NR.sup.9 R.sup.10 or ##STR3## in which R.sup.9 and R.sup.10 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl, said C.sub.2 -C.sub.10 alkyl group being optionally interrupted by one or more nitrogen atoms or carbonyl groups, and R.sup.2 and R.sup.3 are each independently hydrogen, alkyl or aminoalkyl are gram-positive antibacterial agents, especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus (also referred to below as MRSA or methicillin-resistant S. aureus).Type: GrantFiled: April 25, 1995Date of Patent: April 15, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Joanne J. Bronson, Stanley V. D'Andrea, Shelley E. Hoeft, John D. Matiskella, Peter F. Misco, Jr., Bing Y. Luh, Dane M. Springer, Yasutsugu Ueda, John A. Wichtowski
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Patent number: 5607927Abstract: An aminothiazolyl- or aminothiadiazolyl-cephalosporin derivative represented by the following general formula (I) which has a condensed-ring thio group as a 3-positioned substituent group that contains a thiazolylthio group, an oxazolylthio group or a heterocyclic ring thereof as one of the ring components. The compound according to the present invention has excellent activities to inhibit growth of various bacteria, especially Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), and therefore, the antibacterial agent comprising, as an active ingredient, the inventive compound can be used as a therapeutic drug for the treatment of various bacterial infections.Type: GrantFiled: February 7, 1995Date of Patent: March 4, 1997Assignee: Meiji Seika Kaisha, Ltd.Inventors: Masaki Tsushima, Katsuyoshi Iwamatsu, Atsushi Tamura, Seiji Shibahara
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Patent number: 5596095Abstract: The present invention is a method of protecting a sulfonic acid functional group in an organic molecule as a substituted or unsubstituted neopentyl sulfonate ester. The method allows the conversion of R--SO.sub.3 --H to R'--SO.sub.3 --H, wherein R and R' are different organic radicals. Also disclosed is a method of increasing the bioavailability of drugs with a sulfonic acid functional group by protecting the sulfonic acid functional group as a substituted neopentyl sulfonate ester which has a masked heteroatom nucleophile. The masked nucleophile can be liberated in vivo, resulting in removal of the neopentyl protecting group and regeneration of the parent drug.Type: GrantFiled: May 12, 1995Date of Patent: January 21, 1997Assignee: Procept, Inc.Inventors: John C. Roberts, Raymond J. Patch
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Patent number: 5593985Abstract: Novel cephalosporin compounds of formula (I) exhibit potent and broad antibiotic activities against Gram-negative and Gram-positive bacteria and various resistant bacteria: ##STR1##Type: GrantFiled: May 22, 1995Date of Patent: January 14, 1997Assignee: Korea Institute of Science And TechnologyInventors: Joong H. Kim, Sung H. Kim, Ghil S. Nam, Ha Y. Kim, Hyen J. Son, Eun S. Jang
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Patent number: 5587372Abstract: A syn isomer in (R) or (S) form or a mixture thereof of a compound of the formula ##STR1## syn isomer, in the (R) or (S) form or in the form of an (R,S) mixture, in the form of an internal salt or their salts with organic or mineral acids,wherein the variables are herein below defined, having antibacterial properties.Type: GrantFiled: December 13, 1993Date of Patent: December 24, 1996Assignee: Roussel UclafInventors: Jozsef Aszodi, Jean-Francois Chantot, Patrick Fauveau, Solange G. D'Ambrieres, Daniel Hunbert, Christophe Dini
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Patent number: 5585485Abstract: A cephalosporin intermediate of the formula ##STR1## where R.sub.3 is carboxyl, carboxylate, or a carboxylic acid ester group and,R.sub.8 and R.sub.9 are each independently hydrogen, halogen,(C.sub.1-4) alkyl, hydroxy, carboxamido,(C.sub.1-4) alkoxycarbonyl, amino,mono- (C.sub.1-4) alkylamino, di- (C.sub.1-4) alkylamino, ortogether are a 5 or 6-membered carbocyclic ring or an alkali metal, alkaline earth metal, or acid addition salt thereof. Valuable cephalosporin antibiotics can be produced from the cephalosporin intermediate products of formula I.Type: GrantFiled: June 6, 1995Date of Patent: December 17, 1996Assignee: Biochemie Gesellschaft m.b.h.Inventors: Gerd Ascher, Hubert Sturm, Heinrich Thaler, Werner Veit
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Patent number: 5583217Abstract: Chromogenic and fluorogenic substrates for .beta.-lactamase, methods for synthesis thereof and methods for detecting .beta.-lactamase in a sample are provided. The substrates are substantially colorless or substantially nonfluorescent .beta.-lactam compounds which include an electronegative leaving group. The leaving group comprises a carbamate, carbonate, thiocarbamate or thiocarbonate linkage and a fluorescent moiety or a moiety capable of producing a visually detectable colored product. Upon cleavage of the lactam ring by .beta.-lactamase, the leaving group is liberated and fluorescence or a colored product is produced.Type: GrantFiled: April 6, 1995Date of Patent: December 10, 1996Assignee: Becton, Dickinson and CompanyInventors: J. Michael Quante, Randal A. Hoke, Patrick D. Mize, Daniel L. Woodard, O. Elmo Millner, deceased
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Patent number: RE35754Abstract: Cephem derivatives of the general formula ##STR1## is 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: GrantFiled: July 11, 1990Date of Patent: March 24, 1998Assignee: Hoechst AktiengesellschaftInventors: Walter Durckheimer, Dieter Bormann, Eberhard Ehlers, Elmar Schrinner, Rene Heymes