3-position Substituent Contains Sulfur Patents (Class 540/226)
-
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
-
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
-
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
-
Patent number: 6087355Abstract: The present invention includes novel compounds of formula ##STR1## where A, B, D, and E are selected from the group consisting of carbon, nitrogen and sulfur, 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: July 11, 2000Assignee: Microcide Pharmaceuticals, Inc.Inventors: In-Seop Cho, Scott J. Hecker, Tomasz W. Glinka, Ving J. Lee, Zhijia J. Zhang
-
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
-
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
-
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
-
Patent number: 6030965Abstract: The present invention includes novel compounds of formula where A, B, D, and E are selected from the group consisting of carbon, nitrogen and sulfur, R.sup.99 is selected from the group consisting of sulfur, SO, S0.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, ##STR1## 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 30, 1997Date of Patent: February 29, 2000Assignee: Microcide Pharmaceuticals, Inc.Inventors: In-Seop Cho, Scott J. Hecker, Tomasz W. Glinka, Ving J. Lee, Zhijia J. Zhang
-
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
-
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
-
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
-
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
-
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
-
Patent number: 5756493Abstract: 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: March 29, 1995Date of Patent: May 26, 1998Assignee: Microcide Pharmaceuticals, Inc.Inventors: Scott Hecker, In-Seop Cho, Tomasz Glinka, Burton Christensen
-
Patent number: 5705496Abstract: The present invention relates to benzathine salts of cefonicid, a member of the cephalosporin family of antibiotics, which are crystalline.Type: GrantFiled: September 25, 1995Date of Patent: January 6, 1998Assignee: SmithKline Beecham CorporationInventor: Theodore John Polansky
-
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
-
Patent number: 5663162Abstract: Compounds represented by the following formula (I), that is, cephem derivatives having substituted or unsubstituted imidazo[5,1-b]thiazolium-6-yl as a substituent at the 3-position of the cephem ring: ##STR1## wherein X represents CH or N, R.sup.1 represents H, alkyl, alkenyl or the like, and R.sup.2, R.sup.3, R.sup.4 and R.sup.5 represent H, alkyl, carbamoyl, amino or the like. The above compounds have excellent antibacterial activity, and useful as medicines for the treatment of various infectious diseases caused by bacteria.Type: GrantFiled: July 25, 1995Date of Patent: September 2, 1997Assignee: Meiji Seika Kabushiki KaishaInventors: Kunio Atsumi, Eijiro Umemura, Yuko Kano, Sohjiro Shiokawa, Toshiaki Kudo, Masaki Tsushima, Katsuyoshi Iwamatsu, Atsushi Tamura, Seiji Shibahara
-
Patent number: 5639877Abstract: Novel amidine salts of 7-Amino-3-hydroxymethyl-3-cephem-4-carboxylic acid (=HACA), particular guanidine and diaza-bicyclo-alkylene salts, are useful as intermediates in the synthesis of cephalosporins.Type: GrantFiled: July 28, 1994Date of Patent: June 17, 1997Assignee: Biochemie Gesellschaft m.b.H.Inventors: Johannes Ludescher, Ingolf Macher
-
Patent number: 5635501Abstract: Compound of formula (I) or salts 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 or a pharmaceutically acceptable salt-forming group or in vivo hydrolysable ester group; R.sup.4 represents hydrogen or up to four substituents; X is S, SO, SO.sub.2 or CH.sub.2 ; Y is O, S, SO or SO.sub.2 ; n is 0 or 1; m is 1 or 2; and wherein in the (a) ring system the dotted line indicates that one pair of adjacent ring carbon atoms is joined by a C.dbd.C double bond. These compounds have antibacterial activity.Type: GrantFiled: January 25, 1995Date of Patent: June 3, 1997Assignee: Pfizer Inc.Inventors: George Burton, John H. Bateson, Richard L. Elliott, Stephen C. M. Fell
-
Patent number: 5629306Abstract: Derivatives of 7-alkylidene cephalosporanic acid sulfone and the pharmaceutically active salts thereof are found to be potent inhibitors of .beta.-lactamase enzymes.Type: GrantFiled: December 9, 1994Date of Patent: May 13, 1997Assignee: Research Corporation Technologies, Inc.Inventors: John D. Buynak, Brian Bachmann
-
Patent number: 5625058Abstract: The present invention relates to a process for the preparation of 7-(.alpha.-hydroxyacylamino)-3-(1-sulphoalkyl-tetrazol-5-yl-thiomethyl)-3- cephem-4-carboxylic acids and relevant salts, via acylation of a 7-amino-3-(1-sulphoalkyl-tetrazol-5-yl-thiomethyl)-3-cephem-4-carboxylic acid with the corresponding chloride of .alpha.-formyl oxycarboxylic acid in a diluent, at pH 6.5-7.0; deformylation by treatment with an acid at pH between 0.5 and 1.5; extraction/s with an organic solvent of the acid aqueous phase from deformylation, followed by salting out and extraction with a solvent selected among tetrahydrofuran, methylethylketone, and acetonitrile; solvent evaporation and salification in a non-aqueous medium.Type: GrantFiled: July 12, 1994Date of Patent: April 29, 1997Assignee: Farmabios S.r.1.Inventors: Artemio Pessa, Antonio Lerpini
-
Patent number: 5616703Abstract: Process of depleting 7-amino-3-[(E)-2-(4-methyl-5-thiazolyl)vinyl]-3-cephem-4-carboxylic acid in Z/E mixtures of 7-amino-3-[2-(4-methyl-5-thiazolyl)vinyl]-3-cephem-4-carboxylic acida) by subjecting an amine salt of a Z/E mixture of 7-amino-3-[2-(4-methyl-5-thiazolyl)vinyl]-3-cephen-4-carboxylic acid to crystallization and converting this amine salt into 7-amino-3-[2-(4-methyl-5-thiazolyl)vinyl]-3-cephem-4-carboxylic acid, orb) by subjecting the Z/E mixture to chromatography.Type: GrantFiled: November 16, 1994Date of Patent: April 1, 1997Assignee: Biochemie Gesellschaft m.b.H.Inventors: Johannes Ludescher, Harald Summer, Siegfried Wolf
-
Patent number: 5607926Abstract: 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: March 29, 1995Date of Patent: March 4, 1997Assignee: Microcide Pharmaceuticals, Inc.Inventors: Scott J. Hecker, In-Seop Cho, Burton G. Christensen, Tomasz W. Glinka
-
Patent number: 5604218Abstract: 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: March 30, 1995Date of Patent: February 18, 1997Assignee: Microcide Pharmaceuticals, Inc.Inventors: Scott Hecker, In-Seop Cho, Burton Christensen, Tomasz Glinka, Ving J. Lee
-
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
-
Patent number: 5593986Abstract: 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: March 29, 1995Date of Patent: January 14, 1997Assignee: Microcide Pharmaceuticals, Inc.Inventors: Burton G. Christensen, In-Seop Cho, Tomasz W. Glinka, Scott J. Hecker
-
Patent number: 5594132Abstract: A compound of the formula: ##STR1## in which R.sup.2 is lower alkoxymethyl, lower alkylthiomethyl or lower alkenylthiomethyl,R.sup.3 is carboxy or a protected carboxy group,A.sup.5 is lower alkylene which may have 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, andX.sup.1 is halogen,or a salt thereof.Type: GrantFiled: April 12, 1991Date of Patent: January 14, 1997Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Takao Takaya, Hisashi Takasugi, Takashi Masugi, Hideaki Yamanaka, Kohji Kawabata
-
Patent number: 5580865Abstract: The present invention provides cephalosporin sulphones or formula (I), and pharmaceutically or veterinarily acceptable salts thereof; ##STR1## wherein n is zero, one or two; R.sub.1 is hydrogen, halogen or an optionally substituted C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio or C.sub.1 -C.sub.4 carboxamido group;R.sub.2 is hydrogen or an optionally substituted C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.10 aryl, C.sub.2 -C.sub.5 alkenyl or C.sub.3 -C.sub.6 cycloalkyl group;R.sub.3 is hydrogen or acetoxymethyl, methoxymethyl, methyl or an optionally substituted heterocyclylthiomethyl group;R.sub.4 is an optionally substituted C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, aryl(C.sub.1 -C.sub.8)alkyl or heterocyclyl(C.sub.1 -C.sub.8)alkyl group; andR.sub.5 is an optionally substituted C.sub.6 -C.sub.10 aryl or a heterocyclyl group.The compounds of formula I and the pharmaceutically and veterinarily acceptable salts thereof are elastase inhibitors.Type: GrantFiled: April 5, 1993Date of Patent: December 3, 1996Assignee: Farmitalia Carlo Erba S.r.l.Inventors: Marco Alpegiani, Pierluigi Bissolino, Ettore Perrone, Vincenzo Rizzo
-
Patent number: 5574153Abstract: The invention relates to oxime derivatives of cephalosporanic structure, possessing antibacterial activity.Type: GrantFiled: July 27, 1994Date of Patent: November 12, 1996Assignee: ACS Dobfar S.p.A.Inventors: Maurizio Zenoni, Mario Leone, Riccardo Colombo
-
Patent number: 5527906Abstract: A new and improved process for the preparation of ceftriaxon disodium salt hemiheptahydrate of formula I ##STR1## is described, wherein 7-amino-3-{[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]met hyl}-3-cephem-4-carboxylic acid disodium salt is converted with a reactive 2-(2-aminothiazol-4-yl)-2-syn-metoxyimino acetic acid derivative such as 2-benzo-thiazolyl-thio ester in a water solution and in the presence of a suitable inert organic solvent such as acetone, at a temperature between 0.degree. C. and 40.degree. C. and then the desired compound is isolated in a very pure form and with a high total yield.Ceftriaxon is a cephalosporin antibiotic of the third generation for parenteral application and a valuable agent for the treatment of heavy infections.Type: GrantFiled: January 27, 1993Date of Patent: June 18, 1996Assignee: LEK, tovarna farmacevtskih in kemicnik izdelkovInventors: Natasa H. Milac, Igor Langof, Boris Rusjakovski, Sandi Borisek, Darja Jereb
-
Patent number: 5521308Abstract: Process for the preparation of crystalline TACA ##STR1## in the presence of a base and subsequent precipitation by addition of a TACA solution to a partial amount of an acid, which can also contain a precipitation auxiliary, and subsequent completion of the precipitation by further addition of acid or by further addition of TACA solution and acid.Type: GrantFiled: January 12, 1994Date of Patent: May 28, 1996Assignee: Hoechst AktiengesellschaftInventors: Reinhard Trodel, Manfred Wieduwilt
-
Patent number: 5498787Abstract: A method for preparing cephalosporm derivatives by reacting cephalosporin alkaline metal salts with organic halide in the presence of quaternary ammonium salts catalyst is disclosed. .DELTA..sup.3 .fwdarw..DELTA..sup.2 isomerization, a side reaction commonly reported in preparation of cephalosporin derivatives was successfully eliminated. The desired .DELTA..sup.3 was obtained as a sole product in the reaction.Type: GrantFiled: April 20, 1994Date of Patent: March 12, 1996Assignee: Standard Chemical & Pharmaceutical Co., Ltd.Inventors: Hui-Po Wang, Jia-Shuai Lee
-
Patent number: 5446037Abstract: This invention relates to 2-[(substituted)methylene]cephalosporin sulfones and in particular 2-[(heteroaryl substituted)methylene]cephalosporin sulfones which are effective elastase inhibitors as well as effective thrombin inhibitors and therefore are useful as anti-inflammatory, anti-degenerative and anti-thrombin agents.Type: GrantFiled: December 13, 1993Date of Patent: August 29, 1995Assignee: Synphar Laboratories, Inc.Inventors: Samarendra Maiti, Charles Fiakpui, A. V. N. Reddy, David Czajkowski, Paul Spevak, Harninder Atwal, Ronald G. Micetich
-
Patent number: 5439904Abstract: 2-spiro (2'-spirocycloalkyl) cyclopropyl cephalosporin sulfone compounds, methods of treating patients for elastase inhibition, and processes for preparing such compounds.Type: GrantFiled: December 7, 1993Date of Patent: August 8, 1995Assignee: Synphar Laboratories, Inc.Inventors: Samarendra N. Maiti, Charles Y. Fiakpui, Andhe V. N. Reddy, David P. Czajkowski, Ronald G. Micetich
-
Patent number: 5412093Abstract: Cephalosporin compounds having a 3-position substituent of the formula (I) are described:--CH.sub.2 --S--Q--(Y).sub.n --Pwherein Q is a 5- or 6-membered heterocyclic ring, P is a benzene ring 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 hydrolysable ester thereof and R.sup.2 is hydroxy, an in vivo hydrolysable ester thereof, carboxy, sulpho, hydroxymethyl, methanesulphonamido or ureidos; or P is a group of the formula (II) or (III): ##STR1## wherein M is oxygen or a group NR.sup.3 wherein R.sup.3 is hydrogen or C.sub.1-4 alkyl; said ring P being further optionally substituted; and --(Y).sub.n -- is a bond or various linking groups or --(Y)--.sub.n may be such so that rings Q and P are fused.The use of such compounds as antibacterial agents is described as are processes for their preparation and intermediates therefor.Type: GrantFiled: August 25, 1993Date of Patent: May 2, 1995Assignee: ICI PharmaInventors: Frederic H. Jung, Annie A. Olivier
-
Patent number: 5407930Abstract: The present invention relates to a compound represented by the structural formula I: ##STR1## its pharmaceutically acceptable salt or ester, or its crystalline, which is a novel optically active compound useful as a curing agent for bacterial infections, a process for production thereof and a use thereof.Type: GrantFiled: March 24, 1994Date of Patent: April 18, 1995Assignee: Banyu Pharmaceutical Co., Ltd.Inventors: Susumu Nakagawa, Ryuji Mitomo, Ryosuke Ushijima, Akira Asai, Satoru Kuroyanagi
-
Patent number: 5401841Abstract: The invention relates to a new, economical and simple process for the production of 3-vinylcephalosporin compounds of formula ##STR1## wherein R.sub.1 and R.sub.2 may be the same or different and denote hydrogen or an organic radical.Type: GrantFiled: May 28, 1993Date of Patent: March 28, 1995Assignee: Sandoz Ltd.Inventors: Gerd Ascher, Johannes Ludescher, Hubert Sturm
-
Patent number: 5387679Abstract: The present invention relates to a process for preparing a compound of formula (I) ##STR1## wherein R is an heterocyclic group which contains at least one nitrogen atom with or without oxygen or sulphur and R.sup.1 and R.sup.2 are both hydrogen atoms or one of them is an hydrogen atom and the other is an acyl group; the process comprising reacting a compound of formula (II) ##STR2## wherein R.sup.1 and R.sup.2 are each as defined above, and wherein, if necessary, any reactive group is protected by a suitable protective group, or a salt thereof, with a compound of formula (III)R--SH (III)wherein R is as defined above, or a salt thereof, in the presence of an acid and of a compound of formula (IV) ##STR3## wherein each of R.sup.3 and R.sup.4 is a C.sub.1 -C.sub.4 alkyl group or R.sup.3 and R.sup.4 taken together are a C.sub.2 or C.sub.3 alkylene chain and, if necessary, removing the protective groups possibly present.Type: GrantFiled: March 15, 1993Date of Patent: February 7, 1995Assignee: Antibioticos S.p.A.Inventors: Loris Sogli, Daniele Terrassan, Giuseppe Ribaldone
-
Patent number: 5364848Abstract: New substituted cephalosporin sulfones are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.Type: GrantFiled: May 1, 1992Date of Patent: November 15, 1994Assignee: Merck & Co., Inc.Inventors: James B. Doherty, Raymond A. Firestone, Paul E. Finke, William K. Hagmann, Shrenik K. Shah, Kevan R. Thompson
-
Patent number: 5359058Abstract: A cephalosporin compound substituted in the 7-position with a (cyclo)alkylideneammonio group of formula (II) ##STR1## wherein X' is an anion from an acid HX, R.sub.1 and R.sub.2 are individually a C.sub.1 -C.sub.16 alkyl group, or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a cycloalkylidene ring with up to 8 carbon atoms and a process for the preparation which compounds are useful intermediates.Type: GrantFiled: April 27, 1992Date of Patent: October 25, 1994Assignee: Gist-Brocades, N.V.Inventors: Jan Verweij, Henri G. J. Hirs, Hendrik A. Witkamp, Everardus J. A. M. Leenderts, Jan J. Dekoning, Herman H. Grootveld
-
Patent number: 5356888Abstract: There are provided compounds I ##STR1## wherein A is a hydrogen atom or an organic group,R.sub.1 is hydrogen or halogen atom or an organic group,R.sub.2 is hydrogen or halogen atom, C.sub.1 -C.sub.4 alkyl or acyloxy group,R.sub.3 is hydrogen atom, C.sub.1 -C.sub.4 alkyl or alkoxy, benzyl group or a methylene andR.sub.4 is chloro, fluoro, hydrogen atom or an organic group.The compounds I are elastase inhibitors. A process for their preparation is also provided, as are pharmaceutical compositions containing them.Type: GrantFiled: October 22, 1991Date of Patent: October 18, 1994Assignee: Farmitalia Carlo ErbaInventors: Marco Alpegiani, Pierluigi Bissolino, Ettore Perrone, Francesco Di Matteo, Piergiuseppe Orezzi, Giuseppe Cassinelli
-
Patent number: 5348952Abstract: Cephalosporins of the formula (I): ##STR1## wherein m is one or two; n is zero, one or two; A and B are organic residues; and R.sub.1 and R.sub.2 are halogen or hydrogen atoms or organic groups are endowed with elastase inhibitory activity. Two processes for their preparation starting from the corresponding 4-acyl cephem are also provided.Type: GrantFiled: June 12, 1992Date of Patent: September 20, 1994Assignee: Farmitalia Carlo Erba S.R.L.Inventors: Pierluigi Bissolino, Marco Alpegiani, Ettore Perrone, Piergiuseppe Orezzi, Giuseppe Cassinelli, Giovanni Franceschi
-
Patent number: 5332731Abstract: A new class of cephalosporin derivatives is provided, which is useful as antibacterial agent to be particularly suitable for oral administrations in mammals including man, and which is represented by general formula (I) ##STR1## wherein R.sup.1 is a hydrogen atom or a lower alkyl group; R.sup.2 is a hydrogen atom or an ester-forming group capable of being cleaved easily with an esterase existing in the digestive tracts; n is an integer of zero or 1; Z is a saturated heterocyclic group containing one or two oxygen atoms as the hetero-atoms with or without one or more lower alkyl substituents, or a pharmaceutically acceptable salt thereof.Type: GrantFiled: December 6, 1990Date of Patent: July 26, 1994Assignee: Meiji Seika Kaisha, Ltd.Inventors: Yuichi Yamamoto, Tsuneo Okonogi, Seiji Shibahara, Shigeharu Inoue
-
Patent number: 5319140Abstract: Antibacterial compounds of the formula ##STR1## wherein R is a mononuclear carbocyclic aromatic group, a 5-membered aromatic heterocyclic group which contains as the hereto (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 hereto 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: May 19, 1992Date of Patent: June 7, 1994Assignee: Hoffmann-La Roche Inc.Inventor: Erwin Gotschi
-
Patent number: 5294705Abstract: An ester of 7-acylamido-3-acylthio-3- or -2-cephem-4-carboxylic acid represented by general formula (1) ##STR1## wherein R.sup.1 is an acyl group, R.sup.2 is a carboxyl-protecting group, R.sup.3 is a lower alkyl group, an aryl group or a substituted aryl group, or a mixture of two or more of said ester is used as the starting compound and is reacted wit a tertiary amine and also a secondary amine. Then the tertiary amine salt compound as formed as the reaction product is reacted with a compound of formula (4)R.sup.4 --X (4)wherein R.sup.4 is a lower alkyl group, a cycloalkyl group or a heterocyclic group or a heterocyclic group-substituted methyl group and X is a leaving group, whereby the desired ester of 7-acylamido-3-substituted thio-3-cephem-4-carboxylic acid of formula (5) ##STR2## can be produced preferentially, conveniently and efficiently.Type: GrantFiled: June 3, 1992Date of Patent: March 15, 1994Assignee: Meiji Seika Kaisha, Ltd.Inventors: Yuichi Yamamoto, Tsuneo Okonogi, Seiji Shibahara, Shigeharu Inoue
-
Patent number: 5292733Abstract: The present invention relates to a cephalosporin compound including the pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates thereof of the formula(I) and its isomers: ##STR1## wherein: R.sup.1 is a C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.3-4 alkynyl or --C(R.sup.3)(R.sup.4)COOH wherein R.sup.3 and R.sup.4, which may be the same or different, are hydrogen, C.sub.1-4 alkyl group, or constitute a C.sub.3-7 cycloalkyl group with the carbon atoms to which R.sup.3 and R.sup.4 are attached;R.sup.2, which may be attached to N.sup.a or N.sup.b, is a C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.3-7 cycloalkyl, aryl or amino group; andQ.sub.1 and Q.sub.2, which may be the same or different, are CH or N.Type: GrantFiled: April 9, 1992Date of Patent: March 8, 1994Assignee: Lucky LimitedInventors: Yong Z. Kim, Hun S. Oh, Jae H. Yeo, Jong C. Lim, Won S. Kim, Chan S. Bang, Hyeon J. Yim
-
Patent number: 5276024Abstract: The invention relates to new 3-substituted cephalosporins, to a process for their preparation and to their use as medicaments, in particular as medicaments having antibacterial activity.The invention relates to compounds of the general formula (I) ##STR1## in which X, Y, R.sup.1 and R.sup.2 have the meaning indicated in the description.Type: GrantFiled: November 21, 1991Date of Patent: January 4, 1994Assignee: Bayer AktiengesellschaftInventors: Stephan Schneider, Rainer Endermann, Karl G. Metzger, Klaus-Dieter Bremm
-
Patent number: 5264430Abstract: Derivatives of 2-spirocyclopropyl cephalosporin sulfone of the structural formula I ##STR1## are provided which are useful as potent elastase inhibitors.Type: GrantFiled: April 8, 1991Date of Patent: November 23, 1993Assignee: SynPhar Laboratories, Inc.Inventors: Samarendra N. Maiti, David Czajkowski, Paul Spevak, Kazuo Adachi, Ronald G. Micetich
-
Patent number: 5264429Abstract: Derivatives of 2-spirocyclopropyl cephalosporin sulfone of the structural formula I ##STR1## are provided which are useful as potent elastase inhibitors.Type: GrantFiled: August 20, 1991Date of Patent: November 23, 1993Assignee: SynPhar Laboratories, Inc.Inventors: Samarendra N. Maiti, David Czajkowski, Paul Spevak, Kazuo Adachi, Ronald G. Micetich
-
Patent number: 5262410Abstract: Cephalosporin compounds having a 3-position substituent of the formula (I) are described:--CH.sub.2 --S--Q--(Y).sub.n --Pwherein Q is a 5- or 6-membered heterocyclic ring, P is a benzene ring 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 hydrolysable ester thereof and R.sup.2 is hydroxy, an in vivo hydrolysable ester thereof, carboxy, sulpho, hydroxymethyl, methanesulphonamido or ureido; or P is a group of the formula (II) or (III): ##STR1## wherein M is oxygen or a group NR.sup.3 wherein R.sup.3 is hydrogen or C.sub.1-4 alkyl; said ring P being further optionally substituted; and --(Y).sub.n -- is a bond or various linking groups or --(Y)--.sub.n may be such so that rings Q and P are fused.The use of such compounds as antibacterial agents is described as are processes for their preparation and intermediates therefor.Type: GrantFiled: August 5, 1991Date of Patent: November 16, 1993Assignee: ICI PharmaInventors: Frederic H. Jung, Annie A. Olivier