Sulfur Containing Substituent Patents (Class 540/229)
  • Patent number: 9269884
    Abstract: An ultrasonic transducer includes a substrate, a supporting film, and a piezoelectric element. The substrate includes an opening. The supporting film is configured on the substrate to cover the opening. The piezoelectric element is configured at a part of the supporting film. The part overlaps with the opening in a planar view in a thickness direction of the substrate. A thickness of the part of at a center of gravity in the planar view is smaller than a thickness of an outer edge portion of the part. The outer edge portion is closer to the substrate than the center to the substrate.
    Type: Grant
    Filed: May 17, 2013
    Date of Patent: February 23, 2016
    Assignee: Seiko Epson Corporation
    Inventors: Tomoaki Nakamura, Hironori Suzuki, Jiro Tsuruno
  • Patent number: 9138490
    Abstract: Provided herein are methods for detecting, quantifying, differentiating, diagnosing and imaging pathogenic bacteria or condition associated therewith using substrates for bacterial enzymes. Fluorescent, luminescent or colorimetric signals emitted by substrates or enzyme products in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring a signal emitted from the substrates or products in the presence and absence of the potential therapeutic agent and a diagnostic method for detecting a mycobacterial infection in a subject by contacting biological samples with a substrate and imaging for signals emitted from a mycobacterial beta-lactamase product. Also provided are fluorogenic substrates or substrates comprising a colored dye or a chemical reagent effective to induce a color or pH change.
    Type: Grant
    Filed: December 4, 2012
    Date of Patent: September 22, 2015
    Assignees: The Texas A&M University System, The Board of Trustees of the Leland Stanford Junior University
    Inventors: Jeffrey D. Cirillo, James C. Sacchettini, Jianghong Rao, Hexin Xie
  • Publication number: 20140322739
    Abstract: The present invention relates to compounds for and a method of detecting beta-lactamase activity in a sample. The sample is contacted with a nanoparticulate tag. The nanoparticulate tag comprises a metal or a combination of metals, or it comprises a nanotube of a metal, boron nitride and/or carbon. The respective metal is capable of forming one of a covalent bond, a coordinative bond and a non-covalent interaction with a thio or a seleno group. The sample is contacted with a compound of one of general formulas (I)-(III) and (VII)-(IX). At least one beta-lactam moiety of the compound is cleaved by the beta-lactamase activity in the sample. As a result a cleavage moiety Z-A-Z, Z-A-Z—R15, Z-A-Z—R16, Z-A-Z—R17, Z-A-Z—R18 or Z-G-N(R8)R9 is released that is immobilized on the surface of the nanoparticulate tag by a covalent bond via a Z atom. The presence of beta-lactamase activity is determined based on the presence of the cleavage moiety immobilized onto the surface of the nanoparticulate tag.
    Type: Application
    Filed: July 8, 2014
    Publication date: October 30, 2014
    Inventors: Bengang Xing, Xianfeng Huang, Tingting Jiang, Rongrong Liu
  • Publication number: 20120329770
    Abstract: The present invention relates to cephalosporin derivatives having ?-lactamase inhibitory activity. The compounds are useful in preventing or treating bacterial resistance to an antibiotic, e.g. a ?-lactam antibiotic. Disclosed herein are compounds that are inhibitors of class B metallo-?-lactamases, as well as class A, C, and D serine ?-lactamases. In some preferred embodiments, the compounds are 3?-thiobenzoate derivatives of a cephalosporin. Pharmaceutical compositions, methods, uses, kits and commercial packages comprising the compounds are also disclosed.
    Type: Application
    Filed: February 25, 2011
    Publication date: December 27, 2012
    Inventors: Gary Igor Dmitrienko, Ahmad Ghavami, Valerie Joy Goodfellow, Jarrod W. Johnson, Anthony Paul Krismanich, Laura Marrone, Thammaiah Viswanatha, Sundaramma Viswanatha
  • Patent number: 8148632
    Abstract: Example solar cells and methods for making and using the same are disclosed. An example solar cell may include an electron conductor layer, a quantum dot layer, a bifunctional ligand layer coupling the electron conductor layer and the quantum dot layer, and a hole conductor layer coupled to the quantum dot layer. The bifunctional ligand layer may include an antibiotic, and in some cases, a cephalosporin-based antibiotic.
    Type: Grant
    Filed: July 14, 2009
    Date of Patent: April 3, 2012
    Assignee: Honeywell International Inc.
    Inventors: Bogdan Serban, Mihai N. Mihaila, Viorel Georgel Dumitru, Cazimir Bostan, Stephan Dan Costea, Mircea Bercu
  • Patent number: 7741478
    Abstract: Compounds of general formula (II), wherein R1 represents R4 represents hydrogen or —CHO group, R5 represents hydrogen or trityl, R2 represents hydrogen or methoxy group, R3 represents —CH?CH2 or and M represents a dialkyl or dicycloalkyl ethylenediamine group selected from N,N?-diisobutylethylenediamine, N,N?-dicyclohexylethylenediamine, and N,N?-dicyclopentylethylenediamine, are useful in a process to make cephalosporin antibiotics of formula (I) wherein R represents hydrogen or pharmaceutically acceptable esters or alkali metals salts.
    Type: Grant
    Filed: July 4, 2005
    Date of Patent: June 22, 2010
    Assignee: Orchid Chemicals & Pharmaceuticals Limited
    Inventors: Udayampalayam Palanisamy Senthilkumar, Venu Sanjeevi Lakshmipathi, Gnanaprakasam Andrew, Ramasubbu Chandrasekaran, Dindigala Nagender Rao, Gaddam Om Reddy
  • Patent number: 7700581
    Abstract: Disclosed herein are a cephalosporin compound of formula I, wherein R1 is selected from the following groups: wherein R2 is selected from the following groups: the preparation and uses thereof. A method of preparing the cephalosporin compound as disclosed herein comprises reacting a starting cephalosporin comprising a C7 amino group and a C3 thio-methyl moiety substituted with an N-containing heterocyclic group with bromoacetyl bromide and then with a N,N?-bissubstituted thiourea. Methods of treating an infectious disease are also disclosed, comprising administering to a patient in need thereof the pharmaceutical composition disclosed herein.
    Type: Grant
    Filed: January 31, 2007
    Date of Patent: April 20, 2010
    Assignee: Guangzhou Baiyunshan Pharmaceutical Co., Ltd.
    Inventors: Mao Chen, Shaoxuan Zhu, Xuebin Liu, Chun Luo, Shuwen Xu, Lizhen Zheng, Fang Ye, Chenglong Yi, Xiaona Zhang
  • Patent number: 7488724
    Abstract: The invention provides compounds of formula (I): wherein: R1-R4 and A have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting ?-lactamase enzymes, for enhancing the activity of ?-lactam antibiotics, and for treating ?-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula (I), and intermediates useful for the synthesis of compounds of formula (I).
    Type: Grant
    Filed: May 10, 2005
    Date of Patent: February 10, 2009
    Assignee: Southern Methodist University Foundation for Research
    Inventors: John D. Buynak, Lakshminarayana Vogeti
  • Publication number: 20080306256
    Abstract: The present invention relates to an improved process for the preparation of cephalosporin antibiotics of formula (I). The present invention also provides new salts of compound of formula (II) and a process for the preparation of these new salts, where n=0.5 to 2. The present invention also provides a process for the preparation of compound of formula (I) using the new salts of formula (II).
    Type: Application
    Filed: July 4, 2005
    Publication date: December 11, 2008
    Applicant: Orchid Chemicals & Pharmaceuticals Limited
    Inventors: Udayampalayam P. Senthilkumar, Venu S. Lakshmipathi, Gnanaprakasam Andrew, Ramasubbu Chandrasekaran, Dindigala Nagender Rao, Gaddam Om Reddy
  • Patent number: 7396926
    Abstract: Provided are fluorescent substrates for ?-lactamases having the general formula I: in which R is a benzyl, 2-thienylmethyl, or cyanomethyl group; R? is selected from the group consisting of H, physiologically acceptable salts or metal, ester groups, ammonium cations, —CHR2OCO(CH2)nCH3, —CHR2OCOC(CH3)3, acylthiomethyl, acyloxy-alpha-benzyl, deltabutyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, ?-morpholinoethyl, dialkylaminoethyl, and dialkylaminocarbonyloxymethyl, in which R2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO2 and CH2; and Z is a donor fluorescent moiety. Also provided are methods of use of the compound of general formula I.
    Type: Grant
    Filed: January 11, 2002
    Date of Patent: July 8, 2008
    Assignee: The Regents of the University of California
    Inventors: Roger Y. Tsien, Jianghong Rao
  • Patent number: 6916801
    Abstract: The invention provides compounds of formula (I): wherein: R1-R4 and A have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting ?-lactamase enzymes, for enhancing the activity of ?-lactam antibiotics, and for treating ?-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula (I), wherein R1 and R2 are each independently hydrogen, (C1-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkenyl, (C3-C8)cycloalkyl, (C1-C10)alkoxy, (C1-C10)alkanoyl, (C1-C10)alkanoyloxy, (C1-C10)alkoxycarbonyl, aryl, heterocycle, halo, cyano, nitro, —COORe, —C(?O)NRfRg, —OC(?O)NRfRg, NRfRg, or —S(O)nRh; R3 is hydrogen, halo, aryl, heteroaryl, —S(O)nRh, or —CH?CHC(?O)NRmRp; R4 is hydrogen; A is thio, sulfinyl, or sulfonyl; and intermediates useful for the synthesis of compounds of formula (I).
    Type: Grant
    Filed: July 24, 2002
    Date of Patent: July 12, 2005
    Assignee: Alamx, LLC
    Inventors: John D. Buynak, Lakshminarayana Vogeti
  • Patent number: 6730497
    Abstract: A process for preparing cephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C compound of formula III: into a 3-thiolated-&agr;-ketoadipyl-7-aminocephalosporanic acid derivative of formula IV: wherein R is a heterocyclic group comprising at least a nitrogen atom. Compounds of formula IV are used in the preparation of cephalosporin C antibiotics and derivatives thereof.
    Type: Grant
    Filed: April 19, 2002
    Date of Patent: May 4, 2004
    Assignee: Bioferma Murcia S.A.
    Inventors: Alvaro Sánchez-Ferrer, José Aniceto López-Más, Francisco García-Carmona
  • Patent number: 6683176
    Abstract: The present invention relates to novel processes for the preparation of 3-methylenecephams. More specifically, the present invention relates to the intramolecular cyclization of penicillin sulfoxide derived monocyclic azetidinone derivatives with organometallic catalysts of the formula III. MEx(H2O)y  (III) wherein: M is Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Zr, Hf, Th, Nb, Ta, U, Bi, or In; E is O[SO2(C1-C6 polyfluoroalkyl)], N[SO2(C1-C6 polyfluoroalkyl)]2, or C[SO2(C1-C6 polyfluoroalkyl)]3; x is 3; y is 0, 1, 2, 3, 4, 5, 6, 7, 8, or 9.
    Type: Grant
    Filed: December 31, 2001
    Date of Patent: January 27, 2004
    Inventors: Robin D. G. Cooper, Anthony G. M. Barrett
  • Patent number: 6642020
    Abstract: An enzymatic process for preparing 3-thiolated 7-aminocephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C of the formula I: to form a 3-thiolated-glutaryl-7-ACA of the formula II and enzymatically converting a compound of formula II to form a 3-thiolated-7-ACA of the formula III wherein R is a heterocyclic group comprising at least one nitrogen atom and R1 and R2 are both hydrogen atoms or one of them is a hydrogen atom and the other is an acyl donor.
    Type: Grant
    Filed: April 19, 2002
    Date of Patent: November 4, 2003
    Assignee: Bioferma Murcia S.A.
    Inventors: Álvaro Sánchez-Ferrer, José Aniceto López-Más, Francisco Garcia-Carmona
  • Patent number: 6583133
    Abstract: Disclosed are cephalosporin derivatives of the general formula wherein R is an organic residue with a molecular weight not exceeding 400 bonded to the adjacent sulphur atom via carbon and consisting of carbon, hydrogen, and optional oxygen, sulfur, nitrogen and/or halogen atoms; R1 is hydrogen, lower alkyl or phenyl; and A is a secondary, tertiary or quaternary nitrogen atom bound directly to the propenyl group and being substituted by an organic residue with a molecular weight not exceeding 400 and consisting of carbon, hydrogen, and optional oxygen, sulfur, nitrogen and/or halogen atoms, 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.
    Type: Grant
    Filed: June 22, 1999
    Date of Patent: June 24, 2003
    Assignee: Basilea Pharmaceutica AG
    Inventors: Peter Angehrn, Erwin Götschi, Ingrid Heinze-Krauss, Hans G. F. Richter
  • Patent number: 6531465
    Abstract: A compound of formula wherein Ac, R1 and R2 have various meanings, a process for a preparation thereof and its use as a pharmaceutical, i.e. as antibacterial agent.
    Type: Grant
    Filed: May 21, 2001
    Date of Patent: March 11, 2003
    Assignee: Biochemie Gesellschaft m.b.H.
    Inventors: Gerd Ascher, Johannes Ludescher
  • Publication number: 20020115650
    Abstract: The present invention relates to novel cephalosporin antibiotics, prodrugs thereof and pharmacologically acceptable salts of either, which are active against a wide spectrum of bacteria that are resistant to present clinical beta-lactam antibiotics.
    Type: Application
    Filed: August 8, 2001
    Publication date: August 22, 2002
    Applicant: Microcide Pharmaceuticals.
    Inventor: Tomasz W. Glinka
  • Publication number: 20020115642
    Abstract: The present invention provides compositions comprising improved beta-lactam antibiotics and methods for applying these compositions to inhibit the growth of microbial infections. The improved antibiotics are capable of inhibiting the growth of both antibiotic sensitive and antibiotic resistant microorganisms In addition, the invention provides methods for treating a subject infected with a microorganism by administering the compositions of the invention.
    Type: Application
    Filed: May 1, 2001
    Publication date: August 22, 2002
    Inventors: Ming Fai Chan, Rosario S. Castillo, Qing Li, Venkata Ramana Doppalapudi, Mark Stephen Hixon, Thomas J. Lobl
  • Patent number: 6369049
    Abstract: The invention provides new fluorinated cephalosporin antibiotics of Formula I wherein Ra, Rb, Rc, Rd and Re, independently, are H, F or a C1-C6 alkyl-(Z)n— group having at least one fluorine substituent; X is O or S; Y is S, O, or —CH2—; Z is O, S, —SO—, or —SO2—; m and n independently are 0 or 1; and R1 is H, C1-C6-alkyl, phenyl or benzyl, each of which may optionally have up to three substituents selected from halo, C1-C4-alkoxy, phenyl, NO2, C1-C6-alkanoyl, benzoyl, or C1-C6-alkanoyloxy; or a physiologically acceptable salt thereof; and methods of preventing or treating or treating infection, particularly mastitis in ruminants, using these antibiotics.
    Type: Grant
    Filed: April 12, 1999
    Date of Patent: April 9, 2002
    Assignee: Eli Lilly and Company
    Inventor: Karl Robert Dahnke
  • Publication number: 20020028931
    Abstract: A novel process for the preparation of ceftiofur, a cephalosporin antibiotic useful in the treatment of bovine respiratory disease. The process utilizes a new bromo or chloro intermediate that can be isolated in a pure form by this inventive process subsequently resulting in ceftiofur of high purity. This invention offers a new-to-the-world route to Ceftiofur using novel intermediates.
    Type: Application
    Filed: July 9, 2001
    Publication date: March 7, 2002
    Inventors: Ramesh Dandala, Venkataiah Sunku, Vijay Kumar Handa, Meenakshisunderam Sivakumaran
  • Patent number: 6303592
    Abstract: Derivatives of 7-alkylidene cephalosporanic acid sulfone and the pharmaceutically active salts thereof are found to be potent inhibitors of &bgr;-lactamase enzymes.
    Type: Grant
    Filed: March 14, 1997
    Date of Patent: October 16, 2001
    Assignee: Research Corporation Technologies, Inc.
    Inventors: John D. Buynak, Brian Bachmann
  • Patent number: 6274730
    Abstract: A process for preparing halogenated &bgr;-lactam compounds, characterized in that a &bgr;-lactam amino compound of the formula (1) is reacted with nitrous acid or nitrite in a slurry dispersion state in water, under acid condition in the presence of halogen molecules, thereby obtaining a halogenated &bgr;-lactam compound of the formula (4) wherein n is an integer of 0 to 2; A is the formula (2) or (3); R1 and R2 are the same or different and are hydrogen atom, halogen atom, C1˜C3 alkyl group, C2˜C4 alkenyl group, C2˜C4 alkynyl group, nucleophilic group, or CH2R3; and R3 is halogen atom or nucleophilic group  wherein A is as defined above; X1 is hydrogen atom or halogen atom; and X2 is halogen atom.
    Type: Grant
    Filed: December 1, 1999
    Date of Patent: August 14, 2001
    Assignee: Otsuka Kagaku Kabushiki Kaisha
    Inventors: Akihiro Shimabayashi, Ichirou Kawahara, Shigetoshi Yaguchi, Hiroaki Asai
  • Patent number: 6255479
    Abstract: A method for preparing an &agr;-oxolactam comprising, reacting a corresponding &agr;-diazolactam with an oxygen donor, in the presence of a transition metal catalyst, to yield the corresponding &agr;-oxolactam.
    Type: Grant
    Filed: December 29, 1998
    Date of Patent: July 3, 2001
    Assignee: Research Corporation Technologies, Inc.
    Inventors: John D. Buynak, Akireddy Srinivasa Rao
  • Patent number: 6100393
    Abstract: 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: Grant
    Filed: February 25, 1998
    Date of Patent: August 8, 2000
    Assignee: Antibioticos, S.A.
    Inventors: Juan Francisco Lopez Ortiz, Oscar Ferrero Barruego, Emiliano Gonzalez de Prado, Alejandro Vitaller Alba, Francisco Salto Maldonado
  • Patent number: 6066630
    Abstract: 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: Grant
    Filed: October 11, 1996
    Date of Patent: May 23, 2000
    Assignee: Microcide Pharmaceuticals, Inc.
    Inventors: In-Seop Cho, Scott J. Hecker, Tomaz W. Glinka, Ving J. Lee, Zhijia J. Zhang
  • Patent number: 5756493
    Abstract: 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: Grant
    Filed: March 29, 1995
    Date of Patent: May 26, 1998
    Assignee: Microcide Pharmaceuticals, Inc.
    Inventors: Scott Hecker, In-Seop Cho, Tomasz Glinka, Burton Christensen
  • Patent number: 5698547
    Abstract: 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: Grant
    Filed: May 31, 1995
    Date of Patent: December 16, 1997
    Assignee: Microcide Pharmaceuticals, Inc.
    Inventors: Burton Christensen, In-Seop Cho, Tomasz Glinka, Scott Hecker, Ving J. Lee, Zhijia J. Zhang
  • Patent number: 5629306
    Abstract: Derivatives of 7-alkylidene cephalosporanic acid sulfone and the pharmaceutically active salts thereof are found to be potent inhibitors of .beta.-lactamase enzymes.
    Type: Grant
    Filed: December 9, 1994
    Date of Patent: May 13, 1997
    Assignee: Research Corporation Technologies, Inc.
    Inventors: John D. Buynak, Brian Bachmann
  • Patent number: 5597817
    Abstract: Cephalosporins with an exocyclic allene in the 7-position and their pharmaceutically active salts are potent inhibitors of .beta.-lactamases and are therefore useful in the treatment of penicillin resistant infections.
    Type: Grant
    Filed: December 9, 1994
    Date of Patent: January 28, 1997
    Assignee: Southern Methodist University
    Inventors: John D. Buynak, Brian Bachmann
  • Patent number: 5594132
    Abstract: 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: Grant
    Filed: April 12, 1991
    Date of Patent: January 14, 1997
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Takao Takaya, Hisashi Takasugi, Takashi Masugi, Hideaki Yamanaka, Kohji Kawabata
  • Patent number: 5593986
    Abstract: 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: Grant
    Filed: March 29, 1995
    Date of Patent: January 14, 1997
    Assignee: Microcide Pharmaceuticals, Inc.
    Inventors: Burton G. Christensen, In-Seop Cho, Tomasz W. Glinka, Scott J. Hecker
  • Patent number: 5580865
    Abstract: 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: Grant
    Filed: April 5, 1993
    Date of Patent: December 3, 1996
    Assignee: Farmitalia Carlo Erba S.r.l.
    Inventors: Marco Alpegiani, Pierluigi Bissolino, Ettore Perrone, Vincenzo Rizzo
  • Patent number: 5574153
    Abstract: The invention relates to oxime derivatives of cephalosporanic structure, possessing antibacterial activity.
    Type: Grant
    Filed: July 27, 1994
    Date of Patent: November 12, 1996
    Assignee: ACS Dobfar S.p.A.
    Inventors: Maurizio Zenoni, Mario Leone, Riccardo Colombo
  • Patent number: 5245027
    Abstract: 3-Fluorosulfonyloxyceph-3-ems having a protected amino or acylamino group in the 7-position are subject to carbon-carbon bond formation at the 3-position by means of a palladium catalyzed coupling reaction with substituted organostannanes. A process for preparing cefprozil is disclosed.
    Type: Grant
    Filed: October 31, 1990
    Date of Patent: September 14, 1993
    Assignee: Bristol-Myers Squibb Company
    Inventors: Stephen R. Baker, Chester Sapino, Jr., Gregory P. Roth
  • Patent number: 5169945
    Abstract: The present invention provides a process for protecting an amino group in a compound exposed to nucleophilic reaction conditions in which the imido group used for protection is reacted with a secondary amine to form an acyl group which protects the amino group during exposure to the nucleophilic reaction conditions, after which the acylamino group may be reacted with an acid to reform the imido group so that the compound may then undergo non-nucleophilic manipulations. Also provided is a resolution method in which diasteriometric compounds having the acylamino group as described above are reacted with acid, and as these diasteriomers react at different rates to form the imido group, the reaction may be monitored so as to isolate the desired product at the appropriate point to maximize optical purity.
    Type: Grant
    Filed: August 19, 1991
    Date of Patent: December 8, 1992
    Assignee: Eli Lilly and Company
    Inventor: Leland O. Weigel
  • Patent number: 5106842
    Abstract: A compound of formula I ##STR1## wherein X is sulfur or CH.sub.2 ;R.sup.1 is hydrogen, hydroxy, amino, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, phenyl optionally substituted with one to three C.sub.1-6 alkyl, C.sub.1-6 alkyloxy or hydroxy, C.sub.1-6 alkylthio, phenylthio optionally substituted with one to three C.sub.1-6 alkyl or C.sub.1-6 alkyloxy on the phenyl ring, phenylmethyloxy optionally substituted with one to three C.sub.1-6 alkyl or C.sub.1-6 alkyloxy on the phenyl ring, 1-morpholino, C.sub.1-6 alkyloxy, C.sub.2-6 alkenylmethyloxy, C.sub.3-6 alkynylmethyloxy, C.sub.1-6 alkylamino, C.sub.1-6 dialkylamino or a radical selected from the group consisting of ##STR2## in which n is 0 to 3, R.sup.5 is C.sub.1-6 alkyl or hydrogen, and R.sup.3 and R.sup.4 are independently C.sub.1-6 alkyl;R.sup.2 is hydrogen, a conventional amino protecting group or an acyl group;R.sup.0 is hydrogen or a conventional carboxy protecting group, or --CO.sub.2 R.sup.
    Type: Grant
    Filed: October 22, 1990
    Date of Patent: April 21, 1992
    Assignee: Bristol-Myers Squibb Co.
    Inventors: Thomas W. Hudyma, Richard A. Partyka
  • Patent number: 5043439
    Abstract: Cephalosporin intermediates having a replacable organosulfonylyoxy or heterocyclothio group in the 3-position undergo a carbon alkylation process with organocopper reagents to provide 3-hydrocarbon substituted cephalosporin antibiotics.
    Type: Grant
    Filed: March 8, 1990
    Date of Patent: August 27, 1991
    Assignee: Bristol-Myers Squibb Company
    Inventors: Joydeep Kant, Chester Sapino, Jr.
  • Patent number: 4985555
    Abstract: The invention relates to a cephem compound of high antimicrobial activity of the formula: ##STR1## wherein R.sup.1 is amino, R.sup.2 is hydrogen, phenyl, pyridyl which may have a lower alkyl group, or cyano, and R.sup.3 is carboxy or protected carboxy, or a salt thereof.
    Type: Grant
    Filed: July 27, 1989
    Date of Patent: January 15, 1991
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Takao Takaya, Zenzaburo Tozuka, Nobuyoshi Yasuda, Kohji Kawabata
  • Patent number: 4983732
    Abstract: A method for preparing 2-amino-.beta.-lactams which are substituted by readily-removed protecting groups is provided. According to this invention, an acyl-2-amino-.beta.-lactam is further acylated with a different acyl group and is subsequently treated with base to provide a protected 2-amino .beta.-lactam with allyloxycarbonyl, t-butoxycarbonyl, naphthyloxycarbonyl, trichloroethyloxycarbonyl, p-nitrobenzyloxycarbonyl, benzhydryloxycarbonyl, p-methoxybenzyloxycarbonyl, or o-nitrobenzyloxycarbonyl.
    Type: Grant
    Filed: September 21, 1989
    Date of Patent: January 8, 1991
    Assignee: Eli Lilly and Company
    Inventors: Larry C. Blaszczak, John E. Munroe, Douglas O. Spry
  • Patent number: 4945159
    Abstract: A method for the formation of intramolecular amide bonds by the action of cyanogen, under mild reaction conditions, in the preparation of cyclic amides, including lactams, in biologically active compounds. A compound containing at least one carboxylic acid group and at least one primary or secondary amino group is reacted with cyanogen to form an intramolecular amide bond. The method has utility in the synthesis of B-lactam antibiotics, such as penicillins, cephalosporins, and their derivatives, in enzyme modification, in cyclization of peptides, and in covalent cross-linking of proteins.
    Type: Grant
    Filed: December 2, 1986
    Date of Patent: July 31, 1990
    Assignee: University of Cincinnati
    Inventor: Richard A. Day
  • Patent number: 4931555
    Abstract: A process for producing a 2-cephem or 3-cephem derivative compound of the formula: ##STR1## wherein R.sub.1 represents a substituted or unsubstituted amino radical and R.sub.4 represents hydrogen or a radical selected from the group consisting of carboxy, protected carboxy, ester, acid amide, acid anhydride, acid halide, acid azide and carboxy salt, and the dotted line indicates the alternate bond structure providing 3-cephem or 2-cephem, which comprises:reacting a halogenated derivative selected from the group consisting of a halogenated penam derivative having the formula: ##STR2## a halogenated cepham derivative of the formula: ##STR3## wherein X represents a halogen atom, R.sub.3 represents a radical selected from the group consisting of carboxy, protected carboxy, ester, acid amide, acid anhydride, acid halide, acid azide and carboxy salt, and R.sub.1 is as defined above, or mixtures thereof with a dehydrohalogenoic acid reagent.
    Type: Grant
    Filed: January 26, 1981
    Date of Patent: June 5, 1990
    Assignee: Fujisawa Pharmaceutical Company, Ltd.
    Inventors: Takashi Kamiya, Yoshihisa Saito, Tsutomu Teraji, Osamu Nakaguit, Teruo Oku, Hitoshi Nakamura, Masashi Hashimoto
  • Patent number: 4888100
    Abstract: A process for photochemically converting 3-exomethylene cephams (or 1-carba(1-dethia)cephams or and 1-oxa(1-dethia)cephams) from the corresponding 3-alkyl-3-cephem (or 1-carba(1-dethia)cephem or 1-oxa(1-dethia)cephem) is provided. Further provided are 3-cephams useful as intermediates to 3-cephem compounds.
    Type: Grant
    Filed: March 15, 1989
    Date of Patent: December 19, 1989
    Assignee: Eli Lilly and Company
    Inventors: Larry W. Hertel, John M. Morin, Jr., Robert T. Vasileff
  • Patent number: 4870169
    Abstract: 1-Benzyl(or substituted benzyl)-3.beta.-[4(S)-aryloxazolidin-2-one-3-yl]-4.beta.-(2-arylvinyl)azet idin-2-ones are provided via cycloaddition of a 4(S)-aryloxazolidin-2-one-3-ylacetyl halide and an imine formed with a benzylamine and a 3-arylacrolein, e.g. cinnamaldehyde. The azetidinones are useful chiral intermediates in an asymmetric synthesis of 1-carba(1-dethia)-3-hydroxy-3-cephem-4-carboxylic acids and esters and to monocyclic .beta.-lactam antibiotics.
    Type: Grant
    Filed: April 22, 1988
    Date of Patent: September 26, 1989
    Assignee: President and Fellows of Harvard College
    Inventors: David A. Evans, Eric B. Sjogren
  • Patent number: 4808712
    Abstract: A process for preparing cephalosporin compounds represented by the formula ##STR1## wherein R.sup.1 represents an alkyl group, alkenyl group, substituted or unsubstituted aryl group, substituted or unsubstituted arylmethyl group or substituted or unsubstituted phenoxymethyl group, R.sup.2 represents a carboxyl group or protected carboxyl group, and Y represents the residue of a nucleophilic reagent.
    Type: Grant
    Filed: October 14, 1986
    Date of Patent: February 28, 1989
    Assignee: Otsuka Kagaku Kabushiki Kaisha
    Inventor: Shigeru Torii
  • Patent number: 4772682
    Abstract: The invention relates to intermediates useful in the preparation of antimicrobial compounds, the intermediates being of the formula: ##STR1## wherein R.sup.A is --SCN or --S.sup..sym. (R.sup.3).sub.2, whereinR.sup.3 is lower alkyl, andR.sup.B is carboxy or --COO.sup..crclbar.,or a salt thereof, with the proviso that when R.sup.A is --SCN, then R.sup.B is carboxy and that when R.sup.A is --S.sup..sym. (R.sup.3).sub.2, then R.sup.B is --COO.sup..sym..
    Type: Grant
    Filed: December 22, 1986
    Date of Patent: September 20, 1988
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Tsutomu Teraji, Kazuo Sakane, Jiro Goto
  • Patent number: 4760140
    Abstract: Compounds of the formula: ##STR1## wherein R.sub.1 is hydrogen, alkyl(C.sub.1 -C.sub.3), vinyl, acetyloxy or ##STR2## wherein R.sub.3 is hydrogen or alkyl(C.sub.1 -C.sub.6); R.sub.2 is hydrogen or diphenylmethyl and A is R.sub.4 --C, where R.sub.4 is acetyl or benzoyl, are useful as intermediates in the preparation of biologically active cephalosporin derivatives.
    Type: Grant
    Filed: October 20, 1986
    Date of Patent: July 26, 1988
    Assignee: American Cyanamid Company
    Inventors: Robert Babine, Ving J. Lee
  • Patent number: 4695627
    Abstract: A process for the preparation of 7.beta.-acylamino-3-substituted-3-cephem-4-carboxylic acid compounds comprising reacting at -70.degree. C. to 0.degree. C. in an inert organic solvent phosphorus pentachloride with a cephalosporin compound in the presence of an olefinic compound having at least one carbon-carbon double bond having not more than three hydrogen atoms attached thereto capable of removing chlorine at least in part by addition to a carbon-carbon double bond.
    Type: Grant
    Filed: September 21, 1984
    Date of Patent: September 22, 1987
    Assignee: Gist-Brocades N.V.
    Inventors: Jan Verweij, Herman H. Grootveld, Henri G. J. Hirs, Gerardus J. Van Veen, Jan Kalter, Peter W. Henniger
  • Patent number: 4656264
    Abstract: An azetidinone compound represented by the formula ##STR1## wherein R.sup.1 represents a substituted or unsubstituted phenyl group, R.sup.2 represents a carboxyl-protecting group, X represents a hydrogen atom or chlorine atom and Y represents --I, --ONO.sub.2, --OH, ##STR2## or --SR.sup.4 in which R.sup.3 is a lower alkyl group or --OR.sup.5 (wherein R.sup.5 is a halogen-containing lower alkyl group) and R.sup.4 is a substituted or unsubstituted, 5-membered aromatic heterocyclic residue containing sulphur and/or nitrogen atom or atoms.
    Type: Grant
    Filed: April 29, 1986
    Date of Patent: April 7, 1987
    Assignee: Otsuka Kagaku Kabushiki Kaisha
    Inventors: Shigeru Torii, Hideo Tanaka, Junzo Nogami, Michio Sasaoka, Norio Saito, Takashi Shiroi
  • Patent number: 4622394
    Abstract: In accordance with this invention, it has been found that the oxygen analog of 7-amino-cephalosporanic acid and biologically active derivatives thereof can be formed from esters of 7-amino-cephalosporanic acid. Esters of 7-oxocephalosporanic acid can be formed by diazotization of an ester or 7-amino-cephalosporanic acid and contact of the diazo compound so formed with a hypohalous acid and a base in a water miscible organic solvent. Oxygen analogs of 7-aminocephalosporins isolated as esters are then formed by reducing the aforesaid ester to the corresponding 7.beta.-hydroxy-cephalosporanate and then forming the desired analog by introduction of a side chain via hydroxyl group modification. Oxygen analogs of 7-amino-cephalosporins are then formed by regeneration of the acid via protective group removal.
    Type: Grant
    Filed: December 2, 1977
    Date of Patent: November 11, 1986
    Assignee: Massachusetts Institute of Technology
    Inventors: John C. Sheehan, Young S. Lo
  • Patent number: 4622393
    Abstract: New 3-vinylcephalosporins of the general formula (I), ##STR1## in which n=0 or 1, R.sub.1 is a radical of the general formula (II), ##STR2## in which R.sub.4 is hydrogen or a protective radical and R.sub.5 represents a radical of the general formula (IIa) ##STR3## in which R.sup.a.sub.5 and R.sup.b.sub.5 are hydrogen or alkyl or together form an alkylene radical and R.sup.c.sub.5 is hydrogen or a protective radical, R.sub.2 is hydrogen, a protective radical or a radical which can easily be removed by an enzymatic method, and R.sub.3 is a halogen atom or a radical R'.sub.3 SO.sub.2 O-- or R".sub.3 CO--O--, in which radicals R'.sub.3 and R".sub.3 are substituted or unsubstituted alkyl or phenyl radicals, or alternatively R.sub.1 is a hydrogen atom or a radical of the general formula (II) in which R.sub.4 is defined as above and R.sub.5 is hydrogen, alkyl, vinyl, cyanomethyl or a protective radical, and R.sub.2 is defined as above, or R.sub.1 is hydrogen or a variously substituted acyl radical and R.sub.
    Type: Grant
    Filed: May 14, 1984
    Date of Patent: November 11, 1986
    Assignee: Rhone-Poulenc Industries
    Inventors: Daniel Farge, Pierre Le Roy, Claude Moutonnier, Jean-Francois Peyronel