Patents Represented by Attorney Robert E. Carnahan
  • Patent number: 4956374
    Abstract: Novel antifungal antibiotic compounds have the structural formula ##STR1## A preferred compound where R is 4-hydroxypentyl is denoted BU-3557B.sub.2. A complex of said compounds is produced by fermenting a culture of Sacchrothrix aerocolonigenes strain N806-4 (ATCC 53712). The complex is recovered by adsorption on nonionic porous polymer resin adsorbent and individual component compounds exhibit in vitro activity against fungi and Gram-positive bacteria and BU-3557B.sub.2 demonstrates in vitro antiprotazoal activity. BU-3557B.sub.2 demonstrates in vivo activity against C. albicans vaginal infection and BU-3557A.sub.3 (where R is 1,5-dihydroxy-5,5-dimethylpentyl) demonstrates in vivo activity against C. albicans systemic infection.
    Type: Grant
    Filed: July 29, 1988
    Date of Patent: September 11, 1990
    Assignee: Bristol-Myers Company
    Inventors: Maki Nishio, Shigeyuki Ando, Takeo Miyaki, Masataka Konishi, Toshikazu Oki
  • Patent number: 4954507
    Abstract: There are disclosed new naphthyridine- and quinoline-carboxylic acids having a 1-tertiary-alkyl substituent, compositions containing them, and their use in treating bacterial infections in warm-blooded animals. Also disclosed are novel amines and intermediates used in the preparation of the naphthyridine- and quinoline-carboxylic acids.
    Type: Grant
    Filed: December 19, 1988
    Date of Patent: September 4, 1990
    Assignee: Bristol-Myers Company
    Inventors: Abraham Weber, Daniel Bouzard, Munir Essiz, Pierre Di Cesare, Jean-Pierre Jacquet, Philippe Remuzon
  • Patent number: 4935508
    Abstract: A process for the selective formation of oximino o-protected derivatives of lower alkyl 2-(2-aminothiazol-4-yl)-2-oximinoacetates, and their use in the acylation of 7-amino-cephalosporin compounds is disclosed.
    Type: Grant
    Filed: August 23, 1988
    Date of Patent: June 19, 1990
    Assignee: Bristol-Myers Company
    Inventors: Hajime Kamachi, Takaaki Okita, Satsuki Okuyama, Takayuki Naito
  • Patent number: 4916217
    Abstract: Etoposide-3',4'-quinone is converted into a phosphorane or phosphate ester by reaction with an organic phosphine or phosphite. The resulting phosphoranes and phosphates have anti-tumor activity in animals.
    Type: Grant
    Filed: January 8, 1987
    Date of Patent: April 10, 1990
    Assignee: Bristol-Myers Company
    Inventor: Mark G. Saulnier
  • Patent number: 4910301
    Abstract: Crystalline sulfuric, di-nitric, mono-hydrochloric, di-hydrochloric, and di- and sesqui-orthosphosphoric acid addition salts of 7-[.alpha.-(2-aminothiazol-4-yl)-.alpha.-(Z)-methoxyiminoacetamido]-3-[(1- methyl-1-pyrrolidinio)methyl]-3-cephem-4-carboxylate are stable even at elevated temperatures. The crystalline sulfuric acid addition salt is made by forming an admixture of (a) at least one molar equivalent of sulfuric acid with (b) zwitterion in an amount so as to be present in the admixture at a concentration of greater than 25 milligrams/ml, causing crystallization, separating the crystals, washing and drying. The crystalline monohydrochloride, dihydrochloride, and orthophosphate salts are prepared by dissolving the zwitterion in the appropriate amount of acid, causing crystallization by adding acetone and isolating the crystals. Physical admixtures of the salts with certain bases in proportions to give a pH ranging from about 3.
    Type: Grant
    Filed: January 19, 1988
    Date of Patent: March 20, 1990
    Assignee: Bristol-Myers Company
    Inventors: Murray A. Kaplan, Thomas W. Hudyma, Robert A. Lipper, Kun M. Shih, Susan D. Boettger
  • Patent number: 4908440
    Abstract: There are disclosed novel 2',3'-dideoxy-2'-fluoronucleosides and 2'-3'-dideoxy-2',3'-didehydro-2'-fluoronucleosides and processes for their preparation. The compounds so produced exhibit therapeutically useful antiviral and, more particularly, anti-HIV effects.
    Type: Grant
    Filed: November 12, 1987
    Date of Patent: March 13, 1990
    Assignee: Bristol Myers Company
    Inventors: Roman Z. Sterzycki, Muzammil M. Mansuri, John C. Martin
  • Patent number: 4904770
    Abstract: There are disclosed novel processes for producing 2',3'-dideoxy-2'3'-didehydronucleosides, for example, 2',3'-dideoxy-2',3'-didehydrothymidine in high yields and on a large scale. The compounds so-produced are useful as antiviral agents, especially as agents effective against the human immunodeficiency viruses (HIV).
    Type: Grant
    Filed: March 24, 1988
    Date of Patent: February 27, 1990
    Assignee: Bristol-Myers Company
    Inventors: John E. Starrett, Jr., Muzammil M. Mansuri, John C. Martin, Carl E. Fuller, Henry G. Howell
  • Patent number: 4879377
    Abstract: Process for producing 1-halo-2-deoxy-2-fluoroarabinofuranoside derivatives bearing protective ester groups from 1,3,5-tri-O-acylribofuranose; the 1-halo compounds are intermediates in the synthesis of therapeutically active nucleosidic compounds.
    Type: Grant
    Filed: July 28, 1988
    Date of Patent: November 7, 1989
    Assignee: Bristol-Myers Company
    Inventors: Steven P. Brundidge, Henry G. Howell, Chester Sapino, Jr., Chou Hong-Tann
  • Patent number: 4874856
    Abstract: This invention provides novel cephalosporanic acids and esters thereof having the general formula ##STR1## wherein R.sup.2 is hydrogen, or lower acyl, R.sup.3 is hydrogen, or lower alkanoyloxy, andR.sup.4 is hydrogen, 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl, 1-(ethoxycarbonyloxy)ethyl,1-(pivaloyloxy)ethyl, 1-(cyclohexylacetoxy)ethyl, or 1-(cyclohexyloxycarbonyloxy) ethyl. These compounds, especially esters, are useful as broad spectrum antibiotics in the treatment and prevention of infectious diseases of mammals, and for other purposes known in the art. The acids (R.sup.4 is hydrogen) are useful as intermediates for making the esters.
    Type: Grant
    Filed: August 17, 1987
    Date of Patent: October 17, 1989
    Assignee: Bristol-Myers Company
    Inventors: Seiji Iimura, Yoshio Abe, Jun Okumura, Takayuki Naito, Hajime Kamachi
  • Patent number: 4870168
    Abstract: There is disclosed a process for the production of certain 3-hydrocarbyl-3-cephem derivatives wherein the hydrocarbyl group is selected from 1-alkenyl and conjugated and unconjugated 1-polyalkenyl, 1-alkynl, carbocyclic and heterocyclic aryl, and carbocyclic and heterocyclic arylmethyl and, in the case of the 1-alkenyl and conjugated 1-polyalkenyl derivatives, with substantially complete stereospecificity, by coupling a 3-triflyloxy cephem with a hydrocarbyltributylstannane in the presence of bis(dibenzylideneacetonyl)-palladium, a phosphine, and a metal halide such as, for example, zinc chloride. The 3-unsaturated alkyl-3-cephem derivatives so-produced are useful as broad-spectrum antibacterial agents.
    Type: Grant
    Filed: February 26, 1987
    Date of Patent: September 26, 1989
    Assignee: Bristol-Myers Company
    Inventors: Stephen R. Baker, Vittorio Farina, Chester Sapino, Jr.
  • Patent number: 4866180
    Abstract: This invention refers to 7-amino mitosane analogs (mitomycin C) in which the 7-amino group bears an organic substituent incorporating a disulfide group and to a novel thiol exchange process for producing these compounds. The compounds are inhibitors of experimental animal tumors.
    Type: Grant
    Filed: September 23, 1985
    Date of Patent: September 12, 1989
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Yulin Chiang, Terrence W. Doyle
  • Patent number: 4847373
    Abstract: There is disclosed a process for the production of certain 2-allyl- and 3-butenyl-3-cephem derivatives by coupling a 3-chloromethyl-3-cephem with a hydrocarbyltributystannane in the presence of bis(dibenzylideneacetonyl)-palladium and a phosphine. The 3-allyl- and 3-butenyl-3-cephem derivatives so-produced are useful as broad-spectrum antibacterial agents.
    Type: Grant
    Filed: February 26, 1987
    Date of Patent: July 11, 1989
    Assignee: Bristol-Myers Company
    Inventors: Stephen R. Baker, Vittorio Farina, Chester Sapino, Jr.
  • Patent number: 4841043
    Abstract: There is disclosed a process for producing carbapenam diazo intermediates of the formula ##STR1## wherein R.sup.1 is hydrogen or a hydroxy-protecting group,R.sup.2 is a lower alkyl having from 1-6 carbon atoms, andR.sup.3 represents a conventional carboxyl-protecting group.The processs comprises alkylating a 4-substituted azetidinone with the tin enolate of an .alpha.-bromoketone, in the presence of a silver salt, iodine, or iodine salt as a catalyst, and a strongly polar solvent. The .beta./.alpha. yield of the product diazo intermediate is approximately 3/1.
    Type: Grant
    Filed: August 3, 1987
    Date of Patent: June 20, 1989
    Assignee: Bristol-Myers Company
    Inventors: Robert Deziel, Masaki Endo
  • Patent number: 4803212
    Abstract: The present invention refers to mitomycin analogs containing a disulfide group. These compounds are mitromycin C derivatives in which the 7-amino group bears an organic substituent incorporating a disulfide group. The compounds are inhibitors of experimental animal tumors.
    Type: Grant
    Filed: February 24, 1984
    Date of Patent: February 7, 1989
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Yulin Chiang, Terrence W. Doyle
  • Patent number: 4788282
    Abstract: A process is disclosed for the deprotection of allylic esters and ethers. The process comprises reacting an allyl ester of a carboxylic acid or an allyl ether of a phenol with pyrrolidine or piperidine and a catalytic amount of an organic-soluble palladium complex having a coordinating phosphine ligand to cleave the allyl moiety. The resultant carboxylic acid or phenol is then recovered.
    Type: Grant
    Filed: June 7, 1985
    Date of Patent: November 29, 1988
    Assignee: Bristol-Myers Company
    Inventor: Robert Deziel
  • Patent number: 4780416
    Abstract: The actinomycete "Actinomadura sp." designated in our culture collection as Strain No. G455-101 has been deposited with the American Type Culture Collection under the Accession Number ATCC No. 31491. The taxonomic description of this microorganism is presented in detail in the specification as are instructions for fermenting aqueous nutrient media with it to produce the BBM 928 antibiotic complex. The BBM 928 complex has utility as an antibacterial agent against gram-positive and acid fast bacteria and exhibits antitumor activity against experimental animal tumors.
    Type: Grant
    Filed: December 18, 1986
    Date of Patent: October 25, 1988
    Assignee: Bristol-Myers Company
    Inventors: Hideo Koshiyama, Fumihide Sakai, Hiroaki Ohkuma
  • Patent number: 4727070
    Abstract: The antibiotic 7-[D-2-amino-2-(4-hydroxyphenyl)acetamido]-3-[(Z)-1-propenyl]ceph-3-em-4-c arboxylic acid (BMY-28100) forms imidazolidinone derivatives on reaction with ketones. These derivatives are useful in pharmaceutical dosage forms and as intermediates for separation thereof from mixtures containing the [(E)-1-propenyl]isomer of the antibiotic.
    Type: Grant
    Filed: November 25, 1985
    Date of Patent: February 23, 1988
    Assignee: Bristol-Myers Company
    Inventors: Murray A. Kaplan, Michael W. Lovell, Joseph B. Bogardus
  • Patent number: 4708955
    Abstract: This invention provides novel cephalosporanic acids and esters thereof having the general formula ##STR1## wherein R.sup.2 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl or acyl, R.sup.3 is hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, andR.sup.4 is hydrogen, pivaloyloxymethyl, acetoxymethyl, 1-acetoxyethyl, 5-methyl-2-oxo-1, 3-dioxolen-4-ylmethyl or 4-glycyloxybenzoyloxymethyl. These compounds, especially esters, are useful as broad spectrum antibiotics in the treatment and prevention of infectious diseases of mammals, and for other purposes known in the art.
    Type: Grant
    Filed: June 24, 1985
    Date of Patent: November 24, 1987
    Assignee: Bristol-Myers Company
    Inventors: Seiji Iimura, Yoshio Abe, Jun Okumura, Takayuki Naito, Hajime Kamachi
  • Patent number: 4694079
    Abstract: 7-[(D)-2-Amino-2-(4-hydroxyphenyl)acetamido]-3-[(Z)-1-propenyl]ceph-3-em-4- carboxylic acid in the form of its crystalline dimethylformamide solvate (1/1.5) has been provided.
    Type: Grant
    Filed: July 29, 1985
    Date of Patent: September 15, 1987
    Assignee: Bristol-Myers Company
    Inventor: Leonard B. Crast, Jr.
  • Patent number: 4691023
    Abstract: The present invention refers to mitomycin analogs containing a disulfide group. These compounds are mitomycin C derivatives in which the 7-amino group bears an organic substituent incorporating a disulfide group. The compounds are inhibitors of experimental animal tumors.
    Type: Grant
    Filed: August 7, 1986
    Date of Patent: September 1, 1987
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Yulin Chiang, Terrence W. Doyle