Patents Represented by Attorney, Agent or Law Firm Aldo A. Algieri
  • Patent number: 5374739
    Abstract: The present invention provides novel mitomycin analogs containing a cyclic acetal or thioacetal group. These compounds are mitomycin C analogs in which the 7-amino group bears a 5-membered heterocyclic substituent. Mitomycin C is an antitumor agent of established utility, and the 7-N-substituted mitosane analogs thereof have similar utility.
    Type: Grant
    Filed: May 28, 1993
    Date of Patent: December 20, 1994
    Assignee: Bristol-Myers Squibb Company
    Inventors: Takushi Kaneko, Henry S. L. Wong, Terrence W. Doyle
  • Patent number: 5256548
    Abstract: There is provided a new antiviral antibiotic designated herein as BU-4344V which is produced by fermentation of a BU-4344V-producing strain of a new microorganism, Actinomadura parvosata subsp. kistnae ATCC No. 55076. Antibiotic BU-4344V is recovered and purified from the fermentation broth by use of extraction, chromatography, and crystallization techniques. BU-4344V has been found to have some antibacterial activity and inhibits the growth of viruses, including influenza virus type A.
    Type: Grant
    Filed: April 27, 1992
    Date of Patent: October 26, 1993
    Assignee: Bristol-Myers Squibb Company
    Inventors: Masahisa Oka, Koji Tomita, Osamu Tenmyo, Nobuaki Naruse
  • Patent number: 5244891
    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: May 22, 1992
    Date of Patent: September 14, 1993
    Assignee: Bristol-Myers Squibb Company
    Inventors: Murray A. Kaplan, Thomas W. Hudyma, Robert A. Lipper, Kun M. Shih, Susan D. Boettger
  • Patent number: 5218106
    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: March 26, 1992
    Date of Patent: June 8, 1993
    Assignee: Bristol-Myers Company
    Inventors: Roman Z. Sterzycki, Muzammil M. Mansuri, John C. Martin
  • Patent number: 5140101
    Abstract: There is provided a new antiviral antibiotic designated herein as BU-4344V which is produced by fermentation of a BU-4344V-producing strain of a new microorganism, Actinomadura parvosata subsp. kistnae ATCC No. 55076. Antibiotic BU-4344V is recovered and purified from the fermentation broth by use of extraction, chromatography, and crystallization techniques. BU-4344V has been found to have some antibacterial activity and inhibits the growth of viruses, including influenza virus type A.
    Type: Grant
    Filed: November 21, 1990
    Date of Patent: August 18, 1992
    Assignee: Bristol-Myers Squibb Company
    Inventors: Masahisa Oka, Koji Tomita, Osamu Tenmyo, Nobuaki Naruse
  • Patent number: 5126506
    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: September 13, 1990
    Date of Patent: June 30, 1992
    Assignee: Bristol-Myers Company
    Inventors: Roman Z. Sterzycki, Muzammil M. Mansuri, John C. Martin
  • Patent number: 5120862
    Abstract: There is provided a novel and efficient stereoselective total synthesis of epipodophyllotoxin and related epipodophyllotoxin compounds of the and present invention ##STR1## wherein R.sup.1 and R.sup.2 each are independently hydrogen or (lower)alkoxy, or R.sup.1 ll and R.sup.2, taken together, is methylenedioxy; R.sup.4 and R.sup.6 each are independently hydrogen or (lower)alkoxy; and R.sup.5 is hydrogen or a phenol-protecting group; or an acid addition salt thereof. The present ivnention also provides novel intermediates and processes for the preparation of said intermediates, which are then converted into known antineoplastic agents.
    Type: Grant
    Filed: October 4, 1991
    Date of Patent: June 9, 1992
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Paul M. Skonezny
  • Patent number: 5110940
    Abstract: Compounds of the formula ##STR1## wherein R.sup.1 and R.sup.4 each are independently hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, or trifluoromethyl;R.sup.2,R.sub.3,R.sup.5 and R.sup.6 each are independently hydrogen, halogen C.sub.1-4 alkyl or C.sub.1-4 alkoxy;tet is ##STR2## n is an integer of from 0 to 2, inclusive; A is ##STR3## R.sup.7 is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy(lower) alkyl or (2-methoxyethoxy)methyl;X is --OH or .dbd.O; andR.sup.8 is hydrogen, a hydrolyzable ester group or a cation to form a non-toxic pharmaceutically acceptable salt,are novel antihypercholesterolemic agents which inhibit cholesterol biosynthesis. Intermediates and processes for their preparation are disclosed.
    Type: Grant
    Filed: May 6, 1991
    Date of Patent: May 5, 1992
    Assignee: Bristol-Myers Company
    Inventors: Sing-Yuen Sit, John J. Wright
  • Patent number: 5106996
    Abstract: There are disclosed intermediates which can be converted into podophyllotoxin and related compounds, which are known antineoplastic agents. There are also disclosed processes for the preparation of such intermediates, and processes for the conversion of the intermediates into known intermediates which are readily converted into podophyllotoxin and related compounds.
    Type: Grant
    Filed: July 25, 1990
    Date of Patent: April 21, 1992
    Assignee: Bristol-Myers Company
    Inventors: Takushi Kaneko, Henry S. L. Wong
  • Patent number: 5099016
    Abstract: The present invention provides novel mitomycin analogs containing a disulfide group and processes for the preparation thereof. These compounds are mitomycin A analogs in which the 7-alkoxy group bears an organic substituent incorporating a disulfide group. Mitomycin A is an antibiotic of established utility, and the 7-O-substituted mitosane analogs thereof have similar utility.
    Type: Grant
    Filed: February 26, 1990
    Date of Patent: March 24, 1992
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Terrence W. Doyle, Richard A. Partyka
  • Patent number: 5097036
    Abstract: The present invention provides novel mitomycin analogs containing a disulfide group and processes for the preparation thereof. These compounds are mitomycin A analogs in which the 7-alkoxy group bears an organic substituent incorporating a disulfide group. Mitomycin A is an antibiotic of established utility, and the 7-O-substituted mitosane analogs thereof have similar utility.
    Type: Grant
    Filed: February 26, 1990
    Date of Patent: March 17, 1992
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Terrence W. Doyle, Richard A. Partyka
  • Patent number: 5095011
    Abstract: A stable, amorphous, lyophilized dihydrochloride salt of 7-[.alpha.-(2-aminothiazol-4-yl)-.alpha.-(z)-methoxyiminoacetamido]-3-[(1- methyl-1-pyrrolidinium) methyl]-3-cephem-4-carboxylate is described. This lyophilized salt is more easily prepared than the crystalline counterpart and can be reconstituted in effective concentrations for intramuscular and intravenous injection utilizing suitable organic and inorganic bases to pH 3-7.0.
    Type: Grant
    Filed: December 20, 1990
    Date of Patent: March 10, 1992
    Assignee: Bristol-Myers Company
    Inventors: Murray A. Kaplan, Munir N. Nassar
  • Patent number: 5086182
    Abstract: There is provided a novel and efficient stereoselective total synthesis of epiodophyllotoxin and related epipodophyllotoxin compounds of the general formula ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen or (lower)-alkoxy, or R.sup.1 and R.sup.2, taken together, is methylenedioxy; R.sup.4 and R.sup.6 each are independently hydrogen or (lower) alkoxy; and R.sup.5 is hydrogen or a phenol-protecting group; or an acid addition salt thereof. The present invention also provides novel intermediates and processes for the preparation of said intermediates, which are then converted into known antineoplastic agents.
    Type: Grant
    Filed: February 13, 1991
    Date of Patent: February 4, 1992
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Paul M. Skonezny
  • Patent number: 5071866
    Abstract: Compounds of the formula ##STR1## wherein R.sup.1 and R.sup.2 each are independently hydrogen or phenyl, provided that R.sup.1 and R.sup.2 may not both be hydrogen;m is an integer from 3 to 9;n is an integer from 0 to 3 and the sum ofm+n is an integer from 5 to 12;Z is O, S, SO, SO.sub.2, --CH.dbd.CH-- or a direct bond;A is ##STR2## R.sup.3 is hydrogen or C.sub.1-6 alkyl; and R.sup.4 is hydrogen, C.sub.1-4 alkyl or methylsulfonyl;and pharmaceutically acceptable salts or hydrates thereof are novel inhibitors of adenosine diphosphate and collagen-induced aggregation of human platelet-rich plasma and are particularly useful as inhibitors of mammalian blood platelet aggregation.
    Type: Grant
    Filed: December 10, 1990
    Date of Patent: December 10, 1991
    Assignee: Bristol-Myers Squibb Company
    Inventor: Nicholas A. Meanwell
  • Patent number: 5070206
    Abstract: Compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each are independently hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trifluoromethyl;R is hydrogen, C.sub.1-4 alkyl or phenyl;A is ##STR2## R.sup.5 is hydrogen, a hydrolyzable ester group or a cation to form a non-toxic pharmaceutically acceptable salt,are novel antihypercholesterolemic agents which inhibit cholesterol biosynthesis. Intermediates and processes for their preparation are disclosed.
    Type: Grant
    Filed: February 13, 1991
    Date of Patent: December 3, 1991
    Assignee: Bristol-Myers Company
    Inventors: Sing-Yuen Sit, John J. Wright
  • Patent number: 5068346
    Abstract: Compounds of the formula ##STR1## wherein R.sup.1 and R.sup.4 each are independently hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, or trifluoromethyl;R.sup.2, R.sup.3,R.sup.5 and R.sup.6 each are independently hydrogen, halogen C.sub.1-4 alkyl or C.sub.1-4 alkoxy;tet is ##STR2## n is an integer of from 0 to 2, inclusive; A is ##STR3## R.sup.7 is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy(lower) alkyl or (2-methoxyethoxy)methyl;X is --OH or .dbd.O; andR.sup.8 is hydrogen, a hydrolyzable ester group or a cation to form a non-toxic pharmaceutically acceptable salt,are novel antihypercholesterolemic agents which inhibit cholesterol biosynthesis. Intermediates and processes for their preparation are disclosed.
    Type: Grant
    Filed: November 17, 1989
    Date of Patent: November 26, 1991
    Assignee: Bristol-Myers Company
    Inventors: Sing-Yuen Sit, John J. Wright
  • Patent number: 5037819
    Abstract: The present invention relates to new 3-guanidinoalkyl-2-azetidinones of the formula ##STR1## wherein: U and W can be the same or different and are selected from the group consisting of hydrogen and an amino protecting group;n is 1 to 3;X is a member selected from the group consisting of hydrogen, trialkylsilyl, arylsulfonyl, amino substituted arylsulfonyl, alkylsulfonyl, arylaminocarbonyl, alkylcarbonyl and arylcarbonyl; andY is a member selected from the group consisting of hydrogen, arylalkenyl, arylalkyl, formyl, carboxy, alkoxycarbonyl, acyloxy, arylthio, arylsulfinyl, arylsulfonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, arylaminocarbonyl, the radical ##STR2## in which R is hydrogen, alkyl or arylalkyl, and the radical ##STR3## in which m is 1 to 3 and R' is hydrogen or --CO.sub.2 R" wherein R" is hydrogen, alkyl or arylalkyl.The novel azetidinones of the present invention exhibit anti-thrombin and anti-trypsin activities and are thus useful in controlling blood coagulation and treating pancreatitis.
    Type: Grant
    Filed: June 4, 1990
    Date of Patent: August 6, 1991
    Assignee: Bristol-Myers Squibb Company
    Inventor: William T. Han
  • Patent number: 5028730
    Abstract: Compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each are independently hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trifluoromethyl;A is ##STR2## and R.sup.5 is hydrogen, a hydrolyzable ester group or a cation to form a non-toxic pharmaceutically acceptable salt,are novel antihypercholesterolemic agents which inhibit cholesterol biosynthesis. Intermediates and processes for their preparation are disclosed.
    Type: Grant
    Filed: February 23, 1990
    Date of Patent: July 2, 1991
    Assignee: Bristol-Myers Company
    Inventors: Sing-Yuen Sit, John J. Wright
  • Patent number: 5013851
    Abstract: There are disclosed intermediates which can be converted into podophyllotoxin and related compounds, which are known antineoplastic agents. There are also disclosed processes for the preparation of such intermediates, and processes for the conversion of the intermediates into known intermediates which are readily converted into podophyllotoxin and related compounds.
    Type: Grant
    Filed: February 1, 1989
    Date of Patent: May 7, 1991
    Assignee: Bristol-Myers Company
    Inventors: Takushi Kaneko, Henry S. L. Wong
  • Patent number: 5011948
    Abstract: There is provided a novel and efficient stereoselective total synthesis of epipodophyllotoxin and related epipodophyllotoxin compounds of the general formula ##STR1## wherein R.sup.1 and R.sup.2 each are independently hydrogen or (lower)alkoxy, or R.sup.1 and R.sup.2, taken together, is methylenedioxy; R.sup.4 and R.sup.6 each are independently hydrogen or (lower)alkoxy; and R.sup.5 is hydrogen or a phenol-protecting group; or an acid addition salt thereof. The present invention also provides novel intermediates and processes for the preparation of said intermediates, which are then converted into known antineoplastic agents.
    Type: Grant
    Filed: July 14, 1989
    Date of Patent: April 30, 1991
    Assignee: Bristol-Myers Company
    Inventors: Dolatrai M. Vyas, Paul M. Skonezny