Patents Represented by Attorney David M. Morse
  • Patent number: 5760084
    Abstract: Retinoid-like activity is exhibited by compounds of the formula ##STR1## wherein X is F, Cl, OH or CH.sub.3, Y is H or F, R.sub.1 -R.sub.6 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl, n is an integer of 1 to 4 and R.sub.7 is hydrogen or a carboxyl-protecting group, and pharmaceutically acceptable salts thereof. The compounds of the formula I selectively interact with the retinoic acid subtype RAR.gamma. and have been found to lack the liver toxicity associated with systemic administration of non-relative retinoids.
    Type: Grant
    Filed: October 4, 1996
    Date of Patent: June 2, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: R. Thomas Swann, Daniel Smith, Kenneth M. Tramposch, Fred Christopher Zusi
  • Patent number: 5736578
    Abstract: Novel substituted fluorene compunds of Formula I are active as melatonergic agents: ##STR1## wherein: X=H, halogen, OH or OZ;Z=C.sub.1-6 alkyl; --(CH.sub.2).sub.m --CF.sub.3 (m=0-2); CD.sub.3 ; or ##STR2## n=1 or 2; and R=C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.2-4 alkenyl, halogen substituted C.sub.1-6 alkyl, or C.sub.1-6 alkoxy substituted C.sub.1-6 alkyl.
    Type: Grant
    Filed: May 10, 1996
    Date of Patent: April 7, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: Brett T. Watson, Katherine S. Takaki, Joseph P. Yevich, James R. Epperson, George N. Karageorge, Karen L. Leboulluec
  • Patent number: 5734047
    Abstract: Novel cephem derivatives represented by the general formula ##STR1## wherein Ar is an optionally substituted lipophilic phenyl, naphthyl, benzthiazolyl or pyridyl group; R.sup.1 represents a group of the formula ##STR2## in which R.sup.8 and R.sup.9 are each independently hydrogen, C.sub.1 -C.sub.6 alkyl or (C.sub.1 -C.sub.6)alkoxycarbonyl, said C.sub.1 -C.sub.6 alkyl group being optionally substituted by 1-5 hydroxy or C.sub.1 -C.sub.6 alkoxy groups; m is either 0 or 1; A is a C.sub.2 -C.sub.10 alkyl group optionally substituted by 1-5 hydroxy groups; and R.sup.2 and R.sup.3 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl. The derivatives are gram-positive antibacterial agents especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus.
    Type: Grant
    Filed: December 5, 1996
    Date of Patent: March 31, 1998
    Assignee: Bristol-Myers Squibb Company
    Inventors: Choung U. Kim, Muzammil M. Mansuri, Peter F. Misco, John A. Wichtowski
  • Patent number: 5668290
    Abstract: Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## wherein Ar is a lipophilic optionally substituted phenyl, naphthyl or pyridyl group; R.sup.1 represents either the residue of a heterocyclic amino acid or a C.sub.2 -C.sub.10 alkyl group substituted by both a carboxyl group and a group of the formula --NR.sup.9 R.sup.10 or ##STR3## in which R.sup.9 and R.sup.10 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl, said C.sub.2 -C.sub.10 alkyl group being optionally interrupted by one or more nitrogen atoms or carbonyl groups, and R.sup.2 and R.sup.3 are each independently hydrogen, alkyl or aminoalkyl are gram-positive antibacterial agents, especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus (also referred to below as MRSA or methicillin-resistant S. aureus).
    Type: Grant
    Filed: August 23, 1996
    Date of Patent: September 16, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: Joanne J. Bronson, Stanley V. D'Andrea, Shelley E. Hoeft, John D. Matiskella, Peter F. Misco, Jr., Bing Yu Luh, Dane M. Springer, Yasutsugu Ueda, John A. Wichtowski
  • Patent number: 5668284
    Abstract: Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## wherein Ar is a lipophilic optionally substituted phenyl, naphthyl, pyridyl or benzthiazolyl group; R.sup.1 is selected from certain optionally substituted aliphatic, aromatic, arylaliphatic or sugar moieties and R.sup.2 and R.sup.3 are each independently hydrogen, alkyl or aminoalkylcarbonylamino are gram-positive antibacterial agents, especially useful in the treatment of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA).
    Type: Grant
    Filed: May 8, 1996
    Date of Patent: September 16, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: Choung U. Kim, Peter F. Misco, Jr., John A. Wichtowski, Yasutsugu Ueda, Thomas W. Hudyma, John D. Matiskella, Stanley V. D'Andrea, Shelley E. Hoeft, Raymond F. Miller, Muzammil M. Mansuri, Joanne J. Bronson
  • Patent number: 5648385
    Abstract: The present invention relates to a compound of formula ##STR1## or a nontoxic pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof, in whichX is --O--CO--, --NH--CO--, --CS--NH--, --CO--O--, --CO--NH--, --COS--, --SCO--, --SCH.sub.2 --, --CH.sub.2 --CH.sub.2 --, --C.tbd.C--, --CH.sub.2 --NH--, --COCH.sub.2 --, --NHCS--, --CH.sub.2 S--, --CH.sub.2 O--, --OCH.sub.2 --, --NHCH.sub.2 -- or --CR.sup.5 .dbd.CR.sup.6 --;R.sup.m and R.sup.k are independently hydrogen, halogen, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy or nitro;n is zero or one;R.sup.4 is --(CH.sub.2).sub.t --Y, C.sub.1-6 alkyl, or C.sub.3-6 cycloalkyl;R.sup.1 is --CO.sub.2 Z, C.sub.1-6 alkyl, CH.sub.2 OH, --CONHR.sup.y, or CHO;R.sup.2 and R.sup.3 are independently hydrogen or C.sub.1-6 alkyl;R.sup.a and R.sup.b are independently hydrogen or C.sub.1-6 alkyl; but when n is one, R.sup.a and R.sup.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: July 15, 1997
    Assignee: Bristol-Myers Squibb Co.
    Inventors: John E. Starrett, Jr., Kuo-Long Yu, Muzammil M. Mansuri, David R. Tortolani, Peter R. Reczek
  • Patent number: 5637694
    Abstract: This invention relates to a method of producing 3-alkanoyloxymethyl-3-cephem-4-carboxylic acids from 3-hydroxymethyl-3-cephem-4-carboxylic acids in an aqueous medium for a practical, large-scale production. Moreover, the invention provides an ideal intermediate for the process.
    Type: Grant
    Filed: April 5, 1996
    Date of Patent: June 10, 1997
    Assignee: Briston-Myers Squibb Company
    Inventors: J. Gregory Reid, Paul R. Brodfuehrer, Patrick R. Smith
  • Patent number: 5624957
    Abstract: Retinoid-like activity is exhibited by compounds of the formula ##STR1## wherein X is F, Cl, OH or CH.sub.3, Y is H or F, R.sub.1 -R.sub.6 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl, n is an integer of 1 to 4 and R.sub.7 is hydrogen or a carboxyl-protecting group, and pharmaceutically acceptable salts thereof. The compounds of formula I selectively interact with the retinoic acid subtype RAR.gamma. and have been found to lack the liver toxicity associated with systemic administration of non-selective retinoids.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: April 29, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: R. Thomas Swann, Daniel Smith, Kenneth M. Tramposch, Fred C. Zusi
  • Patent number: 5620969
    Abstract: Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## wherein Ar is a lipophilic optionally substituted phenyl, naphthyl or pyridyl group; R.sup.1 represents either the residue of a heterocyclic amino acid or a C.sub.2 -C.sub.10 alkyl group substituted by both a carboxyl group and a group of the formula --NR.sup.9 R.sup.10 or ##STR3## in which R.sup.9 and R.sup.10 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl, said C.sub.2 -C.sub.10 alkyl group being optionally interrupted by one or more nitrogen atoms or carbonyl groups, and R.sup.2 and R.sup.3 are each independently hydrogen, alkyl or aminoalkyl are gram-positive antibacterial agents, especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus (also referred to below as MRSA or methicillin-resistant S. aureus).
    Type: Grant
    Filed: April 25, 1995
    Date of Patent: April 15, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: Joanne J. Bronson, Stanley V. D'Andrea, Shelley E. Hoeft, John D. Matiskella, Peter F. Misco, Jr., Bing Y. Luh, Dane M. Springer, Yasutsugu Ueda, John A. Wichtowski
  • Patent number: 5618839
    Abstract: The present invention relates to a compound of formula I ##STR1## or a nontoxic pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof, in whichX is --O--CO--, --NH--CO--, --CS--NH--, --CO--O--, --CO--NH--, --COS--, --SCO--, --SCH.sub.2 --, --CH.sub.2 --CH.sub.2 --, --C.tbd.C--, --CH.sub.2 --NH--, --COCH.sub.2 --, --NHCS--, --CH.sub.2 S--, --CH.sub.2 O--, --OCH.sub.2 --, --NHCH.sub.2 -- or --CR.sup.5 .dbd.CR.sup.6 --;R.sup.m and R.sup.k are independently hydrogen, halogen, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy or nitro;n is zero or one;R.sup.4 is --(CH.sub.2).sub.t --Y, C.sub.1-6 alkyl, or C.sub.3-6 cycloalkyl;R.sup.1 is --CO.sub.2 Z, C.sub.1-6 alkyl, CH.sub.2 OH, --CONHR.sup.y, or CHO;R.sup.2 and R.sup.3 are independently hydrogen or C.sub.1-6 alkyl;R.sup.a and R.sup.b are independently hydrogen or C.sub.1-6 alkyl; but when n is one, R.sup.a and R.sup.
    Type: Grant
    Filed: May 2, 1996
    Date of Patent: April 8, 1997
    Assignee: Bristol-Myers Squibb Company
    Inventors: John E. Starrett, Jr., Kuo-Long Yu, Muzammil M. Mansuri, David R. Tortolani, Peter R. Reczek
  • Patent number: 5567698
    Abstract: Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## wherein Ar is a lipophilic optionally substituted phenyl, naphthyl, pyridyl or benzthiazolyl group; R.sup.1 is selected from certain optionally substituted aliphatic, aromatic, arylaliphatic or sugar moieties and R.sup.2 and R.sup.3 are each independently hydrogen, alkyl or aminoalkylcarbonylamino are gram-positive antibacterial agents, especially useful in the treatment of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA).
    Type: Grant
    Filed: May 30, 1995
    Date of Patent: October 22, 1996
    Assignee: Bristol-Myers Squibb Company
    Inventors: Choung U. Kim, Peter F. Misco, Jr., John A. Wichtowski, Yasutsugu Ueda, Thomas W. Hudyma, John D. Matiskella, Stanley V. D'Andrea, Shelley E. Hoeft, Raymond F. Miller, Muzammil M. Mansuri, Joanne J. Bronson
  • Patent number: 5559248
    Abstract: This invention relates to a compound of formula I ##STR1## in which T is --CONH-- or --CH.dbd.CH--;R.sup.a and R.sup.b are independently C.sub.1-6 alkyl;R.sup.c is C.sub.1-6 alkyl or hydrogen; andR is heteroaryl and these compounds are useful in preventing and treating skin disorders.
    Type: Grant
    Filed: April 5, 1995
    Date of Patent: September 24, 1996
    Assignee: Bristol-Myers Squibb Co.
    Inventors: John E. Starrett, Jr., David R. Tortolani, Muzammil M. Mansuri, Nicholas A. Meanwell
  • Patent number: 5559108
    Abstract: Novel cephem derivatives represented by the general formula ##STR1## in which the Acyl substituent is a group of the formula ##STR2## where Ar is a substituted phenyl or optionally substituted naphthyl or benzthiazolyl group and A is a substituted-pyridinium group are gram-positive antibiotics, especially useful in the treatment of diseases caused by methicillin-resistant Staphylococcus aureus.
    Type: Grant
    Filed: May 22, 1995
    Date of Patent: September 24, 1996
    Assignee: Bristol-Myers Squibb Company
    Inventors: Choung U. Kim, Muzammil M. Mansuri, Peter F. Misco, Jr., John A. Wichtowski, Joanne J. Bronson, Stanley V. D'Andrea, Thomas W. Hudyma
  • Patent number: 5552542
    Abstract: This invention relates to a method of producing 3-alkanoyloxymethyl-3-cephem-4-carboxylic acids from 3-hydroxymethyl-3-cephem-4-carboxylic acids in an aqueous medium for a practical, large-scale production. Moreover, the invention provides an ideal intermediate for the process.
    Type: Grant
    Filed: May 10, 1995
    Date of Patent: September 3, 1996
    Assignee: Bristol-Myers Squibb Company
    Inventors: J. Gregory Reid, Paul R. Brodfuehrer, Patrick R. Smith
  • Patent number: 5162330
    Abstract: The novel antitumor antibiotic designated herein as dynemicin C is produced by fermentation of Micromonospora chersina M956-1 mutant F1085 (ATCC-55077). Dynemicin C and its triacetate derivative possess antibacterial and antifungal activity and also inhibit the growth of mammalian tumors.
    Type: Grant
    Filed: November 5, 1990
    Date of Patent: November 10, 1992
    Assignee: Bristol-Myers Squibb Co.
    Inventors: Kyoichiro Saitoh, Takeo Miyaki, Haruaki Yamamoto, Nahomi Oda
  • Patent number: 5143906
    Abstract: Kedarcidin chromophore, a non-protein chromophore isolated from kedarcidin antitumor antibiotic, is obtained from purified or partially purified kedarcidin by solvent extraction and chromatographic procedures. The chromophore is characterized and found to contain substantially all of the antitumor activity of kedarcidin.
    Type: Grant
    Filed: September 26, 1991
    Date of Patent: September 1, 1992
    Assignee: Bristol-Myers Squibb Company
    Inventor: John E. Leet
  • Patent number: 5124150
    Abstract: Production of an antiviral antibiotic complex, BU-3889V and its bioactive components A.sub.1, A.sub.2, A.sub.3, D.sub.1, D.sub.2 and D.sub.3, by fermentation of a BU-3889V producing strain of the new microorganism Amycolatopsis orientalis ATCC-53884 is disclosed. Complex BU-3889V is recovered and the components separated by the use of ion exchange chromatography techniques. The bioactive components are characterized by their physico-chemical characterizing properties. The products have been found to be effective to inhibit viruses including herpes simplex virus, human immunodeficiency virus (HIV) and influenza virus.
    Type: Grant
    Filed: March 11, 1991
    Date of Patent: June 23, 1992
    Assignee: Bristol-Myers Squibb Co.
    Inventors: Masataka Konishi, Mitsuaki Tsunakawa, Osamu Tenmyo, Takeo Miyaki, Toshikazu Oki
  • Patent number: 5116845
    Abstract: The novel antitumor antibiotic designated herein as BU-3420T is produced by fermentation of Micromonospora chersina strain M956-1 (ATCC 53710). BU-3420T and its triacetate derivative possess antibacterial and antifungal activity and also inhibit the growth of mammalian tumors such as P388 leukemia in mice.
    Type: Grant
    Filed: May 4, 1990
    Date of Patent: May 26, 1992
    Assignee: Bristol-Myers Company
    Inventors: Hiroaki Ohkuma, Masataka Konishi, Kiyoshi Matsumoto, Toshikazu Oki, Yutaka Hoshino
  • Patent number: 5098708
    Abstract: Production of an antiviral antibiotic complex, BU-3889V and its bioactive components A.sub.1, A.sub.2, A.sub.3, D.sub.1, D.sub.2 and D.sub.3, by fermentation of a BU-3889V producing strain of the new microorganism Amycolatopsis orientalis ATCC-53884 is disclosed. Complex BU-3889V is recovered and the components separated by the use of ion exchange chromatography techniques. The bioactive components are characterized by their physico-chemical characterizing properties. The products have been found to be effective to inhibit viruses including herpes simplex virus, human immunodeficiency virus (HIV) and influenza virus.
    Type: Grant
    Filed: July 6, 1990
    Date of Patent: March 24, 1992
    Assignee: Bristol-Myers Squibb Company
    Inventors: Masataka Konishi, Mitsuaki Tsunakawa, Osamu Tenmyo, Takeo Miyaki, Toshikazu Oki
  • Patent number: H1649
    Abstract: Combinations of certain HIV-1 protease inhibitors are provided which effectively inhibit the HIV-1 protease enzyme while eliminating or substantially reducing the viral cross-resistance seen with use of individual HIV-1 protease inhibitors. Such combinations are useful in the treatment of diseases associated with the AIDS virus.
    Type: Grant
    Filed: May 17, 1995
    Date of Patent: May 6, 1997
    Inventors: Joel C. Barrish, Richard J. Colonno, Pin-Fang M. Lin