Abstract: The present invention relates to the derivatives of the formula ##STR1## and to their use in therapeutics, especially as drugs with anti-inflammatory and analgesic properties.
Abstract: The present invention provides a stable, crystalline syn-isomer of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetyl chloride hydrochloride substantially free of the anti-isomer and a process for the preparation thereof which may be used in an acylation process for the preparation of useful broad-spectrum antibiotics.
Abstract: There is provided a novel series of O-carboxymethylated .alpha.- and .beta.-glycolipid compounds of the formula ##STR1## wherein R is an acyl residue of a fatty acid;R.sup.1 is --(CH.dbd.CH).sub.m --(CH.sub.2).sub.n --CH.sub.3 ;R.sup.2, R.sup.3, R.sup.4 R.sup.5 and R.sup.6 each are independently hydrogen, unsubstituted or substituted alkanoyl, arylalkyl or arylcarbonyl wherein said substituent is selected from halogen, C.sub.1-4 alkyl, trifluoromethyl, hydroxy and C.sub.1-4 alkoxy;R.sup.3, R.sup.4 and R.sup.6 each are independently --CH.sub.2 COOR.sup.7, provided at least two of the R.sup.3, R.sup.4 and R.sup.6 substituents are --CH.sub.2 COOR.sub.7 ;m is an integer of 0 or 1;n is an integer of from 5 to 14, inclusive; andR.sup.
Abstract: The present invention relates to the carbocyclic diarylmethylene derivatives of formula (I): ##STR1## and to their use in therapeutics, especially as drugs with anti-inflammatory and analgesic properties.
Type:
Grant
Filed:
October 7, 1996
Date of Patent:
November 11, 1997
Assignee:
Laboratoires UPSA
Inventors:
Eric Nicolai, Michele Launay, Dominique Potin, Jean-Marie Teulon
Abstract: Novel substituted carbazole compounds of Formula I are active as melatonergic agents: ##STR1## wherein: R.sub.1 is C(O)R.sub.3 or SO.sub.2 R.sub.4 ;R.sub.2 is H or C.sub.1-6 alkoxy;R.sub.3 is C.sub.1-6 alkyl, (CH.sub.2).sub.n SR.sub.4, (CH.sub.2).sub.n OR.sub.4, (CH.sub.2).sub.n SO.sub.2 R.sub.4, or NHR.sub.4 ;R.sub.4 is C.sub.1-4 alkyl; andm is 1 or 2; andn is 1 to 4.
Type:
Grant
Filed:
October 30, 1996
Date of Patent:
October 14, 1997
Assignee:
Bristol-Myers Squibb Company
Inventors:
Katherine S. Takaki, Marc A. Bruce, Graham S. Poindexter, Brett T. Watson, Joseph P. Yevich
Abstract: Compounds of the formula ##STR1## wherein A is an unsubstituted or hydroxy-substituted straight or branched C.sub.1-10 alkylene group or a straight or branched C.sub.1-10 alkylene group having an intervening heteroatom selected from oxygen, sulfur and nitrogen;R.sup.2 is hydroxy, halogen, C.sub.1-4 alkoxy, nitrile, azido, a quaternary ammonio group, --NR.sup.5 R.sup.6, ##STR2## azetidinyl, or a 5- or 6-membered heterocyclic group selected from heteroaromatic and heteroalicyclic joined through a carbon atom thereof;or a non-toxic pharmaceutically acceptable salt thereof, are novel antimicrobial agents which are useful in the treatment of infectious disease in humans and other animals. Novel intermediates and processes for their preparation are also disclosed.
Type:
Grant
Filed:
January 26, 1995
Date of Patent:
September 30, 1997
Assignee:
Bristol-Myers Squibb Company
Inventors:
Alain Martel, Carol Bachand, Marcel Menard
Abstract: There is provided novel sulfated .alpha.-glycolipid compounds of the formula ##STR1## wherein R is an acyl residue of a fatty acid;R.sup.1 is --(CH.dbd.CH).sub.m --(CH.sub.2).sub.n --CH.sub.3 ;R.sup.2, R.sup.3, R.sup.4and R.sup.6 are independently at least two --SO.sub.3 H;R.sup.2, R.sup.3, R.sup.4R.sup.5 and R.sup.6 each are independently hydrogen, unsubstituted or substituted alkanoyl, arylalkyl or arylcarbonyl wherein said substituent is selected from halogen, C.sub.1-4 alkyl, trifluoromethyl, hydroxy and C.sub.1-4 alkoxy;m is an integer of 0 or 1;n is an integer of from 5 to 14, inclusive;or a non-toxic pharmaceutically acceptable salt, solvate or hydrate thereof which are inhibitors of selectin-mediated cellular adhesion and are useful in the treatment or prevention of inflammatory diseases and other pathological conditions in mammals.
Type:
Grant
Filed:
January 27, 1995
Date of Patent:
September 2, 1997
Assignee:
Bristol-Myers Squibb Company
Inventors:
Alain Martel, Jacques Banville, Alejandro A. Aruffo
Abstract: New melatonergic agents are phenyl alkanyl or phenyl alkyl substituted carboxamides and ureas of Formula I: ##STR1## wherein: R.sub.1 =C.sub.1-3 alkyl, allyl, C.sub.3-6 cycloalkyl substituted C.sub.1-4 alkyl;R.sub.2 =hydrogen, halogen or C.sub.1-4 alkoxy;R.sub.3 =hydrogen or C.sub.1-4 alkyl;R.sub.4 =C.sub.1-4 alkyl, C.sub.1-4 alkyl substituted amino, carboxylic acid substitutedC.sub.1-4 alkyl or C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl, or straight or branched chainC.sub.2-4 alkenyl;A=a linear C.sub.2-4 alkanediyl or alkenediyl chain, provided that A not be --CH.sub.2 CH.sub.2 -- when X is a bond; andX=a covalent bond or oxygen.
Type:
Grant
Filed:
December 14, 1995
Date of Patent:
August 26, 1997
Assignee:
Bristol-Myers Squibb Co.
Inventors:
Katherine S. Takaki, George N. Karageorge, Daniel J. Keavy, Michael F. Parker, Brett T. Watson
Abstract: Certain aminomethyl-benzodioxanes and benzopyrans are useful serotonergic agents. They possess anxiolytic properties with few of the side effects often associated with dopaminergic agents.
Abstract: There is provided novel substituted 3-phenyl oxindole derivatives of the formula ##STR1## whereinR is hydrogen, hydroxy or fluoro;R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each are independently hydrogen, C.sub.1-4 alkyl, halogen, trifluoromethyl, phenyl, p-methylphenyl or p-trifluoromethylphenyl; or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 are joined together to form a benzo fused ring;R.sup.5 is hydrogen or C.sub.1-4 alkyl; andR.sup.6 is chlorine or trifluoromethyl; or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof, which are openers of the large-conductance calcium-activated potassium channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels.
Type:
Grant
Filed:
April 19, 1996
Date of Patent:
February 11, 1997
Assignee:
Bristol-Myers Squibb Company
Inventors:
Piyasena Hewawasam, Nicholas A. Meanwell, Valentin K. Gribkoff
Abstract: The present invention provides an anhydrous acylation process for the preparation of antibiotic, cefepime dihydrochloride hydrate which is substantially free of the anti-isomer and the .DELTA..sup.2 isomer comprising the N-acylation of a silylated derivative of 7-amino-3-[(1-methyl-1-pyrrolidinio)-methyl]ceph-3-em-4-carboxylate with the syn-isomer of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetyl chloride hydrochloride.
Type:
Grant
Filed:
December 19, 1994
Date of Patent:
January 14, 1997
Assignee:
Bristol-Myers Squibb Company
Inventors:
Gary M. F. Lim, John M. Roubie, Elizabeth A. Garofalo
Abstract: The present invention provides a process for the preparation of stable, crystalline cephalosporin intermediates of the formula ##STR1## wherein X is HI, HCl or H.sub.2 SO.sub.4 which are substantially free of the .DELTA..sup.2 isomer, and which are convertible into broad-spectrum cephalosporin antibiotics.
Abstract: The present invention provides an aqueous acylation process for the preparation of antibiotic, cefepime dihydrochloride hydrate which is substantially free of the anti-isomer and the .DELTA..sup.2 isomer comprising the N-acylation of 7-amino-3-[(1-methyl-1-pyrrolidinio)-methyl]ceph-3-em-4-carboxylate with the syn-isomer of 2-(2-aminothiazol-4-yl)-2-methoxyimino acetyl chloride hydrochloride.
Abstract: There is provided novel sulfated p-glycolipid compounds of the formula ##STR1## wherein R is an acyl residue of a fatty acid;R.sup.1 is --(CH.dbd.CH).sub.m --(CH.sub.2).sub.n --CH.sub.3 ;R.sup.2, R.sup.3, R.sup.4 and R.sup.6 each are independently --SO.sub.3 H, hydrogen, unsubstituted or substituted alkanoyl, arylalkyl or arylcarbonyl wherein said substituent is selected from the group consisting of halogen, C.sub.1-4 alkyl, trifluoromethyl, hydroxy and C.sub.1-4 alkoxy; or R.sub.4 and R.sub.6, taken together are isopropylidene; provided at least two of R.sup.2, R.sup.3, R.sup.4 and R.sup.6 are --SO.sub.3 H;R.sup.5 is hydrogen, unsubstituted or substituted alkanoyl, arylalkyl or arylcarbonyl wherein said substituent is selected from the group consisting of halogen, C.sub.1-4 alkyl, trifluoromethyl, hydroxy and C.sub.
Type:
Grant
Filed:
February 12, 1996
Date of Patent:
October 15, 1996
Assignee:
Bristol-Myers Squibb Company
Inventors:
Jacques Banville, Alain Martel, Alejandro A. Aruffo
Abstract: There is provided novel substituted 3-phenyl oxindole derivatives of the formula ##STR1## wherein R is hydrogen, hydroxy or fluoro; R.sup.1, R.sup.2, R.sup.3and R.sup.4 each are independently hydrogen, C.sub.1-4 alkyl, halogen, trifluoromethyl, phenyl, p-methylphenyl or p-trifluoromethylphenyl; or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 are joined together to form a benzo fused ring;R.sup.5 is hydrogen or C.sub.1-4 alkyl; andR.sup.6 is chlorine or trifluoromethyl;or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof, which are openers of the large-conductance calcium-activated potassium channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
October 15, 1996
Assignee:
Bristol-Myers Squibb Company
Inventors:
Piyasena Hewawasam, Nicholas A. Meanwell, Valentin K. Gribkoff
Abstract: A novel antibiotic complex designated BU-4224V produced by fermentation of Kibdelosporangium albatum sp. nov. Strain R761-7. The complex may be separated chromatographically into bioactive components designated BU-4224V A, B.sub.1, B.sub.2, and C. The components BU-4224V B.sub.1 and B.sub.2 display both antiviral and antimicrobial activity, while component BU-4224V A has antimicrobial activity and component BU-4224V C has antiviral activity.
Type:
Grant
Filed:
July 20, 1993
Date of Patent:
November 14, 1995
Assignee:
Bristol-Myers Squibb Co.
Inventors:
Mitsuaki Tsunakawa, Tetsuro Yamasaki, Koji Tomita, Osamu Tenmyo
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:
June 15, 1993
Date of Patent:
May 30, 1995
Assignee:
Bristol-Myers Squibb Co
Inventors:
Stephen R. Baker, Chester Sapino, Jr., Gregory P. Roth
Abstract: The present invention provides physical admixtures of a new crystalline dihydrochloride dihydrate salt of the cephalosporin antibiotic, cefepime with a pharmaceutically acceptable non-toxic organic or inorganic base. In particular, this invention provides physical admixtures having a temperature and moisture stable crystalline dihydrochloride dihydrate form of cefepime having a specific X-ray powder diffraction pattern as described herein.
Abstract: The present invention relates to a new crystalline dihydrochloride dihydrate salt of the cephalosporin antibiotic, cefepime. In particular, this invention provides a temperature and moisture stable crystalline dihydrochloride dihydrate form of cefepime having enhanced stability and a specific x-ray powder diffraction pattern as described herein.
Type:
Grant
Filed:
May 28, 1993
Date of Patent:
February 21, 1995
Assignee:
Bristol-Myers Squibb Company
Inventors:
Elizabeth A. Garofalo, Gary M. F. Lim, Murray A. Kaplan