Patents Represented by Attorney, Agent or Law Firm William T. Han
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Patent number: 5175283Abstract: 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: GrantFiled: February 11, 1992Date of Patent: December 29, 1992Assignee: Bristol-Myers Squibb CompanyInventor: William T. Han
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Patent number: 5173486Abstract: This invention relates to a compound of formula I ##STR1## wherein p is 1 to 3;R.sup.1 and R.sup.2 each are independently hydrogen or an acyl group R.sup.6 CO--, in which R.sup.6 is C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-7 alkenyl, aryl or radical of the formula ##STR2## R.sup.3 is hydrogen or chloro; R.sup.4 and R.sup.5 each are independently C.sub.1-6 alkyl.Compounds of formula I are useful for the reversal of multidrug resistance of cancer drugs.Type: GrantFiled: August 26, 1991Date of Patent: December 22, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Ivo Monkovic, Lotte Wang
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Patent number: 5169843Abstract: A compound for 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.2-5 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: GrantFiled: December 23, 1991Date of Patent: December 8, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Thomas W. Hudyma, Richard A. Partyka
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Patent number: 5162521Abstract: This invention relates to a novel process for making a cephem of formula II from 2-(3-amino-2-oxo-azetidin-1-yl)-2,3-butadienoate of formula I. In another aspect, this invention is concerned with a process of further converting a compound of formula II into an antibacterial cephem of formula III. ##STR1## In formulae I, II and III, R.sup.1 is hydrogen, a conventional amino protecting group or an acyl group; R.sup.2 is an aromatic heterocyclic or aryl group; R.sup.3 is a conventional carboxy protecting group or --CO.sub.2 R.sup.3 taken together forms a physiologically hydrolyzable ester; and R.sup.4 is a group selected from the group consisting of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, cyclic C.sub.3-6 alkyl, and aryl; and n is 0 or 2.Type: GrantFiled: June 6, 1991Date of Patent: November 10, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Vittorio Farina, Stephen R. Baker
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Patent number: 5162524Abstract: This invention relates to a novel process for making a cephem of formula II from a 2-(3-amino-2-oxo-azetidin-1-yl)-2,3-butadienoate intermediate of formula I using an organo-copper reagent. In another aspect, this invention is concerned with said intermediate. ##STR1## In the compounds of Scheme (A), R.sup.1 is a conventional amino protecting group or an acyl group; R.sup.2 is an aromatic heterocyclic or aryl group; R.sup.3 is a conventional carboxy protecting group or --CO.sub.2 R.sup.3 taken together forms a physiologically hydrolyzable ester; and R.sup.4 is a group selected from the group consisting of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, cyclic C.sub.3-6 alkyl, and aryl; and n is 0 or 2.This invention also relates to an intermediate represented by formula ##STR2## in which R.sup.1, R.sup.2, R.sup.3 and n are as defined above.Type: GrantFiled: June 6, 1991Date of Patent: November 10, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Vittorio Farina, Joydeep Kant
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Patent number: 5143911Abstract: The present invention relates to new cephalosporins of the Formula ##STR1## wherein Y is N or CH;R.sup.1 is hydrogen, a straight, branched, or cyclic lower alkyl group having up to six carbon atoms or a radical of the formula ##STR2## in which R.sup.3 and R.sup.4 are each independently hydrogen, methyl, or ethyl, or R.sup.3 and R.sup.4 taken together with the carbon atom to which they are attached, may be a cycloalkylidene ring containing from 3 to 5 carbon atoms;R.sup.2 is a radical selected from the group consisting of ##STR3## in which R.sup.5 is hydrogen or acetyl. In another aspect, this invention relates to processes for the preparation of the compounds of Formula I, to pharmaceutical compositions containing at least one compound of Formula I, and to intermediates in their preparation.Type: GrantFiled: August 23, 1990Date of Patent: September 1, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Hajime Kamachi, Kiyoto Imae, Takaaki Okita
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Patent number: 5126336Abstract: This invention relates to novel cephalosporin derivatives of the formula ##STR1## wherein R.sup.1 is hydrogen, a straight, branched, or cyclic lower alkyl group having up to six carbon atoms or a radical of the formula ##STR2## in which R.sup.3 and R.sup.4 are each independently hydrogen, methyl or ethyl, or R.sup.3 and R.sup.4, taken together with the carbon atom to which they are attached, may be a cycloalkylidene ring containing from 3 to 5 carbon atoms;R.sup.2 is a radical selected from the group consisting of ##STR3## wherein R.sup.5 is hydrogen or acetyl; R.sup.6, R.sup.7 and R.sup.8 each are independently C.sub.1-5 alkyl; n is 1 or 2; and y is 1 to 5.In another aspect, this invention relates to compounds of formula I and their nontoxic pharmaeutically acceptable salts, physiologically hydrolyzable esters or solvates.Representative compounds of this invention were selected for testing and were shown to display potent antibacterial activity.Type: GrantFiled: August 23, 1990Date of Patent: June 30, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Kiyoto Imae, Hajime Kamachi, Shinji Masuyoshi, Seiji Iimura, Takayuki Naito
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Patent number: 5116845Abstract: 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: GrantFiled: May 4, 1990Date of Patent: May 26, 1992Assignee: Bristol-Myers CompanyInventors: Hiroaki Ohkuma, Masataka Konishi, Kiyoshi Matsumoto, Toshikazu Oki, Yutaka Hoshino
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Patent number: 5114920Abstract: New antibiotics designated BU-3292T A and B are provided which exhibit antimicrobial activity and also inhibit the growth of tumors in experimental animal systems. BU-3292T A is produced by fermentation of Elytrosporangium sp. nov. (ATCC 53784) while the BU-3292T B compound is obtained by oxidation of BU-3292T A.Type: GrantFiled: September 14, 1988Date of Patent: May 19, 1992Assignee: Bristol-Myers Squibb Co.Inventors: Koko Sugawara, Yuji Nishiyama, Koji Tomita, Masataka Konishi, Toshikazu Oki
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Patent number: 5106842Abstract: 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: GrantFiled: October 22, 1990Date of Patent: April 21, 1992Assignee: Bristol-Myers Squibb Co.Inventors: Thomas W. Hudyma, Richard A. Partyka
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Patent number: 5098904Abstract: A series of pyprimidinyl compounds of formulae I, II and III; ##STR1## wherein R.sup.1 and R.sup.2 are independently selected from hydrogen and hydroxy;R.sup.3 is selected from hydrogen, hydroxy, or oxo, with the proviso that R.sup.3 can only be oxo when R.sup.1 and R.sup.2 are hydrogen, and further that R.sup.1, R.sup.2, and R.sup.3 cannot all be hydrogen or hydroxy at the same time; andthe solid and dotted lines refer to either a double covalent bond or a single covalent bond with another hydrogen atom covalently bonded to the carbon terminus end.The compounds of this invention possess cognition and memory enhancing activity.Type: GrantFiled: June 27, 1990Date of Patent: March 24, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Ronald J. Mattson, Robert Mayol, Michael E. Brady
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Patent number: 5096884Abstract: Glidobactin PF-1 of the formula ##STR1## having antitumor activity is prepared by cultivation of Polyangium brachysporum in a nutient medium containing a suitable fatty acid ester, such linolenate, together with other assimilable sources of carbon and nitrogen.Type: GrantFiled: January 9, 1990Date of Patent: March 17, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Keiichi Numata, Masahisa Oka
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Patent number: 5087567Abstract: An antitumor antibiotic designated BMY-42428 is produced by fermentation of Actinomadura madurae ATCC-53806. The BMY-42428 antibiotic exhibits both antimicrobial and antitumor activities.Type: GrantFiled: January 12, 1990Date of Patent: February 11, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Thomas T. Dabrah, Grace A. Hesler, Sandra J. Hofstead, Kin S. Lam, Jacqueline M. Mattei, Daniel R. Schroeder, Koji Tomita
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Patent number: 5086045Abstract: An antitumor antibiotic designated BMY-41339 is produced by fermentation of certain strains of Actinomadura verrucosospora. BMY-41339 exhibits antimicrobial activity and also inhibits the growth of tumors in experimental animals.Type: GrantFiled: August 24, 1990Date of Patent: February 4, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Jerzy Golik, John Beutler, Pat Clark, John Ross, John Roach, Gary Muschik, William B. Lebherz, III
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Patent number: 5064831Abstract: Naphthothiophenimines of formula I ##STR1## wherein R.sup.1 is, inter alia, alkyl, cycloaklyl, alkenyl, phenalkyl or aminoalkyl.Formula I compounds are useful in treating brain ischemia and resulting disorders.Type: GrantFiled: September 14, 1990Date of Patent: November 12, 1991Assignee: Bristol-Myers Squibb Co.Inventor: Katherine S. Takaki
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Patent number: 5037819Abstract: 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: GrantFiled: June 4, 1990Date of Patent: August 6, 1991Assignee: Bristol-Myers Squibb CompanyInventor: William T. Han
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Patent number: 5011947Abstract: 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 C.sub.1-7 alkyl, C.sub.3-6 cycloalkyl, fluoromethyl, difluoromethyl, trifluoromethyl;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: GrantFiled: June 12, 1990Date of Patent: April 30, 1991Assignee: Bristol-MyersInventors: John D. Catt, John J. Wright
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Patent number: 4975462Abstract: Disclosed herein are novel .alpha.-arylcarbamoyl cyanoacetic esters, thioesters, and amides which exhibit anti-inflammatory/antiarthritic activities.Type: GrantFiled: July 29, 1988Date of Patent: December 4, 1990Assignee: Bristol-Myers CompanyInventor: William T. Han
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Patent number: 4956368Abstract: Various metabolites and prodrug formulations of 8-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-8-azaspiro[4.5]deca ne-7,9-dione which are particularly useful in the treatment of psychotic disorders, especially derivatives thereof which have been oxygenated at specified sites about the original structure, rearranged compounds, and prodrug formulations of these species. One particularly desired group of compounds have the general Formula I where ##STR1## R.sup.1 is hydrogen, hydroxyl, alkoxy, acyloxy and oxo; R.sup.2 is hydrogen, methyl, hydroxyl, alkoxy, and acyloxy;R.sup.3 is hydrogen, hydroxyl, and methoxy:R.sup.4 is hydrogen, methyl and oxo; andX is S, SO, and SO.sub.2.Type: GrantFiled: July 24, 1989Date of Patent: September 11, 1990Assignee: Bristol-Myers CompanyInventors: Joseph A. Cipollina, Edward H. Ruediger