Abstract: 3-Exomethylenecepham sulfoxide esters are obtained in improved yields via cyclization of 3-methyl-2-(4-chlorosulfinyl-2-oxo-3-amino-1-azetidinyl)-3-butenoic acid esters under anhydrous conditions with a Lewis acid-type Friedel-Crafts catalyst in the presence of a nitro compound, e.g., nitromethane, nitroethane, nitropropane or nitrobenzene.
Type:
Grant
Filed:
January 4, 1991
Date of Patent:
June 30, 1992
Assignee:
Eli Lilly and Company
Inventors:
Frank Brown, Jr., Francis O. Ginah, Leonard L. Winneroski, Jr.
Abstract: Disclosed herein is an improved apparatus for conducting immunoassays. The apparatus comprises a container, and a test zone to which is bound an antibody, typically a monoclonal antibody, or which is capable of extracting cells from a fluid sample. The test zone may be a membrane, filter or a porous matrix in which microspheres to which are bound antibody are entrapped. The apparatus further comprises a liquid absorbing zone which is composed of absorbent material which acts when in contact with the test zone to induce flow through the test zone when a fluid sample is added to it. At least one port in communication with the liquid absorbing zone and the opening of the container is provided to allow gas displaced by the addition of fluid to be discharged from the container. The flow of the displaced gas being in a direction opposite to the flow of assay reagents through the liquid absorbing zone.
Type:
Grant
Filed:
July 12, 1989
Date of Patent:
June 9, 1992
Assignee:
Hybritech Incorporated
Inventors:
Virginia Petro-Roy, Kim D. Blickenstaff
Abstract: This invention provides certain N-[(phenyl)amino]carbonyl-bicyclicsulfonamide sulfonamide derivatives, their pharmaceutical formulations, and their use in the treatment of susceptible neoplasms in mammals.
Abstract: Pharmaceutical compositions containing pergolide or a salt thereof stabilized to oxidation by incorporation therewith of a stabilizing agent selected from methionine, cysteine, and cysteine hydrochloride.
Type:
Grant
Filed:
October 19, 1989
Date of Patent:
May 19, 1992
Assignee:
Eli Lilly and Company
Inventors:
James W. Conine, Denis L. Sparks, Julian L. Stowers
Abstract: This invention provides orally administerable pharmaceutical formulations having a semi-solid matrix containing a hydrophilic substance capable of creating channels in a hydrophobic carrier matrix thereby providing a sustained rate of release of an active agent from the formulation.
Abstract: This invention provides the use of certain benzenesulfonamide derivatives in the treatment of susceptible neoplasms in mammals. Also provided are certain novel benzenesulfonamide derivatives and their pharmaceutical formulations.
Type:
Grant
Filed:
September 13, 1990
Date of Patent:
May 5, 1992
Assignee:
Eli Lilly and Company
Inventors:
Richard W. Harper, Gerald A. Poore, Brent J. Rieder
Abstract: Three new groups of 9-N-substituted derivatives of erythromycylamine with superior oral activity against Gram-positive pathogens, new processes for preparing derivatives of erythromycylamine and aliphatic aldehydes by controlling the pH of the reaction and by catalytic hydrogenation, and pharmaceutical compositions and methods using the new compounds are provided.
Type:
Grant
Filed:
August 18, 1989
Date of Patent:
May 5, 1992
Assignee:
Eli Lilly and Company
Inventors:
Rosanne Bonjouklian, Manuel Debono, Herbert A. Kirst, Julie A. Wind
Abstract: A biocompatible thin film electrical component is configured for use in a human body or other ionic liquid environment. A polyimide substrate is bonded to a glass carrier plate sized for handling by automatic equipment and a multiple-layer metal conductor is deposited on the substrate and patterned to define an electrical circuit or biosensor. The polyimide and the glass establish a bond therebetween that withstands handling yet is know using biocompatible releasing agents and techniques. The polyimide substrate and glass carrier plate preferably have similar thermal expansion properties to reduce the likelihood of fracture and delamination problems during release of the substrate from the carrier plate. An insulation layer covers the metal conductor and, in one embodiment, is made of polyimide having a cure temperature lower than the temperature at which interediffusion occurrs in the metal layers in the conductor.
Type:
Grant
Filed:
February 14, 1990
Date of Patent:
April 28, 1992
Assignee:
Eli Lilly and Company
Inventors:
James W. Heller, David Lipson, Kirk W. Johnson
Abstract: Novel 12-membered lactone and 11-membered lactone derivatives of erythromycin, having antimicrobial activity against certain Gram-positive pathogens such as Steptococcus pyogenes and Gram-negative cocci such as Haemophilus influenzae, and useful as intermediates to other macrolide derivatives, are disclosed.
Abstract: A process for preparing 3-4-cis-.beta.,.beta.-(4)-substituted and 3-4-trans,.beta.,.alpha.-(4)-substituted azetidinones is provided. Also provided are novel 4,4-disubstituted azetidinones.
Type:
Grant
Filed:
October 16, 1990
Date of Patent:
April 21, 1992
Assignee:
Eli Lilly and Company
Inventors:
John M. Morin, Jr., Robert J. Ternansky, David A. Hall
Abstract: 1-Carbapenam-2-one-3-carboxylic acid and 1-carba-3-hydroxy-3-cephem-4-carboxylic acid and esters thereof are provided by a process comprising a rhodium C.sub.2 -C.sub.10 carboxylate catalyzed cyclization of an ester of a 4-(1-alkoxy- or 1-substituted alkoxy)-2-oxo-4-azetidinyl)-.beta.-ketobutyric acid and an ester of a 5-(1-alkoxy- or 1-substituted alkoxy-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketovaleric acid respectively. The process is carried out in an inert organic solvent at a temperature between about 15.degree. C. and about 85.degree. C. The 1-carba bicyclic .beta.-lactams are intermediates for preparing antibiotics.
Type:
Grant
Filed:
July 22, 1991
Date of Patent:
April 21, 1992
Assignee:
University of Notre Dame du Lac College of Science
Abstract: This invention provides novel benzene derivatives which are leukotriene antagonists, formulations of those derivatives, intermediates for preparing the derivatives, and a method of using those derivatives for the treatment of conditions characterized by an excessive release of leukotrienes.
Abstract: Spiramycin antibiotic biosynthetic genes of Streptomyces ambofaciens are provided by the present invention, in addition to a variety of recombinant DNA vectors. The genes also function in other macrolide producing organisms. The genes can be used to increase or otherwise alter the macrolide antibiotic-producing ability of an organism. The present invention also provides host strains comprising mutant spiramycin biosynthetic genes which can be used to generate novel antibiotics. Also provided is a method for preparing the mutant gene comprising mutating cloned spiramycin biosynthetic DNA by transposon mutagenesis with subsequent transformation into a macrolide-antibiotic producing host and homologous recombination into its genome, to generate stable mutant cell lines.
Type:
Grant
Filed:
June 7, 1988
Date of Patent:
March 24, 1992
Assignee:
Eli Lilly and Company
Inventors:
Robert J. Beckmann, Karen L. Cox, R. Nagaraja Rao, Mark A. Richardson, Eugene T. Seno
Abstract: 7-.beta.-Acylamino-1-carba-(1-dethia)-3-trifluoromethyl-3-cephem-4-carboxyl ic acids and derivatives are provided as antibiotics. Pharmaceutical formulations comprising the antibiotics, intermediates, and a process for their preparation are also provided.
Type:
Grant
Filed:
January 10, 1991
Date of Patent:
March 24, 1992
Assignee:
Eli Lilly and Company
Inventors:
Gwendolyn K. Cook, William J. Hornback, John H. McDonald, John E. Munroe
Abstract: New Polyether antibiotic A82810, its acyl and alkyl ester, acyl ester and urethane derivatives, and salts thereof, are useful antibacterial and anticoccidial agents and increase feed-utilization efficiency in animals. Methods of making A82810 by culture of Actinomodura fibrosa sp. nov. NRRL 18348 and synergistic compositions of the A82810 compounds with nicarbazin, 4,4'-dinitrocarbanilide, certain napthalenamine and benzenamine compounds and metichlorpindol are also provided.
Abstract: This invention provides benzene derivatives, pharmaceutical formulations of those derivatives, and a method of using the derivatives for the treatment of inflammation in mammals.
Type:
Grant
Filed:
July 11, 1990
Date of Patent:
March 24, 1992
Assignee:
Eli Lilly and Company
Inventors:
Nancy G. Bollinger, Theodore Goodson, Jr., David K. Herron
Abstract: The present invention provides a method of inhibiting gastric acid secretion in mammals by administering a 5-HT1A agonist compound or a pharmaceutically acceptable salt thereof.
Abstract: Chiral epoxybutyrates are prepared in high yield from novel dihydro-3R-substituted sulfonyloxy-4R-hydroxy-2-(3H)furanones via based catalyzed alcoholysis. The product chiral epoxy butyrates are useful intermediates for the synthesis of 1-carba-1-dethia cephem antibiotics.