Merck + Co., Inc.

Ucb S.a.

California Institute of Technology

University of Virginia Patent Foundation

Merck Sharp & Dohme-chibret

Merck & Co., Inc. & Laboratories

Tsung-Ying Shen

Howard Jones

Conrad P Dorn

Arthur F Wagner

Mitree M Ponpipom

Philippe L Durette

Robert L Bugianesi

Tesfaye Biftu

Bruce E Witzel

Nathaniel Grier

Arsenio A Pessolano

Robert L Clark

Thomas R Beattie

Dennis M Mulvey

San-Bao Hwang

Richard T Dean

Changgeng Qian

James B Doherty

Shu S Yang

Thomas J Lanza, Jr

Thomas W Doebber

Jorge P Li

Tongchuan Li

Timothy Francis Gallagher

Ralph F Hirschmann

Ronald C Gamble

John C Chabala

John D Baldeschwieler

Norman P Jensen

Bruce O Linn

Debra L Allison

Frederick W Holly

W Dean Harman

Javier Gonzalez

Dao Fei Huang

James C Robbins

Michael W Fordice

Marcia R Mauk

Robert Stevenson

Richard B Greenwald

Howard M Katzen

Jean-Claude Le Douarec

Philippe Conquet

Tsau-Yen Lin

The present invention provides methods of treatment utilizing pharmaceutical compositions comprising an effective nicotine agonist amount of epibatidine (1) or a synthetic 7-azabicyclo&lsqb;2.2.1&rsqb;-heptane or heptene derivative thereof, and a pharmaceutically acceptable earner, excipient or diluent.

Epibatidine and derivatives thereof as nicotine cholinergic receptor agonists

7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and

Epibatidine and derivatives thereof as cholinergic receptor agonists and

Indene derivatives have been found to have potent and specific PAF (Platelet-Activating-Factor) antagonistic activities and are thereby useful in the treatment of various diseases or disorders mediated by the PAF, for example, inflammation, cardiovascular disorder, asthma, lung edema, and adult respiratory distress syndrome.

Indene derivatives and their use as PAF-antagonists

Analogs of 2,5-Diaryl tetrahydrofurans which were substituted or unsubstituted at 3,4-positions were prepared. These compounds are found to have potent and specific PAF (Platelet Activating Factor) antagonistic activities and thereby useful in the treatment of various diseases or disorders mediated by the PAF, for example, inflammation, cardiovascular disorder, asthma, lung edema, adult respiratory distress syndrome, pain, and aggregation of platelets.

Method of use of 2,5-diaryl tetrahydrofurans and analogs thereof as

The invention disclosed herein relates to novel 1-deoxyglycosides, preferably 1-deoxy-D-mannopyranosides and 1-deoxy-L-rhamnopyranosides, having in the 1-position of the pyranose ring an aralkylthio/aralkenylthio, aralkyloxy/aralkenyloxy or aralkanoylamino/aralkenoylamino substituent; and to novel processes for preparing these 1-substituted-1-deoxyglycosides starting with the corresponding tetra-O-acetylglycopyranosyl bromide or amine. The 6-hydroxy group of 1-substituted-1 deoxyglycopyranosides can also be replaced by other functional groups. These aralkylthio/aralkenylthio, aralkyloxy/aralkenyloxy and aralkanoylamino/aralkenoylamino 1-deoxyglycosides are potent inhibitors of antigen-specific T-cell proliferation and are also useful as inhibitors of delayed-type hypersensitivity reactions.

Aralkyl and aralkenyl glycosides as inhibitors of antigen-specific

Mercaptoalkylpyridines carrying an ethenyl or ethynyl substituent are prepared from known pyridine compounds, principally pyridoxine, by known chemical procedures, and are useful in the treatment of rheumatoid arthritis and related inflammatory diseases.

Anti-inflammatory

2,5-Diaryl tetrahydrofurans and analogs thereof as PAF-antagonists

Phosphatidyl inositol analogs are found to be effective phospholipase C inhibitors and thereby potent anti-inflammatory and analgesic agents. These phosphatidyl inositol analogs are prepared by condensation of a protected inositol with a substituted phosphonic or phosphorous acid followed by removal of protecting groups.

Phosphatidyl inositol analogs useful as anti-inflammatory/analgesic

Fluorescein esters and ethers including the dioleyl derivative of fluorescein are disclosed. These compounds have the useful property of being fluorescent under the influence of the proper frequency of electromagnetic irradiation. Further, dioleyl fluorescein is readily incorporated into low-density lipoproteins which can then become part of the cell matter; the compounds retain their fluorescent properties during this procedure. The fluorescence allows cells to be indentified and separated. The fluorescein esters and ethers are prepared from fluorescein and the novel reagent O-alkenyl-N,N'-dialkylisourea.

Imino ethers

Tricyclic derivatives of substituted pyrrole acids, e.g., substituted 4,10-dihydro-10-oxo-1H-[1]benzoxepino[4,3-b]pyrrole-2-acetic acids or the 5-thia analogs thereof have been prepared via hydrolysis of a precursor or decarboxylation of a precursor-diacid. These tricyclic compounds are found to have high analgesic and anti-inflammatory activities but low ulcerogenic side effects.

Tricyclic derivatives of substituted pyrrole acids as analgesic and

This invention relates to ophthalmic preparations which include 5-fluoro-2-methyl-1-(p-methylthiobenzylidene)-3-indenylacetic acid or ophthalmologically acceptable salts thereof as the active entity for reducing or controlling inflammation of the eye.

Ophthalmic formulations of

2-Amino-2-deoxy-.beta.-D-glucopyranosyl-(1-4)-2-amino-2-deoxy-D-glucoses of the general structural formula: ##STR1## wherein R.sub.1 is hydrogen, alkyl (1-7C), substituted alkyl (1-7C), phenyl, substituted phenyl, benzyl, or substituted benzyl;

Immunologically active peptidyl disaccharides and methods of preparation

Cell-specific ligands comprising conjugates of saccharides and amino acids or peptides are synthesized from amino acids such as ornithine, lysine, peptides such as dilysine, diornithine or oligolysine and selected saccharides having reactive functional groups protected by appropriate blocking groups. Such glycopeptides are useful as tissue specific substances, which when coupled with bioactive materials through metabolizable or hydrolyzable linkages, deliver such bioactive materials to the selected site. In this manner, antiinflammatory drugs such as dexamethasone are linked through a metabolizable or hydrolyzable linkage and on administration to an animal suffering from inflammatory disease carries the drug to the site of inflammation for intracellular release. Other examples include the macrophage ligand N.sup.2 -N.sup.2, N.sup.6 -Bis-[3-(.alpha.-D-mannopyranosylthio)propionyl]-6-lysyl-N.sup.6 -[3-(.alpha.-D-mannopyranosylthio)propionyl]-L-lysine, 5, which when coupled to .beta.-glucocerebrosidase, can deliver the enzyme selectively to kupffer cells. This is useful in the enzyme replacement therapy of Gaucher's disease.

Cell-specific glycopeptide ligands

2-Amino-2-deoxy-glycoses of the general structural formula: ##STR1## wherein R.sub.1 is hydrogen, alkyl (1-7C), substituted alkyl (1-7C), phenyl, substituted phenyl, benzyl, or substituted benzyl;

Immunologically active dipeptidyl saccharides and methods of preparation

Growing community of inventors

Westfield, NJ, United States of America

Tsung-Ying Shen