Merck + Co., Inc.

Robert L Bugianesi

Mitree M Ponpipom

Tesfaye Biftu

Tsung-Ying Shen

Soumya P Sahoo

Nirindar N Girotra

Chan H Kuo

Robert M Burk

Matthew J Wyvratt

Michael H Fisher

William H Parsons

Mark T Goulet

Narindar N Girotra

Gregory D Berger

James D Bergstrom

Lori L Whiting

Sander G Mills

Philippe L Durette

Thomas F Walsh

George A Doherty

Jeffrey John Hale

Kathleen M Rupprecht

Wallace T Ashton

Feroze Ujjainwalla

Danqing D Feng

Christopher L Lynch

Michael N Chang

Lin Chu

XiaoXia Qian

John C Chabala

John J Acton, Iii

Yuan-Ching P Chiang

Peter Lin

Roy G Smith

Gui-Bai Liang

Conrad Santini

Claude Dufresne

Chan-Hwa Kuo

San-Bao Hwang

William E Neway, Iii

Robert W Marquis, Jr

James C Robbins

Amy Gentry

Tesfaye Bitfu

Yi Tien Yang

C H Kuo

Sandra P Plevyak

Howard M Katzen

The present invention encompasses compounds of Formula 1: as well as the pharmaceutically acceptable salts and hydrates thereof. The compounds are useful for treating immune mediated diseases and conditions, such as bone marrow, organ and tissue transplant rejection. Pharmaceutical compositions and methods of use are included. 

Edg receptor agonists

Trisubstituted pyrroles are antiprotozoal agents useful in the treatment and prevention of protozoal diseases in human and animals, including the control of coccidiosis in poultry.

Aliphatic hydroxy substituted piperidyl diaryl pyrrole derivatives as antiprotozoal agents

There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.

Antagonists of gonadotropin releasing hormone

Cholesterol lowering compounds

This invention relates to compounds of structural formula (I): ##STR1## which are squalene synthase inhibitors and thus useful as cholesterol lowering agents and antifungal agents. These compounds are also inhibitors of farnesyl protein transferase and farnesylation of the oncogene protein Ras and thus useful in treating cancer.

Cholesterol-lowering agents

The present invention is directed to a specifically substituted tetrahydrofuran of the formula (I) ##STR1## wherein R.sup.4 is an alkylthio, alkylsulfinyl or alkylsulfonyl containing group and at least one of the substituents at positions 3, 4 or 5 contains a heterocyclic, heteroaryl or substituted phenylthio moiety.

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

The present invention is directed to a specifically substituted tetrahydrofuran of the formula (I) ##STR1## wherein R.sup.4 is an alkylthio, alkylsulfinyl or alkylsulfonyl containing group, Y is an alkyl or substituted alkyl group and R.sup.6 is an alkoxy or a substituted alkoxy or alkyl group.

Certain 2,5-diaryl tetrahydrofurans and analogs thereof as PAF

The present invention is directed to a specifically substituted tetrahydrofuran of the formula (I) ##STR1## wherein Ar is a pyridyl, a dimethoxy-pyridyl or dimethoxy-pyrazyl group, R.sup.4 is an alkylthio, alkylsulfinyl or alkylsulfonyl containing group and at least one of the substituents at positions 3,4 or 5 contains a heterocyclic, heteroaryl or substituted phenylthio group.

The present invention is directed to a specifically substituted tetrahydrofuran of the formula (I) ##STR1## wherein R.sup.4 is an alkylthio, alkylsulfinyl or alkylsulfonyl containing group and at least one of the substituents at positions 3,4 or 5 contains a heterocyclic, heteroaryl or substituted phenylthio moiety.

There are disclosed phospholipid analogs which are useful as PAF synthesis inhibitors. These compounds inhibit PAF (platelet-activating factor) biosynthesis and are thereby useful in the treatment of various diseases or disorders mediated by the PAF such as, for example, pain, fever, inflammation, cardiovascular disorder, asthma, lung edema, allergic disorders, skin diseases, psoriasis, and adult respiratory distress syndrome.

Phospholipid analogs useful as PAF synthesis inhibitors

Substituted 2,3,3a,6-tetrahydro-6-oxobenzofuran derivatives have been prepared. These neolignans 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 PAF, for example, pain, fever, inflammation, cardiovascular disorder, asthma, lung edema, allergic disorders, skin diseases, psoriasis, toxic shock syndrome and adult respiratory distress syndrome.

Substituted 2,3,3a,6-tetrahydro-6-oxobenzofuran derivative useful as PAF

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

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

Compounds of the formulae Y--R wherein Y is 1-thio-.beta.-L-fucose, 1-thio-.beta.-D-galactose or 1-thio-.beta.-lactose and R is 2-(1-adamantyl)ethyl, 3-[(p-tetrafluorophenethyl)phenyl]propyl, 6-(5-cholesten-3.beta.-yloxy)hex-3-ynl, oleyl, or hexadecyl are useful immunologic adjuvants in vaccines.

Immunologic adjuvant thio glycoside compounds and compositions

Growing community of inventors

Colonia, NJ, United States of America

Robert L Bugianesi