Abstract: Oxadiazole substituted benzenesulfonamides are selective .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.
Type:
Grant
Filed:
June 4, 1997
Date of Patent:
March 7, 2000
Assignee:
Merck & Co., Inc.
Inventors:
Tesfaye Biftu, Michael H. Fisher, Danqing Dennis Feng, Chan-Hwa Kuo, Gui-Bai Liang, Elizabeth M. Naylor, Ann E. Weber
Abstract: 4-Substituted-4-piperidinecarboxamides of Formula I are antagonists of VLA-4 and/or .alpha..sub.4 .beta..sub.7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of asthma, allergies, inflammation, multiple sclerosis, and other inflammatory and autoimmune disorders.
Type:
Grant
Filed:
November 13, 1998
Date of Patent:
February 1, 2000
Assignee:
Merck & Co., Inc.
Inventors:
Stephen E. DeLaszlo, William K. Hagmann
Abstract: Thiazole substituted benzenesulfonamides are .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for decreasing gut motility are also disclosed.
Type:
Grant
Filed:
January 15, 1998
Date of Patent:
January 4, 2000
Assignee:
Merck & Co., Inc.
Inventors:
Robert J. Mathvink, Emma R. Parmee, Samuel Tolman, Ann E. Weber
Abstract: Substituted 5-aryl-2,4-thiazolidinediones are potent agonists of PPAR, and are therefore useful in the treatment, control or prevention of diabetes, hyperglycemia, hyperlipidemia (including hypercholesterolemia and hypertriglyceridemia), atherosclerosis, obesity, vascular restenosis, and other PPAR .alpha., .delta. and/or .gamma. mediated diseases, disorders and conditions.
Type:
Grant
Filed:
December 17, 1998
Date of Patent:
December 28, 1999
Assignee:
Merck & Co., Inc.
Inventors:
Soumya P. Sahoo, Richard L. Tolman, Wei Han, Jeffrey Bergman, Conrad Santini, Victoria K. Lombardo, Ranjit Desai, Julia K. Boueres, Dominick F. Gratale
Abstract: 4-Cyano-4-deformylsordarin derivatives are antifungal agents useful in the treatment and/or prevention of human and animal fungal infections, as well as in the control of phytopathogenic fungi in crops.
Abstract: 4-Cyano-4-deformylsordaricin derivatives are antifungal agents useful in the treatment and/or prevention of human and animal fungal infections, as well as in the control of phytopathogenic fungi in crops.
Abstract: The present invention relates to novel nodulosporic acid derivatives, which are acaricidal, antiparasitic, insecticidal and anthelmintic agents.
Type:
Grant
Filed:
March 23, 1998
Date of Patent:
October 5, 1999
Assignee:
Merck & Co., Inc.
Inventors:
Peter T. Meinke, Thomas Shih, Michael H. Fisher
Abstract: 2,4-Diaryl-5-pyridylimidazoles are glucagon antagonists and inhibitors of the biosynthesis and/or action of TNF-.alpha. and IL-1. The compounds block the action of glucagon at its receptor and thereby decrease the levels of plasma glucose. The instant imidazoles are also inhibitors of TNF-.alpha. and IL-1. Compounds of the present invention may be used for glucagon-mediated as well as cytokine mediated diseases. Cytokine mediated diseases refers to diseases or conditions in which excessive or unregulated production of one or more cytokines occurs. Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) are cytokines produced by a variety of cells, which are involved in immunoregulation and other physiological conditions, such as inflammation.
Abstract: Compounds of Formula I: ##STR1## are antagonists of the actions of leukotrienes. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
Type:
Grant
Filed:
March 10, 1998
Date of Patent:
September 14, 1999
Assignee:
Merck & Co., Inc.
Inventors:
Byron H. Arison, Thomas A. Baillie, Suresh K. Balani, Claude Dufresne
Abstract: The present invention provides novel cyclic tetrapeptides useful in the treatment or prevention of protozoal diseases; in particular, the novel compounds are active against the causative pathogens in malaria, toxoplasmosis, and coccidiosis. The invention also relates to the use of known compounds which are histone deacetylase inhibitors as antiprotozoal agents.
Type:
Grant
Filed:
January 27, 1997
Date of Patent:
July 13, 1999
Assignee:
Merck & Co., Inc.
Inventors:
Peter T. Meinke, Sandra J. Rattray, Dennis M. Schmatz
Abstract: 2,4-Diaryl-5-pyridylimidazoles are glucagon antagonists. The compounds block the action of glucagon at its receptor. Thus, the compounds can be used in the prophylaxis or treatment of disease states in mammals mediated by elevated levels of glucagon. Examples of such disease states include diabetes, obesity, hypertension, and cachexia and the like.
Abstract: Aryl, alkyl, alkenyl and alkynyl macrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by modification at C-30, C-33, and/or C-34 of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.
Abstract: Macrolides of the general structural Formula I: ##STR1## are immunosuppressants useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.
Abstract: The yield of monoaldehyde ##STR1## from 7-chloroquinaldine and isophthalaldehyde is increased to about 82% by using a 2 molar excess of isophthalaldehyde, conditions favoring precipitation of product during the reaction and recycling unreacted isophthalaldehyde. The recycling leads to a reduced net consumption of about 1.2 molar equivalents of isophthalaldehyde.
Abstract: The present invention provides novel cyclic tetrapeptides useful in the treatment or prevention of protozoal diseases; in particular, the novel compounds are active against the causative pathogens in malaria, toxoplasmosis, and coccidiosis.
Type:
Grant
Filed:
January 28, 1997
Date of Patent:
January 19, 1999
Assignee:
Merck & Co., Inc.
Inventors:
Christine Lange Cannova, Anne W. Dombrowski, Michael A. Goetz, Sandra J. Rattray, Sheo Bux Singh, Jon Polishook, Gerald F. Bills, Joyce A. Greene, Gary K. Darland
Abstract: Compounds having the formula I: ##STR1## are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
Type:
Grant
Filed:
February 8, 1996
Date of Patent:
January 5, 1999
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Michel L. Belley, Serge Leger, Patrick Roy, Marc Labelle, Yi Bin Xiang, Daniel Guay
Abstract: Asymmetric bioreduction of a ketone substrate with yeast produces the corresponding (R)-alcohol of structure: ##STR1## a key intermediate in the synthesis of a .beta..sub.
Type:
Grant
Filed:
June 26, 1997
Date of Patent:
December 8, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Michel M. Chartrain, John Y. L. Chung, Christopher Roberge
Abstract: Disclosed herein are compounds of Formula (I) ##STR1## and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These disease and disorders include hypotension, septic shock, toxic shock syndrom, hemodialysis, IL-2 therapy such as in cancer patients, cachexia, immnunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn or psoriasis and respiratory conditions such as bronchitis, asthma, and acure respiratory distress (ARDS), myocarditis, heart failure, atherosclerosis, arthritis, rheumatoid arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis.