Abstract: Compound 9 is prepared by a 9-step ##STR1## process in an overall yield of about 35% from 3-acetylpyridine. Compound 10 is prepared by a seven-step ##STR2## process in an overall yield of about 30% from 3-acetyl pyridine. These compounds are key intermediates in the synthesis of Compound 11, an important .beta.-3 agonist useful in the treatment of obesity and diabetes.
Type:
Grant
Filed:
June 26, 1997
Date of Patent:
August 11, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Michel M. Chartrain, Christopher Roberge, John Y. L. Chung, Dalian Zhao
Abstract: Imidazolmethyloxy-substituted tricyclo-macrolide immunosuppressants are prepared by reacting a tricyclo-macrolide with an imidazolmethyl trichloroacetimidate in the presence of an acid. The invention further provides a crystalline salt of imidazolmethyloxy-substituted tricyclo-macrolide, as well as novel compounds useful in the process of the present invention.
Type:
Grant
Filed:
July 23, 1996
Date of Patent:
July 7, 1998
Assignee:
Merck & Co., Inc.
Inventors:
David J. Mathre, Richard F. Shuman, Paul Sohar, Zhiguo Song
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:
June 7, 1995
Date of Patent:
May 12, 1998
Assignee:
Merck Frosst Canada
Inventors:
Yves Gareau, Claude Dufresne, Marc Labelle, James Yergey, Xin Xu, Deborah Nicoll-Griffith, Nathalie Chauret, Laird Trimble
Abstract: Compounds of formula ##STR1## 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.
Type:
Grant
Filed:
September 23, 1996
Date of Patent:
February 3, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Michael H. Fisher, Hyun O. Ok, Ann E. Weber
Abstract: The present invention is concerned with an oral pharmaceutical formulation containing a proton pump inhibitor (PPI) which is suitable for the treatment of gastric acid related diseases in man and animals. More specifically, the composition is a paste, and is particularly suitable for delivery of a proton pump inhibitor to horses.
Abstract: 3-Cyclopentylpropylazide and p-chlorosulfonylphenylisocyanate undergo cycloaddition to form 1-cyclopropyl-4-(p-chlorosulfonylphenyl) tetrazone-5-one, a key intermediate in the synthesis of an important .beta.3-agonist.
Abstract: Substituted sulfonamides 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:
July 25, 1996
Date of Patent:
January 6, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Michael H. Fisher, Elizabeth M. Naylor, Emma R. Parmee, Thomas Shih, Hyun Ok, Ann E. Weber
Abstract: The present invention relates to an improved process for the in situ preparation of diisopinocampheylchloroborane which comprises reacting sodium borohydride and boron trichloride with .alpha.-pinene. The diisopinocampheylchloroborane thus obtained may be used, without isolation, to reduce prochiral ketones to their corresponding alcohols in high optical purity.
Type:
Grant
Filed:
January 16, 1996
Date of Patent:
December 2, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Anthony On-Ping King, Robert D. Larsen, Thomas R. Verhoeven, Mangzhu Zhao
Abstract: Substituted compounds of the FK-506 Type. These compounds are useful for the same or essentially the same purposes as FK-506 and are applied in the same or a similar manner. These compounds are immunosuppressants and useful for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. Still other uses are described in the disclosure.
Type:
Grant
Filed:
March 27, 1996
Date of Patent:
December 2, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Mark Goulet, Helen M. Organ, William H. Parsons, Peter J. Sinclair, Frederick Wong, Matthew J. Wyvratt
Abstract: The present invention relates to an improved method for controlling coccidiosis in poultry which comprises administering to poultry on shuttle medication an additional medication prior to switching from the starter compound to the grower compound, and continuing the additional medication for a period after the switching.
Abstract: The present invention concerns antitumor compounds. More particularly, the invention provides novel taxane derivatives, pharmaceutical compositions thereof, and their use as antitumor agents.
Type:
Grant
Filed:
May 19, 1995
Date of Patent:
July 8, 1997
Assignee:
Bristol-Myers Squibb Company
Inventors:
Jerzy Golik, Dolatrai Vyas, John J. Wright, Henry Wong, John F. Kadow, John K. Thottathil, Wen-Sen Li, Murray A. Kaplan, Robert K. Perrone, Mark D. Wittman
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:
May 23, 1995
Date of Patent:
April 15, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Christine L. Cannova, Michael A. Goetz, Anne W. Dombrowski, Sandra J. Rattray, Sheo B. Singh, Gerald F. Bills, Jon Polishook, Joyce A. Greene, Gary K. Darland
Abstract: The invention is an assay, including a series of peptides, which allow screening for inhibitors of C5a binding targeted to the subsite on the C5a receptor occupied by the C-terminus of C5a. These peptides allow compound testing efforts to be targeted to this same subsite so that C5a agonists and antagonists can be identified. These peptides have much greater affinity (Ki<10 nM) than does the natural C-terminus of C5a (Ki=300 .mu.M) and have been labeled to allow for detection of molecules which inhibit binding of these peptides at this receptor subsite. The invention is useful to develop agonists, partial agonists, and antagonists of C5a, and the invention includes compounds identified according to the method of this invention and methods of their use.
Type:
Grant
Filed:
March 18, 1994
Date of Patent:
March 25, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Zenon Konteatis, Salvatore J. Siciliano, Martin S. Springer
Abstract: The present invention relates to a process for the preparation of a compound of formula (I) or a sodium salt thereof ##STR1## wherein HET is 7-chloroquinolin-2-yl or 6,7-difluoroquinolin-2-yl, which comprises: reacting the dilithium dianion of 1-(mercaptomethyl)cyclopropaneacetic acid with a compound of formula (II) ##STR2## wherein HET is as defined above and L is arylsulfonyl or alkylsulfonyl. The invention further provides the dicyclohexylamine salt of a compound of formula (I).
Type:
Grant
Filed:
May 12, 1995
Date of Patent:
March 25, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Mahadevan Bhupathy, James M. McNamara, Daniel R. Sidler, Ralph P. Volante, James Bergan
Abstract: There are disclosed novel compounds which are derived from the fermentation of a strain of Nodulisporium sp. The compounds are highly potent ectoparasiticidal, antiparasitic and, insecticidal gents.
Type:
Grant
Filed:
December 20, 1994
Date of Patent:
March 25, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Anne W. Dombrowski, Richard G. Endris, Gregory L. Helms, Otto D. Hensens, John G. Ondeyka, Dan A. Ostlind, Jon D. Polishook, Deborah L. Zink
Abstract: The present invention provides a method for the treatment of helminthiasis which comprises administering to an infected host an effective amount of nodulisporic acid or a analog thereof.
Type:
Grant
Filed:
March 20, 1995
Date of Patent:
January 21, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Wesley Shoop, Dan A. Ostlind, Bruce F. Michael
Abstract: Compounds having the Formula I: ##STR1## are 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 and in preventing the formation of atherosclerotic plaques.
Type:
Grant
Filed:
February 15, 1995
Date of Patent:
November 19, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Richard Friesen, Yves Ducharme, Daniel Dube', Carole Lepine, Daniel Delorme, Pierre Hamel
Abstract: O-Aryl, O-alkyl, O-alkenyl and O-alkynyl-macrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and/or arylation at C-3" and/or C-4" 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.
Type:
Grant
Filed:
October 4, 1993
Date of Patent:
October 15, 1996
Assignee:
Merck & Co., Inc.
Inventors:
Mark Goulet, Helen M. Organ, William H. Parsons, Peter J. Sinclair, Frederick Wong, Matthew J. Wyvratt
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 23, 1995
Date of Patent:
October 15, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Michel L. Belley, Serge Leger, Marc Labelle, Patrick Roy, Yi B. Xiang, Daniel Guay
Abstract: Phosphate derivatives of 4'-demethylepipodophyllotoxin glucosides are novel antitumor agents and the salts thereof offer the pharmaceutical advantage of high water solubility.
Type:
Grant
Filed:
April 19, 1994
Date of Patent:
June 3, 1997
Assignee:
Bristol-Myers Squibb Company
Inventors:
Mark G. Saulnier, Peter D. Senter, John F. Kadow