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:
May 22, 1995
Date of Patent:
October 1, 1996
Assignee:
Merck & Co., Inc.
Inventors:
Michael H. Fisher, Elizabeth M. Naylor, Dong Ok, Ann E. Weber, Thomas Shih, Hyun Ok
Abstract: Compounds having the Formula I:R.sup.1 R.sup.2 C(OR.sup.3)--Ar.sup.1 --X--Ar.sup.2 --Ar.sup.3Ire 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:
October 27, 1994
Date of Patent:
September 3, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Daniel Delorme, Daniel Dub e, Yves Ducharme, Erich L. Grimm, Richard Friesen, Carole Lepine
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:
August 11, 1994
Date of Patent:
August 13, 1996
Assignee:
Merck & Co., Inc.
Inventors:
Anthony O. King, Robert D. Larsen, Thomas R. Verhoeven, Mangzhu Zhao
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:
March 21, 1995
Date of Patent:
July 30, 1996
Assignee:
Merck & Co., Inc.
Inventors:
Michael H. Fisher, Elizabeth M. Naylor, Ann E. Weber
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:
May 12, 1995
Date of Patent:
July 2, 1996
Assignee:
Merck Co., Inc.
Inventors:
Mark Goulet, William H. Parsons, Helen M. Organ, Peter J. Sinclair, Frederick Wong, Matthew J. Wyvratt
Abstract: Compounds having the Formula I:R.sup.1 R.sup.2 C(OR.sup.3)--Ar.sup.1 --X--Ar.sup.2 --C(Ar.sup.3).dbd.CHCO.sub.2 H Iare 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:
October 27, 1994
Date of Patent:
June 18, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Daniel Delorme, Yves Ducharme, Richard Friesen, Erich L. Grimm, Carole Lepine
Abstract: The present invention provides a novel process for the preparation of 1,1-cyclopropanedimethanol cyclic sulfite which comprises: (a) contacting 1,1-cyclopropanedimethanol with dialkylsulfite in the presence of a base; and (b) removing from the reaction mixture the alcohol reaction by-product. This process is incorporated in the additional novel processes for preparing 1-(hydroxymethyl)cyclopropaneacetonitrile and 1-(thiomethyl)cyclopropaneacetic acid.
Type:
Grant
Filed:
January 23, 1995
Date of Patent:
June 4, 1996
Assignee:
Merck & Co., Inc.
Inventors:
Steven King, Brenda Pipik, David A. Conlon
Abstract: The present invention relates to a process for converting a racemic mixture of 3,3-diethyl-4-[(4-carboxy)phenoxy]-2-azetidinone esters into the corresponding (S)-acid using lipase derived from Pseudomonas sp. The process provides the target acid in high enantiomeric excess.
Type:
Grant
Filed:
May 3, 1995
Date of Patent:
June 4, 1996
Assignee:
Merck & Co., Inc.
Inventors:
Michel M. Chartrain, Raymond Cvetovich, Christopher Roberge
Abstract: Compounds having the 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:
April 13, 1992
Date of Patent:
April 9, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Robert Zamboni, Daniel Guay, Jacques-Yves Gauthier
Abstract: The present invention provides a process for the stereoselective reduction of phenylalkyl ketones to their corresponding (S)-hydroxy compounds. The process utilizes the novel microorganism Microbacterium MB 5614 to effectuate the chiral reduction. The present invention also provides said novel Microbacterium, which has been deposited with the ATCC and assigned the accession number ATCC 55557.
Type:
Grant
Filed:
July 20, 1994
Date of Patent:
February 13, 1996
Assignee:
Merck & Co., Inc.
Inventors:
Michel M. Chartrain, Shieh-Shung T. Chen, George M. Garrity, Brian Heimbuch, Christopher Roberge, Ali Shafiee
Abstract: Compounds having the 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 16, 1994
Date of Patent:
December 5, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Robert N. Young, Marc Labelle, Yves Leblanc, Yi B. Xiang, Cheuk K. Lau, Claude Dufresne, Yves Gareau
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:
July 20, 1993
Date of Patent:
October 17, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Richard W. Friesen, Yves Girard, Daniel Dube
Abstract: A new homogeneous cytosolic binding protein (FKBP12.6), having a specific binding activity of about 4.8 mg FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506, but not cyclosporine A (CSA). The protein is unstable to heating at 56.degree. C. for 30 minutes losing its FK-506 binding affinity. The FKBP12.6 protein is isolated from the cytosol of mammalian tissues, preferably bovine or human brain tissue, and can be used in diagnostic and purification procedures involving FK-506-type macrolide immunosuppressants. The FKBP12.6 protein also has peptidyl-proline isomerase enzymatic activity, catalyzing the cis-trans isomerization of proline-containing peptide bonds. In addition, FKBP12.6 binds to and inhibits the phosphatase calcineurin in the presence of FK-506.
Type:
Grant
Filed:
February 15, 1994
Date of Patent:
October 10, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Gregory J. Wiederrecht, Tonya J. Sewell
Abstract: Substituted phenylsulfonamides 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 alkyl 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:
December 15, 1993
Date of Patent:
September 19, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Michael H. Fisher, Robert J. Mathvink, Hyun O. Ok, Emma R. Parmee, Ann E. Weber
Abstract: A process is described for the total synthesis of the macrolide immunosuppressant, FK-506, and important tricarbonyl process intermediates thereof. The tricarbonyl intermediates can be produced by the mild oxidation of 2,3-dihydroxy carboxylate compounds containing olefin moieties.
Type:
Grant
Filed:
October 12, 1990
Date of Patent:
August 29, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Todd K. Jones, Sander G. Mills, David Askin, Robert A. Reamer, Richard Desmond, David M. Tschaen, Ralph P. Volante, Ichiro Shinkai
Abstract: Compounds having the 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:
May 21, 1993
Date of Patent:
August 1, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Marc LaBell, Yves LeBlanc, Michel Belley, Erich L. Grimm, Daniel Guay, Yi B. Xiang
Abstract: Described is a new immunosuppressant, L-687,819, a C-31 demethylated derivative of L-683,795 (FK-523), produced under fermentation conditions utilizing the new mutant microorganism, Streptomyces hygroscopicus subsp. ascomyceticus (Merck Culture Collection MA 6646) ATCC No. 53855, being a blocked mutant of Streptomyces hygroscopicus subsp. ascomyceticus (MA 6475) ATCC No. 14891. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.
Type:
Grant
Filed:
July 30, 1992
Date of Patent:
July 11, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Louis Kaplan, Robert P. Borris, Kevin M. Byrne, Linda S. Wicker, Deborah L. Zink
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:
October 10, 1991
Date of Patent:
June 27, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Michel L. Belley, Serge Leger, Patrick Roy, Yi B. Xiang, Marc Labelle
Abstract: Compounds having the formula: ##STR1## are antagonists of leukotrienes and inhibitors of their biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.
Type:
Grant
Filed:
May 26, 1989
Date of Patent:
June 27, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Robert N. Young, Robert Zamboni, Serge Leger
Abstract: A process for reducing a phenylalkyl ketone to the corresponding (S)-hydroxy derivative is disclosed. The process comprises contacting the phenylalkyl ketone with Mucor hiemalis IFO 5834 and recovering the (S)-hydroxy derivative.