Abstract: Compounds having the formula I: ##STR1## are inhibitors of the PLA.sub.2 s enzymes. These compounds are useful as anti-allergic, anti-asthmatic, they are also useful in treating various inflammatory diseases such as rheumatoid arthritis, osteoarthritis, bursitis, psoriasis; immunoinflammatory disorders such as contact dermatitis, irritable bowel disease and the like.
Type:
Grant
Filed:
July 20, 1994
Date of Patent:
September 26, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Helene Perrier, Petpiboon Prasit, Ian Street, Zhaoyin Wang
Abstract: Compounds of the structures shown below are specific inhibitors of cyclooxygenase-2 useful in the treatment of cyclooxygenase-2 mediated disease states such as inflammation, pain and fever, and are non-ulcerogenic.
Type:
Grant
Filed:
November 12, 1993
Date of Patent:
July 25, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Cameron Black, Joseph A. Mancini, Cheuk K. Lau, Petpiboon Prasit, Philip J. Vickers
Abstract: Disclosed are spiro-substituted azacycles of formula I ##STR1## are selective neurokinin-3 antagonists useful in the treatment of CNS disorders.
Abstract: Novel peptidyl derivatives of formula I are found to be potent inhibitors of interleukin-1.beta. converting enzyme (ICE). Compounds of formula I may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula I are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediator of cachexia.
Type:
Grant
Filed:
June 2, 1993
Date of Patent:
July 18, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Kevin T. Chapman, Herb G. Bull, Malcolm MacCoss, Nancy A. Thornberry, Jeffrey R. Weidner, Adnan M. Mjalli
Abstract: Novel peptidyl derivatives of formula I are found to be potent inhibitors of interleukin-1.beta. converting enzyme (ICE). Compounds of formula I may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula I are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediator of cachexia.
Type:
Grant
Filed:
November 21, 1994
Date of Patent:
July 4, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Kevin T. Chapman, Malcolm MacCoss, Adnan Mjalli
Abstract: N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.
Type:
Grant
Filed:
July 30, 1993
Date of Patent:
May 30, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Paul E. Finke, William K. Hagmann, William A. Hanlon, John L. Humes, Wilson B. Knight, Malcolm MacCoss, Richard A. Mumford, Shrenik K. Shah
Abstract: Novel peptidyl derivatives of formula I are found to be potent inhibitors of interleukin-1.beta. converting enzyme (ICE). Compounds of formula I may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula I are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediator of cachexia.
Type:
Grant
Filed:
May 17, 1993
Date of Patent:
May 2, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Gerald F. Bills, Otto D. Hensens, Jerrold M. Liesch, Russel B. Lingham, Jon D. Polishook, Michael J. Salvatore, Susan L. Raghoobar
Abstract: Disclosed are compounds of Formula I useful in the treatment of cyclooxygenase mediated diseases such as pain, fever and inflammation of a variety of conditions including rheumatic fever, symptoms associated with influenza or other viral infections, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, myositis, neuralgia, synovitis, arthritis, including rheumatoid arthritis degenerative joint diseases (osteoarthritis), gout and ankylosing spondylitis, bursitis, burns, injuries.
Type:
Grant
Filed:
March 12, 1993
Date of Patent:
April 25, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
W. Cameron Black, Chun-Sing Li, Daniel Guay, Petpiboon Prasit, Patrick Roy
Abstract: Novel substituted cyclic compounds of Formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. The matrix metalloendoproteinases are a family of zinc-containing proteinases including but not limited to stromelysin, collagenase, and gelatinase, that are capable of degrading the major components of articular cartilage and basement membranes. The inhibitors claimed herein may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to a permanent disability. These compounds may also be useful as novel birth control agents by preventing ovulation or implantation.
Type:
Grant
Filed:
October 8, 1993
Date of Patent:
April 4, 1995
Assignee:
Merck & Co., Inc.
Inventors:
William Hagmann, Charles G. Caldwell, Paul R. Gooley
Abstract: Described is a process for converting an alcohol to an azide with S.sub.N 2 inversion using a phosphoryl azide, e.g. diphenylphosphoryl azide (DPPA). Good yields of azide in high enantiomeric excess can be achieved specifically for benzylic alcohols and alpha-hydroxy alkyl esters. The process is carried at preferably room temperature in an inert dry aprotic solvent, e.g. toluene, and in the presence of a proton acceptor, e.g. 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford high yields of high enantiomeric purities.
Type:
Grant
Filed:
July 8, 1993
Date of Patent:
February 21, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Andrew S. Thompson, Edward J. J. Grabowski
Abstract: New substituted cephalosporin sulfones are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.
Type:
Grant
Filed:
May 1, 1992
Date of Patent:
November 15, 1994
Assignee:
Merck & Co., Inc.
Inventors:
James B. Doherty, Raymond A. Firestone, Paul E. Finke, William K. Hagmann, Shrenik K. Shah, Kevan R. Thompson
Abstract: New substituted azetidinones of the general formula (I) which have been found to be potent elastase inhibitors and thereby useful anti-inflammatory and antidegenerative agents are described.
Type:
Grant
Filed:
December 17, 1992
Date of Patent:
September 20, 1994
Assignee:
Merck & Co., Inc.
Inventors:
James B. Doherty, Paul E. Finke, William K. Hagmann, Amy L. Kissinger, Malcolm MacCoss, Shrenik K. Shah
Abstract: A cyclosporin derivative with incorporated "8-(3-fluoro-D-alanine)" or "8-(2-deutero-3-fluoro-D-alanine)" has been isolated from the fermentation broth of incubating Tolypocladium inflatum MF5080 (NRRL 8044) with 3-fluoro-D-alanine or its 2-deuterated isomer respectively. The modified cyclosporins exhibit immunosuppressive properties.
Type:
Grant
Filed:
July 10, 1992
Date of Patent:
June 7, 1994
Assignee:
Merck & Co., Inc.
Inventors:
Arthur A. Patchett, Raymond F. White, Robert T. Goegelman
Abstract: The present invention is directed to in-situ preparation of diisopinocamphenylchloroborane, and the use of same in the reduction of prochiral ketones to optically active alcohols such as those of formula B. ##STR1## The compound of Formula B is useful in the production 2,5-diaryltetrahydrofurans useful as PAF antagonists.
Type:
Grant
Filed:
March 23, 1992
Date of Patent:
March 8, 1994
Assignee:
Merck & Co., Inc.
Inventors:
Pamela M. Simpson, David M. Tschaen, Thomas R. Verhoeven
Abstract: Affinity chromatography matrices are disclosed which are useful in purifying interleukin-1.beta. converting enzyme (ICE) from crude or partially purified cell lysate preparations. The chromatographic matrices comprise a specific ICE inhibitor of Formula I which is attached to an affinity column support by means of a bifunctional spacer.
Abstract: N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the radioimmune assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.
Type:
Grant
Filed:
August 26, 1991
Date of Patent:
January 4, 1994
Assignee:
Merck & Co., Inc.
Inventors:
Paul E. Finke, William K. Hagmann, Richard A. Mumford, Shrenik K. Shah
Abstract: Inhibitors of human leukocytes elastase are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the radioimmunoassay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured utilizing polyclonal antibodies capable of binding to one or more haptens of formula II ##STR1## wherein M is allyl or n-propyl,Z.sub.1 is(a) 5-benzofuranyl or(b) substituted phenyl wherein the substituent is methyl or ethyloxy.The assays utilizing these antibodies are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.
Abstract: Cyclosporin analogs containing a MeAla or MeAbu residue at the 6-position of the cyclic undecapeptide have been discovered to sensitize multidrug resistant cells to certain chemotherapeutic agents. These cyclosporin analogs have also been shown to increase the sensitivity of cells already susceptible to the chemotherapeutic agents. In addition, these cyclosporin A analogs lack the nephrotoxic and immunosuppressive activity of cyclosporin A.
Abstract: N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.
Type:
Grant
Filed:
August 26, 1991
Date of Patent:
July 20, 1993
Assignee:
Merck & Co., Inc.
Inventors:
William A. Hanlon, John L. Humes, Wilson B. Knight, Richard A. Mumford