Abstract: Novel phosphinic acid-containing peptidyl 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, dystrophobic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. These inhibitors may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to permanent disability. These compounds may also have utility as a means for birth control by preventing ovulation or implantation.
Type:
Grant
Filed:
November 9, 1995
Date of Patent:
October 21, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Charles G. Caldwell, Philippe L. Durette, Joung L. Goulet, William K. Hagmann, Soumya P. Sahoo
Abstract: The invention encompasses the novel compound of Formula I as well as a method of treating COX-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of COX-2 mediated diseases comprising compounds of Formula I.
Abstract: Novel Carboxy-peptidyl 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, dystrophobic epidermolysis bullosa, coronary thrombosis associated with atherosclerotic plaque rupture, and aneurysmal aortic disease. 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 have utility as a means for birth control by preventing ovulation or implantation.
Type:
Grant
Filed:
May 17, 1995
Date of Patent:
September 30, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Kevin Chapman, William Hagmann, Philippe Durette, Craig Esser, Ihor Kopka, Charles Caldwell
Abstract: The invention encompasses a method of inhibiting bone resorption in patients in need of such inhibition to a degree sufficient to halt or retard loss of bone mass, reduce fractures, improve bone repair and prevent or treat osteoporosis comprising: the administration of a non-toxic therapeutically effective amount of a selective cyclooxygenase-2 inhibitor such as the compounds of formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for the purposes described above.
Abstract: The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
May 22, 1995
Date of Patent:
June 17, 1997
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Cheuk Kun Lau, Cameron Black, Daniel Guay, Jacques-Yves Gauthier, Yves LeBlanc, Patrick Roy, Yves Ducharme, Pierre Hamel
Abstract: Novel N-(mercaptoacyl)peptidyl compounds are useful as inhibitors of matrix metalloendoproteinases which degrade major components of articular cartilage and basement membranes causing degenerative diseases such as arthritis, periodontal disease, corneal ulceration, are described. For example, N-(2-thiomethyl-4-phenyl-butanoyl)-L-leucinamide was prepared and its inhibitory activity against stromelysin was tested in vitro.
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, immunosuppression 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.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
May 13, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Ravindra N. Guthikonda, Stephan K. Grant, Malcolm Maccoss, Shrenik K. Shah, Kothandaraman Shankaran, Charles G. Caldwell, Philippe L. Durette
Abstract: Disclosed are substituted aryl piperazines of Formula I ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis. In particular compounds of Formula I are shown to be neurokinin antagonists.
Type:
Grant
Filed:
September 30, 1994
Date of Patent:
March 4, 1997
Assignee:
Merck & Co., Inc.
Inventors:
Yuan-Ching P. Chiang, Paul E. Finke, Malcolm Maccoss, Laura C. Meurer, Daniel J. Miller, Sander G. Mills, Albert J. Robichaud, Shrenik K. Shah
Abstract: The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
May 22, 1995
Date of Patent:
February 18, 1997
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Cheuk K. Lau, Cameron Black, Daniel Guay, Jacques Y. Gauthier, Yves LeBlanc, Patrick Roy, Yves Ducharme, Pierre Hamel
Abstract: The Compound of Formula I and pharmaceutically acceptable salts thereof in the treatment of cyclooxygenase-2 mediated diseases are disclosed.
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. ##STR1## wherein R.sub.4 is (a) ##STR2## or (b) ##STR3## where R.sub.x is carboxy C.sub.1-6 alkyl, benzyloxycarbonylC.sub.1-3 alkyl, or t-butoxycarbonylC.sub.1-3 alkyl,whereinQ is a covalent bond or ##STR4## wherein R.sub.5 and R.sub.6 are each individually C.sub.1-3 alkyl or hydrogen,Y is ##STR5## or a covalent bond.
Type:
Grant
Filed:
December 16, 1993
Date of Patent:
January 7, 1997
Assignee:
Merck & Co., Inc.
Inventors:
James B. Doherty, Conrad P. Dorn, Philippe L. Durette, Paul E. Finke, Malcolm Maccoss, Sander G. Mills, Shrenik K. Shah, Soumya P. Sahoo, Jeffrey J. Hale, Thomas J. Lanza, William K. Hagmann
Abstract: The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
January 11, 1995
Date of Patent:
September 3, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Jacques Y. Gauthier, Cheuk K. Lau, Yves LeBlanc, Chun-Sing Li, Patrick Roy, Michel Therien, Zhaoyin Wang
Abstract: The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
May 8, 1995
Date of Patent:
August 27, 1996
Assignee:
Merck Frosst Canada Inc.
Inventors:
Yves Ducharme, Jacques Y. Gauthier, Petpiboon Prasit, Yves Leblanc, Zhaoyin Wang, Serge Leger, Michel Therien
Abstract: The invention discloses a human cyclooxygenase-2 cDNA, a human cyclooxygenase-2 and assays for preferentially and independently measuring cyclogenase-2 or cyclooxygenase-1 activity present in a given sample.
Type:
Grant
Filed:
May 6, 1993
Date of Patent:
August 6, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Wanda A. Cromlish, Brian P. Kennedy, Gary O'Neill, Philip J. Vickers, Elizabeth Wong, Joseph A. Mancini
Abstract: The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
May 8, 1995
Date of Patent:
July 16, 1996
Assignee:
Merck Frosst Canada Inc.
Inventors:
Yves Ducharme, Jacques Y. Gauthier, Petpiboon Prasit, Yves Leblanc, Zhaoyin Wang, Serge Leger, Michel Therien
Abstract: The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
August 29, 1994
Date of Patent:
May 28, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Petpiboon Prasit, Daniel Guay, Zhaoyin Wang, Serge Leger, Michel Therien
Abstract: The invention encompasses the novel compound of Formula I as well as a method of treating inflammation and, in particular, cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of inflammation and, in particular, cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
May 22, 1995
Date of Patent:
April 23, 1996
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Cheuk K. Lau, Cameron Black, Michel Belley
Abstract: The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases, ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
January 10, 1994
Date of Patent:
December 12, 1995
Assignee:
Merck Frosst Canada, Inc.
Inventors:
Yves Ducharme, Jacques Y. Gauthier, Petpiboon Prasit, Yves Leblanc, Zhaoyin Wang, Serge Leger, Michel Therien
Abstract: This invention discloses novel immunogenic peptide sequences, derived from the human cyclooxygenase-1 and cyclooxygenase-2 cDNAs which elicit specific non cross-reactive antibody responses. Assays are also disclosed for selectively and independently detecting cyclooxygenase-1 or cyclooxygenase-2 proteins present in a given biological sample.
Type:
Grant
Filed:
January 24, 1994
Date of Patent:
October 17, 1995
Assignee:
Merck Frosst Canada Inc.
Inventors:
Gary O'Neill, Philip J. Vickers, Stacia Kargman, Jillian F. Evans