Abstract: The invention encompasses the novel class of compounds represented by formula I which are inhibitors of the PTP-1B enzyme.
The invention also encompasses pharmaceutical compositions and methods of treating or preventing PTP-1B mediated diseases.
Type:
Grant
Filed:
September 17, 1999
Date of Patent:
January 16, 2001
Assignee:
Merck Frosst Canada & Co.
Inventors:
Zhaoyin Wang, Claude Dufresne, Yves Leblanc, Chun Sing Li, Jacques Y. Gauthier, Cheuk K. Lau, Michel Therien, Patrick Roy
Abstract: The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases.
The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
Type:
Grant
Filed:
October 21, 1999
Date of Patent:
January 2, 2001
Assignee:
Merck Frosst Canada & Co.
Inventors:
Michel Belley, Jacques Yves Gauthier, Erich Grimm, Yves LeBlanc, Chun-Sing Li, Michel Therien, Cameron Black, Petpiboon Prasit, Cheuk-Kun Lau, Patrick Roy
Abstract: This invention encompasses a novel process for synthesizing the compound represented by formula I: ##STR1## These compounds are useful as non-steroidal anti-inflammatory agents.
Type:
Grant
Filed:
January 14, 2000
Date of Patent:
November 21, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Paul O'Shea, Richard D. Tillyer, Xin Wang, Sophie-Dorothee Clas, Chad Dalton
Abstract: The invention encompasses compounds of Formula I as well as a method of treating COX-2 mediated diseases comprising administration to a patient need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I ##STR1## e.g. (5R)-3-(3,4-difluorophenyl)-5-ethyl-5-methyl-4-[4-(methylsulfonyl)phenyl]- 2,5-dihydro-2-furanone.
Abstract: This invention relates to prostaglandin-bisphosphonate conjugates. These conjugates are effective for treating or preventing bone diseases such as osteoporosis. These conjugates simultaneously deliver a prostaglandin agent for increasing bone formation and a bisphosphonate agent for inhibiting bone resorption.
Type:
Grant
Filed:
November 15, 1999
Date of Patent:
September 19, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Yongxin Han, Robert N. Young, Laurent Gil, Rejean Ruel
Abstract: Disclosed is a binding assay for proteases and phosphatases, which contain cysteine in their binding sites or as a necessary structural component for enzymatic binding. The sulfhydryl group of cysteine is the nucleophilic group in the enzyme's mechanistic proteolytic and hydrolytic properties. The assay can be used to determine the ability of new, unknown ligands and mixtures of compounds to competitively bind with the enzyme versus a known binding agent for the enzyme, e.g., a known enzyme inhibitor. By the use of a mutant form of the natural or native wild-type enzyme, in which serine, or another amino acid, e.g., alanine, replaces cysteine, the problem of interference from extraneous oxidizing and alkylating agents in the assay procedure is overcome. The interference arises because of oxidation or alkylation of the sulfhydryl, --SH (or --S.sup.-), in the cysteine, which then adversely affects the binding ability of the enzyme.
Type:
Grant
Filed:
November 4, 1997
Date of Patent:
September 5, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Sylvie Desmarais, Michael Gresser, Richard Friesen, Brian Kennedy, Don Nicholson, Kathryn Skorey, Chidambaran Ramachandran, Anthony Ford-Hutchinson
Abstract: A complementary DNA (cDNA) encoding full length form of ICE.sub.rel -II is identified, sequenced and isolated. The cDNA is cloned into expression vectors for expression in recombinant hosts. The cDNA is useful to produce recombinant full length ICE.sub.rel -II. The cDNA and the recombinant ICE.sub.rel -II protein derived therefrom are useful in diagnostic kits, laboratory reagents and assays. The cDNA and the recombinant ICE.sub.rel -II protein may be used to identify compounds that affect ICE.sub.rel -II function, inflammation and cell apoptosis. ICE.sub.rel -II function, inflammation and cell apoptosis may also be modulated by ICE.sub.rel -II antisense or gene therapy.
Type:
Grant
Filed:
April 8, 1994
Date of Patent:
August 29, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Donald W. Nicholson, Ambereen Ali, Neil A. Munday, John P. Vaillancourt
Abstract: The invention discloses a cDNA consisting of human cyclooxygenase-2 cDNA attached to 3'flanking sequence of human cyclooxygenase-1 methods for increasing the expression of human cyclooxygenase-2 in transformed cell and assays for preferentially and independently measuring cyclogense-2 in samples.
Abstract: A complementary DNA (cDNA) encoding full length form of ICE.sub.rel -II is identified, sequenced and isolated. The cDNA is cloned into expression vectors for expression in recombinant hosts. The cDNA is useful to produce recombinant full length ICE.sub.rel -II. The cDNA and the recombinant ICE.sub.rel -II protein derived therefrom are useful in diagnostic kits, laboratory reagents and assays. The cDNA and the recombinant ICE.sub.rel -II protein may be used to identify compounds that affect ICE.sub.rel -II function, inflammation and cell apoptosis. ICE.sub.rel -II function, inflammation and cell apoptosis may also be modulated by ICE.sub.rel -II antisense or gene therapy.
Type:
Grant
Filed:
February 10, 1997
Date of Patent:
August 15, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Donald W. Nicholson, Ambereen Ali, Neil A. Munday, John P. Vaillancourt
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.
Type:
Grant
Filed:
May 17, 1999
Date of Patent:
June 6, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Daniel Dube, Rejean Fortin, Richard Friesen, Zhaoyin Wang, Jacques Yves Gauthier
Abstract: Disclosed are new ligands for use in a binding assay for proteases and phosphatases, which contain cysteine in their binding sites or as a necessary structural component for enzymatic binding. The sulfihydryl group of cysteine is the nucleophilic group in the enzyme's mechanistic proteolytic and hydrolytic properties. The assay can be used to determine the ability of new, unknown ligands and mixtures of compounds to competitively bind with the enzyme versus a known binding agent for the enzyme, e.g., a known enzyme inhibitor. By the use of a mutant form of the natural or native wild-type enzyme, in which serine, or another amino acid, e.g., alanine, replaces cysteine, the problem of interference from extraneous oxidizing and alkylating agents in the assay procedure is overcome. The interference arises because of oxidation or alkylation of the sulfihydryl, --SH (or --S.sup.-), in the cysteine, which then adversely affects the binding ability of the enzyme.
Type:
Grant
Filed:
November 4, 1997
Date of Patent:
May 23, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Sylvie Desmarais, Richard Friesen, Robert Zamboni
Abstract: The invention encompasses the novel compound of formula (I) useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of formula (I).
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:
September 11, 1998
Date of Patent:
April 4, 2000
Assignee:
Merck Frosst Canada & Co.
Inventors:
Richard Friesen, Rejean Fortin, Daniel Dube, Denis Deschenes
Abstract: A novel human DP prostaglandin receptor has been identified and DNA encoding the receptor has been isolated, purified, sequenced and expressed in host cells. This DNA encoding the novel prostaglandin receptor and host cells expressing the receptor are used to identify modulators of the prostaglandin receptor.
Type:
Grant
Filed:
March 6, 1997
Date of Patent:
September 28, 1999
Assignee:
Merck Frosst Canada & Co.
Inventors:
Mark Abramovitz, Yves Boie, Kathleen Metters, Nicole Sawyer, Deborah M. Slipetz
Abstract: A method for the rapid estimation of hyperplastic and hypertrophic changes in animal airways is an assay which specifically measures acidic and neutral mucoproteins in a linear fashion from 0.5 to at least 10 .mu.g. The assay comprises exposure of a test animal to a suspected metaplastic inducer, removal of the lungs, homogenization in an appropriately buffered solution containing reducing agents and protease inhibitors; removal of particulate matter; and size-fractionation of the SDS treated soluble extract. The high molecular weight material is immobilized and stained for either acidic or neutral mucosubstances and the specific staining is quantitated. The changes observed are consistent with those seen in histological sections of the exposed tissues.
Type:
Grant
Filed:
March 23, 1998
Date of Patent:
August 3, 1999
Assignee:
Merck Frosst Canada & Co.
Inventors:
Douglas J. Pon, Louise Boulet, Carlo J. van Staden, Rejean Fortin