Abstract: The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring;X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen;A represents a group of formula II: ##STR2## in which: R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl;R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarobnyl;V represents nitrogen, ##STR3## W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.
Type:
Grant
Filed:
July 13, 1990
Date of Patent:
August 20, 1991
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, John Saunders, Christopher Swain
Abstract: Peptide compounds of formula I are antagonists of oxytocin and are useful in the treatment of preterm labor and dysmenorrhea, and for the stoppage of labor prepatory to Caesarian delivery.
Type:
Grant
Filed:
June 11, 1990
Date of Patent:
June 25, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Mark G. Bock, Roger M. Freidinger, Robert M. DiPardo
Abstract: Recombinant hepatitis B antigen bound to yeast membranes in yeast expression systems is rapidly purified by subjecting the membrane bound protein to agents that release undesired proteins, followed by agents that release the recombinant hepatitis B antigen.
Abstract: A fibrinogen receptor antagonist of the formula: ##STR1## wherein A, B, C, D, E, R, R.sup.1 and X-Y are preferably defined as follows:A is acylamido;R and R.sup.1 are H;X-Y is S--S;B is L-asparagine;C is proline or thioproline or .beta., .beta.-dimethylthroprolineD is arginine; andE is COOH.
Type:
Grant
Filed:
July 28, 1989
Date of Patent:
June 11, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Ruth F. Nutt, Stephen F. Brady, Daniel F. Veber
Abstract: A process for introducing a 1,2 double bond into a compound of the formula ##STR1## which comprises the process of (a) treating the compound of formula I with oxalyl chloride; (b) brominating the product of step (a) followed by in situ dehydrobromination; (c) deprotecting the product of step (b) to yield the .alpha. and .beta. isomers; (d) dehydrobrominating the product of step (c), which results in the introduction of a double bond at the 1,2 position.
Type:
Grant
Filed:
November 13, 1989
Date of Patent:
June 4, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Anthony O. King, Robert K. Anderson, Richard E. Shuman, Leonard M. Weinstock
Abstract: An improved process is described for the preparation of 4-amino-1-hydroxybutylidene-1,1-bisophosphonic acid (ABP) or salts thereof which comprises:(a) reacting 4-aminobutyric acid with a mixture of phosphorous acid and PCl.sub.3 in the presence of methanesulfonic acid;(b) contacting the mixture from Step (a) with an aqueous hydrolysis mixture, wherein the pH is maintained in the range of 4 to 10 during the contacting; and(c) recovering said 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof.
Abstract: A galactose-regulated yeast strain expresses a desired protein in improved yield by growing the transformed yeast cells in culture in fed-batch mode and replacing the culture medium with fresh medium before adding the galactose to induce expression of the foreign protein.
Abstract: Methods of purifying recombinant surface antigen of hepatitis B virus are disclosed. In one protocol, purification is achieved by selective extraction of the antigen from yeast membranes, followed by solubilization with urea and dithiothreitol.
Abstract: A new antifungal agent which exhibits a moderately broad spectrum of activity towards filamentous fungi and also against Cryptococcus species of the yeast fungi, and which has been isolated from a solid stationary fermentation of an unidentified species of Fusarium is described.
Type:
Grant
Filed:
December 1, 1988
Date of Patent:
April 16, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Louis Chaiet, Sheldon B. Zimmerman, Richard L. Monaghan, George M. Garrity
Abstract: Enzyme di- or tripeptides of the formula: ##STR1## and analogs thereof which inhibit renin and are useful for treating various forms of renin-associated hypertension, hyperaldosteronism and congestive heart failure; compositions containing these renin-inhibitory peptides, optionally with other antihypertensive agents; and methods of treating hypertension, hyperaldosteronism or congestive heart failure or of establishing renin as a causative factor in these problems which employ these novel peptides.
Type:
Grant
Filed:
August 26, 1988
Date of Patent:
April 9, 1991
Assignee:
Merck & Co., Inc.
Inventors:
William J. Greenlee, Daniel F. Veber, Peter D. Williams
Abstract: Methods of antagonizing gastrin and/or cholecystokinin (CCK) with benzodiazepine analogs are disclosed, as well as related pharmaceutical compositions, which are useful in treating disorders of the gastrointestinal tract, central nervous system, and of the appetite.
Type:
Grant
Filed:
November 9, 1988
Date of Patent:
April 2, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Ben E. Evans, Mark G. Bock, Roger M. Freidinger
Abstract: Enzyme di- or tripeptides of the formula: ##STR1## and analogs thereof which inhibit renin and are useful for treating various forms of renin-associated hypertension, hyperaldosteronism and congestive heart failure; compositions containing these renin-inhibitory peptides, optionally with other antihypertensive agents; and methods of treating hypertension, hyperaldosteronism or congestive heart failure or of establishing renin as a causative factor in these problems which employ these novel peptides.
Abstract: The present invention relates to the use of peptide hormone analogues as inhibitors of their respective naturally occurring peptide hormone. The structure of the peptide hormone analogues is exemplified by parathyroid hormone wherein Phe.sup.7 is substituted by NMePhe, D-Phe, desamino Phe, or Met.sup.8 is substituted by NMeMet.
Type:
Grant
Filed:
March 2, 1989
Date of Patent:
March 19, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Michael Rosenblatt, Lynn H. Caporale, Michael Chorev
Abstract: Novel fungicidal compositions comprising a 14.alpha.-methyldemethylase inhibiting azole compound and a .beta.-lactone compound and a method for controlling mycotic infections is disclosed.
Abstract: A solid support chemistry system which, with a dinitrofluorobenzene based assay, can be used to define titers of ligands and chemistry distal to the support. Cleavable diamine cystamines or 1,6-diamino-3,4-dihydroxyhexane are bonded to the solid support.
Abstract: A phenyl derivative of pepstatin A, which is much more potent than pepstatin in inhibiting renin enzyme activity and has significantly greater selectivity for renin over pepsin inhibition than does pepstatin, which is useful in treating hypertension and congestive heart failure.
Type:
Grant
Filed:
June 2, 1989
Date of Patent:
December 25, 1990
Assignee:
Merck & Co., Inc.
Inventors:
Leeyuan Huang, Joseph Dunn, Jr., Lawrence Koupal, Jerrold Liesch, Otto Hensens, H. Boyd Woodruff