Abstract: The present invention is concerned with 4-benzyl-2-hydroxy-1,4-oxazin-3-one, and novel processes for the preparation therof. This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.
Type:
Grant
Filed:
June 8, 2001
Date of Patent:
March 25, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Louis S. Crocker, Karel M. Jos Brands, Todd D. Nelson, Philip J. Pye, Jonathan D. Rosen, Kai Rossen
Abstract: Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions and are selected from the group consisting of:
or a pharmaceutically acceptable salt thereof, wherein
A is
Type:
Grant
Filed:
March 22, 2001
Date of Patent:
March 18, 2003
Assignee:
Merck & Co., Inc.
Inventors:
James C. Barrow, Bruce D. Dorsey, Harold G. Selnick, Phung L. Ngo
Abstract: There is disclosed 3-(5-methylisoxazol-3-yl)-6-(1-methyl-1,2,3-triazol-4-yl)methyloxy-1,2,4-triazolo[3,4-a]phthalazine in the form of a dihydrate, a dehydrate of the dihydrate and a pentahydrate, pharmaceutical compositions comprising the forms, the use of the forms for enhancing cognition, processes for producing the forms, their incorporation in pharmaceutical compositions comprising pamoate ions and the use of such ions for solubilizing neutral molecules.
Abstract: Pyrrolidine compounds of Formula I:
(wherein R1, R2, R3, R4, R5, R6, R7, R8a, R8b, j, k, 1, m, and n are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.
Type:
Grant
Filed:
October 10, 2001
Date of Patent:
March 11, 2003
Assignee:
Merck & co., Inc.
Inventors:
Christopher A. Willoughby, Keith Rosauer, Kevin T. Chapman, Sander G. Mills, Dong-Ming Shen, Min Shu
Abstract: A tachykinin antagonist is useful, alone or in conjunction with other agents, for altering circadian rhythmicity and alleviating circadian rhythm disorders and for enhancing and improving the quality of sleep.
Abstract: Crystalline 3-hydroxylactone-containing products can be prepared in high yield and purity in a one-pot process by treating the corresponding 3,5-dihydroxy acid with a strong mineral acid in a cold, aprotic, water-miscible solvent to effect lactonization, followed by addition of excess acid to effect crystallization of the lactonized product from the reaction mixture.
Type:
Grant
Filed:
April 5, 2002
Date of Patent:
February 25, 2003
Assignee:
Merck & Co., Inc.
Inventors:
James McManus, Nicholas Anousis, John F. Genus, Christopher Hancock
Abstract: Certain N-substituted indoles having aryloxyacetic acid, substituents are agonists or partial agonists of PPAR gamma, and are useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR mediated diseases, disorders and conditions.
Type:
Grant
Filed:
July 25, 2001
Date of Patent:
February 25, 2003
Assignee:
Merck & Co., Inc.
Inventors:
John J. Acton, III, Regina Marie Black, Anthony Brian Jones, Harold Blair Wood
Abstract: Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions and are selected from the group consisting of 3-Fluoro-2-pyridylmethyl-3-(2,2-difluoro-2-(2-pyridyl)ethylamino)-6-chloropyrazin-2-one-1-acetamide polymorphic crystalline Anhydrous Form B, 3-Fluoro-2-pyridylmethyl-3-(2,2-difluoro-2-(2-pyridyl)ethylamino)-6-chloropyrazin-2-one-1-acetamide polymorphic crystalline form Type A Monohydrate, and 3-Fluoro-2-pyridylmethyl-3-(2,2-difluoro-2-(2-pyridyl)ethylamino)-6-chloropyrazin-2-one-1-acetamide polymorphic crystalline form Type B monohydrate, or a pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
May 31, 2001
Date of Patent:
February 18, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Cameron J. Cowden, V. Brett Cooper, Daniel J. Rush, Patricia Frech
Abstract: The present invention relates to compounds of the formula (I):
wherein R1a, R1b, R2, R3, R4, R5, X and n are defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migraine, emesis and postherpetic neuralgia.
Type:
Grant
Filed:
September 4, 2001
Date of Patent:
February 11, 2003
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Kevin Tyler Chapman, Kevin Dinnell, Jason Matthew Elliott, Gregory John Hollingworth, Steven Michael Hutchins, Duncan Edward Shaw, Christopher Alan Willoughby
Abstract: The instant invention is concerned with aryl and heteroaryl acetic acid and oxyacetic acid compounds, which are useful as antidiabetic compounds. Compositions and methods for their use in the treatment of diabetes and related diseases and for lowering triglyceride levels are disclosed.
Type:
Grant
Filed:
October 24, 2000
Date of Patent:
February 4, 2003
Assignee:
Merck & Co. Inc.
Inventors:
Alan Adams, Derek Von Langen, Hiroo Koyama, Richard Tolman
Abstract: Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure:
or a pharmaceutically acceptable salt thereof, e.g. where R3 is —CH2NH2, —CH2CH2NH2, or —CH2NHC(O)OC(CH3)3.
Type:
Grant
Filed:
December 18, 2001
Date of Patent:
February 4, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Harold G. Selnick, James C. Barrow, Philippe G. Nantermet, Peter D. Williams, Kenneth J. Stauffer, Philip E. Sanderson, Kenneth E. Rittle, Matthew M. Morrissette, Catherine M. Wiscount, Lekhanh O. Tran, Terry A. Lyle, Donnette D. Staas
Abstract: The present invention relates to a process for the preparation of a compound of formula (I)
wherein Ts is a tosylate group and R is an alkyl group, an unsubstituted phenyl or substituted phenyl ring, or a benzyl or substituted benzyl group; which comprises:
(i) cyclising a compound of formula (II)
in the presence of a suitable catalyst; and
(ii) purifying and collecting the resultant compound of formula (I).
Type:
Grant
Filed:
February 27, 2001
Date of Patent:
February 4, 2003
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Michael Stewart Ashwood, Ian Frank Cottrell, Cameron John Cowden, Debra Jane Wallace
Abstract: A thrombin receptor antagonist having the formula
useful for inhibiting the aggregation of blood platelets. The compounds can be used in a method of acting upon a thrombin receptor which comprises administering a therapeutically effective but non-toxic amount of such compound to a mammal, preferably a human.
Type:
Grant
Filed:
January 30, 2001
Date of Patent:
February 4, 2003
Assignee:
Merck & Co., Inc.
Inventors:
James C. Barrow, Philippe G. Nantermet, Harold G. Selnick, John H. Hutchinson, Michael J. Breslin, Kristen L. Glass, Thomas M. Connolly, Andrew Stern
Abstract: Compounds of Formula I:
(wherein R1, R2, R3, R4, Q, and X are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.
Type:
Grant
Filed:
October 10, 2001
Date of Patent:
January 28, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Ronald M. Kim, Jiang Chang, Kevin T. Chapman, Sander G. Mills
Abstract: The invention provides a method for treating, preventing, or reducing the risk of developing a condition selected from the group consisting of acute coronary ischemic syndrome, thrombosis, thromboembolism, thrombotic occlusion and reocclusion, restenosis, transient ischemic attack, and first or subsequent thrombotic stroke, in a patient, comprising administering to the patient a therapeutically effective amount of an antiplatelet agent in combination with a therapeutically effective amount of a COX-2 inhibitor. The invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a COX-2 inhibitor, or a pharmaceutically acceptable salt thereof, and an antiplatelet agent, or a pharmaceutically acceptable salt thereof.
Abstract: The present invention is directed to compounds of the formula I:
(wherein R1, R2, R3, R4, R5, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
Type:
Grant
Filed:
June 8, 2000
Date of Patent:
January 14, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Paul E. Finke, Jennifer L. Loebach, Malcolm Maccoss, Sander G. Mills
Abstract: Processes are disclosed for preparing 3-hydroxymethylcyclopentanone compounds, which are useful as intermediates in the preparation of HIV chemokine CCR-5 receptor antagonists. A process is described in which the compounds are prepared by opening the cyclopropyl ring of a (1-alkoxycarbonyl-2-oxo)-trans-bicyclo[3.1.0]hexane compound by addition of a nucleophile to the cyclopropyl ring, and then decarboxylating the resulting 2-alkoxycarbonyl-3-(Nu-methyl)-cyclopentanone (Nu=the added nucleophilic group) via base solvolysis. Also described is a process for preparing the bicyclo[3.1.0]hexane precursors by the catalyzed cyclopropanation of a suitable alpha-diazo-beta-ketoester. The preparation of the alpha-diazo-beta-ketoesters and precursors thereto are also disclosed.
Type:
Grant
Filed:
April 20, 2001
Date of Patent:
January 14, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Nobuyoshi Yasuda, Michael Palucki, Joann M. Um, David Alan Conlon, Barry M. Trost
Abstract: The present invention is concerned with novel processes for the preparation of (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol. This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.
Abstract: 1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing a difluoro-or tri-fluoro-substituted phenyl ring at the 3-position, a triazolyl moiety at the 6-position, and a tert-butyl group at the 7-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, and are useful in the treatment of anxiety and convulsions.
Type:
Grant
Filed:
July 23, 2001
Date of Patent:
December 31, 2002
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
William Robert Carling, Jose Luis Castro Pineiro, Richard Thomas Lewis, Kevin William Moore, Leslie Joseph Street
Abstract: The present invention is directed to compounds of the formula I:
(wherein R1, R2, R3, R7, R8, X, Y, Z, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
Type:
Grant
Filed:
June 8, 2000
Date of Patent:
December 31, 2002
Assignee:
Merck & Co., Inc.
Inventors:
Paul E. Finke, Kevin T. Chapman, Malcolm Maccoss, Sander G. Mills, Bryan Oates