Abstract: The present invention relates compounds of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 each independently represents a phenyl group optionally substituted by a variety of substituents;R.sup.3 represents a variety of substituents;R.sup.4, R.sup.5, R.sup.6, and R.sup.7 each independently represents hydrogen or C.sub.1-6 alkyl;A represents --O-- or --S--;B represents --O--, --S--, --NR.sup.a -- or --CHR.sup.a --; andn is zero, 1, 2, 3, 4 or 5;or a pharmaceutically acceptable salt or a prodrug thereof.The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migaine, emesis or postherpetic neuralgia.
Type:
Grant
Filed:
February 22, 2000
Date of Patent:
October 24, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Angus Murray MacLeod, Christopher John Swain, Monique Bodil van Niel
Abstract: The present invention is directed to cyclic amines of the formula I: ##STR1## (wherein R.sup.1, R.sup.2, R.sup.3, m and n 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-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.
Type:
Grant
Filed:
July 21, 1998
Date of Patent:
October 24, 2000
Assignee:
Merck & Co., Inc.
Inventors:
Charles G. Caldwell, Paul E. Finke, Malcolm Maccoss, Laura C. Meurer, Sander G. Mills, Bryan Oates
Abstract: The present invention relates to a process for the preparation of substantially pure N-((S)-(-)-.alpha.-methylbenzyl)-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one hydrochloride, which comprises selectively crystallising the (S,S)-diastereomer as the hydrochloride salt from a mixture of the (S,R)- and (S,S)-diastereomers in an organic solvent, and collecting the resultant crystalline product.
Type:
Grant
Filed:
September 8, 1999
Date of Patent:
October 10, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Michael Stewart Ashwood, Ian Frank Cottrell, Brian Christopher Bishops, John Simon Edwards
Abstract: The present invention is directed to compounds of the formula (I): ##STR1## (wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9a, R.sup.9b, m and n are as defined herein) which are tachykinin antagonists and which are particularly useful in the treatment of pain, inflammation, migraine, emesis and postherpetic neuralgia.
Type:
Grant
Filed:
August 13, 1998
Date of Patent:
October 3, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Jason Matthew Elliott, Fintan Kelleher, Christopher John Swain
Abstract: The present invention relates to a pharmaceutical composition and a process for the preparation of a tablet containing a growth hormone secretagogue as the active ingredient. The tablet is prepared by forming a powder blend of the active ingredient N-[1(R)-[(1,2-dihydro-1-methanesulfonyl-spiro[3H-indole-3,4'-piperdin]-1'- yl)carbonyl]-2-(phenylmethyl-oxy)ethyl]-2-amino-2-methyl-propanamide, or a pharmaceutically acceptable salt thereof, in particular the methanesulfonate salt, with a binder/diluent, a first diluent, a second diluent, a first portion of a disintegrant, and a lubricant; wet granulating the powder blend with a solution of ethanol/water to form granules; drying the granules to remove the ethanol/water; adding a second portion of a disintegrant; lubricating the granules; and compressing the dried granules into the desired tablet form.
Type:
Grant
Filed:
October 27, 1998
Date of Patent:
September 26, 2000
Assignee:
Merck & Co., Inc.
Inventors:
Mandana Asgharnejad, Jerome Draper, David Dubost, Michael Kaufman, David Storey
Abstract: The present invention is directed to 3,3-disubstituted piperidines of the formula I: ##STR1## (wherein X, Y, Z, Ar, R, m and n 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-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.
Abstract: A tachykinin receptor antagonist is useful for treating or preventing attention deficit disorder, optionally associated with hyperactivity, in a patient.
Type:
Grant
Filed:
November 19, 1998
Date of Patent:
September 19, 2000
Assignee:
Merck & Co., Inc.
Inventors:
David L. Glatt, Mark S. Kramer, Nadia Rupniak
Abstract: The present invention is directed to certain compounds of the general structural formula: ##STR1## wherein R.sub.1, R.sub.1a, R.sub.2a, R.sub.3, R.sub.3a, R.sub.4, R.sub.5, R.sub.6, A, W, and n are as defined herein. These compounds promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Growth hormone releasing compositions containing such compounds as the active ingredient thereof are also disclosed.
Type:
Grant
Filed:
March 27, 1997
Date of Patent:
September 19, 2000
Assignee:
Merck & Co., Inc.
Inventors:
Meng Hsin Chen, Gregori J. Morriello, Ravi Nargund, Arthur A. Patchett, Lihu Yang
Abstract: The present invention relates to the treatment or prevention of depression and/or anxiety by the administration of a combination of CNS-penetrant NK-1 receptor antagonists and an antidepressant or anti-anxiety agent.
Type:
Grant
Filed:
December 19, 1997
Date of Patent:
September 12, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Emma Joanne Carlson, Nadia Melanie Rupniak
Abstract: The present invention provides methods for the treatment or prevention of major depressive disorder with anxiety without concomitant therapy with other anti-depressant or anti-anxiety agents which comprises oral administration of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist and pharmaceutical compositions comprising such a NK-1 receptor antagonist.
Type:
Grant
Filed:
June 11, 1998
Date of Patent:
September 5, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Neil Roy Curtis, Jason Matthew Elliott, Timothy Harrison, Gregory John Hollingworth, Philip Stephen Jackson, Janusz Jozef Kulagowski, Nadia Melanie Rupniak, Eileen Mary Seward, Christopher John Swain, Brian John Williams
Abstract: The present invention provides a method for the treatment or prevention of schizophrenic disorders using an orally active, long acting, CNS-penetrant NK-1 receptor antagonist and pharmaceutical compositions comprising such a NK-1 receptor antagonist.
Type:
Grant
Filed:
June 11, 1998
Date of Patent:
August 8, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Neil Roy Curtis, Jason Matthew Elliott, Timothy Harrison, Gregory John Hollingworth, Philip Stephen Jackson, Janusz Jozef Kulagowski, Nadia Melanie Rupniak, Eileen May Seward, Christopher John Swain, Brian John Williams
Abstract: The present invention provides methods for the treatment or prevention of amnestic disorders which comprises oral administration of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist.
Type:
Grant
Filed:
December 1, 1997
Date of Patent:
August 1, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Neil Roy Curtis, Jason Matthew Elliott, Timothy Harrison, Gregory John Hollingworth, Philip Stephen Jackson, Janusz Jozef Kulagowski, Nadia Melanie Rupniak, Eileen Mary Seward, Christopher John Swain, Brian John Williams
Abstract: The present invention relates to certain 3-benzylaminopiperidines which are tachykinin receptor antagonists and are useful in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.
Type:
Grant
Filed:
June 9, 1998
Date of Patent:
August 1, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Jason Matthew Elliott, Christopher John Swain
Abstract: This invention is concerned with a novel polymorphic form of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)-ethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic form has advantages over the other known forms of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.
Abstract: A method for the treatment or prevention of mania or hypomania is disclosed comprising administering 3-[2-cyclopropoxy-5-(trifluoromethoxy)phenyl]-6-phenyl-1-oxa-7-aza-spiro[4 .5]decane.
Abstract: The present invention provides the use of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist for the manufacture of a medicament adapted for oral administration for the treatment or prevention of stress disorders without concomitant therapy with other anti-stress agents, methods of treatment using such a NK-1 receptor antagonist and pharmaceutical compositions comprising it.
Type:
Grant
Filed:
June 9, 1999
Date of Patent:
July 11, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Neil Roy Curtis, Jason Matthew Elliott, Timothy Harrison, Gregory John Hollingworth, Philip Stephen Jackson, Janusz Jozef Kulagowski, Nadia Melanie Rupniak, Eileen Mary Seward, Christopher John Swain, Brian John Williams
Abstract: The present invention is directed to spiro-ketal derivatives of the formula (I): ##STR1## (wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9a, R.sup.9b, m and n are defined herein) which are tachykinin antagonists and are useful, for example, in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.
Type:
Grant
Filed:
August 13, 1998
Date of Patent:
June 27, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Jonathan David Moseley, Christopher John Swain
Abstract: The present invention relates to certain spiro-piperdine derivatives which are tachykinnin antagonists and are useful, for example, in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.
Type:
Grant
Filed:
December 16, 1998
Date of Patent:
June 6, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Neil Roy Curtis, Jason Matthew Elliott, Timothy Harrison, Gregory John Hollingworth, Philip Stephen Jackson, Janusz Jozef Kulagowski, Eileen Mary Seward, Christopher John Swain, Brian John Williams
Abstract: The present invention relates to compounds of formula (I), wherein R is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, which groups are optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.a R.sup.b, where R.sup.a and R.sup.b each independently repesent hydrogen or C.sub.1-4 alkyl; or R is C.sub.1-4 alkyl substituted by Ar, and optionally further substituted by one or both of R.sup.4 and R.sup.5 ; R.sup.1, R.sup.2 and R.sup.3 represent a variety of substituents; R.sup.9 and R.sup.10 are each hydrogen, halogen, C.sub.1-6 alkyl, CH.sub.2 OR.sup.c, oxo, CO.sub.2 R.sup.a or CONR.sup.a R.sup.b where R.sup.c represents hydrogen, C.sub.1-6 alkyl or phenyl; X is --CH.sub.2, or --CH.sub.2 CH.sub.2 --; Y is --CH--, --CH.sub.2 --, --CH.sub.2 CH-- or --CH.sub.2 CH.sub.2 --, with the proviso that the sum total of carbon atoms in X+Y is 2 or 3; and when Y is --CH-- or --CH.sub.
Type:
Grant
Filed:
December 16, 1998
Date of Patent:
June 6, 2000
Assignee:
Merck Sharp & Dohme, Ltd.
Inventors:
Neil Roy Curtis, Ian Thomas Huscroft, Janusz Jozef Kulagowski, Christopher John Swain
Abstract: The present invention is directed to a process for the preparation of titanocene dichloride (Cp.sub.2 TiCl.sub.2) from the titanocene dimer (Cp.sub.2 TiMe).sub.2 O), which is produced as a by-product from employing the reagent dimethyl titanocene (Cp.sub.2 Ti(CH.sub.3).sub.2) in the methylenation of carbonyl compounds, such as esters and lactones.