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 provides the use of 2-(4-methoxyphenyl)-pyrazolo[4,3-c]quiniolin-3-one or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for enhancing cognition, particularly in Alzheimer's Disease, a method of enhancing cognition and pharmaceutically acceptable salts such as the hemi camphor sulfonate.
Type:
Grant
Filed:
May 25, 1999
Date of Patent:
July 11, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Gerard Raphael Dawson, Angus Murray MacLeod, Guy Ralph Seabrook
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 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 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 patent application discloses compounds having formula (I) ##STR1## or a pharmaceutically acceptable salt thereof or an oxide thereof, wherein R.sup.3 is (II), ##STR2## wherein A, B and D each is CH, or one or two of A, B and D is N and the others are CH; R.sub.11 is phenyl, benzimidazolyl, or monocyclic heteroaryl all of which may be substituted one or more times with substituents selected from alkyl, alkoxy, phenyl, halogen, CF.sub.3, amino, nitro, cyano, acyl, acylamino, phenyl and monocyclic heteroaryl; and one of R.sup.6 and R.sup.7 is hydrogen and the other is furanyl or isoxazolyl each of which may be substituted one or more times with substituents selected from halogen, alkyl, alkoxy and phenyl. The compounds are useful for the treatment of various central nervous system disorders such as epilepsy and other convulsive disorders, anxiety, sleep disorders and memory disorders.
Type:
Grant
Filed:
July 20, 1999
Date of Patent:
June 6, 2000
Assignee:
Merck Sharpe & Dohme Ltd.
Inventors:
Timothy Harrison, Timothy Jason Sparey, Martin Richard Teall
Abstract: A class of substituted 7,8-ring fused 1,2,4-triazolo[4,3-b]pyridazine derivatives as shown in Formula I, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position and a substituted alkoxy moiety at the 6-position, are selective ligands for GABA.sub.A receptors, in particular having high affinity for the .alpha.2 and/or .alpha.3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of pain.
Type:
Grant
Filed:
December 10, 1998
Date of Patent:
May 16, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Jose Luis Castro Pineiro, Raymond George Hill
Abstract: The present invention relates to compounds of formula (I), ##STR1## wherein R.sup.1 represents halogen, hydroxy, C.sub.1-6 alkyl group optionally substituted by one or three fluorine atoms, C.sub.1-6 alkoxy group optionally substituted by one to three fluorine atoms, or C.sub.1-6 alkylthio optionally substituted by one to three fluorine atoms; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl or C.sub.1-6 alkoxy; or when R.sup.2 is adjacent to R.sup.1, they may be joined together such that there is formed a 5- or 6-membered saturated or unsaturated ring containing one or two oxygen atoms; R.sup.3 represents an optionally substituted 5- or 6-membered aromatic heterocyclic group containing 1, 2, 3 or 4 heteroatoms, selected from nitrogen, oxygen and sulphur; m is 0-3 and n is 0-3, with the proviso that the sum total of m+n is 2 or 3; p is zero or 1; q is 1 or 2; and when m is 1 and n is 1 or 2, the broken line represents an optional double bond; R.sup.4, R.sup.5, R.sup.6, R.sup.9 and R.sup.
Type:
Grant
Filed:
May 18, 1998
Date of Patent:
May 9, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Timothy Harrison, Christopher John Swain, Brian John Williams
Abstract: The present invention provides a compound of formula I, or a pharmaceutically acceptable salt thereof: ##STR1## wherein Z, E, Q, T, U, V and L are as defined herein; processes for its preparation and its use in the treatment of conditions for which the administration of an agonist selective for the 5-HT.sub.1D.alpha. receptor subtype is indicated, such as migraine.
Type:
Grant
Filed:
May 26, 1998
Date of Patent:
April 25, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Tamara Ladduwahetty, Angus Murray MacLeod, Michael Rowley
Abstract: Compounds having formula I, or salts or prodrugs thereof: ##STR1## are selective agonists of the 5-HT.sub.1D.alpha. receptor and are useful in the treatment of migraine and associated conditions.
Type:
Grant
Filed:
April 29, 1998
Date of Patent:
April 25, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Sylvie Bourrain, Angus Murray MacLeod, Graham Andrew Showell
Abstract: A class of azetidine, pyrrolidine and piperidine derivatives, substituted by inter alia a phenylmorpholinyl, phenylpiperidinyl or benzimidazolone moiety, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.
Abstract: A class of 2,7-diazabicyclo[3.3.0]octane derivatives represented by formula I are selective agonists of the 5-HT.sub.1D.alpha. receptor. The compounds are useful in the treatment of migraine and related conditions.
Abstract: A compound of formula (I), or a salt or prodrug thereof, is described, wherein G is attached at position 3 or 4 of the piperidine ring and represents halogen or C.sub.1-6 alkoxy; R1 represents C.sub.3-6 alkenyl, C.sub.3-6 alkynyl, aryl(C.sub.1-6)alkyl or heteroaryl (C.sub.1-6)alkyl, any of which groups may be optionally substituted; processes for its preparation and its use in therapy, particularly in the treatment of migraine.
Type:
Grant
Filed:
May 13, 1998
Date of Patent:
April 11, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Jose Luis Castro Pineiro, Ian James Collins, Angus Murray MacLeod, Christopher Richard Moyes, Michael Rowley, Graham Andrew Showell
Abstract: The present invention relates to certain spiro-azacyclic derivatives 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:
March 23, 1999
Date of Patent:
April 4, 2000
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Karen Elizabeth Haworth, Eileen Mary Seward, Christopher John Swain
Abstract: A class of substituted 7,8-ring fused 1,2,4-triazolo[4,3-b]pyridazine derivatives, as shown in Formula I possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position and a substituted alkoxy moiety at the 6-position, are selective ligands for GABA.sub.A receptors, in particular having high affinity for the .alpha.2 and/or .alpha.3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of muscle spasm or spasticity, e.g. in paraplegic patients.
Abstract: A class of substituted azetidine, pyrrolidine and piperidine derivatives are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.
Type:
Grant
Filed:
May 28, 1997
Date of Patent:
February 15, 2000
Assignee:
Merck Sharp & Dohme, Ltd.
Inventors:
Jose Luis Castro Pineiro, Caroline Henry, Victor Giulio Matassa, Austin John Reeve, Francine Sternfeld, Leslie Joseph Street
Abstract: A class of piperazinones, homopiperazinones and thione analogues thereof, substituted at the 1-position by an optionally substituted alkenyl, alkynyl, aryl-alkyl or heteroaryl-alkyl moiety, and linked at the 4-position via an alkylene spacer to a fused bicyclic heteroaromatic moiety, typically indolyl, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype while possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, while eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.
Type:
Grant
Filed:
April 17, 1998
Date of Patent:
December 7, 1999
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Mark Stuart Chambers, Sarah Christine Hobbs, Leslie Joseph Street
Abstract: A class of N-substituted piperazine, piperidine, and tetrahydropyridine derivatives, further subltitutedat the 4-position by an optionally substituted alkenyl, alkynyl, aryl-alkyl or heteroaryl-alkyl moiety, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.
Type:
Grant
Filed:
October 26, 1998
Date of Patent:
December 7, 1999
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Sylvie Bourrain, Angus Murray MacLeod, Graham Andrew Showell, Leslie Joseph Street
Abstract: A class of substituted azetidine, pyrrolidine and piperidine derivatives, linked by a fluoro-substituted alkylene chain to a fused bicyclic heteroaromatic moiety such as indolyl, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype while possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, while eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.
Type:
Grant
Filed:
May 8, 1998
Date of Patent:
December 7, 1999
Assignee:
Merck Sharpe & Dohme Ltd.
Inventors:
Jose Luis Castro Pineiro, Angus Murray MacLeod, Monique Bodil Van Niel