Abstract: The present invention discloses a compound of formula 1, or a pharmaceutically acceptable salt thereof: wherein X1 represents hydrogen, halogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy; X2 represents hydrogen or halogen; Y represents a chemical bond, an oxygen atom, or a —NH— linkage; Z represents an optionally substituted aryl or heteroaryl group; R1 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, —ORa, —SRa, —SORa, —SO2Ra, —SO2NRaRb, NRaRb, —NRaCORb, —NRaCO2Rb, —CORa, —CO2Ra, —CONRaRb or —CRa&?NORb; and Ra and Rb independently represent hydrogen, hydrocarbon or a heterocyclic group; a pharmaceutical composition comprising it; its use in a method of treatment; use of it to manufacture a medicament; and a method of using it to prevent or treat anxiety, convulsions or cognitive disorders.
Type:
Grant
Filed:
October 29, 2003
Date of Patent:
December 12, 2006
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Simon Charles Goodacre, David James Hallett
Abstract: The present invention relates to sulfone derivatives of formula (I): Ar—SO2—CR2R3-L-N(R1)2I wherein Ar, L, R1, R2 and R3 are as defined herein, and pharmaceutically acceptable salts and N-oxides thereof, useful in the treatment of a condition which is susceptible to treatment by modulation of 5-HT7 receptor activity, such as depression or a sleep disorder.
Type:
Grant
Filed:
May 14, 2004
Date of Patent:
September 5, 2006
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Sylvie Bourrain, Peter Alan Hunt, Ian Thomas Huscroft, Janusz Jozef Kulagowski, Clare London, Elizabeth Mary Naylor, Piotr Antoni Raubo, Eileen Mary Seward
Abstract: Compounds of formula I: are antagonists of the human 5-HT2A receptor, and hence useful in treatment or prevention of a variety of neurological conditions.
Type:
Grant
Filed:
November 9, 2004
Date of Patent:
August 22, 2006
Assignee:
Merk Sharp & Dohme Ltd.
Inventors:
Mark Stuart Chambers, Neil Roy Curtis, Angus Murray MacLeod, Robert James Maxey, Helen Jane Szekeres
Abstract: A method for the inhibition of high affinity glycine transporters, compounds that inhibit these transporters; pharmaceutically active compositions comprising such compounds; and the use of such compounds either as above, or in formulations for the control or prevention of disease states in which glycine is involved are disclosed.
Type:
Grant
Filed:
September 7, 2001
Date of Patent:
May 23, 2006
Assignee:
Merck & Co., Inc.
Inventors:
Syed M. Ali, Kurt R. Brunden, Dario Doller, Brian Herbert, Jack B. Jiang, Amy Jordan
Abstract: A class of imidazo[1,2-?]pyrimidine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, are selective ligands for GABAA receptors, in particular having good affinity for the ?2 and/or ?3 and/or ?5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
Type:
Grant
Filed:
March 19, 2002
Date of Patent:
April 18, 2006
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Wesley Peter Blackaby, Jose Luis Castro Pineiro, Mark Stuart Chambers, Simon Charles Goodacre, David James Hallett, Philip Jones, Richard Thomas Lewis, Angus Murray MacLeod, Robert James Maxey, Kevin William Moore, Leslie Joseph Street
Abstract: The compound (I) is a GABAa receptor ligand, functionally selective for the ?2 and/or ?3 subunit, and is useful in the treatment of deleterious mental states, in particular anxiety.
Type:
Grant
Filed:
September 13, 2002
Date of Patent:
March 21, 2006
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Robert William Carling, Kevin William Moore, Leslie Joseph Street
Abstract: A class of 7-phenylimidazo[1,2-b][1,2,4]triazine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, and substituted on the phenyl ring by one or two further substituents as defined herein, being selective ligands for GABAA receptors, in particular having good affinity for the ?2 and/or ?3 and/or ?5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
Type:
Grant
Filed:
May 1, 2003
Date of Patent:
February 28, 2006
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Michela Bettati, Mark Stuart Chambers, Simon Charles Goodacre, David James Hallett, Michael Geoffrey Neil Russell, Leslie Jospeh Street
Abstract: The present invention provides a compound of formula I, or an N-oxide thereof or a pharmaceutically acceptable salt thereof: wherein X1 represents hydrogen, halogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy; X2 represents hydrogen or halogen; Z represents hydrogen, halogen, cyano, cyanomethyl, trifluoromethyl, nitro, hydroxy, hydroxy(C1-6)alkyl, C1-6 alkoxy, C1-6 alkoxy(C1-6)alkyl, trifluoromethoxy, trifluoromethylthio, trifluoromethanesulfinyl, formyl, C2-6 alkoxycarbonyl, oxopyrrolidinyl, or an optionally substituted aryl, heteroaryl or heteroaryl(C1-6)alkoxy group; and R1 represents aryl or heteroaryl, either of which groups may be optionally substituted; pharmaceutical compositions comprising it, its use in therapy and methods of treatment of anxiety and/or depression using it.
Type:
Grant
Filed:
January 30, 2004
Date of Patent:
November 29, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Wesley Peter Blackaby, Simon Charles Goodacre, David James Hallett, Andrew Jennings, Richard Thomas Lewis, Leslie Joseph Street, Kevin Wilson
Abstract: The present invention relates compounds that are NK-1 antagonists and that are of use in the treatment or prevention of depression, anxiety, pain, inflammation, migaine, emesis or postherpetic neuralgia.
Type:
Grant
Filed:
September 10, 2001
Date of Patent:
November 15, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Brian John Williams, Christopher John Swain, Simon Neil Owen
Abstract: A class of [1,8] naphthyridine analogues which are substituted in the 4-position by a substituted phenyl ring. These compounds are ligands for GABAA receptors and useful in the therapy of deleterious mental states such as anxiety.
Type:
Grant
Filed:
July 3, 2002
Date of Patent:
November 1, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
William Robert Carling, Andrew Mitchinson, Michael Geoffrey Russell, Leslie Joseph Street
Abstract: The present invention provides trichloroethyl-sulfonylurea-containing compounds that inhibit glycing transporters, pharmaceutical compositions comprising such compounds, methods for using such compounds for inhibiting glycine transporters and methods for using such compounds for the treatment of disease states in which glycine is involved.
Type:
Grant
Filed:
September 13, 2001
Date of Patent:
September 20, 2005
Assignee:
Merck & Co., Inc.
Inventors:
Syed M. Ali, Kurt R. Brunden, Jack B. Jiang
Abstract: A class of 7-phenylimidazo[1,2-b][1,2,4]triazine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, being selective ligands for GABAA receptors, in particular having good affinity for the ?2 and/or ?3 and/or ?5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
Type:
Grant
Filed:
November 8, 2001
Date of Patent:
August 30, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Michela Bettati, Peter Blurton, William Robert Carling, Mark Stuart Chambers, David James Hallett, Andrew Jennings, Richard Thomas Lewis, Michael Geoffrey Neil Russell, Leslie Joseph Street, Helen Jane Szekeres, Monique Bodil Van Neil
Abstract: A class of 3-phenylimidazo[1,2-c]pyrimidine derivatives, of the formula I: (wherein R1, X, Y, and Z are defined herein) are selective ligands for GABA-A receptors and are useful in the treatment or prevention of adverse conditions of the central nervous system, including anxiety and convulsions.
Type:
Grant
Filed:
November 8, 2001
Date of Patent:
July 5, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
David James Hallett, Michael Geoffrey Neil Russell, Leslie Joseph Street
Abstract: The present invention relates to imidazo[2,1-f]triazin-4-one analogues which are substituted in the 7-position by a substituted phenyl ring, being ligands for GABAA receptors and accordingly of benefit in the therapy of deleterious neurological disorders.
Abstract: A class of imidazo[1,2-?]pyrazine analogues substituted in the 3-position by a substituted phenyl ring, being selective ligands for GABAA receptors which interact more favourably with the ?2 and/or ?3 subunit than with the ?1 subunit, are accordingly of benefit in the treatment and/or prevention of a variety of disorders of the central nervous system, including anxiety and convulsions, with a reduced propensity to cause sedation.
Type:
Grant
Filed:
July 18, 2001
Date of Patent:
July 5, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Simon Charles Goodacre, David James Hallett, Leslie Joseph Street
Abstract: The present invention relates compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7 and R8 represent a variety of substituents; and pharmaceutically acceptable salts thereof. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia.
Type:
Grant
Filed:
January 16, 2002
Date of Patent:
June 14, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Jose Luis Castro Pineiro, Piotr Antoni Raubo, Christopher John Swain
Abstract: A class of 3-phenylimidazo[1,2-?]pyrimidine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, and further substituted on the phenyl ring by alkyl, trifluoromethyl, alkoxy or one or two halogen atoms, especially fluoro, are selective ligands for GABAA receptors, in particular having good affinity for the ?2 and/or ?3 and/or ?5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
Type:
Grant
Filed:
March 19, 2002
Date of Patent:
May 31, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Mark Stuart Chambers, Simon Charles Goodacre, David James Hallett, Andrew Jennings, Philip Jones, Richard Thomas Lewis, Kevin William Moore, Michael Geoffrey Neil Russell, Leslie Joseph Street, Helen Jane Szekeres
Abstract: A compound of formula I, or a pharmaceutically acceptable salt thereof: wherein X1 represents hydrogen, halogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy; X2 represents hydrogen or halogen; Y represents a chemical bond, an oxygen atom, or a —NH— linkage; Z represents an optionally substituted aryl or heteroaryl group; R1 represents hydrocarbon, a heterocyclic group, trifluoromethyl, —SO2Ra, —SO2NRaRb, —CORa, —CO2Ra or —CONRaRb; and Ra and Rb independently represent hydrogen, hydrocarbon or a heterocyclic group; pharmaceutical compositions including the compound and methods for treating anxiety, convulsions and cognitive disorders are disclosed.
Abstract: A class of 3-phenylimidazo[1,2-a]pyridine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH-linkage, are selective ligands for GABAA receptors, in particular having high affinity for the ?2 and/or ?3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.
Type:
Grant
Filed:
May 23, 2002
Date of Patent:
March 29, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
James Michael Crawforth, Simon Charles Goodacre, Timothy Harrison, David James Hallett, Andrew Pate Owens, Michael Rowley, Martin Richard Teall
Abstract: A class of substituted pyrazolo[1,5-d][1,2,4]triazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 7-position, an alkyl group at the 4-position, and a substituted alkoxy moiety at the 2-position, are selective ligands for GABAA receptors, in particular having high affinity for the ?2 and/or ?3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.
Type:
Grant
Filed:
April 4, 2001
Date of Patent:
March 29, 2005
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
William Robert Carling, Andrew Mitchinson, Michael Geoffrey Russell, Leslie Joseph Street