Abstract: There is provided stereoselective route to a compound of formula I: wherein R represents H or an alkali metal, Ar1 represents 4-chlorophenyl and Ar2 represents 2,5-difluorophenyl.
Inventors:
Karel Marie Joseph Brands, Sarah Elizabeth Brewer, Antony John Davies, Ulf H. Dolling, Deborah Camille Hammond, David Ross Lieberman, Jeremy Peter Scott
Abstract: Compounds of formula I: inhibit gamma-secretase and hence find use in treatment or prevention of Alzheimer's disease.
Type:
Grant
Filed:
May 7, 2004
Date of Patent:
August 12, 2008
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Kevin Dinnell, Karl Richard Gibson, Timothy Harrison, Richard Alexander Jelley, Alan John Nadin, Paul Joseph Oakley, Andrew Pate Owens, Duncan Edward Shaw, Brian John Williams
Abstract: Disclosed are sulphones which modulate the action of gamma-secretase. The compounds are useful in the treatment or prevention of Alzheimer's disease.
Type:
Grant
Filed:
August 21, 2001
Date of Patent:
August 12, 2008
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Timothy Harrison, Paul Joseph Oakley, Martin Richard Teall
Abstract: The present invention relates to compounds of formula (Ia) wherein A, B, n, m, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are defined herein, 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:
March 4, 2004
Date of Patent:
July 1, 2008
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Olivier Dirat, Jason Matthew Elliott, Ian Thomas Huscroft, Richard Alexander Jelley, Janusz Jozef Kulagowski, Piotr Antoni Raubo, Duncan Edward Shaw, Francine Sternfeld, Christopher John Swain
Abstract: A class of pyridazine derivatives, substituted in the 4-position by an optionally substituted heteroaromatic ring, being selective ligands for GABAA receptors, in particular having high 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:
August 4, 2003
Date of Patent:
June 3, 2008
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Stephen Robert Fletcher, Angus Murray MacLeod, Monique Bodil Van Niel, Kevin Wilson
Abstract: Compounds of formula (I) are disclosed: wherein R4 is an alkenyl group of defined structure. The compounds inhibit gamma-secretase, and hence are useful for treatment of Alzheimer's disease.
Type:
Grant
Filed:
April 24, 2003
Date of Patent:
May 13, 2008
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Jose Luis Castro Pineiro, Joanne Claire Hannam, Timothy Harrison, Andrew Madin, Mark Peter Ridgill
Abstract: A class of compounds is disclosed, comprising sulphonamido-substituted bridged bicycloalkyl structures. The compounds are inhibitors of gamma-secretase, and hence are useful in the treatment of and/or prevention of Alzheimer's disease.
Inventors:
Patrice Charles Belanger, Ian James Collins, Joanne Claire Hannam, Timothy Harrison, Stephen John Lewis, Andrew Madin, Edward Giles McIver, Alan John Nadin, Joseph George Neduvelil, Mark Steven Shearman, Adrian Leonard Smith, Timothy Jason Sparey, Graeme Irvine Stevenson, Martin Richard Teall
Abstract: The invention provides the combined use of an inhibitor of formation or release of ?-amyloid and a nitric oxide releaser for the treatment or prevention of Alzheimer's disease.
Abstract: The present invention relates to the synthesis of intermediates for the preparation of compounds of formula (A): wherein n is 2 or 3 and various salt forms of these compounds.
Inventors:
Brian Christopher Bishop, Karel Marie Joseph Brands, Ian Frank Cottrell, Cameron John Cowden, Antony John Davies, Stephen Philip Keen, David Ross Lieberman, Gavin William Stewart
Abstract: A class of 8-fluoroimidazo[1,2-?]pyridine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, being selective ligands for GABAA receptors, in particular having high 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 23, 2003
Date of Patent:
June 5, 2007
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Wesley Peter Blackaby, Jose Luis Castro Pineiro, Simon Charles Goodacre, David James Hallett, Alexander Charles Humphries, Philip Jones, Kevin John Merchant, Michael Reader
Abstract: The present invention provides a compound of formula I: 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; pharmaceutical compositions comprising this compound and methods of treating and/or preventing anxiety and convulsions using it.
Abstract: There is disclosed a novel class of sulphonamido-substituted bridged bicycloalkyl derivatives comprising a substitute on the bridgehead position. The compounds modulate the production of the ?-amyloid precursor protein, and hence are useful in the treatment of Alzheimer's Disease.
Type:
Grant
Filed:
July 31, 2002
Date of Patent:
April 17, 2007
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Joanne Clare Hannam, Timothy Harrison, Andrew Madin, Timothy Jason Sparey
Abstract: A class of imidazo[1,2b][1,2,4]triazine derivatives, substituted at the 7-position by an optionally substituted five-membered or six-membered heteroaromatic ring, 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 13, 2007
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Mark Stuart Chambers, Simon Charles Goodacre, David James Hallett, Robert James Maxey, Michael Geoffrey Neil Russell, Leslie Joseph Street
Abstract: Compounds of formula I: wherein X represents a 5-(R-substituted)-1,2,4-oxadiazole-3-yl moiety are inhibitors of gamma-secretase, and hence useful for treating Alzheimer's disease
Type:
Grant
Filed:
April 24, 2003
Date of Patent:
January 2, 2007
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Ian James Collins, Laura Catherine Cooper
Abstract: The present invention relates to the cloning of novel cDNA sequences encoding the ?4 and ? receptor subunits of the human GABA A receptor; to stably co-transfected eukaryotic cell lines capable of expressing a human GABAA receptor, which receptor comprises at least one of the novel ?4 and ? receptor subunits; and to the use of such cell lines in screening for and designing medicaments which act upon the human GAGAA receptor.
Type:
Grant
Filed:
August 2, 2002
Date of Patent:
January 2, 2007
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Beatrice Le Bourdelles, Paul John Whiting
Abstract: The present invention provides a method of treatment of a subject suffering from a disease, such as schizophrenia, for which the administration of an NK-3 antagonist is indicated which comprises administering to that subject a therapeutically effective amount of a compound of formula I: wherein, generally, Q is R1 is benzyl, phenyl, thiophene or imidazolyl optionally substituted with C1-4alkyl or halogen, such as methyl, fluorine or bromine; R2 is hydrogen or C1-4alkyl such as methyl; R3 is phenyl; R4 is hydrogen; R5 is hydrogen or C1-6alkylcarbonyl such as methylcarbonyl; X is —SO2— or —C(O)N(R2)SO2— where R2 is preferably hydrogen; Y is a bond, CH2 or Z1 where Z1 is —N(Rf)— in which Rf is C1-6alkylcarbonyl such as ethylcarbonyl; and R6 is phenyl, pyrazolyl, pyridyl, pyrimidinyl or benzimidazolonyl optionally substituted with one or two groups chosen from C1-6alkyl and benzyl, such as methyl, ethyl and benzyl; or a pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
April 16, 2003
Date of Patent:
December 26, 2006
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Mark Stuart Chambers, Philip Jones, Helen Jane Szekeres
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 provides a compound of formula (I) in which R1 is generally hydrogen or CF3, R2 is generally hydrogen, W is a cyclic amine, a heterocycle or a group L-Y—X where L-Y is a linking portion and X is generally an aromatic or non-aromatic heterocycle, alkyl or alkylcarbonyl and Z is generally a heterocycle such as 5-methylisoxazol-3-yl, and pharmaceutically acceptable salts thereof for enhancing cognition in conditions such as Alzheimer's Disease, pharmaceutical compositions comprising them, their use for manufacturing medicaments and methods of treatment using them
Type:
Grant
Filed:
December 11, 2000
Date of Patent:
December 5, 2006
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Helen Jane Bryant, Mark Stuart Chambers, Philip Jones, Angus Murray MacLeod, Robert James Maxey