Abstract: The present invention provides compounds of formula I: wherein R1 is an alkyl, phenyl, heterocyclyl, cycloalkyl, alkoxy, ester, amino or amide group; R2 is a phenyl, heterocyclyl, alkyl, cycloalkyl or cycloalkylalkyl group; R3 is an alkyl, cycloalkyl, cycloalkylalkyl, amino or heterocyclyl group; R4 and R5 are hydrogen or alkyl or form a cycloalkyl ring; A is O or N; and m is zero or one; as inhibitors of GlyT1 and thus as useful for treating or preventing diseases such as schizophrenia; with the provision of pharmaceutical compositions, first and second medical uses and methods of treatment.
Type:
Grant
Filed:
June 5, 2006
Date of Patent:
December 1, 2009
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Wesley Peter Blackaby, Jose Luis Castro Pineiro, Richard Thomas Lewis, Elizabeth Mary Naylor, Leslie Joseph Street
Abstract: Novel sulphones of Formula I are disclosed: wherein A completes a 4-7 membered ring optionally comprising up to two heteroatoms. The compounds modulate the action of ?-secretase and are therefore useful in the treatment or prevention of Alzheimer's disease.
Type:
Grant
Filed:
April 23, 2007
Date of Patent:
October 6, 2009
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Jose Luis Castro Pineiro, Ian Churcher, Kevin Dinnell, Timothy Harrison, Sonia Kerrad, Alan John Nadin, Paul Joseph Oakley, Andrew Pate Owens, Duncan Edward Shaw, Martin Richard Teall, Susannah William, 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:
May 6, 2008
Date of Patent:
September 29, 2009
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Jose Luis Castro Pineiro, Ian Churcher, Kevin Dinnell, Timothy Harrison, Sonia Kerrad, Alan John Nadin, Paul Joseph Oakley, Andrew Pate Owens, Duncan Edward Shaw, Martin Richard Teall, Susannah William, Brian John Williams
Abstract: Compounds of formula (I) are potent and selective 5-HT2A antagonists, useful in treatment of a variety of adverse conditions of the CNS.
Type:
Grant
Filed:
November 28, 2005
Date of Patent:
September 22, 2009
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Mark Stuart Chambers, Neil Roy Curtis, Emanuela Gancia, Myra Gilligan, Alexander Charles Humphries, Tamara Ladduwahetty, Robert James Maxey, Kevin John Merchant
Abstract: The present invention is directed to azetidine compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neurotransmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.
Abstract: The present invention discloses a compound of formula I, or a pharmaceutically acceptable salt thereof: (I) wherein —U—V— represents —CH?CH—, or —CH2—CH2—, —N?CH— or —CH?N—; 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— or —OCH2— 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 comprising it; its use in methods of treatment; use of it in the manufacture of a medicament for treating and/or preventing anxiety; convulsions or a cognitive disorder; and methods of treatment using it.
Type:
Grant
Filed:
October 29, 2003
Date of Patent:
February 3, 2009
Assignee:
Merck Sharp & Dohme Limited
Inventors:
William Robert Carling, Jose Luis Castro Pineiro, Simon Charles Goodacre, David James Hallett, Leslie Joseph Street
Abstract: Compounds of Formula (I): inhibit the processing of APP by gamma-secretase, and hence are useful for treatment or prevention of Alzheimer's disease.
Type:
Grant
Filed:
July 29, 2004
Date of Patent:
November 18, 2008
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Michela Bettati, Amanda Louise Boase, Ian Churcher, Tamara Ladduwahetty, Kevin John Merchant, Abdul Quddus
Abstract: Compounds of formula I: inhibit the processing of AP by gamma-secretase, and hence are useful for treatment or prevention of Alzheimer's disease.
Type:
Grant
Filed:
October 31, 2003
Date of Patent:
September 23, 2008
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Ian James Collins, Joanne Clare Hannam, Timothy Harrison, Andrew Madin, Mark Peter Ridgill
Abstract: The present invention provides a compound of formula (I): in which Ar and R1 are phenyl or a heteroaromatic group, R2 is generally hydrogen, R3 is hydrogen or alkyl and X, Y and Z are generally CH or N as VR-1 antagonists; or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising it; its use in therapy; use of it to manufacture medicaments to treat pain or inflammation; and methods of treating pain or inflammation
Type:
Grant
Filed:
April 5, 2004
Date of Patent:
February 12, 2008
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Peter Blurton, Frank Burkamp, Stephen Robert Fletcher, A. Brian Jones, Edward Giles McIver
Abstract: There is provided an assay for identifying compounds which interact with the ?-secretase complex, in particular compounds that lower the production of A?42.
Abstract: Compounds of formula I are disclosed: in which X is a 5-membered heteroaryl ring and R is as defined herein. The compounds are inhibitors of the processing of APP by gamma-secretase, and hence are useful in the treatment or prevention of Alzheimer's disease.
Type:
Grant
Filed:
March 2, 2006
Date of Patent:
October 16, 2007
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Ian James Collins, Laura Catherine Cooper, Timothy Harrison, Linda Elizabeth Keown, Andrew Madin, Mark Peter Ridgill
Abstract: A class of 8-fluoro-3-phenylimidazo[1,2-?]pyridine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group, or by a pyrrolidinonyl group, which is directly attached or bridged by an oxygen atom or by a —NH— or —OCH2— linkage, 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:
October 9, 2007
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Simon Charles Goodacre, David James Hallett, Alexander Charles Humphries, Philip Jones, Sarah Margaret Kelly, Kevin John Merchant, Kevin William Moore, Michael Reader
Abstract: A novel process for preparing cyclohexanone derivatives of formula (I) is described. The products are useful as gamma secretase inhibitors, or as intermediates in the synthesis of other gamma secretase inhibitors.
Type:
Grant
Filed:
July 30, 2003
Date of Patent:
October 2, 2007
Assignees:
Merck Sharp & Dohme Limited, Merck & Co., Inc.
Inventors:
Karel Marie Joseph Brands, Antony John Davies, Paul Joseph Oakley, Jeremy Peter Scott, Duncan Edward Shaw, Martin Richard Teall
Abstract: Substituted carbocyclic sulphonamide derivatives of formula (I), in which n is 0 or 1 and the other variables are as defined in the claims, are selective 5-HT7 receptor antagonists and are thereby effective in the treatment of a variety of neurological conditions, including depression and sleep disorders.
Type:
Grant
Filed:
November 29, 2002
Date of Patent:
October 2, 2007
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Neil Roy Curtis, Peter Alan Hunt, Janusz Jozef Kulagowski
Abstract: The present invention relates compounds of the formula (I); wherein R1, R2, R3, R4, R5, R6, R7, R8, and R10 represent a variety of substituents; A represents NR9 or O; B represents a bond, CH2, NR9 or O, wherein one or both hydrogen atoms in said CH2 moiety may be replaced with one or both of R7 and R8, or alternatively, one of the hydrogen atoms in said CH2 moiety together with a hydrogen atom from an adjacent carbon are replaced by a double bond; with the proviso that when A is O, then B is NR9; n is zero, 1 or 2; and pharmaceutically acceptable salts thereof.
Type:
Grant
Filed:
September 6, 2002
Date of Patent:
September 4, 2007
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Jose Luis Castro Pineiro, Duncan Edward Shaw, Brian John Williams
Abstract: The present invention is directed to the improved synthesis of compounds of formula (I) an intermediate compound which is useful in the synthesis of the anticancer agents known as PSA conjugates.
Inventors:
Michael Stewart Ashwood, Brian Christopher Bishop, Ian Frank Cottrell, Khateeta Moneek Emerson, David Hands, Guo Jie Ho, Joseph Edward Lynch, Yao Jun Shi, Robert Darrin Wilson
Abstract: The present invention relates compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 represent a variety of substituents, ring A is a phenyl or pyridyl ring; d is zero, 1 or 2; and pharmaceutically acceptable salts and N-oxides thereof.
Type:
Grant
Filed:
June 10, 2002
Date of Patent:
August 7, 2007
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Jose Luis Castro Pineiro, Kevin Dinnell, Jason Matthew Elliott, Gregory John Hollingworth, Duncan Edward Shaw, Christopher John Swain
Abstract: The present invention is directed to compounds of the formula I: I(wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X, n and the dashed line are defined herein) which are useful as modulators of chemokine receptor activity.
Inventors:
Richard Jiao, Stephen D. Goble, Sander G. Mills, Gregori Morriello, Alexander Pasternak, Lihu Yang, Changyou Zhou, Gabor Butora, Shankaran Kothandaraman, Deodialsingh Guiadeen, Christopher Moyes
Abstract: The invention provides compounds of formula I: which are inhibitors of ?-secretase and hence useful in the treatment or prevention of Alzheimer's disease.
Type:
Grant
Filed:
September 25, 2003
Date of Patent:
January 9, 2007
Assignee:
Merck Sharp & Dohme Limited
Inventors:
James Michael Crawforth, Jason Matthew Elliott, Andrew Pate Owens, Francine Sternfeld