Merck Sharp + Dohme Corp.

Andrew S Jennings

Leslie Joseph Street

Richard Thomas Lewis

David James Hallett

Wesley Peter Blackaby

Simon Charles Goodacre

Mark Stewart Chambers

Kevin William Moore

Helen Jane Szekeres

Michael Geoffrey Neil Russell

Elizabeth Mary Naylor

George D Hartman

Craig William Lindsley

Philip Jones

Mark E Duggan

William Robert Carling

Kevin J Wilson

Stephen Robert Fletcher

Scott E Wolkenberg

Zhijian Zhao

Peter Blurton

Michela Bettati

David Wisnoski

Joanne Thomson

Monique Bodil Van Neil

William H Leister

Yi Wang

David D Wisnoski

The present invention is directed to pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl piperidine 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.

Heteroaryl piperidine glycine transporter inhibitors

The present invention provides compounds of formula (I), wherein both p's are one or two, Ris generally heteroaryl or cycloalkyl, Ris Ccycloalkyl or phenyl and Ris heteroaryl, and pharmaceutically acceptable salts thereof, as GlyT1 inhibitors for treating schizophrenia, pharmaceutical compositions comprising the same and methods for their preparation. 

Piperidine and azetidine derivatives as GlyT1 inhibitors

The present invention provides a compound of formula I, or an N-oxide thereof or a pharmaceutically acceptable salt thereof:wherein Xrepresents hydrogen, halogen, Calkyl, trifluoromethyl or Calkoxy; Xrepresents hydrogen or halogen; Z represents hydrogen, halogen, cyano, cyanomethyl, trifluoromethyl, nitro, hydroxy, hydroxy(C)alkyl, Calkoxy, Calkoxy(C)alkyl, trifluoromethoxy, trifluoromethylthio, trifluoromethanesulfinyl, formyl, Calkoxycarbonyl, oxopyrrolidinyl, or an optionally substituted aryl, heteroaryl or heteroaryl(C)alkoxy group; and Rrepresents 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.

5-phenyl[1,2,4]triazines as ligands for GABA-A &#x3b1;2/&#x3b1;3 receptors for treating anxiety or depression

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 &#x2014;NH&#x2014; linkage, being selective ligands for GABAreceptors, in particular having good affinity for the &#x3b1;2 and/or &#x3b1;3 and/or &#x3b1;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.

Imidazo-triazine derivatives as ligands for GABA receptors

A class of 3-phenylimidazo[1,2-&#x3b1;]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 &#x2014;NH&#x2014; linkage, and further substituted on the phenyl ring by alkyl, trifluoromethyl, alkoxy or one or two halogen atoms, especially fluoro, are selective ligands for GABAreceptors, in particular having good affinity for the &#x3b1;2 and/or &#x3b1;3 and/or &#x3b1;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.

Imidazo-pyrimidine derivatives as ligands for gaba receptors

A class of 3-phenylimidazo(1,2-a)pyrimidine derivatives (of Formula I, or salt or prodrug thereof: I) wherein Y represents a chemical bond, an oxygen atom, or a &mdash;NH&mdash; linkage; Z represents an optionally substituted aryl or heteroaryl group; R represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano trifluoromethyl, nitro, &mdash;OR , &mdash;SR , &mdash;SOR , &mdash;SO R , &mdash;SO NR R , &mdash;NR R , &mdash;NR COR , &mdash;NR CO R , &mdash;COR , CO R , &mdash;CONR R or &mdash;CR &boxH;NOR ; and R and R independently represent hydrogen, hydrocarbon or a heterocyclic group.), 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 &mdash;NH&mdash; linkage, are selective ligands for GABA receptors, in particular having good affinity for the a2 and/or a3 and/or a5 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.

3-Phenyl-imidazo-pyrimidine derivatives as ligands for GABA receptors

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Harlow, United Kingdom

Andrew S Jennings