Merck Sharp + Dohme Corp.

Simon Charles Goodacre

David James Hallett

Leslie Joseph Street

Philip Jones

Mark Stewart Chambers

Richard Thomas Lewis

Wesley Peter Blackaby

Kevin William Moore

Jose Luis Castro Pineiro

Robert James Maxey

Michael Geoffrey Neil Russell

Andrew S Jennings

Kevin John Merchant

Alexander Charles Humphries

Michael Reader

Timothy Harrison

Angus Murray MacLeod

William Robert Carling

Ian James Collins

Kevin J Wilson

Andrew Pate Owens

Michael Rowley

Martin Richard Teall

Helen Jane Szekeres

Linda Elizabeth Keown

Michela Bettati

James Michael Crawforth

Sarah Margaret Kelly

Leslie Jospeh Street

The present invention discloses a compound of formula I, or a pharmaceutically acceptable salt thereof: (I) wherein &#x2014;U&#x2014;V&#x2014; represents &#x2014;CH&#x2550;CH&#x2014;, or &#x2014;CH&#x2014;CH&#x2014;, &#x2014;N&#x2550;CH&#x2014; or &#x2014;CH&#x2550;N&#x2014;; Xrepresents hydrogen, halogen, Calkyl, trifluoromethyl or Calkoxy; Xrepresents hydrogen or halogen; Y represents a chemical bond, an oxygen atom, or a &#x2014;NH&#x2014; or &#x2014;OCH&#x2014; linkage; Z represents an optionally substituted aryl or heteroaryl group; Rrepresents hydrocarbon, a heterocyclic group, trifluoromethyl, &#x2014;SOR, &#x2014;SONRR, &#x2014;COR, &#x2014;CORor &#x2014;CONRR; and Rand Rindependently 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. 

Imidazopyrazinones as GABA-A receptor anxiolytics

A class of 8-fluoro-3-phenylimidazo[1,2-&#x3b1;]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 &#x2014;NH&#x2014; or &#x2014;OCH&#x2014; linkage, being selective ligands for GABAreceptors, in particular having high 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-pyridine derivatives as ligands for GABA receptors

A class of 8-fluoroimidazo[1,2-&#x3b1;]pyridine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, being selective ligands for GABAreceptors, in particular having high 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.

8-fluoroimidazo 1,2-a pyridine derivatives as ligands for GABA receptors

A class of imidazo[1,2][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 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

The present invention discloses a compound of formula 1, or a pharmaceutically acceptable salt thereof: wherein Xrepresents hydrogen, halogen, Calkyl, trifluoromethyl or Calkoxy; Xrepresents hydrogen or halogen; Y represents a chemical bond, an oxygen atom, or a &#x2014;NH&#x2014; linkage; Z represents an optionally substituted aryl or heteroaryl group; Rrepresents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, &#x2014;OR, &#x2014;SR, &#x2014;SOR, &#x2014;SOR, &#x2014;SONRR, NRR, &#x2014;NRCOR, &#x2014;NRCOR, &#x2014;COR, &#x2014;COR, &#x2014;CONRRor &#x2014;CR&&#x2550;NOR; 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. 

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A class of imidazo[1,2-&#x3b1;]pyrimidine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, 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 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, and substituted on the phenyl ring by one or two further substituents as defined herein, 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.

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 imidazo[1,2-&#x3b1;]pyrazine analogues substituted in the 3-position by a substituted phenyl ring, being selective ligands for GABAreceptors which interact more favourably with the &#x3b1;2 and/or &#x3b1;3 subunit than with the &#x3b1;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.

Imidazo-pyrazine derivatives as ligands for GABA receptors

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 GABAreceptors and accordingly of benefit in the therapy of deleterious neurological disorders.

Imidazotriazinone 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 compound of formula I, or a pharmaceutically acceptable salt thereof:wherein

Imidazo[4,5-c]pyridin-4-one analogues as GABAA receptor ligands

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 &#x2014;NH-linkage, are selective ligands for GABAreceptors, in particular having high affinity for the &#x3b1;2 and/or &#x3b1;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.

A class of substituted or 6,7-ring fused &lsqb;1, 2, 3&rsqb;triazolo&lsqb;1,5-&agr;&rsqb;-pyrimidine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position and an amino moiety at the 5-position, are selective ligands for GABA receptors, in particular having high affinity for the &agr;2 and/or &agr;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.

Triazolo-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.

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Benington, United Kingdom

Simon Charles Goodacre