Merck Sharp + Dohme Corp.

Peter Blurton

Stephen Robert Fletcher

Frank Burkamp

Angus Murray MacLeod

Edward Giles McIver

Susan Koon-Fung Cheng

A Brian Jones

Daniel Spinks

Leslie Joseph Street

William Robert Carling

Mark Stewart Chambers

Richard Thomas Lewis

David James Hallett

Gregory John Hollingworth

Christopher Richard Moyes

Helen Jane Szekeres

Michael Geoffrey Neil Russell

Andrew S Jennings

Michela Bettati

Lauren Rogers

Monique Bodil Van Neil

The present invention provides a compound of formula (I): wherein V represents NR, O, S, SO or S(O); W and X each independently represent CH or N; Y represents N, CH or C&#x2014;Ar, with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C&#x2014;Ar, with the proviso that when Y is N or CH then Z is C&#x2014;Ar, and with the further proviso that when Y is C&#x2014;Arthen Z is CH; Arrepresents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Arrepresents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; Rrepresents halogen, hydroxy, oxo, Calkyl, Calkenyl, Calkynyl, haloCalkyl, hydroxyCalkyl, Calkoxy, haloCalkoxy, hydroxyCalkoxy, Ccycloalkyl, Ccycloalkoxy, CcycloalkylCalkyl, cyano, nitro, SR, SOR, SOR, COR, NRCOR, CONRR, NRSOR, SONRR, &#x2014;(CH)carboxy, esterified &#x2014;(CH)carboxy or &#x2014;(CH)NRR; Rrepresents hydrogen, halogen, hydroxy, Calkyl, haloCalkyl, Ccycloalkyl, Calkoxy, haloCalkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, Calkyl, haloCalkyl, Ccycloalkyl, Calkoxy or haloCalkoxy; Rand Rare each independently hydrogen, Calkyl, Calkenyl, Calkynyl, Ccycloalkyl or fluoroCalkyl; or Rand Rand the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or Calkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O), or NR; Rrepresents hydrogen, Calkyl, hydroxyCalkyl or CalkoxyCalkyl; Rrepresents hydrogen, Calkyl, fluoroCalkyl, Ccycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, Calkyl, haloCalkyl, Ccycloalkyl, Calkoxy or haloCalkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it. 

Amino-heterocycles as VR-1 antagonists for treating pain

The present invention provides a compound of formula (I): in which Ar and Rare phenyl or a heteroaromatic group, Ris generally hydrogen, Ris 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 

Substituted-1-phthalazinamines as vr-1 antagonists

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 phenylsulphonyl derivatives wherein the sulphonyl moiety is also attached to an N-arylalkyl-substituted azetidine, pyrrolidine or piperidine ring are selective antagonists of the human 5-HT receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including schizophrenia and depression.

Phenylsulphonyl derivatives as 5-HT receptor ligands

Pyrazolo&lsqb;4,3-c&rsqb;pyridazin-3-one analogues, represented by

Tricyclic pyrazolo-pyridazinone analogues as GAGA-A receptor ligands

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Hitchin, United Kingdom

Peter Blurton