Smithkline Beecham Corporation

Glaxo Group Limited

Arrow Therapeutics Limited

Glaxosmithkline LLC

Glaxo Wellcome Inc.

Novartis Ag

Astrazeneca Ab

Malcolm Clive Carter

George Stuart Cockerill

Stephen Barry Guntrip

Kathryn Jane Smith

Karen Elizabeth Lackey

Alan Naylor

John Bradshaw

Neil Anthony Pegg

Jeremy John Payne

Debra Taylor

Richard Kelsey

Lara Wilson

Elisa Henderson

John W Clitherow

Eric W Collington

Christopher J Wallis

Peter Hallett

Norman F Hayes

Philip Blatcher

Roy Hornby

Martin Richard Owen

Phil Chambers

Stan Tyms

Verity Dowdell

Alexander W Oxford

Peter C North

William L Mitchell

Richard Angell

Neil Mathews

Martin Pass

James Lumley

Alan Wadsworth

Christopher Pilkington

Christopher James Wheelhouse

Alexander James Floyd Thomas

David John Bushnell

Dagmar Alber

James Iain Salter

Philip Chambers

Stanley Tyms

Kenneth Powell

Christopher John Pilkington

Richard Martyn Angell

A pharmaceutical formulation comprising the compound of formula 

Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors

A pharmaceutical composition which comprises a pharmaceutically acceptable carrier or diluent and: (a) an inhibitor of the RSV fusion protein; and (b) a benzodiazepine derivative capable of inhibiting RSV replication is found to be highly active against RSV.

Pharmaceutical composition comprising a benzodiazepine derivative and an inhibitor of the RSV fusion protein

A process for the preparation of a compound of formula (I) comprising the steps:(a) reacting a compound of formula (II) wherein L and L' are suitable leaving groups,with a compound of formula (III)UNH&#x2003;&#x2003;(III)to prepare a compound of formula (IV) and subsequently (b) substituting the group Rby replacement of the leaving group L&#x2032;.

Benzodiazepine derivative of formula (I), and pharmaceutically acceptable salts thereof, are found to be active against RSV Formula (I) Wherein: &#x2014;Rrepresents Calkyl, aryl or heteroaryl; &#x2014;Rrepresents hydrogen or Calkyl; -each Ris the same or different and represents halogen, hydroxy, Calkyl, Calkoxy, Calkylthio Chaloalkyl, Chaloalkoxy, amino, mono(Calkyl)amino, di(Calkyl)amino, nitro, cyano, &#x2014;COR', CONR&#x2032;R&#x2033;, &#x2014;NH&#x2014;CO&#x2014;R&#x2032;, &#x2014;S(O)R&#x2032;, &#x2014;S(O)R&#x2032;, &#x2014;NH&#x2014;S(O)R&#x2032;, &#x2014;S(O)NR&#x2032;R&#x2033; or &#x2014;S(O)NR&#x2032;R&#x2033; wherein each R&#x2032; and R&#x2033; is the same or different and represents hydrogen or Calkyl; -n is from 0 to 3; Rrepresents hydrogen or Calkyl; &#x2014;Rrepresents Calkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(Calkyl)-, heteroaryl-(Calkyl)-, carbocyclyl-(Calkyl)-, heterocyclyl-(Calkyl)-, aryl-C(O)&#x2014;C(O)&#x2014;, heteroaryl-C(O)&#x2014;C(O)&#x2014;, carbocyclyl-C(O)&#x2014;C(O)&#x2014;, heterocyclyl-C(O)&#x2014;C(O)&#x2014; or, &#x2014;XR; &#x2014;X represents &#x2014;CO&#x2014;, &#x2014;S(O)&#x2014; or &#x2014;S(0)&#x2014;; and &#x2014;Rrepresents Calkyl, hydroxy, Calkoxy, Calkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(Calkyl)-, heteroaryl-(Calkyl)-, carbocyclyl-(Calkyl)-, heterocyclyl-(Calkyl)-, aryl-(Chydroxyalkyl)-, heteroaryl-(Chydroxyalkyl)-, carbocyclyl-(Chydroxyalkyl)-, heterocyclyl-(Chydroxyalkyl)-, aryl-(Calkyl)-O&#x2014;, heteroaryl-(Calkyl)-O&#x2014;, carbocyclyl-(Calkyl)-O&#x2014;, heterocyclyl-(Calkyl)-O&#x2014; or &#x2014;NR&#x2032;R&#x2033; wherein each R&#x2032; and R&#x2033; is the same or different and represents hydrogen, Calkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl-(Calkyl)-, heteroaryl-(Calkyl)-, carbocyclyl-(Calkyl)- or heterocyclyl-(Calkyl)-. 

Benzodiazepine derivatives and pharmaceutical compositions containing them

Use of a compound which is a biphenyl derivative of formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of Hepatitis C wherein the variables are described herein.

Biphenyl derivatives and their use in treating hepatitis C

Benzodiazepine derivative of formula (I), and pharmaceutically acceptable salts thereof, are found to be active against RSV. Formula (I) Wherein: &#x2014;Rrepresents Calkyl, aryl or heteroaryl; &#x2014;Rrepresents hydrogen or Calkyl; &#x2014;each Ris the same or different and represents halogen, hydroxy, Calkyl, Calkoxy, Calkylthio, Chaloalkyl, Chaloalkoxy, amino, mono(Calkyl)amino, di(Calkyl)amino, nitro, cyano, &#x2014;COR', &#x2014;CONR&#x2032;R&#x2033;, &#x2014;NH&#x2014;CO&#x2014;R&#x2032;, &#x2014;S(O)R&#x2032;, &#x2014;S(O)R&#x2032;, &#x2014;NH&#x2014;S(O)R&#x2032;, &#x2014;S(O)NR&#x2032;R&#x2033; or &#x2014;S(O)NR&#x2032;R&#x2033; wherein each R&#x2032; and R&#x2033; is the same or different and represents hydrogen or Calkyl; &#x2014;n is from 0 to 3; Rrepresents hydrogen or Calkyl; &#x2014;Rrepresents Calkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(Calkyl)-, heteroaryl-(Calkyl)-, carbocyclyl-(Calkyl)-, heterocyclyl-(Calkyl)-, aryl-C(O)&#x2014;C(O)&#x2014;, heteroaryl-C(O)&#x2014;C(O)&#x2014;, carbocyclyl-C(O)&#x2014;C(O)&#x2014;, heterocyclyl-C(O)&#x2014;C(O)&#x2014; or, &#x2014;XR; &#x2014;X represents &#x2014;CO&#x2014;, &#x2014;S(O)&#x2014; or &#x2014;S(O)&#x2014;; and &#x2014;Rrepresents Calkyl, hydroxy, Calkoxy, Calkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(Calkyl)-, heteroaryl-(Calkyl)-, carbocyclyl-(Calkyl)-, heterocyclyl-(Calkyl)-, aryl-(Chydroxyalkyl)-, heteroaryl-(Chydroxyalkyl)-, carbocyclyl-(Chydroxyalkyl)-, heterocyclyl-(Chydroxyalkyl)-, aryl-(Calkyl)-O&#x2014;, heteroaryl-(Calkyl)-O&#x2014;, carbocyclyl-(Calkyl)-O&#x2014;, heterocyclyl-(Calkyl)-O&#x2014; or &#x2014;NR&#x2032;R&#x2033; wherein each R&#x2032; and R&#x2033; is the same or different and represents hydrogen, Calkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl-(Calkyl)-, heteroaryl-(Calkyl)-, carbocyclyl-(Calkyl)- or heterocyclyl-(Calkyl)-. 

A process for the preparation of a compound of formula (I) comprising the steps:  

Heterocyclic compounds

A compound of formula (I): and pharmaceutically acceptable derivatives thereof, wherein Ris H or Calkyl; Ris wherein defines the point of attachment of the ring; and Ris Calkyl or NH. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of pain, fever, inflammation of a variety of conditions and diseases.

Substituted pyrimidines as selective cyclooxygenase-2 inhibitors

The invention provides the compounds of formula (I) and pharmaceutically acceptable salts thereof, in which: Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever, inflammation of a variety of conditions and diseases.

Pyrimidine derivatives as selective inhibitors of COX-2

Substituted heteroaromatic compounds, and in particular substituted quinolines and quinazolines, are protein tyrosine kinase inhibitors. The compounds are described as are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine, for example in the treatment of cancer and psoriasis.

Substituted heteroaromatic compounds of formula (I), wherein X is N or CH; Y is CR and V is N; or Y is N and V is CR ; or Y is CR and V is CR ; or Y is CR and V is CR ; R represents a group CH SO CH CH NHCH &mdash;Ar&mdash;, wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which may optionally be substituted by one or two halo, C alkyl or C alkoxy groups; R is selected from the group comprising hydrogen, halo, hydroxy, C alkyl, C alkoxy, C alkylamino and di&lsqb;C alkyl&rsqb;amino; U represents a phenyl, pyridyl, 3H-imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1H-indazolyl, 2,3-dihydro-1H-indazolyl, 1H-benzimidazolyl, 2,3-dihydro-1H-benzimidazolyl or 1H-benzotriazolyl group, substituted by an R group and optionally substituted by at least one independently selected R group; R is selected from a group comprising benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and trihalobenzyloxy and benzenesulphonyl, or R represents trihalomethylbenzyl or trihalomethylbenzyloxy; or R represents a group of formula (a) wherein each R is independently selected from halogen, C alkyl, C alkoxy; and n is 0 to 3; each R is independently hydroxy, halogen, C alkyl, C alkenyl, C alkynyl, C alkoxy, amino, C alkylamino, di&lsqb;C alkyl&rsqb;amino, C alkylthio, C alkylsulphinyl, C alkylsulphonyl, C alkylcarbonyl, carboxy, carbamoyl, C alkoxycarbonyl, C alkanoylamino, N-(C alkyl)carbamoyl, N,N-di(C alkyl)carbamoyl, cyano, nitro and trifluoromethyl; and salts and solvates thereof, are disclosed, as are methods for their preparation, pharmaceutical compositions containing them and their use in medicine.

Substituted heteroaromatic compounds, and in particular substituted bicyclic heteroaromatic compounds of formula (I), wherein X is N or CH; A represents a fused 5, 6 or 7-membered heterocyclic ring containing 1 to 5 heteroatoms which may be the same or different and which are selected from N, O or S(O) , wherein m is as defined above, the heterocyclic ring containing a total of 1, 2 or 3 double bonds inclusive of the bond in the pyridine or pyrimidine ring to which it is fused, with the provisos that the heterocyclic ring does not form part of a purine and that the fused heterocyclic ring does not contain two adjacent O or S(O) atoms. U represents a 5 to 10-membered mono or bicyclic ring system in which one or more of the carbon atoms is optionally replaced by a heteroatom independently selected from N, O and S(O) , wherein m is 0,1 or 2 and wherein the ring system is substituted by at least one independently selected R group and is optionally substituted by at least one independently selected R group, with the proviso that U does not represent phenyl; are protein tyrosine kinase inhibitors. The compounds are described as are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine, for example in the treatment of cancer and psoriasis.

Protein tyrosine kinase inhibitors

The present invention relates to substituted heteroaromatic compounds, methods for their preparation, pharmaceutical compositions containing them and their use in medicine. Specifically, the invention relates to quinazoline derivatives useful in treating disorders mediated by protein tyrosine kinase activity, in particular erbB-2 and/or EGFR activity.

Growing community of inventors

Stevenage, United Kingdom

Malcolm Clive Carter