Cancer Research Technology Limited

Other

The Institute of Cancer Research

Vernalis (cambridge) Limited

Vernalis &r&d) Ltd.

Institute of Cancer Research of Royal Cancer Hospital

Vernalis Limited

Xavier Barril-Alonso

Brian William Dymock

Martin James Drysdale

Allan Michael Jordan

Christofe Fromont

Edward McDonald

Paul Workman

Laurence Pearl

Chrisostomos Prodromou

Brian William Evotec Oai Ltd Dymock

Allan Vernalis Limited Jordan

Martin James Vernalis Ltd Drysdale

Christofe Vernalis Ltd Fromont

Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, cancer: wherein Ris a group of formula &#x2014;(Ar)-(Alk)-(Z)-(Alk2)-Q wherein Aris an optionally substituted aryl or heteroaryl radical, Alk' and Alk 2 are optionally substituted divalent C-Calkylene or C-Calkenylene radicals, m, p, r and s are independently 0 or 1, Z is &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;(C&#x2550;O)&#x2014;, &#x2014;(C&#x2550;S)&#x2014;, &#x2014;SO&#x2014;, &#x2014;C(&#x2550;O)O&#x2014;, &#x2014;C(&#x2550;O)NR&#x2014;, &#x2014;C(&#x2550;S)NR&#x2014;, &#x2014;SONR&#x2014;, &#x2014;NRC(&#x2550;O)&#x2014;, &#x2014;NRSO&#x2014; or &#x2014;NR&#x2014; wherein Ris hydrogen or C-Calkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; Ris hydrogen, an optional substituent, or an optionally substituted (C-C)alkyl, aryl or heteroaryl radical; and Ris a carboxylic ester, carboxamide or sulfonamide group. 

Substituted thieno[2,3-d]pyrimidines as HSP90 inhibitors

Compounds of formula (1) are inhibitors of HSP90 activity in vitro or in vivo, and of use in the treatment of inter alia, Cancer: wherein Ris a group of formula &#x2014;(Ar)-(Alk)-(Z)-(Alk 2)-Q wherein Aris an optionally substituted aryl or heteroaryl radical, Alk' and Alk 2 are optionally substituted divalent C-Calkylene or C-Calkenylene radicals, m, p, r and s are independently 0 or 1, Z is &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;(C&#x2550;O)&#x2014;, &#x2014;(C&#x2550;S)&#x2014;, &#x2014;SO&#x2014;, &#x2014;C(&#x2550;O)O&#x2014;, &#x2014;C(&#x2550;O)NR&#x2014;, &#x2014;C(&#x2550;S)NR&#x2014;, &#x2014;SONR&#x2014;, &#x2014;NRC(&#x2550;O)_, &#x2014;NRSO- or &#x2014;NR&#x2014;wherein Ris hydrogen or C-Calkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; Ris hydrogen, an optional substituent, or an optionally substituted (C-C)alkyl, aryl or heteroaryl radical; and Ris a carboxylic ester, carboxamide or sulfonamide group. 

The present invention pertains to the use of certain 3,4-diarylpyazoles of formula (I), both in vitro and in vivo, to inhibit heat shock protein 90 (HSP90), and in the treatment of conditions mediated by HSP90, including, for example, cancer; wherein: Aris independently: a Caryl group, and is optionally substituted; Aris independently: a Caryl group, and is optionally substituted; Ris independently: hydrogen; halo; hydroxyl; ether; formyl; acyl; carboxy; ester; acyloxy; oxycarbonyloxy; amido; acylamido; aminocarbonyloxy; tetrazolyl; amino; nitro; cyano; azido; sulfhydryl; thioether; sulfonamide; Calkyl; Cheterocycyl; or Caryl; R&#x3c;SP&#x3e;N&#x3c;/SP&#x3e; is independently: &#x2014;H; Calkyl; Cheterocycyl; or, Caryl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, such compounds for medical use, such compounds use in the treatment of conditions mediated by HSP90, including, for example, cancer, and use of such compounds in the preparation of medicaments for such treatments.

3,4-diarylpyrazoles and their use in the therapy of cancer

Growing community of inventors

Abington, United Kingdom

Xavier Barril-Alonso