Chroma Therapeutics Limited

Kenneth William John Baker

Sanjay Ratilal Patel

Stephen John Davies

Alan Hornsby Davidson

Francesca Ann Mazzei

Alan Hastings Drummond

Alistair David Graham Donald

David Festus Moffat

David Festus Charles Moffat

Alastair David Graham Donald

Oliver James Philps

David Festus C Moffat

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein Ris a carboxylic acid group (&#x2014;COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; Ris the side chain of a natural or non-natural alpha amino acid; Y is a bond, &#x2014;C(&#x2550;O), &#x2014;S(&#x2550;O)&#x2014;, &#x2014;C(&#x2550;O)O&#x2014;, &#x2014;C(O)NR&#x2014;, &#x2014;C(&#x2550;S)&#x2014;NR, &#x2014;C(&#x2550;NH)NRor &#x2014;S(&#x2550;O)NR&#x2014; wherein Ris hydrogen or optionally substituted C-Calkyl; Lis a divalent radical of formula -(Alk)(Q)(Alk)- wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula &#x2014;X-Q- or -Q-X&#x2014; wherein Xis &#x2014;O&#x2014;, S&#x2014; or NR&#x2014; wherein Ris hydrogen or optionally substituted C-Calkyl, and Qis an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, Alkand Alkindependently represent optionally substituted divalent C-Ccycloalkyl radicals, or optionally substituted straight or branched, C-Calkylene, C-Calkenylene, or C-Calkynylene radicals which may optionally contain or terminate in an ether (&#x2014;O&#x2014;), thioether (&#x2014;S&#x2014;) or amino (&#x2014;NR&#x2014;) link wherein Ris hydrogen or optionally substituted C-Calkyl; Xrepresents a bond; &#x2014;C(&#x2550;O); or &#x2014;S(&#x2550;O)&#x2014;; &#x2014;NRC(&#x2550;O)&#x2014;, &#x2014;C(&#x2550;O)NR&#x2014;, &#x2014;NRC(&#x2550;O)NR&#x2014;, &#x2014;NRS(&#x2550;O)&#x2014;, or &#x2014;S(&#x2550;O)NR&#x2014; wherein Rand Rare independently hydrogen or optionally substituted C-Calkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals RRNH&#x2014;Y-L-X-[CH]&#x2014; and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONIIOII, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms. 

Enzyme inhibitors

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers: 

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers. 

Growing community of inventors

Abingdon, United Kingdom

Kenneth William John Baker