Pharma Mar, S.a.

Jonathan Charles Morris

Ignacio Manzanares

Regan James Anderson

Carmen Cuevas

Simon Munt

Andres Francesh

Juan Jose Gonzalez

Carlos Del Pozo

Modesto Remuiñan

Modesto Remuiñán

Variolin derivatives of formula (5) are provided, wherein the substituent groups defined by X, R, R, R, R, R, and Rare each independently selected from the group consisting of H, OH, OR', SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), NHCOR&#x2032;, NHSOR&#x2032;, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)R&#x2032;, COH, COR&#x2032;, carboxyalkyl, C-Calkyl, C-Calkenyl, C-Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; wherein each of the R&#x2032; groups is independently selected from the group consisting of H, OH, SH, NO, NH, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)CH, COH, COCH, C-Calkyl, C-Calkenyl, C-Calkynyl, aryl, aralkyl and heteroaromatic; wherein the pairs of groups of Rand R, Rand R, Rand R, Rand R, or Rand Rmay be joined into a carbocyclic or heterocyclic ring system.

Variolin derivatives and their use as antitumor agents

Variolin derivatives of formula (5) are provided, wherein the substituent groups defined by X, R, R, R, R, Rand Rare each independently selected from the group consisting of H, OH, OR', SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), NHCOR&#x2032;, NHSOR&#x2032;, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)R&#x2032;, COH, COR&#x2032;, carboxyalkyl, C-Calkyl, C-Calkenyl, C-Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; wherein each of the R&#x2032; groups is independently selected from the group consisting of H, OH, SH, NO, NH, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)CH, COH, COCH, C-Calkyl, C-Calkenyl, C-Calkynyl, aryl, aralkyl and heteroaromatic; wherein the pairs of groups Rand R, Rand R, Rand R, Rand R, or Rand Rmay be joined into a carbocyclic or heterocyclic ring system. 

The invention provides variolin derivatives of formula (I), wherein: Rand Rare each independently selected from the group consisting of H, OH, OR, SH, SR, SOR, SOR, NO, NH, NHR, N(R), NHCOR, N(COR), NHSOR, CN, halogen, C(&#x2550;O)H, C(&#x2550;O)R, COH, COR, C-Calkyl, C-Chaloalkyl, C-Calkenyl, C-Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; and Ris selected from the group consisting of H, OH and OMe; wherein the or each group R is independently selected from the group consisting of OH, C-Calkyl, C-Chaloalkyl, C-Calkenyl, C-Calkynyl, substituted or unsubstituted aryl, substituted unsubstituted aralkyl, substituted or unsubstituted arylalkenyl and substituted or unsubstituted heteroaromatic, and wherein the group R, Ror Ris a group of formula N(R)or N(COR), each of the R groups may be the same or different, or the two R groups, together with the nitrogen atom to which they are attached, may form a 5-14 membered heterocyclic ring. These compounds display activity against a range of mammalian cancer cell lines. New synthetic routes to new and known variolin compounds, together with novel intermediates, are also disclosed. New antitumour activity of known variolin compounds is also described.

Variolin derivatives as anti-cancer agents

Growing community of inventors

Christchurch, New Zealand

Jonathan Charles Morris