POLYMER CONJUGATE COMPOUNDS FOR THE INHIBITION OF APOPTOSIS

摘要

The present invention relates to polymer conjugate compounds, as well as to processes for their preparation, to pharmaceutical compositions containing them and their use in medicine. Recently, anti-apoptotic polymer drug conjugates have been described. These conjugates employ a diglycil sequence as a linker. However, experimental results have shown that for some applications the drug release rate for compounds comprising a GIy residue at P1 is too slow to achieve the effective concentrations in the desired time range and therefore there is the need of the provision of linker sequences which permit to obtain drug release rates within the suitable time interval. A deeper study of these systems regarding the polymer-drug linker has revealed a good but unexpected improvement. By changing GIy at P1 position by an amino acid selected from VaI, Leu, lie, Ala, Arg and Phe, it is possible to markedly modulate drug release rate. This could be translated in the possibility to use the same biological agent in different human pathologies where a specific and fast drug release is required such as acute lesions or organ transplantation.