Synthesis of 2-amino-benzamide derivatives designed as fetal hemoglobin inducers

Abstract

Sickle Cell Disease is a hematological disease characterized by a punctual mutation in the sixth codon of the ²-globin gene, responsible for the substitution of thymine for adenine (GAG to GTG). The discovery that butyrates promote increased production of fetal hemoglobin (HbF) by inhibiting histone deacetylases (HDACs) provides a new perspective of research on new drugs for treating this disease. Recent studies have demonstrated that inhibition of class I histone deacetylase (HDACs), mainly HDAC-1 and HDAC-2, causes increase in the production of HbF without causing changes in cell cycle and proliferation. Based on these advances, we propose in this project the synthesis of new HDAC-1 and HDAC-2 inhibitors potentially useful to treat the symptoms of sickle Cell Disease. (AU)