Company News: biocrea and Pfizer Jointly Presented Details on Novel PDE10 Inhibitors at the 241st ACS National Meeting & Exposition
– Novel treatment opportunities for CNS diseases –
biocrea, a biopharmaceutical company focusing on novel treatments for disorders of the central nervous system (CNS), today reported details on the design and synthesis of novel, brain-penetrating phosphodiesterase-10 (PDE10) inhibitors developed in collaboration with Pfizer Inc. (NYSE: PFE). The data were featured in joint presentations with Pfizer at the recent 241st ACS National Meeting & Exposition, an event organized by the American Chemical Society (ACS).
The data demonstrated that the scientists at Pfizer and biocrea were able to eliminate undesired activity on adenosine receptors and to considerably improve the compounds´ physicochemical properties and potency. The team had started with initial high-throughput hits characterized by low potency and selectivity. Further lead optimization led to a number of compounds with very robust activity in a range of preclinical models of anti-psychotic efficacy. Moreover, these PDE10 inhibitors produced low levels of catalepsy, suggesting a minimal risk for the induction of side-effects involving the extrapyramidal system (EPS), the most common adverse reaction observed with anti-psychotic drugs.
Phosphodiesterases (PDEs) have been identified as key regulators of intracellular cyclic nucleotide levels in the brain. Mechanistically, PDE10 inhibition has two major benefits, mimicking, (1) the effects of antagonists of the dopamine-2 receptor, the current standard treatment for psychosis, and (2) the effects of agonists of dopamine-1 receptors, which may decrease the side-effect liabilities while contributing to a pro-cognitive profile.
 Malamas M et al., 241st ACS National Meeting & Exposition Abstract 65 – Imidazo[1,5-a]quinoxalines as selective PDE10A inhibitors for the treatment of schizophrenia, http://redir.ec/Qr3C; Malamas, M. et al., 241st ACS National Meeting & Exposition Abstract 66 – Benzo[e]imidazo[5,1-c][1,2,4]triazines as selective PDE10A inhibitors for the treatment of schizophrenia, http://redir.ec/pl1Q