SYNTHESIS OF NOVEL DERIVATIVES OF 1H-IMIDAZO[1,2-B]PYRAZOLE AS POTENTIAL CNS-AGENTS

As part of a preliminary study on novel 5-HT3 ligands, the synthesis o f a series of 1H-imidazo[1,2-b]pyrazole derivatives is described. The bicyclic heteroaromatic nucleus was functionalized at positions 1, 6 a nd 7 to give the series of tropanyl derivatives 4a-g, 12a, 12d (Table 1). Different synthetic approaches were utilized to obtain the desired molecules: endo and exo 6-amides 4a, 12a and 6-ester 4b required two independent schemes due to the opposite behavior of the intermediate i midazolide 3 towards tropine and tropanamine. The 7-congeners, ester 4 c, its tropinium salt 4e, the endo and exo amides 4d and 12d were prep ared from the known common precursor 8 [1], while derivatives 4f-g, or iginated by functionalizing position 1, were obtained from 1H-imidazo[ 1,2-b]pyrazole by direct N-acylation. Since the structural features of these molecules seemed to meet the main rules of the S.A.R. studies p ublished so far [2-5], they were evaluated ''in vitro'' for 5-HT3 rece ptor affinity (Table 2). The biochemical data show significant activit y for derivatives 4a-e, 4g. These results are encouraging and justify further investigational work on this class of molecules.