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Synthesis of novel derivatives of 1 H ‐imidazo[1,2‐ b ]pyrazole as potential CNS‐agents
Author(s) -
Vanotti E.,
Fiorentini F.,
Villa M.
Publication year - 1994
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570310408
Subject(s) - chemistry , pyrazole , bicyclic molecule , acylation , molecule , stereochemistry , combinatorial chemistry , organic chemistry , catalysis
As part of a preliminary study on novel 5‐HT 3 ligands, the synthesis of a series of 1H‐imidazo[1,2‐ b ]‐pyrazole derivatives is described. The bicyclic heteroaromatic nucleus was functionalized at positions 1, 6 and 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 imidazolide 3 towards tropine and tropanamine. The 7‐congeners, ester 4c , its tropinium salt 4e , the endo and exo amides 4d and 12d were prepared from the known common precursor 8 [1], while derivatives 4f‐g , originated by functionalizing position 1, were obtained from 1 H ‐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 published so far [2‐5], they were evaluated “ in vitro ” for 5‐HT 3 receptor affinity (Table 2). The biochemical data show significant activity for derivatives 4a‐e, 4g. These results are encouraging and justify further investigational work on this class of molecules.