1070709-36-2Relevant academic research and scientific papers
SPIRO [PIPERIDINE-4, 4' -THIENO [3, 2-C] PYRAN] DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE SIGMA RECEPTOR FOR THE TREATMENT OF PSYCHOSIS
-
, (2009/01/23)
The present invention relates to compounds having pharmacological activity towards the sigma (s) receptor, and more particularly to some thieno-pyrano-pyrazole derivatives, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy and prophylaxis, in particular for the treatment of psychosis or pain.
Thiophene bioisosteres of spirocyclic σ receptor ligands. 1. N-substituted spiro[piperidine-4,4′-thieno[3,2-c]pyrans]
Oberdorf, Christoph,Schepmann, Dirk,Vela, Jose Miguel,Diaz, Jose Luis,Holenz, J?rg,Wünsch, Bernhard
supporting information; experimental part, p. 6531 - 6537 (2009/10/17)
Herein, the synthesis and pharmacological evaluation of thiophene bioisosteres of the highly potent spirocyclic benzopyran 1 are detailed. The synthesis of 1-benzyl-6′-methoxy-6′,7′- dihydrospiro[piperidine-4,4′-thieno[3.2-c]pyran] (2a) was performed starting with 3-bromothiophene (3). After introduction of the acetaldehyde substructure (7), halogen metal exchange, addition of 1-benzylpiperidin-4-one, and cyclization led to the spirocyclic thienopyran 2a. The removal of the benzyl group afforded the secondary amine 2f, which was substituted with various residues. With respect to σ1 affinity the N-benzyl derivative 2a, the N-cyclohexylmethyl derivative 2d, and the N-p-fluorobenzyl derivative 2i represent the most potent compounds of this series binding with Ki values of 0.32, 0.29, and 0.62 nM, respectively. Electronic properties of the substituents have only little impact on σ1 affinity. The most potent σ1 ligands display high selectivity against σ2, 5-HT1A, 5-HT6, 5-HT7, α1A, α2, and NMDA receptors. The activity of 2a in the mouse capsaicin assay seems to indicate σ1 antagonistic activity.
