1093379-02-2Relevant academic research and scientific papers
Thiophene bioisosteres of spirocyclic σ receptor ligands: Relationships between substitution pattern and σ receptor affinity
Oberdorf, Christoph,Schepmann, Dirk,Vela, Jose Miguel,Buschmann, Helmut,Holenz, J?rg,Wünsch, Bernhard
, p. 5350 - 5360 (2012/08/29)
On the basis of the 6′,7′-dihydrospiro[piperidine-4,4′- thieno[3,2-c]pyran] framework, a series of more than 30 σ ligands with versatile substituents in 1-, 2′-, and 6′-position has been synthesized and pharmacologically evaluated in order to find novel structure-affinity relationships. It was found that a cyclohexylmethyl residue at the piperidine N-atom instead of a benzyl moiety led to increased σ2 affinity and therefore to decreased σ1/ σ2 selectivity. Small substituents (e.g., OH, OCH3, CN, CH2OH) in 6′-position adjacent to the O-atom were well tolerated by the σ1 receptor. Removal of the substituent in 6′-position resulted in very potent but unselective σ ligands (13). A broad range of substituents with various lipophilic and H-bond forming properties was introduced in 2′-position adjacent to the S-atom without loss of σ1 affinity. However, very polar and basic substituents in both 2′- and 6′-position decreased the σ1 affinity considerably. It is postulated that the electron density of the thiophene moiety has a big impact on the σ1 affinity.
SPIRO [PIPERIDINE-4, 4' -THIENO [3, 2-C] PYRAN] DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE SIGMA RECEPTOR FOR THE TREATMENT OF PSYCHOSIS
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, (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.
