Si bioisosterism

G Ligands of the l,4 -Silaspiro[tetralin-l,4 -piperidine] Type and the Serotonin/Noradrenaline Reuptake Inhibitor Sila-venlafaxine Studies on C/Si Bioisosterism... 

Keywords C/Si bioisosterism, carbon/silicon switch, chirality, o ligands,... 

Reuptake Inhibitor Sila-venlafaxine Studies on C/Si Bioisosterism.575... 

C/Si bioisosterism has been considered repeatedly due to some fundamental differences between carbon and silicon that are useful in drug design [50-52]. These include ... 

Replacement of the central carbon atom by a silicon atom in the (R)-enantiomers of the hydroxymethyl analogue of HHD (3->4) and THP (8- 9) lowered affinity and stereoselectivity, whereas the receptor selectivity for compounds 3 and 4 was unchanged. In contrast, the corresponding (R)- and (S)-enantiomers of the Si/Ge analogues exhibited very similar affinities to the different muscarinic receptors indicating a strongly pronounced Si/Ge bioisosterism. 

Finally, both fexofenadine and its sila-bioisostere exhibited similar in vitro pharmacological profiles. Evaluation of the effects in vivo of the C/Si switch, though, was not reported. 

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