Sila drugs, structure

R. Tacke, Recent Results in Bioorganosilicon Chemistry Novel Sila-Drugs and Microbial Transformations of Organosilicon Compounds , in Organosilicon and Bioorganosilicon Chemistry Structure, Bonding, Reactivity and Synthetic Application (Ed. H. Sakurai), Ellis Horwood, Chichester, 1985, pp. 251-262. 

In context with our systematic studies on sila-substituted drugs [1,2], we have been interested in the pharmacological properties of novel potential a ligands of the l,4 -silaspiro[tetralin-l,4 -piperidine] tj, compoimds lb - 4b (cf Ref. [2e] for structurally related o ligands of the... 

As can be seen from Fig. 2, sila-substitution of rac-Sa (-> rac-Sh) substantially affects the pharmacological profile with respect to serotonin reuptake inhibition. The other (major) structural changes in the molecular shape of rac-5b (-> rac-6, rac-7) also influenced the pharmacological profile with respect to monoamine selectivity rac-1) and/or absolute potency rac-6). These results clearly demonstrate that the carbon/silicon switch strategy is a powerful tool for drug design. 

From these simple considerations it becomes clear that organic drugs and their sila-analogues may differ in their chemical (reactivity) and in their physicochemical properties (e.g. lipophilicity) as well as in their structure (shape and size, bonding geometries, conformational behavior). It can be expected that these chemical, physicochemical and structural sila-substitution effects may, in principle, result in biological sila-substitution effects—by influencing the pharmacodynamics and/or the pharmacokinetics. 

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