Stereospecific synthesis and structure-activity relationships of unsymmetrical 4,4-diphenylbut-3-enyl derivatives of nipecotic acid as GAT-1 inhibitors.

Two complementary stereospecific synthetic approaches for the preparation of unsymmetrical ortho-substituted N-(4,4-diphenylbut-3-enyl) derivatives of nipecotic acid are described. Determination of the activity of the prepared compounds at the GAT-1 transporter highlighted differing SAR requirements of the E- and Z-phenyl rings, and led to the discovery of a compound with comparable potency to tiagabine. Some attempts to replace nipecotic acid with alternative novel amino acids are also described.

Impact of prebiotics on human health.

It is becoming clear that intestinal microflora plays an important role in the development of local and systemic immune response. Nutritional ingredients have been added to infant formula in an attempt to make its composition similar to that of human milk. The effects of these modifications have been observed in the composition of intestinal microflora.