Stereospecific synthesis and structure-activity relationships of unsymmetrical 4,4-diphenylbut-3-enyl derivatives of nipecotic acid as GAT-1 inhibitors.
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Pizzi DA, Leslie CP, Di Fabio R, Seri C, Bernasconi G, Squaglia M, Carnevale G, Falchi A, Greco E, Mangiarini L, Negri M
Stereospecific synthesis and structure-activity relationships of unsymmetrical 4,4-diphenylbut-3-enyl derivatives of nipecotic acid as GAT-1 inhibitors.
Bioorg Med Chem Lett. 2011 Jan 1;21(1):602-5. doi: 10.1016/j.bmcl.2010.09.025. Epub 2010 Sep 15.
- PubMed ID
- 21134748 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Tiagabine Sodium- and chloride-dependent GABA transporter 1 Ki (nM) 16.98 N/A N/A Details