Structure-activity relationships of pregabalin and analogues that target the α2-δ protein

…, T Capiris, IV Ekhato, JJ Kinsora, MJ Field…

Index: Belliotti, Thomas R.; Capiris, Thomas; Ekhato, I. Victor; Kinsora, Jack J.; Field, Mark J.; Heffner, Thomas G.; Meltzer, Leonard T.; Schwarz, Jacob B.; Taylor, Charles P.; Thorpe, Andrew J.; Vartanian, Mark G.; Wise, Lawrence D.; Zhi-Su, Ti; Weber, Mark L.; Wustrow, David J. Journal of Medicinal Chemistry, 2005 , vol. 48, # 7 p. 2294 - 2307

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Citation Number: 174

Abstract

Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the α2-δ subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their α2-δ binding affinity as demonstrated by their ability to inhibit binding of [3H] gabapentin to pig ...