Regiospecific and conformationally restrained analogs of melphalan and DL-2-NAM-7 and their affinities for the large neutral amino acid transporter (system LAT1) of …

J Matharu, J Oki, DR Worthen, QR Smith…

Index: Matharu, Jyothi; Oki, Jun; Worthen, David R.; Smith, Quentin R.; Crooks, Peter A. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 12 p. 3688 - 3691

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Citation Number: 5

Abstract

Regiospecific and conformationally restrained analogs of melphalan and dl-2-NAM-7 have been synthesized and their affinities for the large neutral amino acid transporter (LAT1) of the blood–brain barrier have been determined to assess their potential for accessing the CNS via facilitated transport. Several analogs had Ki values in the range 2.1–8.5 μM with greater affinities than that of either l-phenylalanine (Ki= 11μM) or melphalan (Ki= 55μM), ...