75116-77-7Relevant academic research and scientific papers
The Effects of Prodrug Size and a Carbonyl Linker on l-Type Amino Acid Transporter 1-Targeted Cellular and Brain Uptake
Venteicher, Brooklynn,Merklin, Kasey,Ngo, Huy X.,Chien, Huan-Chieh,Hutchinson, Keino,Campbell, Jerome,Way, Hannah,Griffith, Joseph,Alvarado, Cesar,Chandra, Surabhi,Hill, Evan,Schlessinger, Avner,Thomas, Allen A.
supporting information, p. 869 - 880 (2020/12/15)
The l-type amino acid transporter 1 (LAT1, SLC7A5) imports dietary amino acids and amino acid drugs (e. g., l-DOPA) into the brain, and plays a role in cancer metabolism. Though there have been numerous reports of LAT1-targeted amino acid-drug conjugates (prodrugs), identifying the structural determinants to enhance substrate activity has been challenging. In this work, we investigated the position and orientation of a carbonyl group in linking hydrophobic moieties including the anti-inflammatory drug ketoprofen to l-tyrosine and l-phenylalanine. We found that esters of meta-carboxyl l-phenylalanine had better LAT1 transport rates than the corresponding acylated l-tyrosine analogues. However, as the size of the hydrophobic moiety increased, we observed a decrease in LAT1 transport rate with a concomitant increase in potency of inhibition. Our results have important implications for designing amino acid prodrugs that target LAT1 at the blood-brain barrier or on cancer cells.
A NEW METHOD OF SYNTHESIS OF α-ARYLPROPIONIC ACIDS INVOLVING COPPER(I) HOMOGENEOUS CATALYSIS
Ugo, Renato,Nardi, Paola,Psaro, Rinaldo,Roberto, Dominique
, p. 511 - 514 (2007/10/02)
The synthesis of α-arylpropionic acids involving, as first step, the facile coupling af an aryl bromide and diethyl malonate in the presence of Cu(I) bromide is described.The limits of application are discussed.
ENANTIOSELECTIVE SYNTHESIS AND ABSOLUTE CONFIGURATION OF (+)-α-(3-BENZOYLPHENYL)PROPIONIC ACID
Comisso, Giovanni,Mihalic, Mladen,Kajfez, Franjo,Sunjic, Vitomir,Snatzke, Guenther
, p. 123 - 128 (2007/10/02)
Asymmetric homogeneous hydrogenation of α-(3-benzoylphenyl)acrylic acid (4), which is preparared in 90percent overall yield from (3-benzoylphenyl)acetic acid (1), affords (+)-α-(3-benzoylphenyl)propionic acid, (+)-5, in 93.7percent chemical and 67.4percent optical yield.The absolute configuration of (+)-5 is correlated with that of (+)-(S)-hydratropic acid via (+)-α-(3-benzylphenyl)propionic acid, (+)-6.The origin of the CD bands of (+)-6 is discussed and comparison of chiroptical data with those of (+)-(S)-hydratropic acid, reveals that (+)-6 has an S configuration.Since (+)-6 is chemically correlated with (+)-5, the absolute S configuration of this enantiomer is confirmed.
