Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207.

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Crasto CF, Forrest AK, Karoli T, March DR, Mensah L, O'Hanlon PJ, Nairn MR, Oldham MD, Yue W, Banwell MG, Easton CJ

Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207.

Bioorg Med Chem. 2003 Jul 3;11(13):2687-94.

PubMed ID

12788342 [ View in PubMed

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Abstract

Twenty two analogues of SB-203207 have been prepared by total synthesis, and evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic core, removing either the terminal amino substituent or the sulfonyl group from the side chain, and altering either the carbon skeleton or stereochemistry of the isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA synthetase. Substituting the isoleucine residue with other amino acids produces inhibitors of the corresponding synthetases. In particular, a methionine derivative is 50-100 times more potent against methionyl tRNA synthetase than against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl synthetases.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Isoleucine	Isoleucine--tRNA ligase, cytoplasmic	Protein	Humans	Unknown	Not Available	Details