Azido and diazarinyl analogues of bis-tyrphostin as asymmetrical inhibitors of dynamin GTPase

Title: Azido and diazarinyl analogues of bis-tyrphostin as asymmetrical inhibitors of dynamin GTPase
Creator: Odell, Luke R.; Chau, Ngoc; Mariana, Anna; Graham, Mark E.; Robinson, Phillip J.; McCluskey, Adam
Relation: Chemmedchem Vol. 4, Issue 7, p. 1182-1188
Publisher Link: http://dx.doi.org/10.1002/cmdc.200900054
Publisher: Wiley
Resource Type: journal article
Date: 2009
Description: Two azidobenzyl amide (4 and 23) and one 3-trifluoromethyl-3H-diazirin-3-ylphenyl (24) analogues of bis-tyrphostin (1, Bis-T) were synthesised as potential photoaffinity labels for the elucidation of the binding site of compound 1 in dynamin I. Of the two azidobenzyl amide analogues (4 and 23), the terminally substituted 23 retained dynamin I GTPase inhibition (IC₅₀= 6.4±2.8 μm) whilst 4, which was substituted on the central carbon of the amide linker, displayed no activity. Analogue 24 also retained inhibitory activity (IC₅₀=36±9 μm). Photoaffinity labelling experiments did not unequivocally elucidate the binding pocket of compound 1. However, compounds 23 and 24 represent the first asymmetrically substituted Bis-T analogues to retain dynamin inhibitory activity, providing a new direction for analogue synthesis.
Subject: bis tyrphostin; dynamin GTPase I; inhibitors; photoaffinity; synthesis
Identifier: uon:8246
Identifier: http://hdl.handle.net/1959.13/917168
Identifier: ISSN:1860-7179
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