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Synthesis and Conformational Analysis of 2′-Deoxy-2′-(3-methoxybenzamido)adenosine, a rational-designed inhibitor of trypanosomal glyceraldehyde phosphate dehydrogenase (GAPDH)

✍ Scribed by Serge Van Calenbergh; Elfride Van Den Eeckhout; Piet Herdewijn; André De Bruyn; Christophe Verlinde; Wim Hol; Mia Callens; Arthur Van Aerschot; Jef Rozenski


Publisher
John Wiley and Sons
Year
1994
Tongue
German
Weight
926 KB
Volume
77
Category
Article
ISSN
0018-019X

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✦ Synopsis


A series of 2'-benzamido-2'-deoxyadenosine analogues were synthesized in an effort to find new lead structures for the treatment of sleeping sickness. The 2'-deoxy-2'-(3-methoxybenzamido)adenosine (lh) was proved to be a selective inhibitor of the parasite glyceraldehyde 3-phosphate dehydrogenase which confirms the modeling studies. The solution-state conformation of 2'-(thiophene-2-carboxamido) analogue Id demonstrates a 2'-endo conformation, an orientation of the thiophene ring under the ribose moiety, and the base part occupying a 'syn '/'anti' equilibrium.