Development of DANDYs, new 3, 5-diaryl-7-azaindoles demonstrating potent DYRK1A kinase inhibitory activity

…, F Rodrigues-Lima, N Janel, JM Delabar…

Index: Gourdain, Stephanie; Dairou, Julien; Denhez, Clement; Bui, Linh Chi; Rodrigues-Lima, Fernando; Janel, Nathalie; Delabar, Jean M.; Cariou, Kevin; Dodd, Robert H. Journal of Medicinal Chemistry, 2013 , vol. 56, # 23 p. 9569 - 9585

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Citation Number: 14

Abstract

A series of 3, 5-diaryl-1 H-pyrrolo [2, 3-b] pyridines were synthesized and evaluated for inhibition of DYRKIA kinase in vitro. Derivatives having hydroxy groups on the aryl moieties (2c, 2j–l) demonstrated high inhibitory potencies with K is in the low nanomolar range. Their methoxy analogues were up to 100 times less active. Docking studies at the ATP binding site suggested that these compounds bind tightly to this site via a network of multiple H- ...