404337-99-1Relevant academic research and scientific papers
Benzimidazole inhibitors induce a DFG-out conformation of never in mitosis gene a-related kinase 2 (Nek2) without binding to the back pocket and reveal a nonlinear structure-activity relationship
Solanki, Savade,Innocenti, Paolo,Mas-Droux, Corine,Boxall, Kathy,Barillari, Caterina,Van Montfort, Rob L. M.,Aherne, G. Wynne,Bayliss, Richard,Hoelder, Swen
, p. 1626 - 1639 (2011/06/17)
We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.
Nitration of Methyl 3-Hydroxy- and 5-methyl-3-hydroxythipophene-2-carboxylate, and Some Chemistry of the Products
Barker, John M.,Huddelston, Patrick R.,Wood, Michael L.,Burkitt, Simon A.
, p. 1001 - 1023 (2007/10/03)
The nitration of methyl 3-hydroxythiophene-2-carboxylate furnishes two products, the lower melting of which was previously thought to be the 4-(3) and the other the 5-isomer (2); these assignments have been reversed on the basis of carbon-13 n.m.r. data. Further, the revised structures were confirmed both by O to N acyl migrations and by the preparation of the first examples (20) and (23) of the thieno[3,4-b][1,4]oxazine ring system from derivatives of the 4-nitro isomer.
