Inhibitors of the tyrosine kinase EphB4.: part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines

Catherine Bardelle; Tanya Coleman; Darren Cross; Sara Davenport; Jason G. Kettle; Eun Jung Ko; Andrew G. Leach; Andrew Mortlock; Jon Read; Nicola J. Roberts; Peter Robins; Emma J. Williams

doi:10.1016/j.bmcl.2008.09.087

Inhibitors of the tyrosine kinase EphB4. part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines

Catherine Bardelle, Tanya Coleman, Darren Cross, Sara Davenport, Jason G. Kettle, Eun Jung Ko, Andrew G. Leach, Andrew Mortlock, Jon Read, Nicola J. Roberts, Peter Robins, Emma J. Williams

Pharmacy

Research output: Contribution to journal › Article › peer-review

Abstract

Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics.

Original language	English
Pages (from-to)	5717-5721
Number of pages	5
Journal	Bioorganic & medicinal chemistry letters
Volume	18
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2008.09.087
Publication status	Published - 1 Nov 2008

Keywords

EphB4
Tyrosine kinase
Structure-based design
Pyrimidine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmcl.2008.09.087

Cite this

Bardelle, C., Coleman, T., Cross, D., Davenport, S., Kettle, J. G., Ko, E. J., Leach, A. G., Mortlock, A., Read, J., Roberts, N. J., Robins, P., & Williams, E. J. (2008). Inhibitors of the tyrosine kinase EphB4. part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines. Bioorganic & medicinal chemistry letters, 18(21), 5717-5721. https://doi.org/10.1016/j.bmcl.2008.09.087

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abstract = "Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics.",

keywords = "EphB4, Tyrosine kinase, Structure-based design, Pyrimidine",

author = "Catherine Bardelle and Tanya Coleman and Darren Cross and Sara Davenport and Kettle, {Jason G.} and Ko, {Eun Jung} and Leach, {Andrew G.} and Andrew Mortlock and Jon Read and Roberts, {Nicola J.} and Peter Robins and Williams, {Emma J.}",

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Bardelle, C, Coleman, T, Cross, D, Davenport, S, Kettle, JG, Ko, EJ, Leach, AG, Mortlock, A, Read, J, Roberts, NJ, Robins, P & Williams, EJ 2008, 'Inhibitors of the tyrosine kinase EphB4. part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines', Bioorganic & medicinal chemistry letters, vol. 18, no. 21, pp. 5717-5721. https://doi.org/10.1016/j.bmcl.2008.09.087

TY - JOUR

T1 - Inhibitors of the tyrosine kinase EphB4.

T2 - part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines

AU - Bardelle, Catherine

AU - Coleman, Tanya

AU - Cross, Darren

AU - Davenport, Sara

AU - Kettle, Jason G.

AU - Ko, Eun Jung

AU - Leach, Andrew G.

AU - Mortlock, Andrew

AU - Read, Jon

AU - Roberts, Nicola J.

AU - Robins, Peter

AU - Williams, Emma J.

PY - 2008/11/1

Y1 - 2008/11/1

N2 - Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics.

AB - Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics.

KW - EphB4

KW - Tyrosine kinase

KW - Structure-based design

KW - Pyrimidine

U2 - 10.1016/j.bmcl.2008.09.087

DO - 10.1016/j.bmcl.2008.09.087

M3 - Article

SN - 0960-894X

VL - 18

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JO - Bioorganic & medicinal chemistry letters

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