Issue 9, 2012

Property based optimisation of glucokinase activators – discovery of the phase IIb clinical candidate AZD1656

Abstract

Glucokinase plays a central role in glucose homeostasis and small molecule activators of the glucokinase enzyme have been the subject of significant pharmaceutical research in the quest for agents capable of delivering improved glycaemic control. Here we describe our medicinal chemistry campaign to improve on our previously described development candidate in this area, AZD1092, focussed on removal of Ames liability and improved permeability characteristics. This work culminated in the superior compound AZD1656 which has progressed to phase 2 clinical trials.

Graphical abstract: Property based optimisation of glucokinase activators – discovery of the phase IIb clinical candidate AZD1656

Supplementary files

Article information

Article type
Concise Article
Submitted
22 Mar 2012
Accepted
13 Jun 2012
First published
18 Jun 2012

Med. Chem. Commun., 2012,3, 1077-1081

Property based optimisation of glucokinase activators – discovery of the phase IIb clinical candidate AZD1656

M. J. Waring, D. S. Clarke, M. D. Fenwick, L. Godfrey, S. D. Groombridge, C. Johnstone, D. McKerrecher, K. G. Pike, J. W. Rayner, G. R. Robb and I. Wilson, Med. Chem. Commun., 2012, 3, 1077 DOI: 10.1039/C2MD20077E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements