RSC Medicinal Chemistry Blog

Congratulations to all of the recently announced Royal Society of Chemistry Prize and Award winners for 2014.

Below are the winners related to medicinal chemistry, taken from the full list of winners

Bioorganic Chemistry Award 2014 Winner Professor Wilfred van der Donk, University of Illinois at Urbana-Champaign For his creative work on the chemistry, biosynthesis and mechanistic enzymology of the cyclic peptide and phosphonate classes of antibiotics.

Corday-Morgan Prize 2014 Winner Professor David Spring, University of Cambridge For his contributions to chemistry-driven drug discovery through his work in diversity-oriented synthesis and chemical biology.

Rita and John Cornforth Award 2014 Winner Professor Chas Bountra, Structural Genomics Consortium, University of Oxford For world leading collaborative research across the disciplines of structural biology, medicinal chemistry, chemical biology and enzymology towards understanding and exploiting the potential of epigenetics as a target family for future drug discovery.

Harrison-Meldola Memorial Prize 2014 Winner Dr Matthew Fuchter, Imperial College London For his contribution to the study of epigenetic processes in disease and his insights into chiral aromatic compounds, particularly those with helical chirality.

Norman Heatley Award 2014 Winner Dr Edward Tate, Imperial College London For his contributions to the area of antimalarial drug discovery and for pioneering the application of chemical proteomics and its implementation in the identification of novel therapeutic targets

Jeremy Knowles Award 2014 Winner Professor Gurdyal Besra, University of Birmingham For his contributions to our understanding of the basic chemistry and biochemistry of the cell wall of Mycobacterium tuberculosis, and his ground-breaking work in the area of tuberculosis T-cell antigens and the CD1 antigen presentation pathway.

George and Christine Sosnovsky Award in Cancer Therapy 2014 Winner Professor Roger Griffin, Newcastle University For his major contributions to the discovery of inhibitors of proteins involved in the cell cycle and DNA repair, particularly poly-ADP-ribose polymerase, DNA-dependent protein kinase and cyclin-dependent kinases.

To celebrate these, and all the other award winners,  we are delighted to present this web-collection highlighting some of the best research by this year’s winners. Free access until 6^th June 2014.

Did you know?

An incredible 47 previous winners of the Royal Society of Chemistry’s Awards have gone on to win Nobel Prizes for their pioneering work, including Harry Kroto, Fred Sanger and Linus Pauling. Indeed, one of the 2012 Royal Society of Chemistry Prize winners, Arieh Warshel, was awarded the Nobel Prize in Chemistry last year.

US scientists have provided a strategy to improve the properties of active pharmaceutical ingredients (APIs) by combining ionic liquids (used to improve the properties of solid APIs) with prodrugs (used to improve solubility, permeability and bioavailability of APIs). The prodrug ionic liquids present additional advantages such as controlled release of the APIs in simulated body fluids. This work could offer an important strategy to improve the properties of APIs and drug delivery.

Prodrug ionic liquids: functionalizing neutral active pharmaceutical ingredients to take advantage of the ionic liquid form
O. Andreea Cojocaru, Katharina Bica, Gabriela Gurau, Asako Narita, Parker D. McCrary, Julia L. Shamshina, Patrick S. Barber and Robin D. Rogers
MedChemComm, 2013
DOI: 10.1039/C3MD20359J

Scientists in the UK and Sweden have identified compounds that work against a ligand (ghrelin) that’s part of a growth hormone that’s thought to increase the amount of food we eat. The compounds could be used to prevent obesity and diabetes.

Ghrelin, a 28 amino acid acylated peptide hormone, is the endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R1a), and is thought to control food intake. Acylated ghrelin is released from mucosal cells in response to hunger cues, resulting in a peak of plasma ghrelin levels before meals. It has also been shown that ghrelin infusion in both rodents and humans increases appetite and food intake. Therefore, peripheral and central nervous system (CNS) penetrant ghrelin receptor antagonists could be a potential cure for obesity and diabetes.

In this work, the team identified a tool compound within a pyrazolo-pyrimidinone based series of GHS-R1a antagonists that had good overall properties and sufficient oral plasma and CNS exposure to demonstrate reduced food intake in mice through a mechanism involving GHS-R1a.

Identification of pyrazolo-pyrimidinones as GHS-R1a antagonists and inverse agonists for the treatment of obesity
William McCoull, Peter Barton, Anders Broo, Alastair Brown, David Clarke, Gareth Coope, Rob D M Davies, Alastair Dossetter, Elizabeth Kelly, Laurent Knerr, Philip Macfaul, Jane Holmes, Nathaniel Martin, Jane E Moore, David Morgan, Claire Newton,  Krister Osterlund, Graeme Robb, Eleanor Rosevere, Nidhal Selmi, Stephen Stokes, Tor Svensson, Victoria Ullah and Emma Williams
Med. Chem. Commun.
DOI: 10.1039/C2MD20340E

Scientists have optimised a series of compounds that have the potential to treat diabetes and obesity.
The drug candidates work by inhibiting the enzyme diacylglycerol acetyl transferase 1, which is responsible for catalysing the production of triglycerides. Excessive levels of triglycerides contribute to metabolic syndrome, which increases risk of diabetes, heart disease and stroke. Previous drug inhibitors have been unsuccessful in clinical trials due to low solubility. The optimised compounds are highly soluble and exhibit excellent potency for their target.

Optimisation of biphenyl acetic acid inhibitors of diacylglycerol acetyl transferase 1 – the discovery of AZD2353
Michael J. Waring, Alan M. Birch, Susan Birtles, Linda K. Buckett, Roger J. Butlin, Leonie Campbell, Pablo Morentin Gutierrez, Paul D. Kemmitt, Andrew G. Leach, Philip A. MacFaul, Charles O’Donnell and Andrew V. Turnbull
Med. Chem. Commun., DOI: 10.1039/C2MD20190A