研究领域

Organic Chemistry

Our research interests are at the interface of chemistry and biology and focus on the use of synthetic organic chemistry to enable the study of biological problems. Key areas of activity include the synthesis of inositol-based probes to study intracellular calcium signalling, the synthesis of inositol-based compounds to probe pleckstrin homology domains and the use of photolabile protecting groups to develop light-activated molecular tools. We have collaborative interests in bacterial potassium channels and the molecular mechanisms involved in Alzheimer’s disease. Our interests also encompass the synthesis of “drug-like” molecules and we have recently reported an improved synthesis of hydantoins.

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3,5-Dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands. Hewings, D. S.; Wang, M.; Philpott, M.; Fedorov, O.; Uttarkar, S.; Filippakopoulos, P.; Picaud, S.; Vuppusetty, C.; Marsden, B.; Knapp, S.; Conway, S. J.; Heightman, T. D., J. Med. Chem., 2011, 54, 6761-6770. Wavelength-orthogonal photolysis of neurotransmitters in vitro. Stanton-Humphreys, M. N.; Taylor, R. D. T.; McDougall, C.; Hart, M. L.; Brown, C. T. A. B.; Emptage, N. J.; Conway, S. J., Chem. Commun., 2012, 48, 657-659. The use of phosphate bioisosteres in medicinal chemistry and chemical biology. Elliott, T. S.; Slowey, A.; Ye, Y.; Conway, S. J., Med. Chem. Commun., 2012, 3, 735-751. Bromodomains: Are readers right for epigenetic therapy? Conway, S. J., ACS Med. Chem. Lett., 2012, 3, 691-694. The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains. Hay, D.; Fedorov, O.; Filippakopoulos, P.; Martin, S.; Philpott, M.; Hewings, D. S.; Uttakar, S.; Heightman, T. D.; Conway, S. J.; Knapp, S.; Brennan, P. E., Med. Chem. Commun., 2013, 4, 140-144. Progress in the development and application of small molecule inhibitors of bromodomain-acetyl-lysine interactions. Hewings, D. S.; Rooney, T. P. C.; Jennings, L. E.; Hay, D.; Schofield, C. J.; Brennan, P. E.; Knapp, S.; Conway, S. J., J. Med. Chem., 2012, 55, 9393-9413. NAADP activates two-pore channels on T cell cytolytic granules to stimulate exocytosis and killing. Davis, L. C.; Morgan, A. J.; Chen, J.-L.; Snead, C. M.; Bloor-Young, D.; Shenderov, E.; Stanton-Humphreys, M. N.; Conway, S. J.; Churchill, G. C.; Parrington, J.; Cerundolo, V.; Galione, A., Curr. Biol., 2012, 22, 2331-2337. Reflections on stereochemistry. Conway, S. J., Nature Chem., 2013, 5, 86-88. Optimization of 3,5-dimethylisoxazole derivatives as potent BET bromodomain ligands. Hewings, D. S.; Fedorov, O.; Filippakopoulos, P.; Martin, S.; Picaud, S.; Tumber, A.; Wells, C.; Olcina, M. M.; Freeman, K.; Gill, A.; Ritchie, A. J.; Sheppard, D. W.; Russell, A. J.; Hammond, E. M.; Knapp, S.; Brennan, P. E.; Knapp, S.; Conway, S. J., J. Med. Chem., 2013, 56, 3217-3227. CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and Aurora A. Cazares-Körner, C.; Pires, I. M.; Swallow, I. D.; Grayer, S. C.; O’Connor, L.; Olcina, M. M.; Christlieb, M.; Conway, S. J.; Hammond, E. M., ACS Chem. Biol., 2013, 8, 1451-1459. Phenotypic screening and fragment-based approaches to the discovery of small molecule bromodomain ligands. Jennings, L. E.; Measures, A. R.; Wilson, B. G.; Conway, S. J., Future Med. Chem., 2014, 6, 179-204. Understanding the structural requirements for activators of the Kef bacterial potassium efflux system. Healy, J.; Ekkerman, S.; Pliotas, C.; Richard, M.; Bartlett, W.; Grayer, S. C.; Morris, G.; Miller, S.; Booth, I. R.; Conway, S. J.; Rasmussen, T., Biochemistry, 2014, 53, 1982-1992. A series of potent CREBBP bromodomain ligands reveals an induced fit pocket stabilized by a cation-π interaction. Rooney, T. P. C.; Filippakopoulos, P.; Fedorov, O.; Picaud, S.; Cortopassi, W. A.; Hay, D. A.; Martin, S.; Tumber, A.; Rogers, C. M.; Philpott, M.; Wang, M.; Thompson, A. L.; Heightman, T. D.; Pryde, D. C.; Cook, A.; Paton, R. S.; Müller, S.; Knapp, S.; Brennan, P. E.; Conway, S. J., Angew. Chem. Int. Ed., 2014, 53, 6126-6130. Discovery and optimization of small molecule ligands for the CBP/p300 bromodomains. Hay, D. A.; Fedorov, O.; Martin, S.; Singleton, D.; Tallant, C.; Wells, C.; Picaud, S.; Philpott, M.; Monteiro, O. P.; Rogers, C. M.; Conway, S. J.; Rooney, T. P. C.; Tumber, A.; Yapp, C.; Filippakopoulos, P.; Bunnage, M. E.; Müller, S.; Knapp, S.; Schofield, C. J.; Brennan, P. E., J. Am. Chem. Soc., 2014, 136, 9308-9319. Synthesis of highly water soluble adamantyl phosphoinositide derivatives. Gregory, M.; Yin, M-X.; McConville, M.; Williams, E.; Bullock, A. N.; Conway, S. J.; Holmes, A. B., Aust. J. Chem., 2015, in press. Epigenetics: Novel therapeutics targeting epigenetics. Conway, S. J.; Woster, P. M.; Shen, J-K.; Georg, G.; Wang S., J. Med. Chem., 2015, 58, 523-524. Small molecule inhibitors of bromodomain-acetyl-lysine interactions. Brand, M.; Measures, A. R.; Wilson B. G.; Cortopassi, W. A.; Alexander, R.; Höss, M.; Hewings, D. S.; Paton, R.; Conway. S. J., ACS Chem. Biol., 2015, 10, 22-39. Quantitative hopanoid analysis enables robust pattern detection and comparison between laboratories. Wu, C. H.; Kong, L.; Bialecka-Fornal, M.; Park, S.; Thompson, A. L.; Kulkarn, G.; Conway S. J.; Newman. D. K., Giobiol., 2015, 13, in press.