International Journal of Medicinal Chemistry
7
Conflicts of Interest
[13] M. Sitkovsky, D. Lukashev, S. Deaglio, K. Dwyer, S. C. Robson,
and A. Ohta, “Adenosine A2A receptor antagonists: blockade of
adenosinergic effects and T regulatory cells,” British Journal of
Pharmacology, vol. 153, no. 1, pp. S457–S464, 2008.
e authors report no conflicts of interest.
[14] M. V. Sitkovsky, “T regulatory cells: hypoxia-adenosinergic
suppression and re-direction of the immune response,” Trends
in Immunology, vol. 30, no. 3, pp. 102–108, 2009.
[15] M. V. Sitkovsky, J. Kjaergaard, D. Lukashev, and A. Ohta,
“Hypoxia-adenosinergic immunosuppression: Tumor protec-
tion by T regulatory cells and cancerous tissue hypoxia,” Clinical
Cancer Research, vol. 14, no. 19, pp. 5947–5952, 2008.
[16] R. omas, J. Lee, V. Chevalier et al., “Design and evaluation
of xanthine based adenosine receptor antagonists: Potential
hypoxia targeted immunotherapies,” Bioorganic & Medicinal
Chemistry, vol. 21, no. 23, pp. 7453–7464, 2013.
[17] A. Ohta and M. Sitkovsky, “Role of G-protein-coupled adeno-
sine receptors in downregulation of inflammation and protec-
tion from tissue damage,” Nature, vol. 414, no. 6866, pp. 916–
920, 2001.
[18] R. A. Hodgson, R. Bertorelli, G. B. Varty et al., “Characterization
of the potent and highly selective A2A receptor antagonists
preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-
piperazinyl]ethyl]-2-(2-furanyl)-7hpyrazolo[ 4,3-e][1,2,4]tria-
zolo[1,5-c] pyrimidin-5-amine in rodent models of movement
disorders and depression,” e Journal of Pharmacology and
Experimental erapeutics, vol. 330, no. 1, pp. 294–303, 2009.
[19] R. A. Hauser, F. Stocchi, O. Rascol et al., “Preladenant as an
adjunctive therapy with levodopa in Parkinson disease: two ran-
domized clinical trials and lessons learned,” JAMA Neurology,
vol. 72, no. 12, pp. 1491–1500, 2015.
Acknowledgments
is research was supported by Northeastern University
and by grants from the National Institutes of Health
(UL1TR001064 and CA111985-04) and National Science
Foundation (MCB-1517290 and CHE-1305655). e authors
are grateful to AstraZeneca for obtaining the measured
physicochemical properties of 27–29 and Dr. Xi-Ping Huang
for helpful discussions. Steven H. Liang is a recipient of NIH
career development award from the National Institute on
Drug Abuse (DA038000).
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