The discovery of a selective and potent A2a agonist with extended lung retention

Pharmacology Research and Perspectives

Volumn 3, Issue 3, 2015, Pages

  Åstrand, Annika B M ^a   Lamm Bergström, Eva ^a   Zhang, Hui ^a   Börjesson, Lena ^a   Söderdahl, Therese ^a   Wingren, Cecilia ^a   Jansson, Anne Helene ^a   Smailagic, Amir ^a   Johansson, Camilla ^a   Bladh, Håkan ^a   Shamovsky, Igor ^a   Tunek, Anders ^a   Drmota, Tomas ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

A2a; Adenosine receptor; blood pressure; heart rate; inflammation; lung retention; pharmacokinetic pharmacodynamic; therapeutic window

Indexed keywords

2 [4 (2 CARBOXYETHYL)PHENETHYLAMINO]ADENOSINE 5' (N ETHYLCARBOXAMIDE); 4 [2 [7 AMINO 2 (2 FURYL) 1,2,4 TRIAZOLO[2,3 A][1,3,5]TRIAZIN 5 YLAMINO]ETHYL]PHENOL; 5 [6 (2,2 DIPHENYLETHYLAMINO) 2 [2 [(1 METHYLPYRIDIN 1 IUM 4 YL)CARBAMOYLAMINO]ETHYLAMINO]PURIN 9 YL] N ETHYL 3,4 DIHYDROXY TETRAHYDROFURAN 2 CARBOXAMIDE; ADENOSINE A2A RECEPTOR AGONIST; N ETHYL 5 [6 (1 ETHYLPROPYLAMINO) 2 [2 (4 PYRIDYLCARBAMOYLAMINO)ETHYLAMINO]PURIN 9 YL] 3,4 DIHYDROXY TETRAHYDROFURAN 2 CARBOXAMIDE; N ETHYL 5 [6 (1 ETHYLPROPYLAMINO) 2 [2 [(1 METHYLPYRIDIN 1 IUM 4 YL)CARBAMOYLAMINO] ETHYLAMINO]PURIN 9 YL] 3,4 DIHYDROXY TETRAHYDROFURAN 2 CARBOXAMIDE; REGADENOSON; TUMOR NECROSIS FACTOR; UK 432097; UNCLASSIFIED DRUG;

AGONIST POTENCY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CARDIOTOXICITY; CHEMICAL REACTION KINETICS; CONTROLLED STUDY; DRUG EFFICACY; DRUG RETENTION; DRUG SCREENING; DRUG SYNTHESIS; EC50; ENZYME LINKED IMMUNOSORBENT ASSAY; FATIGUE; FEMALE; HEART MUSCLE NECROSIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HYPOTENSION; LIPOPHILICITY; MALE; MOLECULAR MODEL; NONHUMAN; PLASMA PROTEIN BINDING; PNEUMONIA; PRIORITY JOURNAL; RAT; TACHYCARDIA;

EID: 84992216360     PISSN: None     EISSN: 20521707     Source Type: Journal    
DOI: 10.1002/prp2.134     Document Type: Article

References (32)

1. Al Jaroudi W, Iskandrian AE (2012). Regadenoson: a new myocardial stress agent. J Am Coll Cardiol 54 (13): 1123–1130. doi: 10.1016/j.jacc.2009.04.089
2. Albassam MA, Smith GS, Macallum GE (1998). Arteriopathy induced by an adenosine agonist-antihypertensive in monkeys. Toxicol Pathol May-Jun; 26 (3): 375–80. doi: 10.1177/019262339802600311
3. Caruso M, Alamo A, Crisafulli E, Raciti C, Fisichella A, Polosa R (2013). Adenosine signaling pathways as potential therapeutic targets in respiratory disease. Expert Opin Ther Targets 17 (7): 761–772. doi: 10.1517/14728222.2013.795220
4. Chen JF, Eltzschig HK, Fredholm BB (2013). Adenosine receptors as drug targets–what are the challenges? Nat Rev Drug Discov 12 (4): 265–286. doi: 10.1038/nrd3955
5. Cooper AE, Ferguson D, Grime K (2012). Optimisation of DMPK by the inhaled route: challenges and approaches. Curr Drug Metab 13: 457–473. doi: 10.2174/138920012800166571
6. Deflorian F, Kumar TS, Phan K, Gao ZG, Xu F, Wu H, et al. (2012). Evaluation of molecular modeling of agonist binding in light of the crystallographic structure of an agonist-bound A₂A adenosine receptor. J Med Chem 55 (1): 538–552. doi: 10.1021/jm201461q
7. 2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats. J Pharmacol Exp Ther 316: 695–702. doi: 10.1124/jpet.105.095323
8. Fozard JR, Ellis KM, Villela Dantas MF, Tigani B, Mazzoni L (2002). Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat. Eur J Pharmacol 438 (3): 183–188. doi: 10.1016/S0014-2999(02)01305-5
9. Fredholm BB, Cunha RA, Svenningsson P (2002). Pharmacology of adenosine A2A receptors and therapeutic applications. Curr Top Med Chem 3: 1349–1364. doi: 10.2174/1568026033392200
10. Gessi S, Merighi S, Varani K, Borea PA (2011). Adenosine receptors in health and disease. Adv Pharmacol 61: 41–75. doi: 10.1016/B978-0-12-385526-8.00002-3
11. Harada N, Okajima K, Murakami K, Usune S, Sato C, Ohshima K, et al. (2000). Adenosine and selective A(2A) receptor agonists reduce ischemia/reperfusion injury of rat liver mainly by inhibiting leukocyte activation. J Pharmacol Exp Ther 294: 1034–1042.
12. 2A receptor-dependent and independent mechanisms. FASEB J 14: 2065–2074. doi: 10.1096/fj.99-0508com
13. Johnson SG, Peters S (2010). Advances in pharmacologic stress agents: focus on regadenoson. J Nucl Med Technol 38 (3): 163–171. doi: 10.2967/jnmt.109.065581
14. Kaminski GA, Friesner RA, Tirado-Rives J, Jorgensen WL (2001). Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J Phys Chem B 105: 6474–6487. doi: 10.1021/jp003919d
15. Lebon G, Warne T, Edwards PC, Bennett K, Langmead CJ, Leslie AG, et al. (2011). Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 474 (7352): 521–525. doi: 10.1038/nature10136
16. Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, et al. (1997). Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature 388: 674–678.
17. Linden J (2001). Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol 41: 775–787. doi: 10.1146/annurev.pharmtox.41.1.775
18. Macallum GE, Walker RM, Barsoum NJ, Smith GS (1991). Preclinical toxicity studies of an adenosine agonist, N-(2,2-diphenylethyl) adenosine. Toxicology 68: 21–35.
19. Mantell SJ, Stephenson PT, Monaghan SM, Maw GN, Trevethick MA, Yeadon M, et al. (2008). Inhaled adenosine A(2A) receptor agonists for the treatment of chronic obstructive pulmonary disease. Bioorg Med Chem Lett 18 (4): 1284–1287. doi: 10.1016/j.bmcl.2008.01.033
20. Mantell SJ, Stephenson PT, Monaghan SM, Maw GN, Trevethick MA, Yeadon M, et al. (2009). SAR of a series of inhaled A(2A) agonists and comparison of inhaled pharmacokinetics in a preclinical model with clinical pharmacokinetic data. Bioorg Med Chem Lett 19 (15): 4471–4475. doi: 10.1016/j.bmcl.2009.05.027
21. Mantell S, Jones R, Trevethick M (2010). Design and application of locally delivered agonists of the adenosine A(2A) receptor. Expert Rev Clin Pharmacol 3 (1): 55–72. doi: 10.1586/ecp.09.57
22. Mathôt RA, Cleton A, Soudijn W, IJzerman AP, Danhof M (1995). Pharmacokinetic modelling of the haemodynamic effects of the A2a adenosine receptor agonist CGS 21680C in conscious normotensive rats. Br J Pharmacol 114: 761–768.
23. 2A adenosine receptor antagonist, SCH 58261, in the rat. J Pharmacol Exp Ther 285:9–15.
24. Müller CE, Jacobson KA (2011). Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta 1808 (5): 1290–1308. doi: 10.1016/j.bbamem.2010.12.017
25. Nekooeian AA, Tabrizchi R (1996). Effects of adenosine A2A receptor agonist, CGS 21680, on blood pressure, cardiac index and arterial conductance in anaesthetized rats. Eur J Pharmacol 307 (2): 163–169. doi: 10.1016/0014-2999(96)00250-6
26. Ohta A, Sitkovsky M (2001). Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414: 916–920. doi: 10.1038/414916a
27. Stepp DW, Van Bibber R, Kroll K, Feigl EO (1996). Quantitative relation between interstitial adenosine concentration and coronary blood flow. Circ Res 79 (3): 601–610. doi: 10.1161/01.RES.79.3.601
28. Still WC, Tempczyk A, Hawlely RC, Hendrickson TA (1990). General treatment of solvation for molecular mechanics. J Am Chem Soc 112: 6127–6129. doi: 10.1021/ja00172a038
29. Trevethick MA, Mantell SJ, Stuart EF, Barnard A, Wright KN, Yeadon M (2008). Treating lung inflammation with agonists of the adenosine A2A receptor: promises, problems and potential solutions. Br J Pharmacol 155 (4): 463–474. doi: 10.1038/bjp.2008.329
30. Webb RL, McNeal RB Jr, Barclay BW, Yasay GD (1990). Hemodynamic effects of adenosine agonists in the conscious spontaneously hypertensive rat. J Pharmacol Exp Ther 254: 1090–1099.
31. Webb RL, Barclay BW, Graybill SC (1991). Cardiovascular effects of adenosine A2 agonists in the conscious spontaneously hypertensive rat: a comparative study of three structurally distinct ligands. J Pharmacol Exp Ther 259(3): 1203–1212.
32. Xu FX, Wu H, Katritch V, Han GW, Jacobson KA, Gao ZG, et al. (2011). Structure of an agonist-bound human A2A adenosine receptor. Science 332: 322–327. doi: 10.1126/science.1202793