Tonapofylline

Tonapofylline
Identifiers
  • 3-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)-1-bicyclo[2.2.2]octanyl]propanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H32N4O4
Molar mass416.522 g·mol−1
3D model (JSmol)
  • CCCN1C2=C(C(=O)N(C1=O)CCC)NC(=N2)C34CCC(CC3)(CC4)CCC(=O)O
  • InChI=1S/C22H32N4O4/c1-3-13-25-17-16(18(29)26(14-4-2)20(25)30)23-19(24-17)22-10-7-21(8-11-22,9-12-22)6-5-15(27)28/h3-14H2,1-2H3,(H,23,24)(H,27,28)
  • Key:ZWTVVWUOTJRXKM-UHFFFAOYSA-N

Tonapofylline (BG-9928) is a drug which acts as a potent and selective antagonist for the adenosine A1 receptor. It was developed as a potential agent for the treatment of heart failure by increasing sodium excretion by the kidneys, and reached Phase III human clinical trials, showing reasonable efficacy with a good safety profile. However, it was ultimately not adopted for medical use, though it continues to be used in research.[1][2][3][4][5][6][7] Its activity as a phosphodiesterase inhibitor does not appear to have been tested, though most related xanthine derivatives are phosphodiesterase inhibitors as well as adenosine receptor antagonists.

See also

References

  1. ^ Kiesman WF, Zhao J, Conlon PR, Dowling JE, Petter RC, Lutterodt F, et al. (November 2006). "Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists". Journal of Medicinal Chemistry. 49 (24): 7119–7131. doi:10.1021/jm0605381. PMID 17125264.
  2. ^ Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, et al. (August 2007). "Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study". Journal of the American College of Cardiology. 50 (7): 600–606. doi:10.1016/j.jacc.2007.03.059. PMID 17692744.
  3. ^ Dohadwala MM, Givertz MM (2008). "Role of adenosine antagonism in the cardiorenal syndrome". Cardiovascular Therapeutics. 26 (4): 276–286. doi:10.1111/j.1755-5922.2008.00059.x. PMID 19035879.
  4. ^ Kiesman WF, Elzein E, Zablocki J (2009). "A1 Adenosine Receptor Antagonists, Agonists, and Allosteric Enhancers". Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology. Vol. 193. pp. 25–58. doi:10.1007/978-3-540-89615-9_2. ISBN 978-3-540-89614-2. PMID 19639278.
  5. ^ Ensor CR, Russell SD (October 2010). "Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of heart failure". Expert Opinion on Pharmacotherapy. 11 (14): 2405–2415. doi:10.1517/14656566.2010.514605. PMID 20807184.
  6. ^ Tofovic SP, Salah EM, Smits GJ, Whalley ET, Ticho B, Deykin A, et al. (February 2016). "Dual A1/A2B Receptor Blockade Improves Cardiac and Renal Outcomes in a Rat Model of Heart Failure with Preserved Ejection Fraction". The Journal of Pharmacology and Experimental Therapeutics. 356 (2): 333–340. doi:10.1124/jpet.115.228841. PMC 4727158. PMID 26585572.
  7. ^ Koul S, Ramdas V, Barawkar DA, Waman YB, Prasad N, Madadi SK, et al. (March 2017). "Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A1 receptor antagonists and their biological evaluation". Bioorganic & Medicinal Chemistry. 25 (6): 1963–1975. doi:10.1016/j.bmc.2017.02.029. PMID 28238512.
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