TONAPOFYLLINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H32N4O4
Molecular Weight	416.5139
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCN1C2=C(NC(=N2)C34CCC(CCC(O)=O)(CC3)CC4)C(=O)N(CCC)C1=O

InChI

InChIKey=ZWTVVWUOTJRXKM-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19828940 | https://www.ncbi.nlm.nih.gov/pubmed/20807184 | https://www.ncbi.nlm.nih.gov/pubmed/16187697 | https://www.ncbi.nlm.nih.gov/pubmed/17692744 | https://adisinsight.springer.com/drugs/800015498

Tonapofylline is a selective oral adenosine A, receptor antagonist, for the potential treatment of congestive heart failure. Oral tonapofylline over the dose range of 3 to 225 mg/day produced significant increases in sodium excretion in patients with stable heart failure without causing kaliuresis or reducing renal function. Tonapofylline may be useful in the clinical setting for the prevention of kidney failure induced by nephrotoxic agents such as cisplatin. Tonapofylline may be renoprotective in the setting of concomitant treatment with a loop-diuretic. Adverse effects were generally mild. Tonapofylline had been in phase III clinical trial for the treatment of acute heart failure. However, this development was discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
Comparison of three different A1 adenosine receptor antagonists on infarct size and multiple cycle ischemic preconditioning in anesthetized dogs.	2004 Mar	14634049
BG-9928 (Biogen Idec).	2005 Sep	16187697
Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists.	2006 Nov 30	17125264
Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study.	2007 Aug 14	17692744
Role of adenosine antagonism in the cardiorenal syndrome.	2008 Winter	19035879
Protective effect of tonapofylline (BG9928), an adenosine A1 receptor antagonist, against cisplatin-induced acute kidney injury in rats.	2009	19828940
A1 adenosine receptor antagonists, agonists, and allosteric enhancers.	2009	19639278
Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of heart failure.	2010 Oct	20807184
Clinical pharmacokinetics of tonapofylline: evaluation of dose proportionality, oral bioavailability, and gender and food effects in healthy human subjects.	2011 Jul	20926751
Effects of BG9928, an adenosine A₁ receptor antagonist, in patients with congestive heart failure.	2011 Jun	20926754
Pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe renal impairment and in elderly subjects.	2011 Sep	21888869
Pharmacokinetics of oral tonapofylline and its acyl-glucuronide metabolite in patients with mild and moderate hepatic impairment.	2012 Apr	21610206
Dual A1/A2B Receptor Blockade Improves Cardiac and Renal Outcomes in a Rat Model of Heart Failure with Preserved Ejection Fraction.	2016 Feb	26585572
Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A(1) receptor antagonists and their biological evaluation.	2017 Mar 15	28238512

Sample Use Guides

In Vivo Use Guide

3, 15, 75, or 225 mg once daily for 10 days

Route of Administration: Oral

Name

Type

Language

TONAPOFYLLINE

Official Name

English

tonapofylline [INN]

Common Name

English

3-(4-(2,6-DIOXO-1,3-DIPROPYL-2,3,6,7-TETRAHYDRO-1H-PURIN-8-YL)BICYCLO(2.2.2)OCT-1- YL)PROPANOIC ACID

Systematic Name

English

BG-9928

Code

English

TONAPOFYLLINE [USAN]

Common Name

English

BG9928

Code

English

BICYCLO(2.2.2)OCTANE-1-PROPANOIC ACID, 4-(2,3,6,7-TETRAHYDRO-2,6-DIOXO-1,3-DIPROPYL-1H- PURIN-8-YL)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C319