Acadesine

Acadesine

Clinical data
ATC code	C01EB13 (WHO)
Identifiers
IUPAC name 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-imidazole-4-carboxamide
CAS Number	2627-69-2 N
PubChem CID	17513
IUPHAR/BPS	5133
ChemSpider	16560 Y
UNII	53IEF47846
KEGG	D02742 Y
ChEBI	CHEBI:28498 N
ChEMBL	CHEMBL1551724 N
ECHA InfoCard	100.018.271
Chemical and physical data
Formula	C9H14N4O5
Molar mass	258.231 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(c1ncn(c1N)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)CO)N
InChI InChI=1S/C9H14N4O5/c10-7-4(8(11)17)12-2-13(7)9-6(16)5(15)3(1-14)18-9/h2-3,5-6,9,14-16H,1,10H2,(H2,11,17)/t3-,5-,6-,9-/m1/s1 Y Key:RTRQQBHATOEIAF-UUOKFMHZSA-N Y
NY (what is this?)

Acadesine (INN), also known as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, AICA-riboside, and AICAR, is an AMP-activated protein kinase activator which is used for the treatment of acute lymphoblastic leukemia and may have applications in treating other disorders such as diabetes.

Acadesine is an adenosine regulating agent developed by PeriCor Therapeutics and licensed to Schering-Plough in 2007 for phase III studies. The drug is a potential first-in-class agent for prevention of reperfusion injury in CABG surgery. Schering began patient enrollment in phase III studies in May 2009. The trial was terminated in late 2010 based on an interim futility analysis.

Reaction of 2-bromo tribenzoyl ribose with diaminomaleonitrile results in the displacement of the anomeric halogen by one of the amino groups and the formation of the aminosugar largely as the β-anomer. Treatment of this product with methyl orthoformate in the presence of a base leads to the replacement of the alkoxy groups in orthoformate by the adjacent amines, resulting in the formation of the imidazole ring. Reaction with alkoxide then interestingly converts the nitrile nearest the sugar to an iminoester; the benzoyl groups are cleaved in the process. Hofmann rearrangement in the presence of a bromine and a base converts the iminoester to the corresponding primary amine. Basic hydrolysis then converts the remaining nitrile to an amide, affording acadesine.

Acadesine acts as an AMP-activated protein kinase agonist. It stimulates glucose uptake and increases the activity of p38 mitogen-activated protein kinases α and β in skeletal muscle tissue, as well as suppressing apoptosis by reducing production of reactive oxygen compounds inside the cell.