Acadesine
| File:Acadesine structure.png | |
| Systematic (IUPAC) name | |
|---|---|
|
5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-imidazole-4-carboxamide | |
| Identifiers | |
| CAS Number | 2627-69-2 |
| ATC code | C01EB13 (WHO) |
| PubChem | CID 17513 |
| ChemSpider | 16560 |
| Chemical data | |
| Formula | C9H14N4O5 |
| Molar mass | 258.231 g/mol[[Script error: No such module "String".]] |
| Script error: No such module "collapsible list". | |
Acadesine (INN) (5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside, AICA-riboside) is an AMP-activated protein kinase activator[1] which is used for the treatment of acute lymphoblastic leukemia[2] and may have applications in treating other disorders such as diabetes.[3]
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.
Chemistry
Reaction of 2-bromo tribenzoyl ribose with 1,2-diaminomaleionitrile 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.
Ferris, James P.; Devadas, Balekadru; Huang, Chun Hsien; Ren, Wu Yen (1985). "Nucleosides from carbohydrate adducts of diaminomaleonitrile. A novel synthesis of 5-amino-1-(.beta.-D-ribofuranosyl)imidazole-4-carboxamide and 5-amino-1-(.beta.-D-ribopyranosyl)imidazole-4-carboxamide". The Journal of Organic Chemistry. 50: 747. doi:10.1021/jo00206a004.
References
- ↑ Favero CB, Mandell JW. A pharmacological activator of AMP-activated protein kinase (AMPK) induces astrocyte stellation. Brain Research. 2007 Sep 7;1168:1-10. PMID 17706943
- ↑ Cronstein BN, Kamen BA. 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICA-riboside) as a targeting agent for therapy of patients with acute lymphoblastic leukemia: are we there and are there pitfalls? Journal of Pediatric Hematology and Oncology. 2007 Dec;29(12):805-7. PMID 18090925
- ↑ Cuthbertson DJ, Babraj JA, Mustard KJ, Towler MC, Green KA, Wackerhage H, Leese GP, Baar K, Thomason-Hughes M, Sutherland C, Hardie DG, Rennie MJ. 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes. 2007 Aug;56(8):2078-84. PMID 17513706
http://www.reuters.com/article/pressRelease/idUS115105+11-May-2009+PRN20090511
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