Chemistry:Lu AA41063
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Short description: A selective adenosine A2A receptor antagonist
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| Drug class | Adenosine A2A receptor antagonist |
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| Formula | C16H17F2N3O2S |
| Molar mass | 353.39 g·mol−1 |
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Lu AA41063 is a selective adenosine A2A receptor antagonist.[1][2][3][4][5] Structurally, it is a non-xanthine.[2]
The affinities (Ki) of the drug for the human adenosine receptors are 5.9 nM for the adenosine A2A receptor, 410 nM for the adenosine A1 receptor (69-fold lower than for the A2A receptor), 260 nM for the adenosine A2B receptor (44-fold lower than for the A2A receptor), and >10,000 nM for the adenosine A3 receptor (>1,695-fold lower than for the A2A receptor).[2]
Lu AA41063 was first described in the scientific literature by 2014.[1][5]
Lu AA47070, a water-soluble phosphate ester prodrug of Lu AA41063, is orally active and was under development for the treatment of Parkinson's disease but was discontinued.[6][1][2][7][8] In addition to its antiparkinsonian-like effects, Lu AA47070 reverses motivational deficits in animals and hence shows pro-motivational effects.[9][10][11]
References
- ↑ 1.0 1.1 1.2 "Towards next generation adenosine A(2A) receptor antagonists". Curr Med Chem 21 (34): 3918–3935. 2014. doi:10.2174/0929867321666140826115123. PMID 25174927.
- ↑ 2.0 2.1 2.2 2.3 Müller, Christa E. (2015). "Adenosine A2A Receptor Antagonists in Drug Development". The Adenosinergic System. Current Topics in Neurotoxicity. 10. Cham: Springer International Publishing. pp. 39–56. doi:10.1007/978-3-319-20273-0_3. ISBN 978-3-319-20272-3.
- ↑ "Adenosine A2A Receptor as a Potential Drug Target - Current Status and Future Perspectives". Curr Pharm Des 25 (25): 2716–2740. 2019. doi:10.2174/1381612825666190716113444. PMID 31333093.
- ↑ "Development of Adenosine A2A Receptor Antagonists for the Treatment of Parkinson's Disease: A Recent Update and Challenge". ACS Chem Neurosci 10 (2): 783–791. February 2019. doi:10.1021/acschemneuro.8b00313. PMID 30199223.
- ↑ 5.0 5.1 "Synthesis and SAR studies of analogues of 4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-N-thiazol-2-yl-benzamide (Lu AA41063) as adenosine A2A receptor ligands with improved aqueous solubility". Bioorg Med Chem Lett 25 (6): 1212–1216. March 2015. doi:10.1016/j.bmcl.2015.01.062. PMID 25701253.
- ↑ "International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update". Pharmacological Reviews 74 (2): 340–372. April 2022. doi:10.1124/pharmrev.121.000445. PMID 35302044.
- ↑ "Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} ester (Lu AA47070): a phosphonooxymethylene prodrug of a potent and selective hA(2A) receptor antagonist". Journal of Medicinal Chemistry 54 (3): 751–764. February 2011. doi:10.1021/jm1008659. PMID 21210664.
- ↑ "LU AA 47070". AdisInsight. Springer Nature Switzerland AG. 18 May 2009. https://adisinsight.springer.com/drugs/800027391.
- ↑ "Adenosine and its receptors as therapeutic targets: An overview". Saudi Pharmaceutical Journal 21 (3): 245–253. July 2013. doi:10.1016/j.jsps.2012.05.011. PMID 23960840. "Antagonists of the A2A subtype of adenosine receptor have emerged as a leading candidate class of nondopaminergic antiparkinsonian agents (Feigin, 2003). The ability of Lu AA47070, adenosine A2A antagonist to reverse the effects of D2 receptor blockade suggests that this compound could have potential utility as a treatment for parkinsonism, and for some of the motivational symptoms of depression. In the adult male Sprague Dawley rats the tremulous jaw movements induced by subchronic administration of the DA D2 antagonist pimozide were reversed by Lu AA47070. Lu AA47070 was also able to reverse the catalepsy induced by subchronic administration of the D2 antagonist pimozide and it also reverse the locomotor suppression induced by subchronic administration of the D2 antagonist pimozide (Collins et al., 2012).".
- ↑ "The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation". Pharmacological Reviews 70 (4): 747–762. October 2018. doi:10.1124/pr.117.015107. PMID 30209181.
- ↑ "The novel adenosine A2A antagonist Lu AA47070 reverses the motor and motivational effects produced by dopamine D2 receptor blockade". Pharmacology, Biochemistry, and Behavior 100 (3): 498–505. January 2012. doi:10.1016/j.pbb.2011.10.015. PMID 22037410.
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