Lu AA47070

Lu AA47070 is a selective adenosine A_2A receptor antagonist that was under development for the treatment of Parkinson's disease but was never marketed.^[1]^[2]^[3] It has been found to reverse some of the effects of dopamine D₂ receptor antagonists like pimozide and haloperidol, for instance tremulous jaw movements, catalepsy, locomotor suppression, and other anti-motivational effects, in animals.^[2]^[4]^[5] The drug is a prodrug of Lu AA41063.^[6]^[7]^[3] It was discontinued in phase 1 clinical trials because it lacked the intended pharmacological properties in humans.^[7]^[1] Lu AA47070 was first described by 2008.^[8]

Other namesLu-AA47070; LU AA 47070; LU-AA-47070

Drug classAdenosine A_2A receptor antagonist

CAS Number

913842-25-8

PubChem CID

11947802

Quick facts Clinical data, Other names ...

Lu AA47070
Clinical data

Other names	Lu-AA47070; LU AA 47070; LU-AA-47070
Drug class	Adenosine A_2A receptor antagonist
Identifiers
IUPAC name [2-[4-(3,3-dimethylbutanoylamino)-3,5-difluorobenzoyl]imino-1,3-thiazol-3-yl]methyl dihydrogen phosphate
CAS Number	913842-25-8
PubChem CID	11947802
ChemSpider	62804024
UNII	S4AD6SAU9U
ChEMBL	ChEMBL1671940
Chemical and physical data
Formula	C₁₇H₂₀F₂N₃O₆PS
Molar mass	463.39 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(C)(C)CC(=O)NC1=C(C=C(C=C1F)C(=O)N=C2N(C=CS2)COP(=O)(O)O)F
InChI InChI=1S/C17H20F2N3O6PS/c1-17(2,3)8-13(23)20-14-11(18)6-10(7-12(14)19)15(24)21-16-22(4-5-30-16)9-28-29(25,26)27/h4-7H,8-9H2,1-3H3,(H,20,23)(H2,25,26,27) Key:MSWIQSFUBYCFJE-UHFFFAOYSA-N

[1]
"LU AA 47070". AdisInsight. Springer Nature Switzerland AG. 18 May 2009. Retrieved 22 September 2024.
[2]
Sachdeva S, Gupta M (July 2013). "Adenosine and its receptors as therapeutic targets: An overview". Saudi Pharmaceutical Journal. 21 (3): 245–253. doi:10.1016/j.jsps.2012.05.011. PMC 3744929. 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).
[3]
Sams AG, Mikkelsen GK, Larsen M, Langgård M, Howells ME, Schrøder TJ, et al. (February 2011). "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. doi:10.1021/jm1008659. PMID 21210664.{{cite journal}}: CS1 maint: overridden setting (link)
[4]
Salamone JD, Correa M, Ferrigno S, Yang JH, Rotolo RA, Presby RE (October 2018). "The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation". Pharmacological Reviews. 70 (4): 747–762. doi:10.1124/pr.117.015107. PMC 6169368. PMID 30209181.
[5]
Collins LE, Sager TN, Sams AG, Pennarola A, Port RG, Shahriari M, et al. (January 2012). "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. doi:10.1016/j.pbb.2011.10.015. PMID 22037410.
[6]
IJzerman AP, Jacobson KA, Müller CE, Cronstein BN, Cunha RA (April 2022). "International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update". Pharmacological Reviews. 74 (2): 340–372. doi:10.1124/pharmrev.121.000445. PMC 8973513. PMID 35302044.
[7]
Yuan G, Jones GB (2014). "Towards next generation adenosine A(2A) receptor antagonists". Current Medicinal Chemistry. 21 (34): 3918–3935. doi:10.2174/0929867321666140826115123. PMID 25174927.
[8]
Sommer DB, Stacy MA (December 2008). "What's in the pipeline for the treatment of Parkinson's disease?". Expert Review of Neurotherapeutics. 8 (12): 1829–1839. doi:10.1586/14737175.8.12.1829. PMID 19086879.

This pharmacology-related article is a stub. You can help Wikipedia by adding missing information.

References

Related Articles

Timelines

Top Qs

Fact Checks

Related Articles

"Adenosine and its receptors as therapeutic targets: An overview"

"The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation"

"International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update"