Lu AA47070

Lu AA47070
Clinical data
Other names	Lu-AA47070; LU AA 47070; LU-AA-47070
Drug class	Adenosine A2A 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;

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]

References

^ ^a ^b "LU AA 47070". AdisInsight. 18 May 2009. Retrieved 22 September 2024.
^ ^a ^b Sachdeva S, Gupta M (July 2013). "Adenosine and its receptors as therapeutic targets: An overview". Saudi Pharm J. 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).
^ ^a ^b {{cite journal | vauthors = Sams AG, Mikkelsen GK, Larsen M, Langgård M, Howells ME, Schrøder TJ, Brennum LT, Torup L, Jørgensen EB, Bundgaard C, Kreilgård M, Bang-Andersen B | title = 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 = J Med Chem | volume = 54 | issue = 3 | pages = 751–764 | date = February 2011 | pmid = 21210664 | doi = 10.1021/jm1008659 | url = }}
^ 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". Pharmacol Rev. 70 (4): 747–762. doi:10.1124/pr.117.015107. PMC 6169368. PMID 30209181.
^ Collins LE, Sager TN, Sams AG, Pennarola A, Port RG, Shahriari M, Salamone JD (January 2012). "The novel adenosine A2A antagonist Lu AA47070 reverses the motor and motivational effects produced by dopamine D2 receptor blockade". Pharmacol Biochem Behav. 100 (3): 498–505. doi:10.1016/j.pbb.2011.10.015. PMID 22037410.
^ 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". Pharmacol Rev. 74 (2): 340–372. doi:10.1124/pharmrev.121.000445. PMC 8973513. PMID 35302044.
^ ^a ^b Yuan G, Jones GB (2014). "Towards next generation adenosine A(2A) receptor antagonists". Curr Med Chem. 21 (34): 3918–3935. doi:10.2174/0929867321666140826115123. PMID 25174927.
^ Sommer DB, Stacy MA (December 2008). "What's in the pipeline for the treatment of Parkinson's disease?". Expert Rev Neurother. 8 (12): 1829–1839. doi:10.1586/14737175.8.12.1829. PMID 19086879.

[AdisInsight-1] "LU AA 47070". AdisInsight. 18 May 2009. Retrieved 22 September 2024.

[SachdevaGupta2013-2] Sachdeva S, Gupta M (July 2013). "Adenosine and its receptors as therapeutic targets: An overview". Saudi Pharm J. 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).

[SamsMikkelsenLarsen2011-3] {{cite journal | vauthors = Sams AG, Mikkelsen GK, Larsen M, Langgård M, Howells ME, Schrøder TJ, Brennum LT, Torup L, Jørgensen EB, Bundgaard C, Kreilgård M, Bang-Andersen B | title = 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 = J Med Chem | volume = 54 | issue = 3 | pages = 751–764 | date = February 2011 | pmid = 21210664 | doi = 10.1021/jm1008659 | url = }}

[SalamoneCorreaFerrigno2018-4] 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". Pharmacol Rev. 70 (4): 747–762. doi:10.1124/pr.117.015107. PMC 6169368. PMID 30209181.

[CollinsSagerSams2012-5] Collins LE, Sager TN, Sams AG, Pennarola A, Port RG, Shahriari M, Salamone JD (January 2012). "The novel adenosine A2A antagonist Lu AA47070 reverses the motor and motivational effects produced by dopamine D2 receptor blockade". Pharmacol Biochem Behav. 100 (3): 498–505. doi:10.1016/j.pbb.2011.10.015. PMID 22037410.

[IJZermanJacobsonMüller2022-6] 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". Pharmacol Rev. 74 (2): 340–372. doi:10.1124/pharmrev.121.000445. PMC 8973513. PMID 35302044.

[YuanJones2014-7] Yuan G, Jones GB (2014). "Towards next generation adenosine A(2A) receptor antagonists". Curr Med Chem. 21 (34): 3918–3935. doi:10.2174/0929867321666140826115123. PMID 25174927.

[SommerStacy2008-8] Sommer DB, Stacy MA (December 2008). "What's in the pipeline for the treatment of Parkinson's disease?". Expert Rev Neurother. 8 (12): 1829–1839. doi:10.1586/14737175.8.12.1829. PMID 19086879.

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