3-Chlorostyrylcaffeine

3-Chlorostyrylcaffeine
Clinical data
Other names	CSC; 8-CSC; 8-(3-Chlorostyryl)caffeine; 8-(3-Chlorostyryl)-1,3,7-trimethylxanthine
Drug class	Adenosine A2A receptor antagonist
Identifiers
	IUPAC name 1-[3-(3-chlorophenyl)prop-2-enyl]-3,7-dimethylpurine-2,6-dione;
CAS Number	147700-11-6 ;
PubChem CID	129730232;
ChemSpider	4510063;
Chemical and physical data
Formula	C16H15ClN4O2
Molar mass	330.77 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1C=NC2=C1C(=O)N(C(=O)N2C)CC=CC3=CC(=CC=C3)Cl;
	InChI InChI=1S/C16H15ClN4O2/c1-19-10-18-14-13(19)15(22)21(16(23)20(14)2)8-4-6-11-5-3-7-12(17)9-11/h3-7,9-10H,8H2,1-2H3; Key:VYLMWABBINHTEH-UHFFFAOYSA-N;

3-Chlorostyrylcaffeine (CSC), or 8-(3-chlorostyryl)caffeine (8-CSC), is a potent and selective adenosine A_2A receptor antagonist which is used in scientific research.^[1]^[2]

It has 520-fold selectivity for the adenosine A_2A receptor over the adenosine A₁ receptor (K_i = 54 nM and 28,000 nM for the rat receptors, respectively).^[1]^[2] Its affinities for the adenosine A_2B and A₃ receptors are similarly low (K_i = 8,200 nM and >10,000 nM, respectively).^[3]

CSC has been found to reverse the catalepsy induced by the dopamine D₁ receptor antagonist SCH-23390 and the dopamine D₂ receptor antagonists raclopride and sulpiride in animals.^[4]^[5]^[6]

The drug was one of the first selective adenosine A_2A receptor antagonists to be developed.^[1] However, in addition to its adenosine receptor antagonism, CSC was subsequently found to be a potent monoamine oxidase B (MAO-B) inhibitor (K_i = 80.6 nM for baboon MAO-B).^[2]^[1]^[3]^[7]^[8] CSC was first described in the scientific literature by 1993.^[9]

References

^ ^a ^b ^c ^d Cristalli G, Müller CE, Volpini R (2009). "Recent Developments in Adenosine A2A Receptor Ligands". Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology. Vol. 193. pp. 59–98. doi:10.1007/978-3-540-89615-9_3. ISBN 978-3-540-89614-2. PMID 19639279. {{cite book}}: |journal= ignored (help)
^ ^a ^b ^c Müller CE, Jacobson KA (2011). "Xanthines as Adenosine Receptor Antagonists". Methylxanthines. Handbook of Experimental Pharmacology. Vol. 200. pp. 151–199. doi:10.1007/978-3-642-13443-2_6. ISBN 978-3-642-13442-5. PMC 3882893. PMID 20859796. {{cite book}}: |journal= ignored (help)
^ ^a ^b Müller CE, Jacobson KA (May 2011). "Recent developments in adenosine receptor ligands and their potential as novel drugs". Biochim Biophys Acta. 1808 (5): 1290–1308. doi:10.1016/j.bbamem.2010.12.017. PMC 3437328. PMID 21185259.
^ Jenner P (December 2003). "A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD". Neurology. 61 (11 Suppl 6): S32–S38. doi:10.1212/01.wnl.0000095209.59347.79. PMID 14663007.
^ Worden LT, Shahriari M, Farrar AM, Sink KS, Hockemeyer J, Müller CE, Salamone JD (April 2009). "The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists". Psychopharmacology (Berl). 203 (3): 489–499. doi:10.1007/s00213-008-1396-0. PMC 2875246. PMID 19048234.
^ Hauber W, Neuscheler P, Nagel J, Müller CE (October 2001). "Catalepsy induced by a blockade of dopamine D1 or D2 receptors was reversed by a concomitant blockade of adenosine A(2A) receptors in the caudate-putamen of rats". Eur J Neurosci. 14 (8): 1287–1293. doi:10.1046/j.0953-816x.2001.01759.x. PMID 11703457.
^ Chen JF, Steyn S, Staal R, Petzer JP, Xu K, Van Der Schyf CJ, Castagnoli K, Sonsalla PK, Castagnoli N, Schwarzschild MA (September 2002). "8-(3-Chlorostyryl)caffeine may attenuate MPTP neurotoxicity through dual actions of monoamine oxidase inhibition and A2A receptor antagonism". J Biol Chem. 277 (39): 36040–36044. doi:10.1074/jbc.M206830200. PMID 12130655.
^ Pretorius J, Malan SF, Castagnoli N, Bergh JJ, Petzer JP (September 2008). "Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues". Bioorg Med Chem. 16 (18): 8676–8684. doi:10.1016/j.bmc.2008.07.088. PMID 18723354.
^ Jacobson KA, Gallo-Rodriguez C, Melman N, Fischer B, Maillard M, van Bergen A, van Galen PJ, Karton Y (May 1993). "Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists". J Med Chem. 36 (10): 1333–1342. doi:10.1021/jm00062a005. PMC 5975975. PMID 8496902.

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[CristalliMüllerVolpini2009-1] Cristalli G, Müller CE, Volpini R (2009). "Recent Developments in Adenosine A2A Receptor Ligands". Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology. Vol. 193. pp. 59–98. doi:10.1007/978-3-540-89615-9_3. ISBN 978-3-540-89614-2. PMID 19639279. {{cite book}}: |journal= ignored (help)

[MüllerJacobson2011a-2] Müller CE, Jacobson KA (2011). "Xanthines as Adenosine Receptor Antagonists". Methylxanthines. Handbook of Experimental Pharmacology. Vol. 200. pp. 151–199. doi:10.1007/978-3-642-13443-2_6. ISBN 978-3-642-13442-5. PMC 3882893. PMID 20859796. {{cite book}}: |journal= ignored (help)

[MüllerJacobson2011b-3] Müller CE, Jacobson KA (May 2011). "Recent developments in adenosine receptor ligands and their potential as novel drugs". Biochim Biophys Acta. 1808 (5): 1290–1308. doi:10.1016/j.bbamem.2010.12.017. PMC 3437328. PMID 21185259.

[Jenner2003-4] Jenner P (December 2003). "A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD". Neurology. 61 (11 Suppl 6): S32–S38. doi:10.1212/01.wnl.0000095209.59347.79. PMID 14663007.

[WordenShahriariFarrar2009-5] Worden LT, Shahriari M, Farrar AM, Sink KS, Hockemeyer J, Müller CE, Salamone JD (April 2009). "The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists". Psychopharmacology (Berl). 203 (3): 489–499. doi:10.1007/s00213-008-1396-0. PMC 2875246. PMID 19048234.

[HauberNeuschelerNagel2001-6] Hauber W, Neuscheler P, Nagel J, Müller CE (October 2001). "Catalepsy induced by a blockade of dopamine D1 or D2 receptors was reversed by a concomitant blockade of adenosine A(2A) receptors in the caudate-putamen of rats". Eur J Neurosci. 14 (8): 1287–1293. doi:10.1046/j.0953-816x.2001.01759.x. PMID 11703457.

[ChenSteynStaal2002-7] Chen JF, Steyn S, Staal R, Petzer JP, Xu K, Van Der Schyf CJ, Castagnoli K, Sonsalla PK, Castagnoli N, Schwarzschild MA (September 2002). "8-(3-Chlorostyryl)caffeine may attenuate MPTP neurotoxicity through dual actions of monoamine oxidase inhibition and A2A receptor antagonism". J Biol Chem. 277 (39): 36040–36044. doi:10.1074/jbc.M206830200. PMID 12130655.

[PretoriusMalanCastagnoli2008-8] Pretorius J, Malan SF, Castagnoli N, Bergh JJ, Petzer JP (September 2008). "Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues". Bioorg Med Chem. 16 (18): 8676–8684. doi:10.1016/j.bmc.2008.07.088. PMID 18723354.

[JacobsonGallo-RodriguezMelman1993-9] Jacobson KA, Gallo-Rodriguez C, Melman N, Fischer B, Maillard M, van Bergen A, van Galen PJ, Karton Y (May 1993). "Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists". J Med Chem. 36 (10): 1333–1342. doi:10.1021/jm00062a005. PMC 5975975. PMID 8496902.

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3-Chlorostyrylcaffeine

See also

References