ABT-239: Difference between revisions

ABT-239
Identifiers
	IUPAC name 4-(2-{2-[(2R)-2-Methylpyrrolidin-1-yl]ethyl}-; benzofuran-5-yl)benzonitrile;
PubChem CID	9818903;
ChemSpider	7994652 ;
ChEMBL	ChEMBL351231 ;
CompTox Dashboard (EPA)	DTXSID00196710 ;
Chemical and physical data
Formula	C22H22N2O
Molar mass	330.42 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES N#Cc4ccc(c3cc1c(oc(c1)CCN2[C@H](C)CCC2)cc3)cc4;
	InChI InChI=1S/C22H22N2O/c1-16-3-2-11-24(16)12-10-21-14-20-13-19(8-9-22(20)25-21)18-6-4-17(15-23)5-7-18/h4-9,13-14,16H,2-3,10-12H2,1H3/t16-/m1/s1 ; Key:KFHYZKCRXNRKRC-MRXNPFEDSA-N ;
	(verify)

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Revision as of 22:33, 31 August 2011

ABT-239 is an H₃-receptor inverse agonist developed by Abbott. It has stimulant and nootropic effects, and has been investigated as a treatment for ADHD, Alzheimer's disease, and schizophrenia.^[1]^[2]^[3]^[4] ABT-239 is more active at the human H₃ receptor than comparable agents such as thioperamide, ciproxifan, and cipralisant. It was ultimately dropped from human trials after showing the dangerous cardiac side effect of QT prolongation,^[5] but is still widely used in animal research into H₃ antagonists / inverse agonists.

References

^ Esbenshade TA, Fox GB, Krueger KM, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan L, Wetter J, Marsh K, Bennani YL, Cowart MD, Sullivan JP, Hancock AA (2005). "Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H₃ receptor antagonist with drug-like properties". J. Pharmacol. Exp. Ther. 313 (1): 165–75. doi:10.1124/jpet.104.078303. PMID 15608078.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Fox GB, Esbenshade TA, Pan JB, Radek RJ, Krueger KM, Yao BB, Browman KE, Buckley MJ, Ballard ME, Komater VA, Miner H, Zhang M, Faghih R, Rueter LE, Bitner RS, Drescher KU, Wetter J, Marsh K, Lemaire M, Porsolt RD, Bennani YL, Sullivan JP, Cowart MD, Decker MW, Hancock AA (2005). "Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: II. Neurophysiological characterization and broad preclinical efficacy in cognition and schizophrenia of a potent and selective histamine H₃ receptor antagonist". J. Pharmacol. Exp. Ther. 313 (1): 176–90. doi:10.1124/jpet.104.078402. PMID 15608077.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Cowart M, Faghih R, Curtis MP, Gfesser GA, Bennani YL, Black LA, Pan L, Marsh KC, Sullivan JP, Esbenshade TA, Fox GB, Hancock AA (2005). "4-(2-[2-(2(R)-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl)benzonitrile and related 2-aminoethylbenzofuran H₃ receptor antagonists potently enhance cognition and attention". J. Med. Chem. 48 (1): 38–55. doi:10.1021/jm040118g. PMID 15634000.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H (2008). "Correlation between ex vivo receptor occupancy and wake-promoting activity of selective H₃ receptor antagonists". J. Pharmacol. Exp. Ther. 325 (3): 902–9. doi:10.1124/jpet.107.135343. PMID 18305012. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Hancock, AA (2006). "The challenge of drug discovery of a GPCR target: analysis of preclinical pharmacology of histamine H3 antagonists/inverse agonists". Biochemical pharmacology. 71 (8): 1103–13. doi:10.1016/j.bcp.2005.10.033. PMID 16513092.

External links

4-(2-(2-(2-methyl-1-pyrrolidinyl)ethyl)-1-benzofuran-5-yl)benzonitrile at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.

[pmid15608078-1] Esbenshade TA, Fox GB, Krueger KM, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan L, Wetter J, Marsh K, Bennani YL, Cowart MD, Sullivan JP, Hancock AA (2005). "Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H₃ receptor antagonist with drug-like properties". J. Pharmacol. Exp. Ther. 313 (1): 165–75. doi:10.1124/jpet.104.078303. PMID 15608078.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid15608077-2] Fox GB, Esbenshade TA, Pan JB, Radek RJ, Krueger KM, Yao BB, Browman KE, Buckley MJ, Ballard ME, Komater VA, Miner H, Zhang M, Faghih R, Rueter LE, Bitner RS, Drescher KU, Wetter J, Marsh K, Lemaire M, Porsolt RD, Bennani YL, Sullivan JP, Cowart MD, Decker MW, Hancock AA (2005). "Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: II. Neurophysiological characterization and broad preclinical efficacy in cognition and schizophrenia of a potent and selective histamine H₃ receptor antagonist". J. Pharmacol. Exp. Ther. 313 (1): 176–90. doi:10.1124/jpet.104.078402. PMID 15608077.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid15634000-3] Cowart M, Faghih R, Curtis MP, Gfesser GA, Bennani YL, Black LA, Pan L, Marsh KC, Sullivan JP, Esbenshade TA, Fox GB, Hancock AA (2005). "4-(2-[2-(2(R)-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl)benzonitrile and related 2-aminoethylbenzofuran H₃ receptor antagonists potently enhance cognition and attention". J. Med. Chem. 48 (1): 38–55. doi:10.1021/jm040118g. PMID 15634000.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid18305012-4] Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H (2008). "Correlation between ex vivo receptor occupancy and wake-promoting activity of selective H₃ receptor antagonists". J. Pharmacol. Exp. Ther. 325 (3): 902–9. doi:10.1124/jpet.107.135343. PMID 18305012. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[5] Hancock, AA (2006). "The challenge of drug discovery of a GPCR target: analysis of preclinical pharmacology of histamine H3 antagonists/inverse agonists". Biochemical pharmacology. 71 (8): 1103–13. doi:10.1016/j.bcp.2005.10.033. PMID 16513092.

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@@ Line 1: / Line 1: @@
 {{Drugbox
-| verifiedrevid = 413287248
+| verifiedrevid = 413288200
 | IUPAC_name = 4-(2-{2-[(2''R'')-2-Methylpyrrolidin-1-yl]ethyl}-<br>benzofuran-5-yl)benzonitrile
 | image = ABT-239.svg