ABT-239

ABT-239
Identifiers
	IUPAC name 4-(2-{2-[(2R)-2-Methylpyrrolidin-1-yl]ethyl}-; benzofuran-5-yl)benzonitrile;
CAS Number	460746-46-7 ; 460746-51-4 (racemic); 460749-29-5 (S-isomer);
PubChem CID	9818903;
IUPHAR/BPS	1218;
ChemSpider	7994652 ;
UNII	86H6B395PI;
ChEMBL	ChEMBL351231 ;
CompTox Dashboard (EPA)	DTXSID00196710 ;
Chemical and physical data
Formula	C22H22N2O
Molar mass	330.431 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES N#CC1=CC=C(C2=CC3=C(C=C2)OC(CCN4[C@@H](CCC4)C)=C3)C=C1;
	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 ;

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. S2CID 573355.
^ 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. S2CID 15430117.
^ 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.
^ Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H (June 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. S2CID 26536000.
^ 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 US National Library of Medicine Medical Subject Headings (MeSH)

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[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. S2CID 573355.

[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. S2CID 15430117.

[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.

[pmid18305012-4] Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H (June 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. S2CID 26536000.

[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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Identifiers

IUPAC name 4-(2-{2-[(2R)-2-Methylpyrrolidin-1-yl]ethyl}- benzofuran-5-yl)benzonitrile
CAS Number	460746-46-7 460746-51-4 (racemic) 460749-29-5 (S-isomer)
PubChem CID	9818903
IUPHAR/BPS	1218
ChemSpider	7994652^Y
UNII	86H6B395PI
ChEMBL	ChEMBL351231^Y
CompTox Dashboard (EPA)	DTXSID00196710
Chemical and physical data
Formula	C₂₂H₂₂N₂O
Molar mass	330.431 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES N#CC1=CC=C(C2=CC3=C(C=C2)OC(CCN4[C@@H](CCC4)C)=C3)C=C1
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^Y Key:KFHYZKCRXNRKRC-MRXNPFEDSA-N^Y