ABT-239

ABT-239
IUPAC ime
	4-(22-[(2R)-2-Metilpirolidin-1-il]etil; benzofuran-5-il)benzonitril
Identifikatori
ATC kod	none
PubChem	CID 9818903
ChemSpider	7994652
ChEMBL	CHEMBL351231
Hemijski podaci
Formula	C22H22N2O
Molarna masa	330,42 g/mol
	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 ;

ABT-239 je inverzni agonist H₃-receptor, koji je razvila kompanija Abot. On ima stimulantno i nootropno dejstvo, i bio je istraživan za moguću primenu u tretmanu ADHD, Alchajmerove bolesti, i šizofrenije.^[1]^[2]^[3]^[4] ABT-239 je aktivniji na ljudskom H₃ receptoru od sličnih liganda, npr. tioperamida, ciproksifana, i cipralisanta. Razvoj je zaustavljen nakon što je tokom kliničkih ispitivanja pokazano da proizvodi ozbiljne srčane nuspojave QT prolongacije,^[5] ali je još uvek u širokoj upotrebi u životinjskim studijama H₃ antagonista / inverznih agonista.

Reference[uredi | uredi izvor]

^ 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-(22-[(2R)-2-Methylpyrrolidinyl]ethylbenzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H₃ receptor antagonist with drug-like properties”. J. Pharmacol. Exp. Ther. 313 (1): 165—75. PMID 15608078. doi:10.1124/jpet.104.078303.
^ 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-(22-[(2R)-2-Methylpyrrolidinyl]ethylbenzofuran-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. PMID 15608077. doi:10.1124/jpet.104.078402.
^ 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. PMID 15634000. doi:10.1021/jm040118g.
^ 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. PMID 18305012. doi:10.1124/jpet.107.135343.
^ 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. PMID 16513092. doi:10.1016/j.bcp.2005.10.033.

Spoljašnje veze[uredi | uredi izvor]

4-(2-(2-(2-methyl-1-pyrrolidinyl)ethyl)-1-benzofuran-5-yl)benzonitrile на US National Library of Medicine Medical Subject Headings (MeSH)

[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-(22-[(2R)-2-Methylpyrrolidinyl]ethylbenzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H₃ receptor antagonist with drug-like properties”. J. Pharmacol. Exp. Ther. 313 (1): 165—75. PMID 15608078. doi:10.1124/jpet.104.078303.

[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-(22-[(2R)-2-Methylpyrrolidinyl]ethylbenzofuran-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. PMID 15608077. doi:10.1124/jpet.104.078402.

[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. PMID 15634000. doi:10.1021/jm040118g.

[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. PMID 18305012. doi:10.1124/jpet.107.135343.

[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. PMID 16513092. doi:10.1016/j.bcp.2005.10.033.

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