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ABT-239 - Wikipedia

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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^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
(verify)

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 U.S. National Library of Medicine Medical Subject Headings (MeSH)

Histamine receptor modulators

H₁

Agonists

Antagonists

Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, brilaroxazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine)
Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione)
Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline)
Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine)
Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)

H₂

Agonists	Amthamine Betazole Dimaprit Histamine HTMT Impromidine L-Histidine UR-AK49
Antagonists	Bisfentidine Burimamide Cimetidine Dalcotidine Donetidine Ebrotidine Etintidine Famotidine Isolamtidine Lafutidine Lamtidine Lavoltidine (loxtidine) Lupitidine Metiamide Mifentidine Niperotidine Nizatidine Osutidine Oxmetidine Pibutidine Quisultazine (quisultidine) Ramixotidine Ranitidine Roxatidine Sufotidine Tiotidine Tuvatidine Venritidine Xaltidine Zolantidine

H₃

Agonists	α-Methylhistamine Cipralisant Histamine Imetit Immepip Immethridine L-Histidine Methimepip Proxyfan
Antagonists	A-349821 A-423579 ABT-239 ABT-652 AZD5213 Bavisant Betahistine Burimamide Ciproxifan Clobenpropit Conessine Enerisant GSK-189254 Impentamine Iodophenpropit Irdabisant JNJ-5207852 NNC 38-1049 PF-03654746 Pitolisant SCH-79687 Thioperamide VUF-5681

H₄

Agonists	4-Methylhistamine α-Methylhistamine Histamine L-Histidine OUP-16 VUF-8430
Antagonists	JNJ-7777120 Mianserin Seliforant Thioperamide Toreforant VUF-6002

See also: Receptor/signaling modulators; Monoamine metabolism modulators; Monoamine reuptake inhibitors

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