JJC8-089

{{Short description|Dopamine reuptake inhibitor related to modafinil}}

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| class = Dopamine reuptake inhibitor

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| CAS_number = 1627576-64-0

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| PubChem = 90389439

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| ChemSpiderID = 76721417

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| ChEMBL = 3916231

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| IUPAC_name = 1-[4-[2-[bis(4-fluorophenyl)methylsulfanyl]ethyl]piperazin-1-yl]propan-2-ol

| C=22 | H=28 | F=2 | N=2 | O=1 | S=1

| SMILES = CC(CN1CCN(CC1)CCSC(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F)O

| StdInChI = 1S/C22H28F2N2OS/c1-17(27)16-26-12-10-25(11-13-26)14-15-28-22(18-2-6-20(23)7-3-18)19-4-8-21(24)9-5-19/h2-9,17,22,27H,10-16H2,1H3

| StdInChIKey = MQDDJWTVOBHYHX-UHFFFAOYSA-N

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JJC8-089 is a dopamine reuptake inhibitor (DRI) that was derived from modafinil and is related to JJC8-016, JJC8-088, and JJC8-091.{{cite book | vauthors = Aggarwal S, Mortensen OV | chapter = Discovery and Development of Monoamine Transporter Ligands | title = Drug Development in Psychiatry | journal = Adv Neurobiol | series = Advances in Neurobiology | volume = 30 | issue = | pages = 101–129 | date = 2023 | pmid = 36928847 | pmc = 10074400 | doi = 10.1007/978-3-031-21054-9_4 | isbn = 978-3-031-21053-2 | chapter-url = }}{{cite journal | vauthors = Newman AH, Ku T, Jordan CJ, Bonifazi A, Xi ZX | title = New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders | journal = Annu Rev Pharmacol Toxicol | volume = 61 | issue = | pages = 609–628 | date = January 2021 | pmid = 33411583 | pmc = 9341034 | doi = 10.1146/annurev-pharmtox-030220-124205 | url = }} Its affinity (K_i) for the dopamine transporter (DAT) is 37.8{{nbsp}}nM, for the norepinephrine transporter (NET) is 11,820{{nbsp}}nM (313-fold lower than for the DAT), for the serotonin transporter (SERT) is 6,800{{nbsp}}nM (180-fold lower than for the DAT), and for the sigma σ₁ receptor is 2.24{{nbsp}}nM (17-fold higher than for the DAT).{{cite journal | vauthors = Giancola JB, Bonifazi A, Cao J, Ku T, Haraczy AJ, Lam J, Rais R, Coggiano MA, Tanda G, Newman AH | title = Structure-activity relationships for a series of (Bis(4-fluorophenyl)methyl)sulfinylethyl-aminopiperidines and -piperidine amines at the dopamine transporter: Bioisosteric replacement of the piperazine improves metabolic stability | journal = Eur J Med Chem | volume = 208 | issue = | article-number = 112674 | date = December 2020 | pmid = 32947229 | pmc = 7680422 | doi = 10.1016/j.ejmech.2020.112674 | url = }} It also has significant affinity for several dopamine receptors. JJC8-089 has substantially higher affinity for the DAT than modafinil. The drug shows pro-motivational effects in animals.{{cite journal | vauthors = Salamone JD, Correa M | title = The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine | journal = Annu Rev Psychol | volume = 75 | issue = | pages = 1–32 | date = January 2024 | pmid = 37788571 | doi = 10.1146/annurev-psych-020223-012208 | url = | hdl = 10234/207207 | hdl-access = free }}{{cite journal | vauthors = Ecevitoglu A, Meka N, Rotolo RA, Edelstein GA, Srinath S, Beard KR, Carratala-Ros C, Presby RE, Cao J, Okorom A, Newman AH, Correa M, Salamone JD | title = Potential therapeutics for effort-related motivational dysfunction: assessing novel atypical dopamine transport inhibitors | journal = Neuropsychopharmacology | volume = 49 | issue = 8 | pages = 1309–1317 | date = July 2024 | pmid = 38429498 | doi = 10.1038/s41386-024-01826-1 | pmc = 11224370 | url = }} It was first described in the scientific literature by 2016.{{cite journal | vauthors = Cao J, Slack RD, Bakare OM, Burzynski C, Rais R, Slusher BS, Kopajtic T, Bonifazi A, Ellenberger MP, Yano H, He Y, Bi GH, Xi ZX, Loland CJ, Newman AH | title = Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors | journal = J Med Chem | volume = 59 | issue = 23 | pages = 10676–10691 | date = December 2016 | pmid = 27933960 | pmc = 5161041 | doi = 10.1021/acs.jmedchem.6b01373 | url = }}{{cite journal | vauthors = Tunstall BJ, Ho CP, Cao J, Vendruscolo JC, Schmeichel BE, Slack RD, Tanda G, Gadiano AJ, Rais R, Slusher BS, Koob GF, Newman AH, Vendruscolo LF | title = Atypical dopamine transporter inhibitors attenuate compulsive-like methamphetamine self-administration in rats | journal = Neuropharmacology | volume = 131 | issue = | pages = 96–103 | date = March 2018 | pmid = 29217282 | pmc = 5820113 | doi = 10.1016/j.neuropharm.2017.12.006 | url = }}