Fluorenol, also known ashydrafinil,[3] is analcohol derivative offluorene. In the most significant isomer, fluoren-9-ol or 9-hydroxyfluorene, thehydroxy group is located on the bridging carbon between the two benzene rings. Hydroxyfluorene can be converted tofluorenone byoxidants. It is a white-cream colored solid at room temperature.
Fluorenol is toxic to aquatic organisms including algae, bacteria, and crustaceans.[4] Fluorenol was patented as aninsecticide in 1939,[5] and is analgaecide against the green algae generaDunaliella.[6]
The mechanism of action of fluorenol is unknown.[7]
The lipophilicity of fluorenol (LogP 2.4) is higher than that of drugs likemodafinil (LogP 1.7) and amphetamine (LogP 1.8), suggesting that it may penetrate the blood brain barrier more readily.[8][9][10]
A study published byCephalon describing research to develop a successor to theeugeroicmodafinil reported that the corresponding fluorenol derivative was 39% more effective than modafinil at keeping mice awake over a 4-hour period.[11] However, after further investigation it was determined that the eugeroic activity of the fluorenol analog was likely due to anactive metabolite, which they identify as fluorenol itself.[11] Fluorenol is a weakdopamine reuptake inhibitor with an IC50 of 9μM, notably 59% weaker than modafinil (IC50 = 3.70 μM),[11] potentially making it even less liable foraddiction.[12] It also showed no affinity forcytochrome P450 2C19, unlikemodafinil.[11]
There is no evidence (binding assays, occupancy, predicted structure) to suggest that fluorenol acts onserotonin receptors, contrary to some popular claims.[medical citation needed]
The unscheduled nature of fluorenol has caused it to fall into a legal grey area in most countries. Despite being associated with modafinil,[13] fluorenol is not a substituted derivative of it, making its scheduling unimplied byanalogue acts.
Fluorenol is a relatively obscure compound in the research chemical market. According to an online survey with over 3000 respondents, only 2% of modafinil users have reported using fluorenol.[14]
^Clifford W Fong.Modafinil and modafinil analogues: free radical mechanism of the eugeroic and cognitive enhancement effect. [Research Report] Eigenenergy. 2018. ffhal-01933737f
^abcdDunn, D.; Hostetler, G.; Iqbal, M.; Marcy, V. R.; Lin, Y. G.; Jones, B.; Aimone, L. D.; Gruner, J.; Ator, M. A.; Bacon, E. R.; Chatterjee, S. (2012). "Wake promoting agents: Search for next generation modafinil, lessons learned: Part III".Bioorganic & Medicinal Chemistry Letters.22 (11):3751–3753.doi:10.1016/j.bmcl.2012.04.031.PMID22546675.
