2,5-Dimethoxy-4-cyanoamphetamine

vanc 6 DOCN DOCN structure.svg skin-invert-image 225px Serotonergic agent; Serotonin 5-HT2 receptor modulator None 125903-74-4 23900148 23108720 8336 DOCN; 2,5-Dimethoxy-4-cyanoamphetamine; 4-Cyano-2,5-dimethoxyamphetamine 4-(2-aminopropyl)-2,5-dimethoxybenzonitrile 12 16 2 2 CC(CC1=CC(=C(C=C1OC)C#N)OC)N 1S/C12H16N2O2/c1-8(14)4-9-5-12(16-3)10(7-13)6-11(9)15-2/h5-6,8H,4,14H2,1-3H3 ULNMEZQBQBLXMC-UHFFFAOYSA-N 2,5-Dimethoxy-4-cyanoamphetamine (DOCN) is a serotonergic drug of the phenethylamine, amphetamine, and DOx families. Shulgin A, Manning T, Daley PF #55. DOCN 105–106 https://archive.org/details/shulgin-index-vol-1/page/105/mode/1up The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds Transform Press Berkeley, CA 1 2011 978-0-9630096-3-0 709667010 Nelson DL, Lucaites VL, Wainscott DB, Glennon RA Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors Naunyn-Schmiedeberg's Archives of Pharmacology 359 1 1–6 January 1999 9933142 10.1007/pl00005315 Seggel MR, Yousif MY, Lyon RA, Titeler M, Roth BL, Suba EA, Glennon RA A structure-affinity study of the binding of 4-substituted analogues of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors Journal of Medicinal Chemistry 33 3 1032–1036 March 1990 2308135 10.1021/jm00165a023 It is a DOx derivative with a cyano group (–C≡N) at the 4position of the molecule. Use and effects The effects of DOCN in humans and whether it is a psychedelic are unknown. Interactions Psychedelic drug#Interactions Trip killer#Serotonergic psychedelic antidotes Pharmacology DON shows much lower affinities for the serotonin 5-HT2 receptors than other DOx drugs. Trachsel D Synthesis of Novel (Phenylalkyl)amines for the Investigation of Structure–Activity Relationships, Part 3: 4-Ethynyl-2,5-dimethoxyphenethylamine (=4-Ethynyl-2,5-dimethoxybenzeneethanamine; 2C-YN) Helvetica Chimica Acta 86 8 2003 0018-019X 10.1002/hlca.200390224 2754–2759 The Table summarizes some physicochemical data for the ethynyl group compared to other 4-substituents resulting in some of the most-potent 4-substituted 2,5-dimethoxy-α-methylbenzeneethanamines 2a ± d investigated in in vitro and in vivo studies [3j] [6] (compound 2d had considerably lower affinity at 5-HT2A2) sites [4 f] [6] but is used for structural comparison). [...] A Hansch analysis of a series of 4-substituted 2,5-dimethoxyamphetamines [6] gave a significant correlation between 5-HT2A affinity and the hydrophobicity of the 4- substituents. The measured 5-HT2A binding data for compound 2d bearing the 4-CN substituent showed an affinity of approximately two orders of magnitude lower than that of 2a,b [4f] [6]. For the binding affinity at the 5-HT2A receptor, the comparison of the physicochemical data for 4-substituents (Table) suggests that compound 1 should have substantially higher affinity than 4-cyano-2,5-dimethoxyamphetamine (2d; DOCN) or the α-demethyl congener thereof. However, DOCN also showed by far the greatest degree of selectivity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor (22-fold) of any other assessed DOx drug. Halberstadt AL Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens Current Topics in Behavioral Neurosciences 32 283–311 2017 28097528 10.1007/7854_2016_64 978-3-319-52442-9 Similar to other classes of hallucinogens, NBOMes act as 5-HT2C receptor agonists and are relatively nonselective for 5-HT2A vs. 5-HT2C sites [39]. Given their high affinity and efficacy at 5-HT2A receptors, NBOMes have been developed as 5-HT2A agonist radioligands [50] and as PET tracers [51, 52]. Such work has also encouraged development of NBOMes exhibiting selectivity for 5-HT2A receptors compared with 5-HT2C sites. In contrast to other phenylisopropylamines, 2,5-dimethoxy4-cyanoamphetamine (DOCN, Fig. 6) exhibits moderate (22-fold) selectivity for human 5-HT2A (Ki = 45.7 nM) vs. 5-HT2C (Ki = 1,011 nM) sites labeled with [125I]DOI [46], indicating that 4-cyano substitution represents a potential strategy to augment 5-HT2A selectivity. Applying this strategy to the NBOMe class led to the discovery of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenethylamine (25CN-NBOH), which is reportedly 100-fold selective for 5-HT2A receptors (Ki = 1.3 nM vs. [3H]ketanserin) compared with 5-HT2C receptors (Ki = 132 nM vs. [3H]mesulergine) [25]. However, according to a more recent investigation using the same antagonist radioligands, 25CN-NBOH is only 23-fold selective for 5-HT2A receptors (Ki = 2.2 nM) relative to 5-HT2C sites (Ki = 49.8 nM) [38]. Although the selectivity of 25CN-NBOH may be less than was initially believed, it still exhibits moderate 5-HT2A selectivity. [...] Fig. 6 Structures of the 4-cyano-substituted phenylalkylamines DOCN and 25CN-NBOH [...] Blaazer AR, Smid P, Kruse CG Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors ChemMedChem 3 9 1299–1309 September 2008 18666267 10.1002/cmdc.200800133 A near unity slope was found for 5-HT2A and 5-HT2C receptor affinity correlations, revealing a close correspondence. The only exception was the 4-cyano analogue 24 (DOCN), with a 22-fold higher affinity for 5-HT2A (Ki=45.7 nm) over 5-HT2C (Ki=1011 nm).[63] Applying this strategy (i.e., cyano substitution) to the 25-NB series resulted in the discovery of 25CN-NBOH, one of the most selective serotonin 5-HT2A receptor agonists discovered to date. Poulie CB, Jensen AA, Halberstadt AL, Kristensen JL DARK Classics in Chemical Neuroscience: NBOMes ACS Chemical Neuroscience 11 23 3860–3869 December 2020 31657895 9191638 10.1021/acschemneuro.9b00528 Chemistry Analogues Related drugs include DON, 2C-N, DOA, 2C-CN, 25CN-NBOH, and 25CN-NBOMe. Coutts RT, Malicky JL The Synthesis of Some Analogs of the Hallucinogen 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM) Canadian Journal of Chemistry 51 9 1 May 1973 0008-4042 10.1139/v73-210 free 1402–1409 Glennon RA, Seggel MR Interaction of Phenylisopropylamines with Central 5-HT2 Receptors: Analysis by Quantitative Structure—Activity Relationships Probing Bioactive Mechanisms American Chemical Society Washington, DC 413 14 November 1989 978-0-8412-1702-7 10.1021/bk-1989-0413.ch018 264–280 https://bitnest.netfirms.com/external/10.1021/bk-1989-0413.ch018 Jensen AA, Halberstadt AL, Märcher-Rørsted E, Odland AU, Chatha M, Speth N, Liebscher G, Hansen M, Bräuner-Osborne H, Palner M, Andreasen JT, Kristensen JL The selective 5-HT2A receptor agonist 25CN-NBOH: Structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH Biochemical Pharmacology 177 113979 July 2020 32298690 10.1016/j.bcp.2020.113979 History DOCN was first described in the scientific literature by Richard Glennon and colleagues by 1989. Society and culture Legal status Canada DOCN is a controlled substance in Canada under phenethylamine blanket-ban language.Controlled Drugs and Substances Act Department of Justice Canada https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html 19 January 2026 United States DOCN is not a controlled substance in the United States as of 2011. See also DOx (psychedelics) 2C-N 2C-CN 25CN-NBOH 25CN-NBOMe References External links DOCN - Isomer Design DOCN - The Shulgin Index Category:DOx (psychedelics) Category:Nitriles Category:Serotonin receptor modulators