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. 2017:32:19-47.
doi: 10.1007/7854_2016_41.

Structure-Activity Relationships of Synthetic Cathinones

Richard A Glennon  1 , Małgorzata Dukat  2
Affiliations

Structure-Activity Relationships of Synthetic Cathinones

Richard A Glennon et al. Curr Top Behav Neurosci. 2017.

Abstract

Until recently, there was rather little interest in the structure-activity relationships (SARs) of cathinone analogs because so few agents were available and because they represented a relatively minor drug abuse problem. Most of the early SAR was formulated on the basis of behavioral (e.g., locomotor and drug discrimination) studies using rodents. With the emergence on the clandestine market in the last few years of a large number of new cathinone analogs, termed "synthetic cathinones", and the realization that they likely act at dopamine, norepinephrine, and/or serotonin transporters as releasing agents (i.e., as substrates) or reuptake inhibitors (i.e., as transport blockers), it has now become possible to better examine their SAR and even their quantitative SAR (QSAR), in a more effective and systematic manner. An SAR picture is beginning to emerge, and key structural features, such as the nature of the terminal amine, the size of the α-substituent, stereochemistry, and the presence and position of aromatic substituents, are being found to impact action (i.e., as releasing agents or reuptake inhibitors) and transporter selectivity.

Keywords: DAT; Methcathinone; Monoamine transporters; NET; QSAR; SAR; SERT.

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Figures

Figure 1
Figure 1
Examples of three types of SAR studies that can be pursued. Panel A) depicts a non-linear SAR study where the structure of a molecule is modified one substituent at a time; results can be related back to a common molecule in a systematic manner. Panel B) exemplifies how structures can be related to one another by a single and, usually, position-consistent, structural alteration. Panel C) is a combination of these two approaches and depicts the concept of “deconstruction”.
Figure 2
Figure 2
Structures of (±)cathinone (1), S(−)cathinone or S(−)1, R(+)cathinone or R(+)1, (+)cathine (2), S(+)amphetamine or S(+)3, and R(−)amphetamine or R(−)3.
Figure 3
Figure 3
Structures of some cathinone analogs involved in early SAR investigations.
Figure 4
Figure 4
Some amine-modified methcathinone (13) analogs.
Figure 5
Figure 5
Some early methcathinone analogs.
Figure 6
Figure 6
Two early “bath salts” constituents: mephedrone (26) and MDPV (27).
Figure 7
Figure 7
Structures of ethylone (28), pyrovalerone (29), EDMC (30), butylone (31), and naphyrone (32).
Figure 8
Figure 8
Deconstruction of MDPV (27). Values represent the potency of the analogs to block the reuptake of DA (Kolanos et al., 2013).
Figure 9
Figure 9
Deconstructed (39–41) and elaborated (42–48) analogs of α-PVP (34).
Figure 10
Figure 10
Newer MDPV (27) analogs: S(+)MDPV, R(−)MDPV, and Q-MDPV (49).
Figure 11
Figure 11
A structural comparison of mephedrone (26), 4-MEC (54), and 4-MePPP (55).
Figure 12
Figure 12
The structure of cathinone and the various structural alterations (at positions A–E) that have been examined in SAR studies to be summarized below.
Figure 13
Figure 13
Relationship between potencies of seven 4-substituted cathinone analogs (i.e., those in Table 6) to act as releasing agents at DAT and NET (from Sakloth, 2015).
Figure 14
Figure 14
Structures of some novel synthetic cathinones that have not been thoroughly investigated.
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References

    1. Aarde SM, Creehan KM, Vandewater SA, et al. In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: self-administration and locomotor stimulation in male rats. Psychopharmacology (Berl) 2015;232:3045–3055. - PMC - PubMed
    1. Aarde SM, Huang PK, Creehan KM, et al. The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats. Neuropharmacology. 2013;71:130–140. - PMC - PubMed
    1. Baumann MH, Partilla JS, Lehner KR, et al. Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products. Neuropsychopharmacology. 2013;38:552–562. - PMC - PubMed
    1. Bonano JS, Banks ML, Kolanos R, et al. Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues. Br J Pharmacol. 2015;172:2433–2444. - PMC - PubMed
    1. Bondarev ML, Bondareva TS, Young R, et al. Behavioral and biochemical investigations of bupropion metabolites. Eur J Pharmacol. 2003;474:85–93. - PubMed

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