Chemistry:N-Bn-THAZ

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N-Bn-THAZ
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Clinical data
Other namesN-Benzyl-THAZ
Drug classSerotonin receptor agonist; Serotonin 5-HT2A and 5-HT2C receptor agonist
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC14H16N2O2
Molar mass244.294 g·mol−1
3D model (JSmol)

N-Bn-THAZ is a selective agonist of the serotonin 5-HT2A and 5-HT2C receptors.[1][2] It is a derivative of THAZ, which itself is a weak antagonist of the glycine and GABAA receptors related to the experimental drug gaboxadol.[2]

N-Bn-THAZ shows high affinity, activational potency, and efficacy at the serotonin 5-HT2A and 5-HT2C receptors.[1][2] Its affinities (Ki) were 8,800 nM at the serotonin 5-HT2A receptor and 2,300 nM at the serotonin 5-HT2C receptor, while its activational activities (EC50 [Emax]) were 550 to 2,400 nM (80–95%) at the serotonin 5-HT2A receptor and 420 to 1,700 nM (90–92%) at the serotonin 5-HT2C receptor.[1][2] N-Bn-THAZ showed selectivity for these receptors over numerous other targets, notably including the serotonin 5-HT2B receptor antitarget.[2]

The drug has been found to produce pro-cognitive-like effects in rodents.[2] These effects could be fully reversed by the selective serotonin 5-HT2C receptor antagonist SB-242084.[2] The researchers did not assess N-Bn-THAZ in terms of psychedelic-like effects, but as a serotonin 5-HT2A receptor agonist, they noted that the drug could potentially produce hallucinogenic effects.[2] Due to its lack of serotonin 5-HT2B receptor activity, N-Bn-THAZ would not be expected to have the cardiovascular adverse effects of agonists of this receptor.[2]

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O-Bn-THAZ structure.

N-Bn-THAZ was developed by Povl Krogsgaard-Larsen and colleagues and was first described in the scientific literature by 2013.[1][2] Structurally, N-Bn-THAZ is an isoxazole and is distinct from other serotonin 5-HT2 receptor agonists, such as the tryptamines and phenethylamines.[1][2] Other analogues of N-Bn-THAZ, such as O-Bn-THAZ, which is also active as a serotonin 5-HT2 receptor agonist, have been synthesized and studied as well.[1][2]

See also

  • List of miscellaneous 5-HT2A receptor agonists

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews 124 (1): 124–163. January 2024. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. "Besides the three major classes of 5-HT2AR agonists, other compounds with different chemical scaffolds have also been reported. For example, a series of novel 5-HT2A/2C agonists with the 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol (THAZ) as the core scaffold were reported by Jensen et al. in 2013.195 Compounds 160 and 161 (Figure 14A) displayed high affinity for the h5-HT2AR (Ki = 8.8 and 2.3 [μM], respectively; [3H]-ketanserin, membranes from tsA201 cells). Functional studies in the Fluo-4/Ca2+ assay using the h5-HT2AR-HEK293 cell line showed that 160 and 161 are potent 5-HT2AR agonists, with EC50 values of 2.4 [μM] (Emax = 95%) and 1.3 [μM] (Emax = 77%), respectively. However, both compounds exhibited potent binding affinity and agonist activity at the h5-HT2CR as well (160: Ki = 2.3 [μM], EC50 = 1.7 [μM]; 161: Ki = 1.2 [μM], EC50 = 0.23 [μM]).195". 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 "Design, synthesis, and pharmacological characterization of N- and O-substituted 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol analogues: novel 5-HT(2A)/5-HT(2C) receptor agonists with pro-cognitive properties". Journal of Medicinal Chemistry 56 (3): 1211–1227. February 2013. doi:10.1021/jm301656h. PMID 23301527. 



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