N-Bn-THAZ

N-Bn-THAZ
Clinical data
Other namesN-Benzyl-THAZ
Drug classSerotonin receptor agonist; Serotonin 5-HT2A and 5-HT2C receptor agonist
ATC code
  • None
Identifiers
  • 2-benzyl-5,6,7,8-tetrahydro-4H-[1,2]oxazolo[4,5-d]azepin-3-one
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC14H16N2O2
Molar mass244.294 g·mol−1
3D model (JSmol)
  • C1CNCCC2=C1C(=O)N(O2)CC3=CC=CC=C3
  • InChI=1S/C14H16N2O2/c17-14-12-6-8-15-9-7-13(12)18-16(14)10-11-4-2-1-3-5-11/h1-5,15H,6-10H2
  • Key:BWAFYEDXZXBSIK-UHFFFAOYSA-N

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 THIP (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 (EC50Tooltip half-maximal effective concentration [EmaxTooltip maximal efficacy]) 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]

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

References

  1. ^ a b c d e f Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. 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. ^ a b c d e f g h i j k l Jensen AA, Plath N, Pedersen MH, Isberg V, Krall J, Wellendorph P, et al. (February 2013). "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. doi:10.1021/jm301656h. PMID 23301527.



This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.