AZD-3043

AZD-3043
Identifiers
  • propyl 2-[4-[2-(diethylamino)-2-oxoethoxy]-3-ethoxyphenyl]acetate
CAS Number
PubChem CID
Chemical and physical data
FormulaC19H29NO5
Molar mass351.443 g·mol−1
3D model (JSmol)
  • CCCOC(=O)CC1=CC(=C(C=C1)OCC(=O)N(CC)CC)OCC
  • InChI=1S/C19H29NO5/c1-5-11-24-19(22)13-15-9-10-16(17(12-15)23-8-4)25-14-18(21)20(6-2)7-3/h9-10,12H,5-8,11,13-14H2,1-4H3
  • Key:QPUVKSKJCNGSGT-UHFFFAOYSA-N

AZD-3043 (THRX-918661) is an ultra short-acting phenylacetate general anesthetic. It is closely related to propanidid which was marketed for clinical use in the 1960s and 1970s but withdrawn due to cases of anaphylactic reaction, though it is now thought that these were more likely caused by other components of the injectable formulation rather than the drug itself. AZD-3043 is slightly more potent than propanidid but otherwise has similar activity. It acts as a potent positive allosteric modulator of GABAA receptors with a binding site overlapping with that of both propofol and benzodiazepines, even though its chemical structure is quite different. Its effects are rapidly terminated by metabolic cleavage of the labile ester substituent, resulting in a short duration of action and quick recovery period. Research into this family continues and numerous related compounds have been developed with similar properties.

See also

References

  1. ↑ Egan TD, Shafer SL, Jenkins TE, Beattie DT, Jaw-Tsai SS. The pharmacokinetics and pharmacodynamics of THRX-918661, a novel sedative/hypnotic agent. Anesthesiology. 2003;99(3).
  2. ↑ Sneyd JR (November 2004). "Recent advances in intravenous anaesthesia". British Journal of Anaesthesia. 93 (5): 725–736. doi:10.1093/bja/aeh253. PMID 15347606.
  3. ↑ Sneyd JR, Rigby-Jones AE (September 2010). "New drugs and technologies, intravenous anaesthesia is on the move (again)". British Journal of Anaesthesia. 105 (3): 246–254. doi:10.1093/bja/aeq190. PMID 20650920.
  4. ↑ Egan TD, Obara S, Jenkins TE, Jaw-Tsai SS, Amagasu S, Cook DR, et al. (June 2012). "AZD-3043: a novel, metabolically labile sedative-hypnotic agent with rapid and predictable emergence from hypnosis". Anesthesiology. 116 (6): 1267–1277. doi:10.1097/ALN.0b013e31825685a6. PMC 4056591. PMID 22531340.
  5. ↑ Jonsson Fagerlund M, Sjödin J, Dabrowski MA, Krupp J (5 November 2012). "Reduced efficacy of the intravenous anesthetic agent AZD3043 at GABA(A) receptors with β2 (N289M) and β3 (N290M) point-mutations". European Journal of Pharmacology. 694 (1–3): 13–19. doi:10.1016/j.ejphar.2012.07.040. PMID 23009769.
  6. ↑ Gin T (August 2013). "Hypnotic and sedative drugs--anything new on the horizon?". Current Opinion in Anaesthesiology. 26 (4): 409–413. doi:10.1097/ACO.0b013e328362a7a3. PMID 23820101.
  7. ↑ Norberg Å, Koch P, Kanes SJ, Björnsson MA, Barassin S, Ahlén K, et al. (October 2015). "A Bolus and Bolus Followed by Infusion Study of AZD3043, an Investigational Intravenous Drug for Sedation and Anesthesia: Safety and Pharmacodynamics in Healthy Male and Female Volunteers". Anesthesia and Analgesia. 121 (4): 894–903. doi:10.1213/ANE.0000000000000804. PMID 26097986.
  8. ↑ Wang S, Liu Q, Li X, Zhao X, Qiu L, Lin J (November 2018). "Possible binding sites and interactions of propanidid and AZD3043 within the γ-aminobutyric acid type A receptor (GABAAR)". Journal of Biomolecular Structure & Dynamics. 36 (15): 3926–3937. doi:10.1080/07391102.2017.1403959. PMID 29125020.
  9. ↑ Zhang H, Xu X, Chen Y, Qiu Y, Liu X, Liu BF, et al. (5 May 2014). "Synthesis and evaluation of fluorine-substituted phenyl acetate derivatives as ultra-short recovery sedative/hypnotic agents". PLOS ONE. 9 (5) e96518. doi:10.1371/journal.pone.0096518. PMC 4010497. PMID 24796695.
  10. ↑ Zhang H, Xu X, Chen Y, Qiu Y, Liu X, Liu BF, et al. (7 January 2015). "Phenyl acetate derivatives, fluorine-substituted on the phenyl group, as rapid recovery hypnotic agents with reflex depression". European Journal of Medicinal Chemistry. 89: 524–539. doi:10.1016/j.ejmech.2014.10.073. PMID 25462263.
  11. ↑ Qi Z, Li Z, Zhu M, Zhang X, Zhang G, Zhuang T, et al. (1 February 2022). "Design, synthesis, and evaluation of phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents". Bioorganic & Medicinal Chemistry Letters. 57 128497. doi:10.1016/j.bmcl.2021.128497. PMID 34896213.
  12. ↑ Zhu J, Xiao X, Qin H, Luo Z, Chen Y, Huang C, et al. (15 February 2023). "Design, synthesis and evaluation of heterocyclic 2-phenylacetate derivatives as water-soluble rapid recovery hypnotics". Bioorganic & Medicinal Chemistry Letters. 82 129165. doi:10.1016/j.bmcl.2023.129165. PMID 36736494.