5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action

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5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action Publisher Pubmed

Navidpour L¹ ; Shabani S¹ ; Heidari A² ; Bashiri M³ ; Ebrahimhabibi A^{4, 5} ; Shahhosseini S³ ; Shafaroodi H⁶ ; Abbas Tabatabai S³ ; Toolabi M¹

Show Affiliations

1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14176, Iran
2. Department of Medicinal Chemistry, School of Pharmacy, Tehran Azad University of Medical Sciences, Tehran, Iran
3. Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
5. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
6. Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, 14174, Iran

Source: Bioorganic Chemistry Published:2021

Abstract

A new series of 5-(2-aryloxy-4-nitrophenyl)-4H-1,2,4-triazoles and 5-(2-aryloxy-3-pyridyl)-4H-1,2,4-triazoles, possessing C-3 thio or alkylthio substituents, was synthesized and evaluated for their benzodiazepine receptor affinity and anti-seizure activity. These analogues revealed similar to significantly superior affinity to GABAA/benzodiazepine receptor complex (IC50 values of 0.04–4.1 nM), relative to diazepam as the reference drug (IC50 value of 2.4 nM). To determine the onset of anti-seizure activity, the time-dependent effectiveness of i.p. administration of compounds on pentylenetetrazole induced seizure threshold was studied and a very good relationship was observed between the lipophilicity (cLogP) and onset of action of studied analogues (r2 = 0.964). The minimum effective dose of the compounds, determined at the time the analogues showed their highest activity, was demonstrated to be 0.025–0.1 mg/kg, relative to diazepam (0.025 mg/kg). © 2020 Elsevier Inc.

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Style	Citing Format
MLA	Navidpour L, et al.. "5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action." Bioorganic Chemistry, vol. 106, no. , 2021, pp. -.
APA	Navidpour L, Shabani S, Heidari A, Bashiri M, Ebrahimhabibi A, Shahhosseini S, Shafaroodi H, Abbas Tabatabai S, Toolabi M (2021). 5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action. Bioorganic Chemistry, 106(), -.
Chicago	Navidpour L, Shabani S, Heidari A, Bashiri M, Ebrahimhabibi A, Shahhosseini S, Shafaroodi H, Abbas Tabatabai S, Toolabi M. "5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action." Bioorganic Chemistry 106, no. (2021): -.
Harvard	Navidpour L et al. (2021) '5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action', Bioorganic Chemistry, 106(), pp. -.
Vancouver	Navidpour L, Shabani S, Heidari A, Bashiri M, Ebrahimhabibi A, Shahhosseini S, et al.. 5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action. Bioorganic Chemistry. 2021;106():-.
BibTex	@article{ author = {Navidpour L and Shabani S and Heidari A and Bashiri M and Ebrahimhabibi A and Shahhosseini S and Shafaroodi H and Abbas Tabatabai S and Toolabi M}, title = {5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action}, journal = {Bioorganic Chemistry}, volume = {106}, number = {}, pages = {-}, year = {2021} }
RIS	TY - JOUR AU - Navidpour L AU - Shabani S AU - Heidari A AU - Bashiri M AU - Ebrahimhabibi A AU - Shahhosseini S AU - Shafaroodi H AU - Abbas Tabatabai S AU - Toolabi M TI - 5-[Aryloxypyridyl (Or Nitrophenyl)]-4H-1,2,4-Triazoles As Novel Flexible Benzodiazepine Analogues: Synthesis, Receptor Binding Affinity and Lipophilicity-Dependent Anti-Seizure Onset of Action JO - Bioorganic Chemistry VL - 106 IS - SP - EP - PY - 2021 ER -

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