Journals / Anatolian Journal of Pharmaceutical Sciences / 2023 / Cilt: 2 Sayı: 1

Enantioseperation of 2-(1H-imidazol-1-yl)-1-(naphthalen-2-yl)ethan-1-ol which is active metabolite of anticonvulsant nafimidone

Pages
85–95
Publication Date
2023-12-13
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Consequently, further chemical and pharmacological research on nafimidone alcohol and its enantiomers can be facilitated by the proposed HPLC approach.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Nafimidone and nafimidone alcohol, which were synthesized in 1981 and whose anticonvulsant activities were determined, are important anticonvulsant compounds in the structure of (arylalkyl)azole, which reached the stage of clinical human studies but could not pass this stage.
📊
Key Findings & Data:In this study, the commercially available chiral stationary phase amylose tris(3,5-dimethyphenylcarbamate) (Chiralpak AD) was used to establish direct enantiomeric separations of nafimidone alcohol which is the methabolite of nafimidone in the normal phase HPLC mode.
💡
Conclusion & Impact:Consequently, further chemical and pharmacological research on nafimidone alcohol and its enantiomers can be facilitated by the proposed HPLC approach.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Amylose tris(3 · 5-dimethyphenylcarbamate) · Chiralpak AD

Abstract

Nafimidone and nafimidone alcohol, which were synthesized in 1981 and whose anticonvulsant activities were determined, are important anticonvulsant compounds in the structure of (arylalkyl)azole, which reached the stage of clinical human studies but could not pass this stage. In this study, the commercially available chiral stationary phase amylose tris(3,5-dimethyphenylcarbamate) (Chiralpak AD) was used to establish direct enantiomeric separations of nafimidone alcohol which is the methabolite of nafimidone in the normal phase HPLC mode. Investigations were also done into the compositional influences of the mobile phase. When the mobile phase was switched from methanol to n-hexane, the retention times were shortened. The mobile phase of methanol/n-hexane (70:30 v/v) at a flow rate of 0.2 mL/min produced the best results, with an enantiomer resolution of 0.83. Consequently, further chemical and pharmacological research on nafimidone alcohol and its enantiomers can be facilitated by the proposed HPLC approach.

🔖

Cite This Article

KARACA, E., ÖZDEMİR, Z., ZENNİ, Y. N., KARAKURT, A. (2023). Enantioseperation of 2-(1H-imidazol-1-yl)-1-(naphthalen-2-yl)ethan-1-ol which is active metabolite of anticonvulsant nafimidone. Anatolian Journal of Pharmaceutical Sciences, Cilt: 2 Sayı: 1, 85–95. https://ajindex.com/articles/1021498

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (10)

  1. Nardi D, Tajana A, Leonardi A, Pennini R, Portioli F, Magistretti MJ, Subissi A. Synthesis and anticonvulsant activity of N-(benzoylalkyl)imidazoles and N-(omega-phenyl-omega-hydroxyalkyl)imidazoles. J Med Chem., 1981; 24(6):727-73.
  2. Walker KA, Wallach MB, Hirschfeld DR. 1-(Naphthylalkyl)-1H-imidazole derivatives, a new class of anticonvulsant agents. J Med Chem., 1981; 24(1):67-74.
  3. Wingrove PB, Wafford KA, Bain C, Whiting PJ. The Modulatory Action of Loreclezole at the Gamma-Aminobutyric-Acid Type-a Receptor Is Determined by a Single Amino-Acid in the Beta-2 and Beta-3 Subunit. P Natl Acad Sci USA., 1994; 91(10):4569-4573.
  4. Graham DJM, Eadie J, Leadbetter BM, Metcalf R. Simultaneous Determination of Nafimidone [1-(2-Naphthoylmethyl)Imidazole], a New Anti-Convulsant Agent, and a Major Metabolite in Plasma by High-Performance Liquid-Chromatography. J Chromatogr., 1983; 275(1):211-216.
  5. Yang L, Li Y, Hong H, Chang CW, Guo LW, Lyn-Cook B, Shi L, Ning B. Sex Differences in the Expression of Drug-Metabolizing and Transporter Genes in Human. Liver J Drug Metab Toxicol., 2012; 3(3):e111. Özdemir Z, Karakurt A. İlaç Metabolizması ve Farmasötik Kimyada Önemi. Ann. Med. Health Sci. Res. 2016; 5:35-46. Fura A. Role of pharmacologically active metabolites in drug discovery and development. Drug Disc Today., 2006; 11:133-142.
  6. Das N, Dhanawat M, Dash B, Nagarwal RC, Shrivastava SK. Codrug: An efficient approach for drug optimization. Eur J Pharm Sci., 2010; 41:571-588.
  7. Kapetanovic IM, Kupferberg HJ. Nafimidone, an imidazole anticonvulsant, and its metabolite as potent inhibitors of microsomal metabolism of phenytoin and carbamazepine. Drug Metab. Dispos., 1984; 12(5):560-564.
  8. Brooks WH, Guida WC, Daniel KG. The significance of chirality in drug design and development. Curr Top Med Chem., 2011; 11(7):760-770.
  9. Bahar A, Sönmez Nİ, Vızdıklar C, Aydın V, Akıcı A. The concept of chirality and its association with drug safety: Raditional review. J Lit Pharm Sci., 2022; 11:77-85. Gal J. The discovery of stereoselectivity at biological receptors arnaldo piutti and the taste of the asparagine enantiomers historyand analysis on the 125th anniversary. Chiralty., 2012; 24: 959-976. FDA-US Food and Drug Administration (2022, 4 Nov). Development of new stereoisomeric drugs. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-new-stereoisomeric-drug.
  10. Ye X, Liu Y, Li F. Biomarkers of oxidative stress in the assessment of enantioselective toxicity of chiral