Design, Synthesis, and Characterization of 1, 3‐disubstituted‐1,4‐benzodiazepine Derivatives

Ghelani, Satish M.; Naliapara, Yogesh T.

doi:10.1002/jhet.2486

Cited by 8 publications

(5 citation statements)

References 40 publications

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“…Preparative methods for positional isomers of benzodiazepines, on the other hand, are limited in the scientific literature. Though many studies have investigated efficient routes to various benzodiazepine precursors, , most fall short of at least one of three important criteria: (1) they do not showcase precursors with substitution patterns that would lead to positional isomers of the more common parents; (2) they do not tolerate halo- and nitro-substituted benzodiazepines most frequently surveyed in forensic cases; and (3) they have failed to follow through in the actual preparation of the corresponding benzodiazepine products. Consequently, the characterization data to accompany these benzodiazepines, both analytical and biological, are nonexistent.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Flubromazepam Positional Isomers for Forensic Analysis

et al. 2019

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Designer benzodiazepines have recently appeared in many forensic cases as legal alternatives to federally scheduled drugs such as diazepam (Valium) and alprazolam (Xanax). Though current forensic instrumental techniques are often sufficient for identifying novel psychoactive substances, they may not readily differentiate between potential positional isomers. Additionally, characterization data for positional isomers of known designer benzodiazepines are widely nonexistent. In this study, flubromazepam, a recognized designer benzodiazepine since 2012, was targeted for synthesis and characterization due to its potential for federal scheduling and current legal status within the United States. A practical synthetic method was developed to prepare purified reference materials for each positional isomer of flubromazepam in which the positions of the bromine and fluorine substituents were varied. Possible isomers (9 of the 12) were successfully prepared and used for further analysis.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Flubromazepam Positional Isomers for Forensic Analysis

et al. 2019

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“…The way to new 1,4‐diazepines fused with thienopyridine scaffold included a reaction sequence which have been proposed for benzo[1,4]diazepines synthesis .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of β‐Lactam‐containing Pyrido[3′,2′:4,5]thieno[3,2‐e][1,4]diazepines

Строганова

Vasilin

Kovalenko

et al. 2017

Journal of Heterocyclic Chem

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Novel tricyclic 1,4‐diazepine derivatives – pyrido[3′,2′:4,5]thieno[3,2‐e][1,4]diazepin‐2‐ones – have been synthesized. Azetidin‐2‐one moiety has been incorporated into the 1,4‐diazepine scaffold by [2 + 2]cycloaddition of functionalized ketenes to imine C═N bond, and several tetracyclic azetodiazepines which can be considered as potential compounds of biological interest have been prepared. Stereoselectivity of the cycloaddition was proved by NMR and X‐ray analysis data.

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“…Також відомим є синтез бензодіазепіну -меклоназепаму (Рис. 1) наприкінці 70-х років минулого століття, який спершу був синтезований як препарат проти шистосомозу [6], а у подальших дослідженнях виявив анксіолітичну та седативну активність [7].…”

Section: ключові словаunclassified

Synthesis Method of Optically Pure Enantiomers of 5-Aryl Substituted3-Methyl‑7- Nitro‑1,2-Dihydro‑3h‑1,4-Benzodiazepin‑2-Ones

Kornylov¹,

Krysko²,

Krysko³

et al. 2022

Вісник ОНУ

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The aim of this work is to develop a simple, fast and efficient method for the synthesis of optically pure enantiomers of some 5-aryl-substituted 3-methyl‑7-nitro‑1,2-dihydro‑3H‑1,4-benzodiazepin‑2-ones using simple reagents. In the course of the study, we found that the interaction of 2-amino‑5-nitrobenzophenone or 2-amino‑2’-chloro‑5-nitrobenzophenone with optically active L- or D‑α-alanine N‑carboxyanhydrides in the presence of two equivalents of trifluoroacetic acid does not leads to the formation of the corresponding reaction intermediates (2-amino-N-(2-benzoylphenyl)propanamide), even when refluxed for 24 hours in xylene. Acylation of 5-nitro‑2-aminobenzophenones with hydrochlorides of L- or D‑α-alanine acid chlorides, followed by cyclization under mild conditions, leads to target 3-methyl‑7-nitro‑1,2-dihydro‑3H‑1,4-benzodiazepin‑2-ones characterized by high optical purity. It is noteworthy that these reactions allow the coupling of acid chlorides derived from stereospecific α-alanines with weakly reactive 5-nitro derivatives of 2-aminobenzophenone without racemization. It is important to note that the acid chloride hydrochlorides of optically active α-alanines, which are chemically unstable and extremely sensitive to moisture, are used as building blocks in the work. In this case, acid chlorides of individual antipodes of L- or D‑α-alanine were synthesized in absolute chloroform using phosphorus pentachloride and the products were isolated by simple filtration of precipitates, without applying additional purification to them. The structure of the title compound was confirmed by spectroscopy 1H and 13C NMR, and FAB mass spectrometry methods, purity was controlled by HPLC. To analyze the optical purity of the1,2-dihydro‑3H‑1,4-benzodiazepines synthesized in this work, HPLC was applied using stationary chiral phase CiraDex®. This simple preparation method is of potential practical importance for the design and synthesis of optically pure enantiomers of various 3-alkyl derivatives of 1,2-dihydro‑3H‑1,4-benzodiazepin‑2-ones with a wide spectrum of biological activity.

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Design, Synthesis, and Characterization of 1, 3‐disubstituted‐1,4‐benzodiazepine Derivatives

Cited by 8 publications

References 40 publications

Synthesis of Flubromazepam Positional Isomers for Forensic Analysis

Synthesis of Flubromazepam Positional Isomers for Forensic Analysis

Synthesis of β‐Lactam‐containing Pyrido[3′,2′:4,5]thieno[3,2‐e][1,4]diazepines

Synthesis Method of Optically Pure Enantiomers of 5-Aryl Substituted3-Methyl‑7- Nitro‑1,2-Dihydro‑3h‑1,4-Benzodiazepin‑2-Ones

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