Science Journal of Chemistry

Special Issue

Benzopyrazines: Synthesis, Characterization and Evaluation as Aldose Reductase Inhibitors

  • Submission Deadline: Mar. 10, 2020
  • Status: Submission Closed
  • Lead Guest Editor: Huma Bhatti
About This Special Issue
The synthetic route to synthesize desired benzopyrazines has been present in Scheme-1. In the first step, the α-methyl group of acetophenone was oxidized to carbonyl group by using selenium dioxide. The dicarbonyl intermediate 4 was then reacted without purification with 4-methylbenzene-1,2-diamine at room temperature to afford corresponding benzopyrazine (Scheme-1). Following the optimized method, a range of novel benzopyrazines has been prepared (Shah, et al., 2010, Wang, et al., 2009). 1H NMR spectra of the resulting products showed two regio-isomers in 1:1 to 1:0.5 ratio due to difference in reactivity of C-2 keto and C-3 aldehyde moieties in intermediate 4. The structure of two regio-isomers were fully characterize by 1H and 13C NMR two dimensional NMR techniques including COSY, NOESY, HSQC, and HMBC. Regio-isomers separation was proved to be difficult in different solvent systems. Only an isomer of 3'-bromo benzopyrazine 6i' was isolated that help to assign the structure of regioisomers from NMR data.
In this study, we synthesized sixteen benzopyrazine derivatives and screen evaluated them against ARL2 as well as ALR1 for selectivity purpose.
Aims and Scope:
  1. Role of aldose reductase (ALR2) in diabetic complications
  2. (16) methyl benzopyrazines were screened against aldose reductase
  3. 3'-hydroxyphenyl benzopyrazine 6l was found most active (IC50 = 1.34 ± 0.07 µM)
  4. 3'-bromophenyl analogue 6i showed comparable activity for ALR2
  5. Polyol pathway
  6. Benzopyrazines as aldose inhibitors
Lead Guest Editor
  • Huma Bhatti

    Department of Chemistry, University of Karachi, Karachi, Pakistan

Guest Editors
  • Syed Kashif Ali

    Department of Chemistry, University of Karachi, Karachi, Pakistan

  • Abdul Hameed

    Department of Chemistry, Forman Chiristan College, Lahore, Pakistan

  • Dr Ghulam Abbas

    Department of Pharmacology, Zia Uddin Medical University, Karachi, Pakistan

  • Jamseed Iqbal

    Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad, Pakistan

  • Syed Tariq Ali

    Department of Chemistry, Karachi University, Karachi, Pakistan

  • Nizam Uddin

    Department of Chemistry, Karachi University, Karachi, Pakistan

Published Articles
  • Benzopyrazines: Synthesis, Characterization and Evaluation as Aldose Reductase Inhibitors

    Huma Aslam Bhatti , Qurat-Ul-Ain Zaheer , Yildiz Tehseen , Zahid Shaiq , Khalid Mohammed Khan , Abdul Hameed , Jamshed Iqbal

    Issue: Volume 7, Issue 5, October 2019
    Pages: 90-97
    Received: Sep. 14, 2019
    Accepted: Oct. 15, 2019
    Published: Oct. 24, 2019
    DOI: 10.11648/j.sjc.20190705.11
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    Abstract: Role of aldose reductase (ALR2) in diabetic complications such as retinopathy, nephropathy, neuropathy, and cataract etc. is well-evident. ALR2 in the first step of polyol pathway reduces glucose to sorbitol whose elevated level leads to diabetic cataract, characterize by clouding of the lens in the eye that affects vision. Inhibition of ALR2 enzym... Show More