Synthesis of methyl ether analogues of sildenafil (Viagra®) possessing tyrosinase inhibitory potential

Khalid Mohammed Khan, Ghulam Murtaza Maharvi, Shahnaz Perveen, Mahmud Tareq Hassan Kan, Raid J. Abdel-Jalil, Syed Tasadaque Ali Shah, Miriam Fecker, Muhammad Iqbal Choudhary, [No Value] Atta-ur-Rahman, Wolfgang Voelter

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16 Citations (Scopus)

Abstract

The microwave-assisted synthesis and characterization of the ten new sildenafil (Viagra®; 1) analogues 6-15 are described. A detailed structure-activity-relationship (SAR) study revealed that compounds 10 (=4-ethoxy-N-hydroxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo [4,3-d]pyrimidin-5-yl)benzenesulfonamide) and 12 (=S-(2-hydroxyethyl) 4-ethoxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo [4,3-d]pyrimidin-5-yl)benzenesulfonothioate) are extremely potent mushroom tyrosinase inhibitors, with IC50 values (3.59 and 2.15 μM, resp.) below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and 16.67 μM, resp.). Compounds 10 and 12 are, thus, the currently most-effective inhibitors of tyrosinase, and bear great potential to be used for the treatment of various skin disorders such as hyperpigmentation, which is associated with high production of melanocytes.

Original languageEnglish
Pages (from-to)470-476
Number of pages7
JournalChemistry and Biodiversity
Volume2
Issue number4
DOIs
Publication statusPublished - 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

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  • Cite this

    Khan, K. M., Maharvi, G. M., Perveen, S., Kan, M. T. H., Abdel-Jalil, R. J., Shah, S. T. A., Fecker, M., Choudhary, M. I., Atta-ur-Rahman, N. V., & Voelter, W. (2005). Synthesis of methyl ether analogues of sildenafil (Viagra®) possessing tyrosinase inhibitory potential. Chemistry and Biodiversity, 2(4), 470-476. https://doi.org/10.1002/cbdv.200590027