Research Article

Synthesis of Methyl Ether Analogues of Sildenafil (Viagra®) Possessing Tyrosinase Inhibitory Potential

  1. Khalid Mohammed Khan1,
  2. Ghulam Murtaza Maharvi1,
  3. Shahnaz Perveen2,
  4. Mahmud Tareq Hassan Khan1,
  5. Raid J. Abdel-Jalil3,
  6. Syed Tasadaque Ali Shah4,
  7. Miriam Fecker4,
  8. Muhammad Iqbal Choudhary1,
  9. Atta-ur-Rahman1,
  10. Wolfgang Voelter4

Article first published online: 18 APR 2005

DOI: 10.1002/cbdv.200590027

Issue

Chemistry & Biodiversity

Chemistry & Biodiversity

Volume 2, Issue 4, pages 470–476, April 2005

Additional Information

How to Cite

Khan, K., Maharvi, G., Perveen, S., Khan, M., Abdel-Jalil, Raid J., Shah, S., Fecker, M., Choudhary, M., Atta-ur-Rahman and Voelter, W. (2005), Synthesis of Methyl Ether Analogues of Sildenafil (Viagra®) Possessing Tyrosinase Inhibitory Potential. Chemistry & Biodiversity, 2: 470–476. doi: 10.1002/cbdv.200590027

Author Information

  1. 1

    H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi-75270, Pakistan

  2. 2

    PCSIR Laboratories Complex, Off University Road, Karachi-75280, Pakistan (fax: +92-21-9243190-91)

  3. 3

    Chemistry Department, Faculty of Science, Hashemite University, Zarka, Jordan

  4. 4

    Abteilung für Physikalische Biochemie des Physiologisch-chemischen Instituts der Universität Tübingen, Hoppe-Seyler Straße 4, D-72076, Tübingen (phone +49-7071-297 3041; fax +49-7071-293348)

Publication History

  1. Issue published online: 18 APR 2005
  2. Article first published online: 18 APR 2005
  3. Manuscript Received: 2 DEC 2004

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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.

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