title: Synthesis of methyl ether analogues of sildenafil (Viagra) possessing tyrosinase inhibitory potential.
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 microM, resp.) below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and 16.67 microM, 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.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.forename: Ghulam Murtaza
authors.initials: GM
authors.lastname: Maharvi
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.forename: Mahmud Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.forename: Raid J
authors.initials: RJ
authors.lastname: Abdel-Jalil
authors.forename: Syed Tasadaque Ali
authors.initials: ST
authors.lastname: Shah
authors.forename: Miriam
authors.initials: M
authors.lastname: Fecker
authors.forename: Muhammad Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voelter
mesh_terms: D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D013329:Structure-Activity Relationship; D013450:Sulfones
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D014442:Monophenol Monooxygenase