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Synthesis of Methyl Ether Analogues of Sildenafil ( Viagra ® ) Possessing Tyrosinase Inhibitory Potential
Author(s) -
Khan Khalid Mohammed,
Maharvi Ghulam Murtaza,
Perveen Shahnaz,
Khan Mahmud Tareq Hassan,
AbdelJalil Raid J.,
Shah Syed Tasadaque Ali,
Fecker Miriam,
Choudhary Muhammad Iqbal,
Voelter Wolfgang
Publication year - 2005
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200590027
Subject(s) - kojic acid , chemistry , tyrosinase , sildenafil , ic50 , stereochemistry , ether , melanin , alkoxy group , mushroom , inhibitory postsynaptic potential , mimosine , in vitro , biochemistry , enzyme , organic chemistry , alkyl , medicine , botany , food science , neuroscience , leucaena leucocephala , biology
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‐1 H ‐pyrazolo[4,3‐ d ]pyrimidin‐5‐yl)benzenesulfonamide) and 12 (= S ‐(2‐hydroxyethyl) 4‐ethoxy‐3‐(7‐methoxy‐1‐methyl‐3‐propyl‐1 H ‐pyrazolo[4,3‐ d ]pyrimidin‐5‐yl)benzenesulfonothioate) are extremely potent mushroom tyrosinase inhibitors, with IC 50 values (3.59 and 2.15 μ M , resp.) below those of the standard inhibitors L ‐mimosine and kojic acid ( IC 50 =3.68 and 16.67 μ M , 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.