TY - JOUR
T1 - Synthesis of methyl ether analogues of sildenafil (Viagra®) possessing tyrosinase inhibitory potential
AU - Khan, Khalid Mohammed
AU - Maharvi, Ghulam Murtaza
AU - Perveen, Shahnaz
AU - Kan, Mahmud Tareq Hassan
AU - Abdel-Jalil, Raid J.
AU - Shah, Syed Tasadaque Ali
AU - Fecker, Miriam
AU - Choudhary, Muhammad Iqbal
AU - Atta-ur-Rahman, null
AU - Voelter, Wolfgang
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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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U2 - 10.1002/cbdv.200590027
DO - 10.1002/cbdv.200590027
M3 - Article
C2 - 17191995
AN - SCOPUS:21044437985
SN - 1612-1872
VL - 2
SP - 470
EP - 476
JO - Chemistry and Biodiversity
JF - Chemistry and Biodiversity
IS - 4
ER -