synthesis and biological screening of 1,3-dialkyl derivatives of 4-(2’5-dioxopyrrolidine-3-yl) phenyl sulphinic acid as inhibitors of oestrone sulphatase

Authors

farshid hassanzadeh

isfahan pharmaceutical sciences research center, and department of medicinal chemistry, faculty of pharmacy and pharmaceutical sciences, isfahan university of medical sciences, isfahan, iran john smith

department of medicinal chemistry, welsh school of pharmacy, university of wales, cardiff, uk paul j. nicholls

department of medicinal chemistry, welsh school of pharmacy, university of wales, cardiff, uk

abstract

1,3-dialkyl 3-phenylpyrrolidine-2, 5-diones were modified to produce potential steroid sulphatase inhibitors. these modifications were aimed at producing compounds, which could be expected to bind reasonably well to the active site of the steroid sulphatase enzyme but could not be hydrolyzed readily by the enzyme due to the covalent s-c bond present. in this regard the sulphinic acid derivatives of di-substituted 3-phenylpyrrolidine-2, 5-diones were prepared. on biological testing, only compound 4-(2,5-dioxo-1, 3-dipentylpyrrolidine-3-yl) phenylsul-phinic acid (f5) was found to be an inhibitor of the steroid sulphatase enzyme from human placenta and was about twice as potent as the known inhibitor danazol.

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Journal title:
iranian journal of pharmaceutical sciences

جلد ۲، شماره ۴، صفحات ۲۱۵-۲۲۴

Keywords
[ ' b r e a s t c a n c e r ' , ' o e s t r o n e s u l p h a t a s e ' , ' p h e n y l p y r r o l i d i n e ' , 2 , 5 , ' d i o n e ' , ' s t e r o i d s u l p h a t a s e ' ]

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