Hydrophobicity, a physicochemical factor in the inhibition of the enzyme estrone sulfatase (ES).
We report the initial structure-activity relationship study (SAR) (in particular logP) of a series of compounds based upon 4-sulfamated phenyl ketones as potent inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that these compounds are irreversible inhibitors of ES and that they are more potent than COUMATE, but weaker than EMATE. Analysis of the SAR data shows a strong correlation between IC(50) and logP but also supports our previous study, which suggests a very strong relationship between pK(a) and IC(50).
Ahmed
S
S
School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, KT1 2EE, Surrey, UK. ch_s534@kingston.ac.uk
James
K
K
Owen
C P
CP
Patel
C K
CK
Patel
M
M
D002627:Chemistry, Physical / Q000379:methods; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013429:Sulfatases / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
C100463:4-methylcoumarin 7-O-sulfamate; D003374:Coumarins; D004791:Enzyme Inhibitors; D013449:Sulfonamides; C088768:estrone-3-O-sulfamate; D004970:Estrone; D013429:Sulfatases; C020121:estrone sulfatase