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In search of a drug to treat sickle cell anemia, several analogues of the diuretic ethacrynic acid (ECA) have been synthesized and found equivalent in antigelling potency to ECA, but they have moderate or little diuretic activity. Structure-activity studies revealed that most of the highly active derivatives contain an acryloyl moiety. The latter functionality reacts covalently with protein sulfhydryl groups via a Michael addition reaction. Other derivatives, which lack the acryloyl moiety, showed notably lower antigelling activity. Since the antigelling assay is run under anaerobic conditions, activity implies a stereochemical inhibition of polymerization of deoxyhemoglobin S. The solubility ratios obtained from [HbS drug]/[HbS control] of several compounds (Table I) are near those expected for a drug with clinical potential (1.06-1.20 at tolerable doses in vivo).
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
February 1984,
Journal of medicinal chemistry,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
November 1987,
Journal of medicinal chemistry,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
January 1987,
Blood cells,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
April 1983,
Journal of medicinal chemistry,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
April 1987,
International journal of peptide and protein research,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
January 1989,
Annals of the New York Academy of Sciences,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
September 1999,
Medicinal research reviews,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
September 1980,
Journal of medicinal chemistry,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
March 2021,
Heliyon,
D J Abraham, and
A S Mehanna, and
F S Williams, and
E J Cragoe, and
O W Woltersdorf
January 2016,
Recent patents on anti-cancer drug discovery,
