147506-57-8Relevant articles and documents
The squalestatins: Decarboxy and 4-deoxy analogues as potent squalene synthase inhibitors
Chan, Chuen,Andreotti, Daniele,Cox, Brian,Dymock, Brian W.,Hutson, Julie L.,Keeling, Suzanne E.,McCarthy, Alun D.,Procopiou, Panayiotis A.,Ross, Barry C.,Sareen, Meenu,Scicinski, Jan J.,Sharratt, Peter J.,Snowden, Michael A.,Watson, Nigel S.
, p. 207 - 216 (2007/10/03)
Squalestatins without either the hydroxy group at C-4 or the carboxylic acid at C-3 or C-4 were prepared and evaluated for their ability to inhibit rat liver microsomal squalene synthase (SQS) in vitro. These modifications were well tolerated for compounds with the 4,6-dimethylectenoate ester at C- 6 (S1 series). However in analogues without the C-6 ester (H1 series), removal of the C-4 hydroxy group gave compounds with reduced potency, whereas decarboxylation at C-3 resulted in a dramatic loss of SQS inhibitory activity. In comparison with S1 1, C-4 deoxyS1 3 and C-3 decarboxyS1 10 have shorter in vivo durations of action on the inhibition of hepatic cholesterol biosynthesis in rats. C-4 deoxyS1 3 retains good serum cholesterol-lowering ability in marmosets, while C-3 decarboxyS1 10 showed only a marginal effect even at high dose.