Masami Muraoka

Enantioselective aldol reaction mediated by chiral lithium amide bases

Abstract Highly enantioselective aldol reaction mediated by chiral lithium amide bases was achieved between some methylketones and aldehydes

A convenient synthesis of 4-aryl-1,8-naphthyridin-2(1H)-ones by the Suzuki coupling

4-Halo-1,8-naphthyridin-2(1H)-ones readily available from 2-chloronicotinic acid were subjected to the Suzuki coupling reaction with arylboronic acids to give a diversity of 4-aryl-1,8-naphthyridin-2(1H)-ones.

Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties

Abstract Syntheses of new PGI 1 derivatives and inhibitory activities of blood platelet aggregation are described. It is shonw that high potent 3-oxa-methano-PGI 1 compound SM-10906 can be obtained, when the natural α-chain is modified by introducing a 3-oxa-moeity.

Pharmacological profile of SMP-797, a novel acyl-coenzyme A : Cholesterol acyltransferase inhibitor with inducible effect on the expression of low-density lipoprotein receptor

We investigated the pharmacological profile of SMP-797, a novel hypocholesterolemic agent. SMP-797 showed inhibitory effects on acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities in various microsomes and in human cell lines, and hypocholesterolemic effects in rabbits fed a cholesterol-rich diet and hamsters fed a normal diet. In hamsters, the reduction of total cholesterol level by SMP-797 was mainly due to the decrease of low-density lipoprotein (LDL) cholesterol level rather than that of very low-density lipoprotein (VLDL) cholesterol level. Interestingly, SMP-797 increased the hepatic low-density lipoprotein receptor expression in vivo when it decreased the low-density lipoprotein cholesterol level. SMP-797 also increased low-density lipoprotein receptor expression in HepG2 cells like atorvastatin, an HMG-CoA reductase inhibitor, although other acyl-coenzyme A: cholesterol acyltransferase inhibitor had no effect. In addition, SMP-797 had no effect on cholesterol synthesis in HepG2 cells. These results suggested that the increase of low-density lipoprotein receptor expression by SMP-797 was independent of its acyl-coenzyme A: cholesterol acyltransferase inhibitory action and did not result from the inhibition of hepatic cholesterol synthesis. In conclusion, these results suggest that SMP-797 is a novel hypocholesterolemic agent showing a cholesterol-lowering effect in which the increase of hepatic low-density lipoprotein receptor expression as well as the inhibition of acyl-coenzyme A: cholesterol acyltransferase is involved.

A practical synthesis of 1-alkyl-3-amino-4-aryl-1,8-naphthyridin-2-(1H)-one, a partial structure of ACAT inhibitor SMP-797

3-Amino-4-[3-(3-benzyloxypropoxy)phenyl]-1-butyl-1,8-naphthyridin-2(1H)-one, which is a naphthyridine part of a potent ACAT (acyl-CoA: cholesterol acyltransferase) inhibitor SMP-797, was effectively synthesized from m-bromophenol in 5 steps without isolating intermediates. The synthesis involved the intramolecular aldol reaction as a key step.