Thionesters as a probe for electrophilic catalysis in the serine protease mechanism.

Specific and nonspecific thionester substrates for alpha-chymotrypsin and subtilisin Carlsberg have been synthesized and the kinetic parameters for their enzyme-catalyzed hydrolyses measured. Despite equal nonenzymic reactivities of ester-thionester pairs, each thionester is considerably less reactive toward enzymic hydrolysis, the difference being greatest for the specific substrates. The data support the operation of electrophilic catalysis by a hydrogen bond network at the carbonyl oxygen adjacent to the scissile bond of the substrate.

Antilipidemic drugs. Part 2: Experimental study of a new potent hypolipidemic drug, isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF178).

Pharmacological investigations have been carried out on a new p-chlorobenzoyl substituted phenoxy-isobutyric acid derivate with potent antilipidemic activity, isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]propionate (LF 178; procetofene; Lipanthyl¿). The compound depressed total lipids and total cholesterol significantly in the normal rat from 15-20 mg/kg upwards. At 100 mg/kg, the drug-induced depression of total lipids was twice the effect observed with 300 mg/kg of clofibrate.