Hepatic effects of some [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (WY-14,643) analogs in the mouse.

The comparative hypolipidemic and hepatic peroxisome proliferative activities of a series of thioacetic acid pyrimidines were evaluated in male mice. [4-Chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643) produced significant hepatomegaly and peroxisome proliferation in liver cells. This compound also increased the hepatic catalase and carnitine acetyltransferase activities and lowered serum cholesterol and triglyceride levels. The structurally related analogs, Wy-15,690, Wy-15,672, Wy-15,746 and Wy-15,496, which lacked hypolipidemic effect failed to induce hepatomegaly and peroxisome proliferation. No substantial increase in catalase and carnitine acetyltransferase activities was noted. It is concluded that the hepatic peroxisome proliferative effect is closely related to the hypolipidemic activity, rather than to any specific chemical structure.