HEPATIC EFFECTS OF SOME [4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO] ACETIC-ACID (WY-14,643) ANALOGS IN MOUSE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 225  (1) , 51-57
Abstract
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 increased hepatic catalase and carnitine acetyltransferase activities and lowered serum cholesterol and triglyceride levels. The structurally related analogs, Wy-15,690 [ethyl[4-(p-chlorobenzylamino)-6-trifluoromethyl-2-pyrimidinylthio]-acetate], Wy-15,672 [ethyl[4-chloro-6-(m-chlorobenzyl)methylamino-2-pyrimidinylthio] acetate], Wy-15,746 [ethyl[4-chloro-6-(3,4-dichlorobenzylamino)-2-pyrimidinylthio] acetate and Wy-15,496 [ethyl[4-(p-chlorobenzylamino)-2-pyrimidinylthio] acetate], which lacked hypolipidemic effect failed to induce hepatomegaly and peroxisome proliferation. No substantial increase in catalase and carnitine acetyltransferase activities was noted. The hepatic peroxisome proliferative effect apparently is closely related to the hypolipidemic activity, rather than to any specific chemical structure.

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