The detection of a new class of
tumor inhibiting substances is described. Employing a chemical reaction discovered several years ago, a series of imidazolinylureas were prepared. It was found that some compounds of this group were active against
diethylnitrosamine (DENA)-induced tumours in hamsters.
CGP 15720 A (1-[2-[2-(4-pyridyl)-2-
imidazoline-1-yl]-ethyl]-3-(4-carboxy-phenyl)
urea. Xb), the most active compound at present, was developed through a series of structural variations.
CGP 15720 A inhibits significantly in oral or parenteral treatment with well tolerated doses (10-30 mg/kg) the progressive growth of autochthonous, DENA-induced papillary, epidermoid and adenocarcinomatous
tumors of the respiratory system in Syrian hamsters and prolongs significantly the survival. The substance also inhibits significantly the growth of 2 poorly differentiated human epidermoid or anaplastic
bronchogenic carcinomas in nu/nu Balb/c mice and prolongs the mean survival time. In these mice, the substance is also active against the rodent
ascites tumors Ehrlich
carcinoma, CrSa 180 and Yoshida Sa AH 66, although it is only marginally active or inactive against these
tumors in normal mice or rats.-In the therapeutic trials, hamsters tolerated the highest dose administered for 4 weeks, 1000 mg/kg p.o., without signs or symptoms of toxicity.