Comparison of the antitumor activity and toxicity of 2,4-diamino-5-(1-adamantyl)-6-methylpyrimidine and 2,4-diamino-5-(1-adamantyl)-6-ethylpyrimidine.
The effects of two new compounds, 2,4-diamino-5-(1-adamantyl)-6-methylpyrimidine (DAMP) and 2,4-diamino-5-(1-adamantyl)-6-ethylpyrimidine (DAEP), on the growth of Walker carcinoma 256 were studied. In Sprague-Dawley rats, both compounds inhibited the growth of the Walker tumor, which is naturally resistant to methotrexate. Murphy-Sturm lymphosarcoma, which is extremely sensitive to methotrexate, was not inhibited by DAMP. In contrast, 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) inhibited the growth of the Murphy-Sturm and Walker tumors. The toxicity of DAMP and DAEP was charaxterized by convulsions followed by death; DDMP did not show such toxicity at median lethal doses. DAEP and DAMP reversibly reduced the number of polymorphonuclear leukocytes in the peripheral blood of rats, and DAMP also decreased the lymphocytes and platelets; DDMP markedly reduced all these cellular elements. Consistently, bone marrow was also markedly depressed by DDMP.
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents; D001853:Bone Marrow / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D005260:Female; D005493:Folic Acid Antagonists; D007928:Lethal Dose 50; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy*
C016357:2,4-diamino-5-(1-adamantyl)-6-ethylpyrimidine; D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011743:Pyrimidines; D000218:Adamantane