1-Aryl-3,3-dimethyltriazenes: potential central nervous system active analogs of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC)

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Abstract
A series of 19 aryldimethyltriazenes were synthesized as potential CNS active analogs of 5-(3, 3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The compounds were screened in mice against both i.p. and intracerebrally (i.c.) implanted L1210 leukemia. Select compounds were further screened aganist i.c. implanted ependymoblastoma, and 1 compound was additionally screened against i.c. implanted B16 melanoma. Although several compounds were as effective as DTIC at prolonging the life span of mice bearing i.p. implanted L1210 leukemia, only 4-(3, 3-dimethyl-1-triazeno)benzamide (DTB) and 4-(3, 3-dimethyl-1-triazeno)benzoic acid (DTBA) were significantly active against the i.c. implanted tumor. DTB, unlike DTIC, was equally effective against both i.p. and the i.c. implanted tumor, clearly indicating that it penetrated into the CNS in therapeutic concentration. DTB was also active against i.c. implanted ependymoblastoma and i.c. implanted B16 melanoma. Aryldimethyltriazenes, particularly DTB, may have a role in the treatment of tumors metastatic to the CNS. They may also be effective against primary brain tumors.