Farquhar D, Benvenuto J
J Med Chem. 1984 Dec;27(12):1723-7. doi: 10.1021/jm00378a033.
A series of 19 aryldimethyltriazenes were synthesized as potential central nervous system (CNS) active analogues of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). The compounds were screened in mice against both intraperitoneally (ip) and intracerebrally (ic) implanted L1210 leukemia. Select compounds were further screened against ic implanted ependymoblastoma, and one compound was additionally screened against ic implanted B16 melanoma. Although several compounds were as effective as DTIC at prolonging the life span of mice bearing ip 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 ic implanted tumor. DTB, unlike DTIC, was equally effective against both the ip and the ic implanted tumor, clearly indicating that it penetrated into the CNS in therapeutic concentration. DTB was also active against ic implanted ependymoblastoma and ic 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.
合成了一系列19种芳基二甲基三氮烯，作为5-(3,3-二甲基-1-三氮烯基)咪唑-4-甲酰胺（DTIC）潜在的中枢神经系统（CNS）活性类似物。在小鼠体内对这些化合物针对腹腔内（ip）和脑内（ic）植入的L1210白血病进行了筛选。对选定的化合物进一步针对脑内植入的室管膜母细胞瘤进行筛选，另外对一种化合物针对脑内植入的B16黑色素瘤进行筛选。尽管几种化合物在延长携带腹腔内植入L1210白血病小鼠的寿命方面与DTIC一样有效，但只有4-(3,3-二甲基-1-三氮烯基)苯甲酰胺（DTB）和4-(3,3-二甲基-1-三氮烯基)苯甲酸（DTBA）对脑内植入的肿瘤具有显著活性。与DTIC不同，DTB对腹腔内和脑内植入的肿瘤同样有效，清楚地表明它能以治疗浓度渗透到中枢神经系统。DTB对脑内植入的室管膜母细胞瘤和脑内植入的B16黑色素瘤也有活性。芳基二甲基三氮烯，尤其是DTB，可能在治疗转移至中枢神经系统的肿瘤中发挥作用。它们也可能对原发性脑肿瘤有效。
