Abstract
Three derivatives of 2-chloro-5,8,9,13b-tetrahydro-5-methyl-6H-Isoquino[2,1 -GI[1,3,2]benzodiazaphosphorine 6-oxides as well as its sulphides were synthesized with the aim of evaluating their antitumor properties. Three of the twenty one compounds were found to be significantly active (inhibition of tumor growth > 80%) in the Ehrlich ascites carcinoma screen. Several structure-activity relationships were indicated for antitumor activity in this screen. An aziridinyl substituted derivative, bis-(2-chloroethyl)amino substitution (3) also exhibited significant activity against the growth of P-388 lymphocytic Leukemia cells in male BDF, mice (% T/C = 147; % T/C > 125 is considered significant). The reference for activity comparison is cyclophosphamide or cytoxan i.e. [bis(2-chloroethyl)aino]-5,6-dihydro-2H-1,3,2-oxazaphosphorinane 2-oxide [having TIC × 100 = 339 at a dose of 65 mg/kg]
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