Further confirmation of the anti-neoplastic activity of benz-l,3-oxazine derivatives was obtained by the Miyamura test, in vitro*. Similar results were obtained by Leonardi3 when he repeated our experiments in vitro.
All these results seemed to be sufficiently promising to justify searching for anti-neoplastic substances among the derivatives of 1,3-oxazine. Simpler compounds, derivatives of 5-nitrotetrahydro-l,3-oxazines (I) and 6-methyl-6-phenyltetrahydro-1,3-oxazine (II) proved to be fairly efficient in vitro*.C6H5 O
oCH2 - NH
R2 CH2 CH,,\l i "
CH3 CHC N -,
H2O,N CH,T 446 (ref. 7)
R1 - CH3, R2 = CH3, T 398 (ref. 4)Rl = CH3, R* = CH2OH, T 401 (ref. 4)
Ri = CH3, R* = C5H115 T 413 (ref. 5)R1 = C6HX1, Rz = C3H7, T 364 (ref. 6)
Their activity against the solid form of Ehrlich ascites carcinoma is shown in Table 1 and solid form of amytal ascites sarcoma in, mice in, Table 2.It is believed that the active CH2 group in position 2 is responsible for the anti-neoplastic activity of 1,3-oxazine derivatives.
Further experiments will be carried out with a number of the compounds (I) to elucidate the influence of various substituents on their anti-neoplastic activity.Table 1. INHIBITION OF EHRLICH ASCITES CARCINOMA
Code No. of substance Mouse strain No. of mice in group Daily dose of substance (mgm./mouse) Average tumour weight (gm.)