Antifertility effects of substituted acetamidobenzene derivatives in female albino rats.

The use of nitrogen mustards as chemotherapeutic agents in the treatment of certain neoplastic diseases has been well established by a large number of workers (Montgomery, 1959; Creech, Breuninger, Hankwitz, Polsky & Wilson, 1960; Ross, 1962). A large number of different compounds have been screened in various test systems in vitro and in vivo for anticancerous, antibacterial, antimicrobial and antifertility action and some useful results have been reported (see Mori, Clarkson, O'Connor Lawrence, 1962; Schmidt, Fradkin, Sullivan, & Flower, 1965; Burger, 1970). A series of substituted acetamidobenzene derivatives was screened for antifertility effects by the method of Khanna & Chaudhry (1968) to detect any antizygotic, blastocytotoxic, anti-implantation and abortifacient activity. The derivatives contained a monoor bis-, 2\x=req-\ haloethyl moiety linked through a methylene group to the parent benzene ring at position 3 with the general formula ofCH3.CONH. C6H3. R.R\m='\, where R and R\m='\are different substituents as indicated in Table 1, and were prepared originally for the study of anticancerous and antitumour activity. Adult female albino rats (175 to 200 g) of proven fertility were mated with males of known fertility. The day on which thick clumps of spermatozoa were detected in the vaginal smear was termed Day 1 of pregnancy. The acetamidobenzene derivatives were dissolved in distilled water with two drops of concentrated hydrochloric acid and were administered orally from Day 1 to Day 7 at a dose rate of 1 mg/rat. On Day 10, laparotomy was performed and the number of implantation sites in both horns of the uterus was recorded. The number of young born at term was also recorded, and the young were observed for at least 1 month for any evidence of gross malformation. The results are shown in Table 2. The inhibition of implantation by Compounds 1 and 3 indicates the import¬ ance of the ethoxy and methoxy groups, respectively, at position 4 and the bis (2-bromoor chloroethyl) aminomethyl groups at position 3, respectively. Antifertility activity was reduced by 50% with Compounds 4 and 5 in which the bis (2-bromoor chloroethyl) aminomethyl groups are also in position 3, but the alkoxy groups are interchanged. When a single unit of the 2-bromoethylamino group was substituted through a méthylène linkage at position 3