Abstract
In the course of a comprehensive study of the relationship between chemical structure and biological activity in a series of substituted desoxybenzoins it was found that 1,2-bis-(p-aminophenyl)-2-methylpropanone-1 dihydrochloride exhibits progestational activity.
The synthesis and properties of this compound have been previously described (Allen and Corwin) (1). We have employed a modification of the biological test for progesterone described by Clauberg(2). Juvenile female rabbits (New Zealand Whites) initially weighing between 600 and 800 g were utilized. Each test animal was pre-treated daily for 6 days with 10 μg of estradiol benzoate administered subcutaneously in 0.5 cc corn oil. For the ensuing 5 days either Compound I or progesterone was administered subcutaneously in the dosage and form indicated in Table I. Twenty-four hours after the last injection the animals were autopsied, their terminal body weight and uterine weight recorded, and the uterus prepared for histological grading of the progestational response as described by Hisaw and Leonard (3).
The data indicate that of 24 rabbits given a daily dose of 100 mg or more, all but 2 showed a decisive progestational response to Compound I. The grade of response varied considerably but such variability is characteristic of the progestational response in the young rabbit(2). In 2 rabbits treated with 50 mg daily only a doubtful response was elicited and a similarly marginal effect was seen in 2 rabbits receiving 100 mg daily. By comparison with the potency of progesterone under similar experimental conditions, it may be crudely estimated that Compound I is about 0.5 to 0.25% as active as progesterone.
From the observations on uterine weight it is apparent that Compound I brings about less increment in uterine weight than progesterone even in instances in which the progestational effect upon the endometrium is maximal.
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