SOME UNSYMMETRICAL ALKYLARYL UREAS II. PREPARATION, PHYSICAL PROPERTIES AND HYPNOTIC EFFECTS

¹ From The Burroughs Wellcome & Co., U. S. A., Experimental Research Laboratories, Tuckahoe, New York

An attempt has been made to relate the physiological activities of sixty-four of a possible group of eighty unsymmetrical alkylaryl ureas to certain of their physical properties. The results permit the following generalizations:

1. In homologous series the m.h.d. and m.l.d. values vary inversely with the melting points and water solubilities, and directly with the molecular weights, Heptane/Water distribution coefficients. and the powers for lowering the surface tension of water.

2. The isoalkyl ureas usually have higher melting points, lower solubilities in water, lower distribution coefficients, poorer capacities for lowering the surface tension of water and are less active, physiologically, than the normal alkyl isomers.

3. When position isomers are compared there appears to be no uniform agreement between physiological activity and physical properties, save for the frequent inverse relationship of melting points and water solubility to the m.h.d. and m.l.d. values.

4. The physiological activities generally vary directly with the Heptane/Water distribution coefficients in urea analogs, both decreasing in the same order from the tolyl to the anisyl compounds. The anisyl compounds are uniformly the least effective physiologically, and also have the highest melting points and the poorest capacities for lowering the surface tension of water.