Choleretic activities of 1-morpholinoacetyl-2-methyl-3-phenyl-4-oxo-1, 2, 3, 4-tetrahydro quinazoline hydrochloride (HQ-275).

Abstract

In 1959, R. Charlier reported that the most potent choleretic action was found in p-hydroxyphenyl salicylamide (Driol, PHPS) among the derivatives of benzoic acid (1). Moreover, G. Bonola et al. reported that l-morpholinoacetyl-3-phenyl-4-oxo-l,2,3,4,-tetrahydro quinazoline (Moquizone, MQZ) has the most potent choleretic activity among their derivatives (2, 3). Recently, many derivatives of l-aminoacetyl-2-alkyl-3-phenyl-4-oxo-l,2,3,4-tetrahydro quinazoline, which include basically the main structure of PHPS and MQZ, have been synthesized by K. Okumura et al. (4, 5). From the relationship between the chemical structure and the choleretic activity, it was found that l-morpholinoacetyl-2-methyl-3-phenyl-4-oxo-l,2,3,4-tetrahydro quinazoline (hereafter referred to as HQ-275) has the most potent choleretic activity among these derivatives. In the present experiment, qualitative evaluation of the choleretic activities of quinazoline derivatives were carried out mainly in rats. As the choledochal bile of rat devoid of gall bladder, is qualitatively and quantitatively expression of the hepatic bile, it has a constitution very similar to that of humans. In addition to the choleretic action, other pharmacological studies and toxicity of HQ-275 were also compared with those of dehydrocholic acid (DHC), PHPS, α-(l-hydroxy-cyclohexyl)-butylic acid (HCHB) and p-tolylmethyl-carbinol (PTMC) in rabbits, cats and dogs.