(a) Field of the Invention
This invention relates to novel and known aromatic substituted cyclic amidines. In particular, one aspect of the invention relates to a method useful in the treatment of diarrhea. In another aspect of the invention, it relates to novel compounds useful in the treatment of diarrhea.
Diarrhea is a condition in which an abnormally frequent discharge of liquid or semi-liquid material from the bowel is present. The consistency of the normal discharge from the intestine is that of a semi-solid; the frequency of discharge varies but is usually not more than twice in 24 hours. When the stool is more like a liquid and must be discharged three or more times a day, the condition of diarrhea exists. Diarrhea may be caused by the eating of indigestible or irritable foods, or food to which the individual is allergic. It may also be caused by infection or by nervousness, which causes the intestine to discharge before the content can assume its normal form. Too much roughage, taken as a means of relieving constipation, may bring on diarrhea. Bran, cabbage and other fibrous food are often the cause. Lastly, many drugs, notably antibiotics, are known to cause diarrhea as a side effect.
Currently, mild diarrhea has been treated with binding agents such an aluminum hydroxide gel, kaolin, pectin and bismuth. More serious diarrhea has been treated with opiates which act by increasing segmenting activity. Diphenoxylate (a synthetic derivative), tincture of opium, and camphorated tincture of opium (paregoric) are effectively used. However, all the problems associated with opiates exist, and the compounds merely treat symptoms not etiology, and therefore may lead to complication and even death if care is not taken.
(b) Prior Art
Cyclic phenylamidines, such as 2-(3,4-dichlorophenylimino)-N-methylpyrrolidine, are known (U.S. Pat. No. 3,189,648). Furthermore, pharmacodynamically active phenylcycloamidines are known, such as 2-(2,6-dichloroophenylimino)pyrrolidine (Netherlands patent specification No. 6805573). In these compounds, however, the pharmacodynamic activities, such as lowering of blood pressure, hyperglycemic activity and inhibitory action on the central nervous system, are specifically linked to the ortho-substitution of the phenyl nucleus.
Other 2-phenyliminopyrrolines substituted in the meta- and para-positions, for example by chlorine or other halogen atoms, or by an alkyl, nitro or alkoxy group, are pharmacodynamically inactive.
Lastly, the known compounds useful in the method aspect of the invention are described in U.S. Pat. No. 3,769,274. These compounds are described as parasiticides and hypotensive agents.