Patent GB-858911-A (GB)
Title: 2-imino-thiazolidines and their acid addition salts and compositions thereof
IPC: A61K31/00
Filed: 1958-02-27
Abstract: The invention comprises 2-imino-thiazolidin4-ones of the general formula:  <FORM:0858911/IV(b)/1> wherein R1 and R2 each represent an aliphatic hydrocarbon radical containing more than two carbon atoms) and acid addition salts thereof, and their preparation by reacting an N, N1-disubstituted thiourea of the formula:  <FORM:0858911/IV(b)/2> with an acetic acid, or ester thereof, substituted in the a -position by a reactive esterified hydroxyl group (e.g. a halogen atom), followed, if desired, by conversion into an acid addition salt.  The invention also includes pharmaceutical preparations in which one of the above bases or a salt thereof forms the active constituent (see Group VI).  In Examples, 1 : 3-bis-(41-propoxyphenyl),-(41-allyloxyphenyl)-, -(41- isopentoxyphenyl)-, -[41-(311-methylpentoxy) phenyl]-, -(41-heptoxyphenyl)-, -(41-butoxyphenyl)- and -(41-isobutoxyphenyl)- thiourea are heated under reflux with chloroacetic acid, in the presence of anhydrous sodium acetate, in ethanol or isopropanol to give 2-(41-propoxyphenylimino)-3-(41-propoxyphenyl)-, 2-(41-allyloxyphenylimino)-3-(41-allyloxyphenyl)-, 2-(41-isopentoxyphenylimino)-3-(41-isopentoxyphenyl)-, 2-[41-(311-methyl-pentoxy) phenylimino]-3-[41-(311-methylpentoxy)-phenyl]-, 2-(41-heptoxyphenylimino)-3-(41-heptoxyphenyl)-, 2-(41-butoxyphenylimino)-3-(41-butoxyphenyl)- and 2-(41-isobutoxyphenylimino)-3-(41-isobutoxyphenyl) -thiazolidine-4-one respectively.  The hydrochloride and oxalate of the first-named product above are also described.  The N, N1-disubstituted thioureas of the second general formula above are prepared by reacting p-substituted anilines with p-substituted phenylisocyanates, or by the action of carbon disulphide on appropriately substituted anilines.ALSO:Pharmaceutical preparations, useful for the treatment of tubercolosis, leprosy and fungal infections, comprise a compound of the general formula: <FORM:0858911/VI/1> (wherein R1 and R2 each represent an aliphatic hydrocarbon radical of more than 2 carbon atoms), or a therapeutically suitable acid addition salt thereof, in admixture with a pharmaceutical organic or inorganic solid or liquid carrier suitable for internal, parenteral or topical administration.  The preparations may be in the form of tablets, salves, dragees, creams, solutions, suspensions or emulsions, and may contain preserving agents, stabilizing agents, wetting or emulsifying agents, salts for varying the asmotic pressure, buffers, or additional therapeutically useful substances.  Specified salts are hydrohalides, perchlorates, nitrates, thiocyanates, sulphates, phosphates, formates, acetates, propionates, glycollates, lactates, pyrivates, oxalates, malorates, succinates, maleates, fumarates, malates, tartrates, citrates, ascorbates, hydroxymaleates, dihydroxymaleates, benzoates, phenylacetates, p-aminobenzoates, p-hydroxybenzoates anthranilates, cinnamates, mardelates, salicylates, p - aminosalicylates, 2 - phenoxybenzoates, 2 - acetoxybenzoates, methane-, ethane-, hydroxyethane-, benzene-, p - toluene- and napthalene-sulphonates, sulphanilates, and salts with methionine, tryptophane, lysine and arginine.