Patent GB-819315-A (GB)
Title: New thiol esters
Inventor: DRIVER GEORGE WILLIAM
IPC: A61K31/265
Filed: 1956-06-15
Abstract: The invention comprises compounds of the formula <FORM:0819315/IV (b)/1> wherein R is hydrogen or the group COSEt, and wherein the nucleus A is wholly or partly saturated and may optionally be fused to a benzene nucleus, and the preparation of these compounds by reaction of a carboxylic halide of the formula <FORM:0819315/IV (b)/2> wherein X is a halogen atom and R11 is hydrogen or the group COX, with ethanethiol.  The reaction is preferably carried out in an inert solvent such as benzene, and in the presence of an acid-binding agent, for example pyridine.  The compounds are used as therapeutic agents for the treatment of tuberculosis, Johne's disease and leprosy (see Group VI).  Examples describe the preparation of the ethyl esters of cis- and transcyclohexane - 1 : 3 - di (thiolcarboxylic) -, transcyclohexane - 1 : 4 - di (thiolcarboxylic) -, cyclohexanethiolcarboxylic -, 1 : 2 : 3 : 4 - tetarhydronaphthalene - (1 and 2) - thiolcarboxylic-, cis - D 4 - cyclohexene - 1 : 2 - di (thiolcarboxylic) -, and cis - and trans - cyclohexene1 : 3 - di (thiolcarboxylic) -, acids.ALSO:Pharmaceutical compositions for the treatment of tuberculosis, leprosy and Johne's disease comprise compounds of the formula <FORM:0819315/VI/1> wherein R is hydrogen or the group COSEt and A is partly or wholly saturated and is optionally fused to a benzene nucleus (see Group IV (b)) and an inert diluent or carrier.  Compositions for parenteral injection suitably contain 10-95 per cent of the active compound in association with non-toxic injectable liquids such as a vegetable oil, e.g. arachis, sesame, almond, olive, persic, coconut or soya bean oil or cocoa butter, which may contain additional components such as beeswax and aluminium stearate, or the active compound may be disposed in an aqueous medium in the presence of a dispersing agent which is preferably non-ionic, e.g. sorbitan monopalmitate and its condensation products with ethylene oxide and condensation products of cetyl alcohol or p-octylphenol with ethylene oxide.  The compositions may also take the form of creams, ointments or pastes for external application containing as ointment bases animal or vegetable fats or oils such as castor, arachis or coconut oil or lanolin, aliphatic and olefinic acids derived from them for example by hydrolysis such as stearic, palmitic or oleic acid or higher aliphatic alcohols derived from such acids, for example by reduction such as cetyl, stearyl, cetostearyl and wool alcohols. The emulsified bases or creams suitably contain emulsifying agents such as salts of stearic acid with alkali-metal bases or organic bases such as triethanolamine, or combinations of fatty alcohols such as cetyl, stearyl or cetostearyl with long chain quaternary ammonium salts such as cetrimide or mixtures thereof, or with sulphated fatty alcohols or their salts such as sodium dodecyl sulphate or triethanolamine dodecyl sulphate, or polyoxyethylene ethers of fatty alcohols or polyoxyethylene esters of fatty acids. The compositions may also contain additional excipients or thickening agents such as higher paraffin hydrocarbons, spermaceti and beeswax. Active compounds which are liquids may be incorporated into pastes containing as diluents inert, insoluble organic or inorganic powders such as starches, salts of higher aliphatic and olefinic acids such as calcium, aluminium or magnesium stearates or oleates, inorganic powders such as bentonite, fuller's earth and kaolin and metallic oxides, carbonates, silicates and phosphates such as oxides and salts of zinc, calcium, magnesium and aluminium.  The compositions may also contain deodorizing agents, masking agents or perfumes.  Examples describe compositions comprising (4) diethyl cis - cyclohexane - 1 : 3-di(thiolcarboxylate) and arachis oil, for intramuscular or subcutaneous injection; (5) ethyl cyclohexanethiolcarboxylate and coconut-oil, for intramuscular or subcutaneous injection; (6) diethyl cis - D 4 - cyclohexene - 1 : 2 - di-(thiolcarboxylate), arachis oil and aluminium stearate, for injection; (7) ethyl cyclohexanethiolcarboxylate and magnesium stearate, for external application; (8) diethyl cis-cyclohexane - 1 : 3 - di(thiolcarboxylate) and bentonite, for external application; (9) diethyl cyclohexene - 1 : 2 - di(thiolcarboxylate), lanolin, cetyl alcohol and arachis oil, for external application; and (10) diethyl transcyclohexane - 1 : 3 - di(thiolcarboxylate) castor oil and beeswax, for external application.