IL32472A - N-(diaryl-pyridyl-methyl)-imidazoles and their salts,their preparation and pharmaceutical preparations containing them - Google Patents

Description

and their their preparation and preparations containing BAYER 30784 3 compatible the hydrogen the and bifunctional carboxylic and hydroxycarboxylic acids such as lactic or Hydrohalides lactates and salicylates of are of special importance in this The compounds according to the invention can be produced by preferably at reflux a corresponding diar lpyridyl of the in which X and have the same meaning as preferably in an inert organic such as cyclo petroleum ether or methylene with a reactant suitable for the chlorination of tertiary phosphoryl chloride or acetyl chloride and reacting the diar chloride thus after removal of the liberated acid with an binding an aqueous bicarbonate with or without intermediate by heating the solution under with an excess to about of an imidazole of the formula 4 in which R and R have the same meanings as The last step may also be carried out in another solvent than the In this the solution containing the chloride is the residue taken up with a polar organic such as dimethyl dimethyl sulphoxide or nitromethane and the reaction is carried out at temperatures of about 0 to about with an excess of isolated from the resultant reaction for example via the and the free base separated in usual manner of Instead of an excess of an equivalent amount may also be used together with another The usual organic such as trie dimethyl benzylamine or but also inorganic alkali metal or alkaline earth metal carbonates calcium are suitable for the above Some of the diarylpyridyl carbinols of formula II are the others can be prepared by methods analogous to those serving for the preparation of the known The following Table shows the composition at melting point of some of the new compounds 4a Table 1 R phenyl phenyl phenyl phenyl g carbinol are suspended in 150 ml dry methylene There are added while g thionyl The mixture is homogeneous after briefly It is concentrated and the residue taken up with ml The acetone is drawn off in a vacuum at below The residue is again mixed with 50 ml the mixture is briefly cooled with chloride and the hydrochloride of chloride is filtered off g The hydrochloride is dried and introduced in small portions into a hot solution at g imidazole in 150 ml The mixture subsequently boiled for 5 minutes and then poured about litre of kg ice and ml concentrated chloric The solution is with active filtered and slowly adjusted to pH 8 9 with a dilute sodium hydroxide After is precipitated in crystalline filtered off with suction and washed with g of theory referred to the Melting Also the other compounds can be obtained in an analogous Salts of selioylate on Sabourouds milieu are summarized in the followin Table data as Minimum Inhibition Concentration as in vitro A infection and Trichophyton In the therapeutic experiment a rapid healing of the mycotic lesion takes If the compound is replaced by the other mentioned above to or their salts to then similar results are In dogs and cats the ranges from about 300 to about 1000 when orally adminis Of special interest for practical use are the compounds are unsubstituted on the imidazole ring and which may optionally be substituted in one phenyl by a erably chlorine or fluorine or as well as the salts thereof with hydrochloric lactic acid or salicylic As indication spheres for the imidazoles used as herapeutic agents according to the invention the following are taken into human caused b fungi species Trichophytes Candida albicans and other Organomycoses caused by mould fungi and In veterinary Dermatomycoses and organomycoses caused by mould fungi and The therapeutical application can be effected orally parenterally and also locally in the form of solutions dimethyl preferably ethanol and buffer The dosa e for humans ran es avera e between abou 20 end 100 body preferably about to at intervals of hours over a period of about 10 to about 20 It be necessary to deviate from the indicated viz dependent upon the type of the of application but also due to the individual behaviour towards the medicament or the kind of its formulation and the time or interval when it is it may be sufficient in some to need less than the mentioned minimum whereas cases the mentioned upper limit has to be In the case of administering larger amounts it can be advisable to distribute these several individual doses the The agents can be used as such or in combination with pharmaceutically acceptable aqueous injectable syrups and the like in combination with various inert carriers are suitable forms of Carriers of this type include solid diluents or a sterile aqueous medium as well as toxic organic solvents and the Tablets and the like suitable application can obviously also be provided with a sweetening additive and similar In the the therapeutically effective compound should be present at a concentration of about to per cent by weight of the total in amounts sufficient to reach the dosing If the tablets are orally they may obviously also contain such as sodium calcium carbonate and dicalcium phosphate together with various such as preferably potato starch and the and binding such as polyvinyl gelatins and the such as magnesium sulphate and talc may concurrently be used for the of the case of aqueous suspensions elixirs which are intended for oral the substance can be used with various agents improving the colourin emulsifiers together with such as propylene and similar compounds this type or combinations In the case of parenteral solutions of the active substances in sesam or peanut or in aqueous propylene glycol or can also sterile aqueous solutions in the case of soluble Such aqueous solutions if necessary be buffered i conventional the liquid diluent from the rendered isotonic by the addition of the required amounts of or Aqueous solutions this are especially suitable for intramuscular and intraperitoneal The preparation of such sterile aqueous media is carried out known insufficientOCRQuality

Claims (1)

1. 4 - 32472/2 is reacted, preferably in an inert organic solvent, with a reagent suitable for the chlorination of tertiary alcohols and, after removal of the acid liberated in the process, reacted with at least the stoichiometrically required account of an imidazole of the formula H in which formulae R, R , R , X and n have the same meaning as in Claim

1. 3?or the Applicants DR . REINHOLB-OOHJi . AliD PARTNERS RC/rb