SETT FOR FRAMSTELLNING AV 1,3,3-TRISUBSTITUERADE 3-AZOLYLPROPINER MED ANTIMYKOTISK VERKAN

摘要

1332393 1,3,3 - Trisubstituted 3 - azolylpropynes BAYER AG 8 Sept 1971 [9 Sept 1970 13 Feb 1971] 41881/71 Heading C2C Novel compounds of the Formula I wherein R1 is a hydrogen, chlorine, bromine or iodine atom or an alkyl, alkenyl, alkynyl, or an optionally substituted aryl, aryloxyalkyl, arylthioalkyl, arylaminoalkyl or arylalkylaminoalkyl group, or an alkoxyalkyl, alkylmercaptoalkyl, alkylaminoalkyl or dialkylaminoalkyl group [in which dialkylamino group the alkyl groups can be linked together directly or via one or more further hetero-atoms or heterogroups to form together with the nitrogen atom a 5-, 6- or 7-membered heterocyclic ring]; R2 is an alkyl, alkenyl or alkynyl group or an optionally substituted cycloalkyl, cycloalkenyl, or aryl group; R3, R4 and R5, which can be the same or different, are each a hydrogen or halogen atom or an alkyl, alkenyl, alkynyl, alkoxy, or alkylmercapto nitro, halogenoalkyl, nitrile or C 1-6 alkylsulphinyl or alkylsulphonyl; and Az is an optionally substituted nitrogen-containing fivemembered heterocyclic radical, joined to the rest of the molecule via a ring nitrogen atom; and their salts may be prepared by (a) reacting an alcohol (10) with a thionyl-bis-azole Az-SO-Az; (b) when R1 is alkyl, reacting a compound (12) with an alkyl halide R15-Z wherein M is an alkali metal or a halomagnesium radical ZMg-, R15 is alkyl, and Z is halogen followed by addition of water; (c) when R1 is halogen, reacting a compound (12) with a hypohalous acid Z-OH optionally followed by salt formation. The intermediates (10) may be prepared by reaction of a sodium or lithium acetylide with a ketone. 1,1 - Diphenyl - 4 - morpholino - butyn - 2 - ol may be prepared by reacting forming a lithium acetylide from butyl lithium and propargyl chloride and reacting it in situ with benzophenone, hydrolysing the product and reacting it with morpholine. Pharmaceutical compositions of the compounds I show anti-mycotic activity when administered orally, parenterally or topically with the usual excipients.