Patent GB-1034192-A (GB)
Title: New pyrrolidino derivatives of acetamide
IPC: A61K31/40
Filed: 1963-10-28
Abstract: The invention comprises acetamides of the general Formula I <FORM:1034192/C2/1> wherein R is a C1 to C8 alkyl, C3 to C9 cycloalkyl or C7 to C18 monocarbocyclic aralkyl radical; A is a C6 to C15 monocarbocyclic aryl radical; R1 is a C6 to C15 monocarbocyclic aryl or C7 to C18 monocarbocyclic aralkyl radical; R11 is a hydrogen atom or a methyl radical with the proviso that at most two R11 are methyl; and B is a disubstituted basic nitrogen, and acid addition salts of said acetamides. Specified substituents in the phenyl ring of the C6 to C15 monocarbocyclic aryl radicals are C1 to C8 alkyl, C1 to C8 alkoxy, di-C1 to C8 alkylamino and trifluoromethyl radicals and halogen atoms and specified groups B are di-C1 to C8 alkylamino radicals, the alkyl groups of which may be substituted by hydroxy groups, and saturated heterocyclic radicals of less than 12 carbon atoms, the rings of which may be substituted by C1 to C8 alkyl, C1 to C8 alkoxy, C1 to C8 hydroxyalkyl, C1 to C8 aliphatic acyloxy-C1 to C8 alkyl, and C1 to C8 alkoxy-C1 to C8 alkyl radicals.  The compounds of the invention may be prepared by reacting a compound of the formula <FORM:1034192/C2/2> wherein W is a 1-substituted-3-pyrrolidyl radical of the formula present in Formula I or R1, with a compound of the formula Z-X, wherein X is a replaceable non-cromaticbonded halogen atom or an alkylsulphonate or arylsulphonate radical and Z is a 1-substituted-3-pyrrolidyl radical of the formula present in Formula I or a monocarbocyclic aralkyl radical, a 1-substituted-3-pyrrolidyl radical being present in only one of said reactants, in the presence of a metal carbanion-forming reagent.  The reaction is preferably effected in an inert organic solvent and the metal reagent is preferably a Group I or II metal.ALSO:Therapeutic compositions comprise as analgesic and anti-inflammatory agents acetamides of the general formula <FORM:1034192/A5-A6/1> wherein R is a C1 to C8 alkyl, C3 to C9 cycloalkyl or C7 to C18 monocarbocyclic aralkyl radical; A is a C6 to C15 monocarbocyclic aryl radical; R1 is a C6 to C15 monocarbocyclic aryl or C7 to C18 monocarbocyclic aralkyl radical; R11 is a hydrogen atom or a methyl radical, with the proviso that at most two R11 are methyl; and B is a disubstituted basic nitrogen, and acid addition salts of said compounds together with a pharmaceutically acceptable solid or liquid carrier.  Specified substituents in the phenyl ring of the C6 to C15 carbocyclic aryl radicals are C1 to C8 alkyl, C1 to C8 alkoxy, di-C1 to C8 alkylamino and trifluoromethyl radicals and halogen atoms and specified groups B are di-C1 to C8 alkylamino radicals, the alkyl groups of which may be substituted by hydroxyl groups, and saturated heterocyclic radicals of less than 12 carbon atoms, the rings of which may be substitued by C1 to C8 alkyl, C1 to C8 alkoxy, C1 to C8 hydroxyalkyl, C1 to C8 aliphatic acyloxy-C1 to C8 alkyl, and C1 to C8 alkoxy-C1 to C8 alkyl radicals.  The acid addition salts are those pharmacologically acceptable salts derived from inorganic and organic acids.  The compositions advantageously contain 0.1 to 200 mg. of said active ingredient per unit dose, may be formulated for oral, parental or rectal administration and may contain other active ingredients, e.g. buffering agents, antacids, sedatives, stimulants, anticholinergics and other analgesics.