Patent GB-809691-A (GB)
Title: New indole derivatives
Inventor: HULL ROY
IPC: C07D405/06
Filed: 1956-06-08
Abstract: The invention comprises 3-(5-nitro-2-furfurylidene)-oxindole derivatives of the general formula <FORM:0809691/IV (b)/1> wherein R is hydrogen and the nucleus A may optionally bear substituents (for example halogen, nitro, acylamino, alkyl, hydroxy, alkoxy and carboxylic acid radicals) and their preparation by reacting the appropriately substituted oxindole with 5-nitro-2-furaldehyde or a compound capable of action as 5-nitro-2-furaldehyde (for example its diacetate, in the presence of aqueous mineral acid).  The reaction is conveniently carried out in a solvent (for example acetic acid, aqueous ethanol or anhydrous formic acid), optionally in the presence of a basic catalyst, for example, sodium acetate.  The invention further comprises antimicrobial compositions wherein the active ingredient is at least one of the indole derivatives of the above general formula (see Group VI).  Examples describe the preparation of 3 - (5 - nitro - 2 - furfurylidene) - oxindole and 5-bromo-, nitro-, acetamido-, benzamido-, p - chlorobenzamido -, propionamido -, n - valeramido -, n - butyramido -, iso - butyramido-, caproamido-, caprylamido-, capramido-, (2-carboxypropionamido)-, methyl-, hydroxy- and methoxy - 3 - (5 - nitro - 2 - furfurylidene) oxindole; 6 - formamido - and 6 - acetamido -3 - (5 - nitro - 2 - furfurylidene) oxidole; acetamido - 3 - (5 - nitro - 2 - furfurylidene) oxindole; 5 : 7 - dibromo - 3 - (5 - nitro - 2 - furfurylidene)-oxindole, and 3 - (5 - nitro - 2 - furfurylidene)-oxindole-6-carboxylic acid 5-Benzamido-, p-chloro-benzamido-, propionamido-, n-valeramido-, n-butyramido-, iso-butyramido-, caproamido-, caprylamido- and capramido-oxindole are prepared by reacting 5-amino-oxindole with the appropriate acid chloride.  4-Acetamido-oxindole is obtained by reacting acetyl chloride with 4-amino-oxindole (prepared by reducing 2 : 6-dinitrophenylacetic acid with tin and hydrochloric acid). 5-(2-Carboxypropionamido)-oxindole is prepared by reacting 5-amino-oxindole with succinic anhydride.  In the Provisional Specification compounds in which R in the general formula above is an acyl group are mentioned.ALSO:Antimicrobial compositions having useful therapeutic properties comprise at least one indole derivative of the general formula <FORM:0809691/VI/1> (wherein R is hydrogen and the nucleus A may be substituted, for example by halogen atoms or nitro, acylamino, alkyl, hydroxy, alkoxy or carboxylic acid radicals) in admixture with an inert diluent or carrier.  Such compositions may be, for example, (1) solutions in polyethylene glycol (optionally containing wetting agents such as the condensation products of alkylphenols with ethylene oxide, for example octylcresol with 8-10 molecular proportions of ethylene oxide); (2) aqueous dispersions (a suitable dispersing or surface active agent being polyoxyethylene sorbitan mono-oleate) which may contain non-toxic, water-miscible ingredients, for example glycerol, thickening or gelling agents such as ethyl cellulose or condensation products of fatty alcohols and ethylene oxide, for example cetyl or cetostearyl alcohol and 20-24 molecular proportions of ethylene oxide; (3) oily solutions, a suitable solvent medium being castor oil; (4) creams, ointments and pastes containing suitable non-toxic ingredients, for example a base comprising a mixture of polyethylene glycol 400 and polyethyleneglycol 4000 with a thickening agent, for example zinc oxide, in admixture with an oily or fatty base, for example castor oil or white beeswax, optionally in the presence of a fatty alcohol, for example cetyl alcohol or cetostearyl alcohol; suitable cream bases may be formulated from oil-in-water type emulsions, for example from castor oil or fatty alcohols such as cetyl alcohol or cetostearyl alcohol dispersed in water in the presence of condensation products of fatty alcohols with ethylene oxide, for example the condensation product of cetyl or cetostearyl alcohol with 20-24 molecular proportions of ethylene oxide; (6) dusting powders containing inert diluents or carriers, for example talc and/or starch, in the presence of additional ingredients, for example zinc oxide or boric acid.