Patent GB-830223-A (GB)
Title: Thianaphtheno-indoles
IPC: C07D495/04
Filed: 1956-12-03
Abstract: The invention comprises 10-RX-thianaphtheno-[3 : 2-6]-indoles which have the nucleus of the formula <FORM:0830223/IV (b)/1> in which the benzene rings may be substituted by halogen, including fluorine, atoms, lower alkyl, lower alkoxy, including alkylene dioxy; R represents an amino or substituted amino group, including tertiary N,N-lower alkyleneamino groups, wherein the lower alkylene chain may be interrupted by an O2 N or S atom, and X represents a lower alkylene chain ("lower" indicating not more than 7 carbon atoms in the particular group) together with acid addition salts and quaternary ammonium compounds thereof.  The compounds of the invention may be prepared by reacting a 10-unsubstituted thianaphtheno-[3 : 2-6]-indole with a chloro-aminolower hydrocarbon, preferably in the presence of a condensing agent; by reacting a 3-hydroxythianaphthene with an N-phenyl-N-(aminolower hydrocarbon)-hydrazine according to the Fischer indole synthesis; by condensing a 10-unsubstituted thianaphtheno-[3 : 2-6]-indole in the manner indicated above with a halogenated lower fatty amide and reducing the amide carbonyl group or alternatively condensing the 10-unsubstituted thianaphtheno-[3 : 2-6]-indole with a dihalogeno-lower hydrocarbon, the halogen atoms of which are on different carbon atoms so as to obtain a 10-(halogeno-lower hydrocarbon) - substituted - thianaphtheno - [3 : 2-6]-indole which is reacted with an amine to replace the halogen atom by an amino group. Furthermore the cyano group in a 10-(cyanoethyl) - thianaphtheno - [3 : 2-6]-indole may be reduced to an amino group and substituents in the nucleus may be converted into other substituents (e.g. the reduction of a nitro to an amino group) after the introduction of the residue in the 10-position or after ring closure of the 10-substituted thianaphtheno-indole ring. Tertiary amines are converted into quaternary ammonium compounds by reaction with quaternizing agents.  N1 - Phenyl - N1 - (5 - diethylamino - 21 - pentyl)-hydrazine is prepared by treating 1-diethylamino-4-phenylamino-pentane with sodium nitrite followed by reduction with zinc dust. m-Bromo-thiophenol is reacted with chloroacetic acid to give m-bromo-phenylthioglycollic acid which is treated with phosphorus trichloride and then with aluminium chloride to yield 6-bromo-3-hydroxythianaphthene.  10-Unsubstituted - thianaphtheno - [3 : 2-6] - indoles are prepared by reacting a 3-hydroxy thianaphthene with a phenyl hydrazine.ALSO:Pharmaceutical compositions for enteral, parenteral or topical administration comprise 10 - RX - thianaphtheno - [3 : 2-6] - indoles, or acid addition salts thereof, which have the nucleus of the formula <FORM:0830223/VI/1> and in which X represents a lower alkylene chain, R represents an amino or substituted amino group, including tertiary N,N-lower alkyleneamino groups wherein the lower alkylene chain may be interrupted by an O, N or S atom, and in which the benzene rings may be substituted by halogen, including fluorine, atoms, lower alkyl, or lower alkoxy, including alkylene dioxy groups ("lower" indicating not more than 7 carbon atoms in the groups so described), together with a pharmaceutical carrier.  The compositions may be in the form of tablets, dragees, salves, creams, solutions, suspensions or emulsions and may contain auxiliary substances such as preserving agents, stabilizing agents, wetting or emulsifying agents, salts for varying osmotic pressure or buffers.  They may also contain other therapeutically useful substances.