GB789016A - Improvements in or relating to phenthiazines - Google Patents

Abstract

The invention comprises phenthiazine derivatives of the general formula <FORM:0789016/IV (b)/1> and their salts (including quaternary ammonium salts), wherein the fluorine atom is in the 1- or 3-position, B is a divalent straight or branched aliphatic hydrocarbon chain of 2-5 carbon atoms and Z1 and Z2 are the same or different and are hydrogen atoms or lower alkyl groups of not more than 4 carbon atoms. The compounds may be prepared by known processes for the preparation of 10-aminoalkyl phenthiazines, for example by treating a 1- or 3-fluorophenthiazine with a halogenoalkylamine of the formula Y-B-N(Z1)Z2, where Y is a chlorine or bromine atom, preferably in an organic solvent and in the presence of an alkaline condensation agent, or by condensing a 1- or 3-fluorophenthiazine substituted in the 10-position by a group -B-Q, where Q is the residue of a reactive ester, for example a halogen atom or a sulphuric or sulphonic ester radical, with an amine NH(Z1)Z2, or by alkylating a 1- or 3-fluorophenthiazine substituted in the 10-position by a primary aminoalkyl group -B-NH2 (obtained by reduction of the corresponding nitrile). The compounds are used as pharmaceutical products, suitably in the form of acid addition salts such as the hydrohalides, 8-chlorotheophyllinates, phosphates, nitrates, sulphates, maleates, fumarates, citrates, tartrates, oxalates, methane sulphonates and ethane sulphonates or of quaternary salts such as methyl or ethyl iodides, chlorides or bromides or allyl or benzyl chlorides or bromides. Examples describe the preparation of 3-fluoro-10-(3-dimethylaminopropyl)-phenthiazine and 3-fluoro-10-(3-dimethylamino-2-methylpropyl) phenthiazine). Starting materials. 3-Fluorophenthiazine is made by the cyclization of 3-fluorodiphenylamine (obtained by decarboxylating 5-fluorodiphenylamine - 2 - carboxylic acid), with sulphur. 3 - Fluoro - 10 - (3 - chloropropyl) phenthiazine is made by the action of 3-chloropropyl-p-toluene sulphonate on the lithium salt of 3-fluorophenthiazine. Specification 677,798 also is referred to.