Patent GB-951961-A (GB)
Title: New fluoro-amino-alkanols and esters thereof
IPC: A61Q11/00
Filed: 1961-06-08
Abstract: The invention comprises compounds of the formula FCH2CH(OR1)CH2NR2R3, where OR1 is a free hydroxy group or a hydroxy group esterified with phosphoric acid or a carboxylic acid, and R2 and R3 are each hydrogen or an alkyl or benzyl group or together make up an o-phthaloyl group, salts thereof, and quaternary ammonium derivatives of tertiary amino compounds as above with a C1-5 alkyl halide or a benzyl halide. Specified acids R1H are acetic acid, oxalic acid, malonic acid, succinic acid, p-fluorobenzoic acid, p-nitrobenzoic acid, p-aminobenzoic acid, m-methoxybenzoic acid, p-ethoxybenzoic acid, phenylacetic acid, diphenyl-acetic acid and nicotinic acid.  The compounds of the invention may be prepared by (1) reacting a 1-fluoro-2-hydroxypropane having in the 3-position an exchangeable substituent such as Cl or a sulphonic ester group, with ammonia or an amine or a salt of o-phthalimide, and if desired esterifying the -OH and/or quaternising, or producing free compounds from salts, or converting quaternary compounds into other quaternary compounds; (ii) incorporating F or NR2R3 into a propane-2, 3-epoxide containing the other radical in the 1-position, with opening of the epoxide ring. Esters of the -OH compounds may be prepared by standard methods. Other reactions may be used, e.g. the reduction of 1-diethylamino-2-p-nitrobenzoyloxy-3-fluoropropane to the corresponding amino compound. Examples prepare N-(3-fluoro-2-hydroxypropyl)-phthalimide; 1-amino-2-hydroxy-3-fluoropropane and its N-methyl, N,N-dimethyl-, and N,N-diethyl-derivatives and the corresponding trimethylammonium iodide and chloride, N,N-di-(3-fluoro-2-hydroxypropyl)-N-methylamine; 1-amino-3-fluoropropyl-(2) phosphate and the hydrates of the calcium salts of the corresponding N-methyl, N,N-dimethyl- and N,N-diethyl-derivatives and of the corresponding trimethyl-ammonium chloride; (CH3)2NCH2CH(OCOCH3)CH2F.HCl, (CH3)3N+CH2CH(OCOCH3) CH2F.I-, and .Cl-; (C2H5)2NCH2CH(OCOCH3) CH2F.HCl; 1-diethylamino - 2 - nicotinoyloxy-3-fluoropropane and its hydrochloride; and FCH2 CH(OR1)CH2N(C2H5)2, where R1 i p-nitrobenzoyl, p-aminobenzoyl, p-fluorobenzoyl, m-methoxybenzoyl, p-ethoxybenzoyl, phenylacetyl and diphenylacetyl, sometimes as hydrochlorides; and the corresponding di-ester from succinic acid.  The compounds of the invention are of use pharmaceutically (see Division A5).ALSO:Pharmaceutical preparations comprise a pharmaceutically suitable carrier and a compound of formula FCH2CH(OR1)CH2NR2R3, where OR1 is a free hydroxy group or a hydroxy group esterified with phosphoric acid or a carboxylic acid, and R2 and R3 are hydrogen or alkyl or benzyl or together make up an o-phthaloyl group, or a salt thereof or the corresponding quaternary compounds derived from a tertiary amino compound as above and a C1-5 alkyl halide or benzyl halide (see Division C2). The phosphoric esters and their salts may be employed in tooth paste mixtures.  The benzoic acid esters and nicotinic acid esters and their salts have local an sthetic action.  Suitable carriers for the compositions are gelatine, cholesterol, lactose, starch, magnesium stearate, talc, vegetable oils, benzyl alcohol, gums, polyalkylene glycols and petroleum jelly.  The preparations may be in the form of tablets, dragees, powders, ointments, creams, suppositories, solutions, suspensions or emulsions and may contain preserving, stabilising wetting or emulsifying agents or other therapeutic substances.