GB1041986A - Anaesthetic compositions - Google Patents

Abstract

Compounds having the general formula <FORM:1041986/C2/1> wherein X is hydrogen or halogen and R is N-(C1- 4 alkyl)-N-(hydroxy C1- 4 alkyl) amino or -OZ or -NHZ, in which Z is C1- 4 alkylamino C1- 4 alkyl, di-C1- 4 alkylamino C1- 4 alkyl, 1-piperidyl C1- 4 alkyl or 3-(N-methylpiperidyl) may be made by the following methods: (1) 5-carboxylate derivatives may be made by refluxing 10,11 - dihydro - 5H - dibenzo[a,d]cycloheptene-5-carboxylic acid or acid halide with a basically substituted C1- 4 alkyl halide or C1- 4 alkanol respectively in a suitable medium; (2) 5-carboxylate derivatives, wherein R is C1- 4 alkylamino C1- 4 alkyl, may be made by dealkylation of the corresponding di-C1- 4 alkylamino C1- 4 alkyl compound, e.g. by treatment with ethyl chlorocarbonate to form a urethane derivative which on saponification gives the desired dealkylated compound; (3) N-(C1- 4 alkyl) - N - (hydroxy - C1- 4 alkyl) - 10,11-dihydro - 5H - dibenzo[a,d]cycloheptene - 5-carboxamide may be made by treating the acid halide referred to in method (1) with an appropriate secondary amino C1- 4 alkanol in a suitable reaction medium. The product may be converted to the C1- 4 alkylamino C1- 4 alkyl esters by treatment with concentrated HCl; (4) 5-carboxamide derivatives may be prepared by refluxing the above carboxylic acid halides with an appropriately substituted C1- 4 alkylene diamine in a suitable medium; (5) derivatives wherein Z is 1-piperidyl C1- 4 alkyl or 3-(N-methylpiperidyl) may be prepared by refluxing the appropriate carboxylic acid with the appropriately substituted piperidine. Acid addition salts of the above compounds may be formed with inorganic or organic acids, e.g. HCl, HBr, H2SO4, H3PO4, acetic, aminoacetic, lactic, succinic, malic, aconitic, phthalic, tartaric, or ethanesulphonic acids. Quaternary ammonium salts may be formed by addition to the free-bases of MeCl, MeBr, MeI, EtBr, propyl bromide, octyl bromide, benzyl chloride, benzoyl bromide, Me sulphate, Me benzenesulphonate, Me p-toluenesulphonate. Reference has been directed by the Comptroller to Specification 969,024.ALSO:Local anaesthetic compositions comprise <FORM:1041986/A5-A6/1> wherein X is H or halogen and R is N-(C1-4 alkyl)-N-(hydroxy C1-4 alkyl) amino or -OZ or -NHZ, in which Z is C1-4 alkylamino C1-4 alkyl, di C1-4 alkylamino C1-4 alkyl, 1-piperidyl C1-4 alkyl or 3-(N-methylpiperidyl), or an acid addition or quaternary ammonium salt thereof, together with a vehicle. The compositions may be in the form of (a) sterile solutions for irrigation or for injection, (b) dispersions, creams, ointments, gels, aqueous sprays, or aerosols, alone or in combination with other therapeutic agents e.g. antihistamines, sulfa drugs and antibiotics for topical application, or (c) powders, troches, or lozenges for internal administration. Reference has been directed by the Comptroller to Specification 969,024.