GB809585A - Tetracycline derivatives - Google Patents

Abstract

The invention relates to antibacterial substances of general formula <FORM:0809585/IV (b)/1> wherein <FORM:0809585/IV (b)/2> represents a tetracycline chlortetracycline or oxytetracycline radical and B represents a secondary amino group, and the acid addition salts thereof. The compounds are prepared by reacting 1 mol. of the tetracycline with 1 mol. of the secondary amine and at least 1 mol. of formaldehyde or a polymer thereof in absolute alcohol. The materials are refluxed on a steam bath in an atmosphere of nitrogen. The product is recovered by lyophilization or by precipitation by means of a non-solvent such as ether or a petroleum hydrocarbon. The reaction may take place in the presence of t-butanol in place of the ethanol. The free base may be converted to a salt with an inorganic or organic acid by adding the acid to the base. Addition of alkali, e.g. sodium hydroxide, to the acid addition salt produces the base. Specified salts are those prepared from hydrochloric, sulphuric, sulphamic, tartaric, hydrobromic, hydriodic, glycolic, citric, maleic, phosphoric, succinic and acetic acids. Examples describe the preparation of (a) N-(4-morpholinylmethyl) tetracycline; (b) N-dimethylaminomethyltetracycline; (c) N - dibenzylaminomethyltetracycline; (d) N - (1 - piperidyl-methyl) tetracycline; (e) N-(1-pyrrolidylmethyl) tetracycline; (f) N - (4 - morpholinylmethyl) oxytetracycline; (g) N-dimethylaminomethyl oxytetracycline; (h) N - dibenzylaminomethyl - oxytetracycline; (i) N - (1 - piperidylmethyl) oxytetracycline; (j) N - (1 - pyrrolidylmethyl) oxytetracycline; (k) N-(4-morpholinylmethyl) chlortetracycline; (l) N - dimethylaminomethyl - chlortetracycline; (m) N-dibenzylaminomethyl-chlortetracycline; (n) N-(1-piperidylmethyl) chlortetracycline; and (o) N - (1 - pyrrolidylmethyl) chlortetracycline. Other secondary amines which may be used are dialkylamino such as diethylamine, diethanolamine, dipropylamine, di-n-butylamine and diisopropylamine, N1-alkylpiperazino, pipecolino, methyldiethylethylenediamine, methylaniline, piperidine, piperazine, 1,2,3,4-tetrahydroisoquinoline, 6 - methoxy - 1,2,3,4 - tetrahydroisoquinoline, N1-methylpiperazine, N-methylbenzylamine, di - (beta - methallyl) amine, N,N1 - dibenzylethylene diamine, N-methyl dehydroabietylamine and N-methyltaurine. Specifications 684,417 and 690,381 are referred to.