ES352203A1 - 7-substituted tetracyclines - Google Patents

Abstract

The invention comprises 7-[bis-substituted hydrazino] tetracyclines of formul[mu] wherein R is C 1 -C 6 alkoxy, phenyl C 1 -C 6 alkoxy, phenoxy, amino, C 1 -C 6 alkylamino, phenyl C 1 -C 6 alkylamino or anilino R 1 is H, alpha-CH3 or beta-CH 3 R 2 is H or beta OH with the proviso that when R 1 is beta-CH 3 then R 2 is H R 1 and R 2 taken together is CH 2 R 3 is H or OH with the proviso that when R 3 is OH then R 1 is CH 3 or R 1 and R 2 taken together is CH 2 and X is F, Cl or Br. The compounds are prepared by reacting a compound of Formula (I) or Formula (II) wherein the 7-position of the tetracycline nucleus is H, with a substituted azodicarbonyl derivative of formula wherein R has the above meaning, in an acidic medium, e.g. an inert organic solvent such as tetrahydrofuran and a strong acid such as methane-sulphonic acid. The corresponding 7-amino tetracyclines are obtained by treating the compounds of Formul[mu] (I) and (II) with 57% hydriodic acid at 100 C. or with hydrogen in the presence of a catalyst. The 7-[1,2-bis- (carbobenzyloxy) hydrazino] tetracycline may be subjected to reductive alkylation by treatment with a carbonyl compound of formula wherein R 4 is H or C 1 -C 6 alkyl and R 5 is H or C 1 -C 6 alkyl in the presence of a reducing agent (e.g. hydrogen), a catalyst and an inert solvent. The compound produced is the 7- mono-(C 1-6 alkyl) amino or 7-di-(C 1-6 alkyl) amino tetracycline wherein R 1 , R 2 , R 3 and X of the 7-hydrazino compound remain unchanged. A typical compound is 7-[1,2-bis-(carbobenzyloxy) hydrazino] -6-demethyl-6-deoxytetracycline. Salts may be formed with mineral acids (e.g. hydrochloric acid) and organic acids (e.g. trichloroacetic acid).