Erythromycin derivatives

Claim 1

A process for the preparation of a compound of the general formula I or a pharmaceutically acceptable ester or acid addition salt thereof: wherein one of R' and R 2 denotes hydrogen, and the other of R' and R 2 denotes an amino group or a substituted amino group, or the other of R' and R 2 , together with R 5 , denotes a group of the formula III below, or R' and R 2 together denote an oxo group, an oxime group, a substituted oxime group, or an imino group; R 3 denotes a carbamoyl group or an N-substituted carbamoyl group; R' denotes hydrogen or hydroxy, and R 5 denotes hydroxy, or an etherified hydroxy group, or together with R' or R 2 denotes a group of the formula III below as defined above, or R 4 and R 5 together denote a group of the formula II or III: in which each of R A and R B , which may be identical or different, denotes hydrogen or a hydrocarbon group; R" denotes hydrogen, fluorine or hydroxy; R' denotes hydrogen or methyl; one of R 8 and R 9 denotes hydrogen, hydroxy, alkoxy, alkanoyloxy, amino, substituted amino, or a group of the formula R c -SO 2 -O-, in which R c denotes an organic group, and the other of R 8 and R 9 denotes hydrogen, or R 8 and R' together denote an oxo group, an oxime group, or a substituted oxime group; which process comprises reacting a compound of the general formula XVI: wherein R 4 , R 5 , R', R', R 8 and R' are defined as above, and R 1A and R 2A together denote an oxo, oxime or substituted oxime group, or one of R 1A and R 2A denotes a hydrogen atom, and the other of R 1A and R 2A together with R 5 denotes a group of the formula III defined above, in which compound of the general formula XVI any reactive group (other than the 6-hydroxy group) may optionally be protected, with an organic acid isocyanate, to give a compound of the general formula I in which R' and R 2 together denote an oxo, oxime or substituted oxime group, or in which one of R' and R' denotes a hydrogen atom and the other of R' and R 2 together with R 5 denotes a group of the formula III above; and thereafter, if necessary or desired, carrying out one or more of the following steps in any suitable order: (a) converting an oxo group denoted by R' and R 2 together to an oxime group or a substituted oxime group, or, jointly with a hydroxy group denoted by R 5 , to a group of the formula III denoted by R 5 together with R' or R 2 , the other of R' and R 2 denoting a hydrogen atom; (b) converting a substituted oxime group denoted by R' and R 2 together to another substituted oxime group, an oxime group, or an oxo group; (c) converting an oxime group denoted by R' and R' together to a substituted oxime group, an oxo group, or an imino group; (d) converting a resulting imino group denoted by R' and R 2 together to an oxo group or to an amino group denoted by R' or R 2 ; (e) converting a resulting amino group denoted by R' or R 2 to a substituted amino group; (f) converting any one or more of the groups denoted by R 5 , R', R 1 and R' to another such group; (g) removing any protecting group that may be present; and (h) forming a pharmaceutically acceptable ester or acid addition salt.