EP0201166A1 — Erythromycin derivatives

Claim 1

Independent Claim 288 words

A compound of the general formula I or a pharmaceutically acceptable ester or acid addition salt thereof: wherein one of R 1 and R 2 denotes hydrogen and the other of R 1 and R2 denotes an amino group or a substituted amino group, or Rl and R2 together denote an oxo group, an oxime group, a substituted oxime group, or an imino group, and R 5 denotes a hydroxy group or an alkoxy group; or one of R 1 and R 2 denotes a hydroxy group, or an amino group, and the other of R 1 and R 2 together with R 5 denotes an ether oxygen atom, -O-, R 3 denotes a group of the formula II: in which Q denotes one of the following groups: R A denotes an unsubstituted or substituted hydrocarbon group, R B denotes a hydrogen atom or an unsubstituted or substituted hydrocarbon or hydrocarbon-oxy group, each of R C and RD, which may be identical or different, denotes a hydrogen atom or an unsubstituted or substituted hydrocarbon group, or any two of R A , R B , R C and R D together denote a divalent, unsubstituted or substituted, organic group forming a 4- to 7-membered heterocyclic ring together with the intervening atoms of the molecule; R 4 denotes hydrogen or hydroxy; R 7 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 12 -SO 2 -O-. and the other of R 8 and R 9 denotes hydrogen, or R 8 and R9 together denote an oxo group, an oxime group, or a substituted oxime group; and R 12 denotes an organic group.

Claim 2

Dependent Claim 288 words

A compound of the general formula I or a pharmaceutically acceptable ester or acid addition salt thereof: wherein one of R 1 and R 2 denotes hydrogen and the other of R 1 and R2 denotes an amino group or a substituted amino group, or Rl and R2 together denote an oxo group, an oxime group, a substituted oxime group, or an imino group, and R 5 denotes a hydroxy group or an alkoxy group; or one of R 1 and R 2 denotes a hydroxy group, or an amino group, and the other of R 1 and R 2 together with R 5 denotes an ether oxygen atom, -O-, R 3 denotes a group of the formula II: in which Q denotes one of the following groups: R A denotes an unsubstituted or substituted hydrocarbon group, R B denotes a hydrogen atom or an unsubstituted or substituted hydrocarbon or hydrocarbon-oxy group, each of R C and RD, which may be identical or different, denotes a hydrogen atom or an unsubstituted or substituted hydrocarbon group, or any two of R A , R B , R C and R D together denote a divalent, unsubstituted or substituted, organic group forming a 4- to 7-membered heterocyclic ring together with the intervening atoms of the molecule; R 4 denotes hydrogen or hydroxy; R 7 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 12 -SO 2 -O-. and the other of R 8 and R 9 denotes hydrogen, or R 8 and R9 together denote an oxo group, an oxime group, or a substituted oxime group; and R 12 denotes an organic group.

Claim 3

Dependent Claim 58 words

A compound as claimed in claim 1, wherein R 3 denotes a group of one of the following formulae in which R A and R B are defined as in claim 1, R E denotes an unsubstituted or substituted hydrocarbon group, and R F denotes an unsubstituted or substituted, divalent, hydrocarbon group completing a 4- to 7-membered ring.

Claim 4

Dependent Claim 20 words

A compound as claimed in claim 1 or claim 2, wherein R A denotes a 2-substituted-ethyl or 3-substituted propyl group.

Claim 5

Dependent Claim 38 words

A compound as claimed in claim 3, wherein R A denotes a 2-substituted-ethyl or 3-substituted-propyl group, in which the substituent is selected from amino, N-alkylamino, N,N-dialkylamino, halogen, hydroxy, alkoxy, benzoyloxy, alkanesulphonyloxy, trisilyloxy, alkoxycarbonyl, alkanoyloxy, phenoxy, and heterocyclyl groups.

Claim 6

Dependent Claim 43 words

A compound as claimed in any one of claims 1 to 4, wherein R i and R 2 together denote a group of the formula IV: in which R 13 denotes hydrogen or an unsubstituted or substituted hydrocarbon group or an acyl group.

Claim 7

Dependent Claim 18 words

A compound as claimed in claim 5, wherein R 13 denotes a hydrogen atom or a methyl group.

Claim 8

Dependent Claim 19 words

A compound as claimed in any one of claims 1 to 6, wherein R 4 denotes a hydroxy group.

Claim 9

Dependent Claim 19 words

A compound as claimed in any one of claims 1 to 7, wherein R 5 denotes a hydroxy group.

Claim 10

Dependent Claim 19 words

A compound as claimed in any one of claims 1 to 8, wherein R 7 denotes a methyl group.

Claim 11

Dependent Claim 26 words

A compound as claimed in any one of claims 1 to 9, wherein R 8 denotes a hydrogen atom and R 9 denotes a hydroxy group.

Claim 12

Dependent Claim 22 words

The compounds of the general formula I defined in claim 1 specifically named in any one of Examples 1 to 64 herein.

Claim 13

Dependent Claim 144 words

A compound of the aeneral formula IX in which R 4, R5 and R7 are defined as in claim 1; R18 denotes an oxo group, an oxime group, or a substituted oxime group; R 1 9 denotes H or Z; R 23 denotes H or R 3 (where R 3 is defined as in claim 1), with the proviso that, if R 18 denotes oxo or R 5 denotes methoxy, then R 23 denotes R 3 ; one of R 28 and R 29 denotes H, OH, OZ, NZ 2 , NH 2 , NHZ, substituted NH 2 , substituted NHZ, alkoxy, alkanoyloxy, or R 12 -SO 2 -O- (in which R 12 denotes an organic group), and the other of R 28 and R 29 denotes H, or R 2 8 and R 29 together denote oxo; and Z denotes a protecting group.

Claim 14

Dependent Claim 197 words

A process for the preparation of a compound of the general formula I as defined in claim 1 or a pharmaceutically acceptable ester or acid addition salt thereof, which comprises reacting a compound of the general formula VII: wherein R 4 , R 5 , R 7 , R 8 and R 9 are defined as in claim 1, and R 18 denotes an oxo group, an oxime group, or a substituted oxime group, in which compound of the general formula VII any reactive group (other than the 11-hydroxy group) may optionally be protected, with an alkylating agent of the general formula VIII: in which Q and R C are as defined in claim 1, and X denotes a leaving group; to give a compound of the general formula I in which R 1 and R 2 together denote an oxo group or a substituted oxime group; and thereafter, if necessary or desired, carrying out one or more of the following steps in any suitable order: (a) converting a substitutent on the erythromycin structure to another such substituent in conventional manner; (b) removing any protecting groups; and (c) forming a pharmaceutically acceptable ester or acid addition salt.

Claim 15

Dependent Claim 216 words

A process as claimed in claim 13, wherein, subsequent to the reaction of the compound of the general formula VII with the alkylating agent of the general formula VIII one or more of the following steps is carried out in any suitable order: (a) converting an oxo group denoted by R 1 and R 2 together to an oxime group or a substituted oxime group; (b) converting a substituted oxime group denoted by Rl and R2 together to an oxo group (or the corresponding tautomer), another substituted oxime group, or an oxime group; (c) converting a resulting oxime group denoted by R 1 and R 2 together to an oxo group (or the corresponding tautomer), a substituted oxime group or an imino group (or the corresponding tautomer); (d) converting a resulting imino group denoted by R 1 and R 2 together to an amino group denoted by R l or R 2 ; (e) converting a resulting amino group denoted by R 1 or R 2 to a substituted amino group; (f) converting any one or more of the groups denoted by R 3 , R 5 , R 8 and R9 to another such group; (g) removing any protecting group that may be present; and (h) forming a pharmaceutically acceptable ester or acid addition salt.

Claim 16

Dependent Claim 35 words

A process as claimed in claim 14, wherein R A contains an azido or halogen substituent and, wherein, in step (f), such substituent is converted into or replaced by an amino or substituted amino substituent.

Claim 17

Dependent Claim 28 words

A pharmaceutical composition which comprises a compound as claimed in any one of claims 1 to 11 in admixture or conjunction with a pharmaceutically acceptable carrier or excipient.

Claim 18

Dependent Claim 37 words

A method of treating bacterial infections in animals, which comprises administering a compound as claimed in any one of claims 1 to 11 or a composition as claimed in claim 16 to a patient in need thereof.

Claim 19

Dependent Claim 21 words

The use of a compound as claimed in any one of claims 1 to 11 for the manufacture of a medicament.

Erythromycin derivatives

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