6-carbamade erythromycin derivatives

Claim 1

A compountd of the formula I or a pharmaceutically acceptable ester of acid addtion salt thereof: ##STR13## wherein one of R 1 and R 2 is hydrogen, and the other of R 1 and R 2 is amino unsubstituted or substitued by one or two alkyl moieties of 1 to 6 carbon atoms, or the other of R 1 and R 2 together with R 5 , is a group of the formula III below, or R 1 and R 2 together are oxo, oxime unsubstituted or substituted by alkyl, cycloalkyl or alkenyl of up to 6 carbon atoms, phenyl, hydrocarbon-carbonyl or hydrocarbonoxy-carbonyl wherein the gydrocarbon is alkyl of up to 6 carabon atoms or phenyl each of which is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di- or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, sulphamoyl, carbamoyl, amindino, guanidino, nitro, chloro, bromo, fluoro carboxy or salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyl, heterocyclylcarbonyl or --S(O) n R 12 wherein n is 0, 1 or 2 and R 12 is alkyl of 1 to 6 carbon atoms, heterocyclyl or aryl, or an imino; R 3 is carbamoyl or N-substituted carbamoyl of the formula --O--CO--NH--X--R 15 wherein X is --CO-- or --SO 2 -- and R 15 is alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, phenyl, alkylphenyl of 1 to 6 carbon atoms in the alkyl moiety or halophenyl; R 4 is hydrogen or hydroxy, and R 5 is hydroxy, or etherified hydroxy, or R 5 together with R 1 or R 2 is a group of the formula III below as defined above, or R 4 and R 5 together are a group of the formula II or III: ##STR14## is which R A and R B are the same of different, and each is hydrogen, phenyl, or alkyl of 1 to 6 carbon atoms, said alkyl being unsubstituted or substituted by heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di-, or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms, heterocyclylthio, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxyl or a salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyloxy, heterocyclylcarbonyloxy or acyl; R 6 is hydrogen, fluorine or hydroxy; R 7 is hydrogen or methyl; one of R 8 and R 9 is hydrogen, hydroxy, alkoxy, alkanoyloxy, amino, substituted amino of the formula XII or XIII: --NHCOR.sup.16 XII or --NHSO.sub.2 R.sup.16 XIII wherein R 16 is alkyl of 1 to 6 carbon atoms or phenyl, unsubstituted or substituted by heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di-, or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms, heterocyclylthio, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxyl or a salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyloxy, heterocyclylcarbonyloxy or acyl, or a group of the formula R C SO 2 --O--, in which R C is, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, phenyl, nitrophenyl, halophenyl, alkylphenyl of 1 to 6 carbon atoms in the alkyl moiety, benzyl, nitrobenzyl, halobenzyl, alkylbenzyl of 1 to 6 carbon atoms in the alkyl moiety, phenoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, nitrophenoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, halophenyoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, alkylphenoxyalkyl of 1 to 6 carbon atoms in each alkyl moiety or R 17 --CH 2 --CH 2 --wherein R 17 is amino, carbamoyl, sulphamoyl, alkoxy of 1 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms, aryloxy, arylthio, benzyloxy or benzylthio and the other of R 8 and R 9 is hydrogen, or R 8 and R 9 together are oxo, oxime or acetyloxime.

Claim 19

A method of treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof an antibacterially effective amount of the compound of the formula I or a pharmaceutically acceptable ester or acid addition salt thereof: ##STR21## wherein one of R 1 and R 2 is hydrogen, and the other of R 1 and R 2 is amino unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, or the other of R 1 and R 2 , together with R 5 , is a group of the formula III below, or R 1 and R 2 together are oxo, oxime unsubstituted or substituted by alkyl, cycloalkyl or alkenyl of up to 6 carbon atoms, phenyl, hydrocarbon-carbonyl or hydrocarbonoxy-carbonyl wherein the hydrocarbon is alkyl of up to 6 carbon atoms or phenyl each of which is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di- or tri-alkylamino of 1 to 6 carbon atom in each alkyl moiey, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxy or salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyl, heterocyclylcarbonyl or --S(O) n R 12 wherein n is 0, 1 or 2 and R 12 is alkyl of 1 to 6 carbon atoms, heterocyclyl or aryl, or an imino; R 3 is carbamoyl or N-substituted carbamoyl of the formula --O--CO--NH--X--R 15 wherein X is --CO-- or --SO 2 and R 15 is alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, phenyl, alkylphenyl of 1 to 6 carbon atoms in the alkyl moiety or halophenyl; R 4 is hydrogen or hydroxy, and R 5 is hydroxy, or etherified hydroxy, or R 5 together with R 1 or R 2 is a group of the formula III below as defined above, or R 4 and R 5 together are a group of the formula II or III: ##STR22## in which R A and R B are the same or different, and each is hydrogen, phenyl, or alkyl of 1 to 6 carbon atoms, said alkyl being unsubstituted or substituted by heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di-, or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms, heterocyclylthio, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxyl or a salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyloxy, heterocyclylcarbonyloxy or acyl; R 6 is hydrogen, fluorine or hydroxy; R 7 is hydrogen or methyl; one of R 8 and R 9 is hydrogen, hydroxy, alkoxy, alkanoyloxy, amino, substituted amino of the formula XII or XIII: --NHCOR.sup.16 XII or --NHSO.sub.2 R.sup.16 XIII wherein R 16 is alkyl of 1 to 6 carbon atoms or phenyl, unsubstituted or substituted by heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di-, or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms, heterocyclylthio, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxyl or a salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyloxy, heterocyclylcarbonyloxy or acyl, or a group of the formula R C SO 2 --O--, in which R C is, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, phenyl, nitrophenyl, halophenyl, alkylphenyl of 1 to 6 carbon atoms in the alkyl moiety, benzyl, nitrobenzyl, halobenzyl, alkylbenzyl of 1 to 6 carbon atoms in the alkyl moiety, phenoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, nitrophenoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, halophenyoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, alkylphenoxyalkyl of 1 to 6 carbon atoms in each alkyl moiety or R 17 --CH 2 --CH 2 -- wherein R 17 is amino, carbamoyl, sulphamoyl, alkoxy of 1 to 6 carabon atoms, alkylthio of 1 to 6 carbon atoms, aryloxy, arylthio, benzyloxy or benzylthio and the other of R 8 and R 9 is hydrogen, or R 8 and R 9 together are oxo, oxime or acetyloxime, in combination with a pharmaceutically acceptable carrier.

Claim 20

A method of treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof an antibacterially effective amount of the compound of the formula I or a pharmaceutically acceptable ester or acid addition salt thereof: ##STR21## wherein one of R 1 and R 2 is hydrogen, and the other of R 1 and R 2 is amino unsubstituted or substituted by one or two alkyl moieties of 1 to 6 carbon atoms, or the other of R 1 and R 2 , together with R 5 , is a group of the formula III below, or R 1 and R 2 together are oxo, oxime unsubstituted or substituted by alkyl, cycloalkyl or alkenyl of up to 6 carbon atoms, phenyl, hydrocarbon-carbonyl or hydrocarbonoxy-carbonyl wherein the hydrocarbon is alkyl of up to 6 carbon atoms or phenyl each of which is unsubstituted or substituted by alkyl of 1 to 6 carbon atoms, heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di- or tri-alkylamino of 1 to 6 carbon atom in each alkyl moiey, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxy or salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyl, heterocyclylcarbonyl or --S(O) n R 12 wherein n is 0, 1 or 2 and R 12 is alkyl of 1 to 6 carbon atoms, heterocyclyl or aryl, or an imino; R 3 is carbamoyl or N-substituted carbamoyl of the formula --O--CO--NH--X--R 15 wherein X is --CO-- or --SO 2 and R 15 is alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, alkoxyalkyl of 1 to 6 carbon atoms in each of the alkoxy and alkyl moieties, phenyl, alkylphenyl of 1 to 6 carbon atoms in the alkyl moiety or halophenyl; R 4 is hydrogen or hydroxy, and R 5 is hydroxy, or etherified hydroxy, or R 5 together with R 1 or R 2 is a group of the formula III below as defined above, or R 4 and R 5 together are a group of the formula II or III: ##STR22## in which R A and R B are the same or different, and each is hydrogen, phenyl, or alkyl of 1 to 6 carbon atoms, said alkyl being unsubstituted or substituted by heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di-, or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms, heterocyclylthio, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxyl or a salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyloxy, heterocyclylcarbonyloxy or acyl; R 6 is hydrogen, fluorine or hydroxy; R 7 is hydrogen or methyl; one of R 8 and R 9 is hydrogen, hydroxy, alkoxy, alkanoyloxy, amino, substituted amino of the formula XII or XIII: --NHCOR.sup.16 XII or --NHSO.sub.2 R.sup.16 XIII wherein R 16 is alkyl of 1 to 6 carbon atoms or phenyl, unsubstituted or substituted by heterocyclyl, amino, alkanoylamino of 1 to 6 carbon atoms, mono-, di-, or tri-alkylamino of 1 to 6 carbon atoms in each alkyl moiety, hydroxy, alkoxy of 1 to 6 carbon atoms, mercapto, alkylthio of 1 to 6 carbon atoms, heterocyclylthio, arylthio, sulphamoyl, carbamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, carboxyl or a salt or ester thereof, alkanoyloxy of 1 to 6 carbon atoms, arylcarbonyloxy, heterocyclylcarbonyloxy or acyl, or a group of the formula R C SO 2 --O--, in which R C is, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, phenyl, nitrophenyl, halophenyl, alkylphenyl of 1 to 6 carbon atoms in the alkyl moiety, benzyl, nitrobenzyl, halobenzyl, alkylbenzyl of 1 to 6 carbon atoms in the alkyl moiety, phenoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, nitrophenoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, halophenyoxyalkyl of 1 to 6 carbon atoms in the alkyl moiety, alkylphenoxyalkyl of 1 to 6 carbon atoms in each alkyl moiety or R 17 --CH 2 --CH 2 -- wherein R 17 is amino, carbamoyl, sulphamoyl, alkoxy of 1 to 6 carabon atoms, alkylthio of 1 to 6 carbon atoms, aryloxy, arylthio, benzyloxy or benzylthio and the other of R 8 and R 9 is hydrogen, or R 8 and R 9 together are oxo, oxime or acetyloxime, in combination with a pharmaceutically acceptable carrier.