Patent US5527780A successfully refreshed from Google Patents.
US5527780A
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Erythromycin derivatives
Assignee: Aventis Pharma SA
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Filing: 1993-11-01
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Granted: 1996-06-18
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Expires: 2013-11-01
Abstract
Abstract A compound selected from the group consisting of a compound of the formula ##STR1## wherein R is --(CH 2 ) n --Ar 1 or --XAr 2 , n is an integer from 1 to 6, Ar 1 and Ar 2 are individually selected from the group consisting of a) carbocyclic aryl of up to 18 carbon atoms substituted by at least one member of the group consisting of free carboxy, alkoxy carbonyl and carboxyl salified with a pharmaceutically acceptable base, --OH, halogen, --NO 2 , --CN, ##STR2## and alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkenylthio, alkynylthio, N-alkyl, N-alkenyl and N-alkynyl of up to 12 carbon atoms optionally substituted with at least one halogen, R 1 and R 2 are individually hydrogen or alkyl of 1 to 12 carbon atoms, b) ##STR3## wherein R 3 is selected from the group consisting of alkyl of 1 to 12 carbon atoms, optionally substituted carbocyclic aryl, aryloxy and arylthio, optionally substituted heterocyclic aryl, aryloxy and arylthio containing at least one heteroatom with the optional substituents being those of carbocyclic aryl above, X is an alkyl of 1 to 6 carbon atoms interrupted by a member of the group consisting of --O--, --S--, --SO--, --SO 2 , --CO--, ##STR4## Z is hydrogen or acyl of an organic carboxylic acid of up to 18 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having antibiotic activity against gram positive and gram negative bacteria.
Inventors
- 👤 Constantin Agouridas
- 👤 Alain Bonnefoy
- 👤 Jean-Francois Chantot
- 👤 Alexis Denis
- 👤 Odile Le Martret
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 10:27
CPC Classifications
C; C07; C07H; C07H17/00; C07H17/04; C07H17/08; A; A61; A61K; A61K31/00; A61K31/70; A61K31/7042; A61K31/7052; A61P; A61P31/00; A61P31/04
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
290 words
A compound of the formula ##STR49## wherein R is --(CH 2 ) n --Ar 1 or --XAr 2 , n is an integer from 1 to 6, Ar 1 and Ar 2 are individually selected from the group consisting of a) carbocyclic aryl of up to 18 carbon atoms substituted by at least one member of the group consisting of free carboxy, alkoxy carbonyl and carboxyl salified with a pharmaceutically acceptable base, --OH, halogen, --NO 2 , --CN, ##STR50## and alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkenylthio, alkynylthio, N-alkyl, N-alkenyl and N-alkynyl of up to 12 carbon atoms optionally substituted with at least one halogen, R 1 and R 2 are individually hydrogen or alkyl of 1 to 12 carbon atoms, and b) ##STR51## wherein R 3 is selected from the group consisting of alkyl of 1 to 12 carbon atoms, optionally substituted carbocyclic aryl, carbocyclic aryloxy and carbocyclic arylthio and heterocyclic selected from the group consisting of thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, benzofuryl, benzothienyl, quinolinyl and a purine base remainder optionally substituted with a member of the group consisting of free carboxy, alkoxy carbonyl and carboxyl salified with a pharmaceutically acceptable base, --OH, halogen, --NO 2 , --CN, ##STR52## and alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkenylthio, alkynylthio, N-alkyl, N-alkenyl and N-alkynyl of up to 12 carbon atoms optionally substituted with at least one halogen, X is an alkyl of 1 to 6 carbon atoms interrupted by a member of the group consisting of --O--, --S--, --SO--, --SO 2 , --CO--, ##STR53## Z is hydrogen or acyl of an organic carboxylic acid of up to 18 carbon atoms or its non-toxic, pharmaceutically acceptable acid addition salts.
Claim 2
Dependent Claim
290 words
A compound of the formula ##STR49## wherein R is --(CH 2 ) n --Ar 1 or --XAr 2 , n is an integer from 1 to 6, Ar 1 and Ar 2 are individually selected from the group consisting of a) carbocyclic aryl of up to 18 carbon atoms substituted by at least one member of the group consisting of free carboxy, alkoxy carbonyl and carboxyl salified with a pharmaceutically acceptable base, --OH, halogen, --NO 2 , --CN, ##STR50## and alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkenylthio, alkynylthio, N-alkyl, N-alkenyl and N-alkynyl of up to 12 carbon atoms optionally substituted with at least one halogen, R 1 and R 2 are individually hydrogen or alkyl of 1 to 12 carbon atoms, and b) ##STR51## wherein R 3 is selected from the group consisting of alkyl of 1 to 12 carbon atoms, optionally substituted carbocyclic aryl, carbocyclic aryloxy and carbocyclic arylthio and heterocyclic selected from the group consisting of thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, benzofuryl, benzothienyl, quinolinyl and a purine base remainder optionally substituted with a member of the group consisting of free carboxy, alkoxy carbonyl and carboxyl salified with a pharmaceutically acceptable base, --OH, halogen, --NO 2 , --CN, ##STR52## and alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkenylthio, alkynylthio, N-alkyl, N-alkenyl and N-alkynyl of up to 12 carbon atoms optionally substituted with at least one halogen, X is an alkyl of 1 to 6 carbon atoms interrupted by a member of the group consisting of --O--, --S--, --SO--, --SO 2 , --CO--, ##STR53## Z is hydrogen or acyl of an organic carboxylic acid of up to 18 carbon atoms or its non-toxic, pharmaceutically acceptable acid addition salts.
Claim 3
Dependent Claim
9 words
A compound of claim 1 wherein Z is hydrogen.
Claim 4
Dependent Claim
9 words
A compound of claim 1 wherein n is 4.
Claim 5
Dependent Claim
11 words
A compound of claim 1 wherein Ar 1 is substituted phenyl.
Claim 6
Dependent Claim
16 words
A compound of claim 1 wherein Ar 1 is phenyl substituted with at least one halogen.
Claim 7
Dependent Claim
10 words
A compound of claim 5 wherein the halogen is chlorine.
Claim 8
Dependent Claim
10 words
A compound of claim 1 wherein Ar 1 is 4-chloro-phenyl.
Claim 9
Dependent Claim
22 words
A compound of claim 1 wherein Ar 1 is phenyl substituted with at least one alkoxy of 1 to 4 carbon atoms.
Claim 10
Dependent Claim
10 words
A compound of claim 8 wherein the alkoxy is methoxy.
Claim 11
Dependent Claim
10 words
A compound of claim 1 wherein Ar 1 is 4-methoxy-phenyl.
Claim 12
Dependent Claim
13 words
A compound of claim 1 wherein Ar 1 is a 5 membered heterocyclic.
Claim 13
Dependent Claim
12 words
A compound of claim 11 wherein Ar 1 is optionally substituted thienyl.
Claim 14
Dependent Claim
10 words
A compound of claim 1 wherein Ar 1 is thienyl.
Claim 15
Dependent Claim
12 words
A compound of claim 1 wherein Ar 1 is optionally substituted imidazolyl.
Claim 16
Dependent Claim
10 words
A compound of claim 1 wherein Ar 1 is imidazolyl.
Claim 17
Dependent Claim
12 words
A compound of claim 1 wherein Ar 1 is optionally substituted biphenyl.
Claim 18
Dependent Claim
12 words
A compound of claim 16 wherein Ar 1 is optionally substituted ##STR54##
Claim 19
Dependent Claim
11 words
A compound of th claim 16 wherein Ar 1 is ##STR55##
Claim 20
Dependent Claim
35 words
A compound of claim 1 wherein R is --X 1 Ar 2 , X 1 is alkyl of 1 to 6 carbon atoms interrupted by ##STR56## and Ar 2 has the definition of claim 1.
Claim 21
Dependent Claim
68 words
A compound of claim 19 wherein R is ##STR57## and the phenyl is optionally substituted by at least one member of the group consisting of free carboxy, alkoxy carbonyl and carboxy salified with a pharmaceutically acceptable base, --OH, halogen, --NO 2 ,--CN, ##STR58## and alkoxy. alkenyloxy, alkynyloxy, alkylthio, alkenylthio, alkynylthio, N-alkyl, N,alkenyl and N-alkynyl of up to 12 carbon atoms, all optionally substituted with at least one halogen.
Claim 22
Dependent Claim
21 words
A compound of claim 1 selected from the group consisting of 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-chlorophenyl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-methoxyphenyl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(2-thienyl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(1,1'-biphenyl-4-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-((1H)-imidazol-1-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-((2-(phenylcarbonyl)-amino)-ethyl)-imino))-erythromycin and 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-quinolinyl)-butyl]-imino])-erythromycin, 11,12-dideoxy-2-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-1H-benzimidazol-1-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(2-phenyl-5-thiazolyl)butyl)-imino))-erythromycin.
Claim 23
Dependent Claim
19 words
An antibiotic composition comprising an antibiotically effective amount of a compound of claim 1 and an inert pharmaceutical carrier.
Claim 24
Dependent Claim
28 words
A composition of claim 22 wherein the active compound is selected from the group consisting of -11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-chlorophenyl)-butyl)imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-methoxyphenyl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L- ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(2-thienyl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(1,1'-biphenyl-4-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-((1H)-imidazol-1-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-0-methyl-α-L- ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-((2-(phenylcarbonyl)-amino)-ethyl)-imino))-erythromycin and 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-quinolinyl)-butyl]-imino])-erythromycin, 11,12-dideoxy-2-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-1H-benzimidazol-1-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(2-phenyl-5-thiazolyl)butyl)-imino))-erythromycin.
Claim 25
Dependent Claim
25 words
A method of combatting bacterial infections in warm-blooded animals comprising administering to said warm-blooded animals an antibiotically effective amount of a compound of claim 1.
Claim 26
Dependent Claim
28 words
The method of claim 24 wherein the active compound is selected from the group consisting of 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-chlorophenyl)-butyl)-imino])erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L- ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-methoxyphenyl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(2-thienyl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(1,1'-biphenyl-4-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-2-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-((1H)-imidazol-1-yl)-butyl)-imino])-erythromycin, 11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-((2-(phenylcarbonyl)-amino)-ethyl)-imino))-erythromycin and 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(4-quinolinyl)-butyl]-imino])-erythromycin, 11,12-dideoxy-2-de[(2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-1H-benzimidazol-1-yl)-butyl)-imino])-erythromycin and 11,12-dideoxy-3-de([2,6-dideoxy-3-C-methyl-3-0-methyl-α-L-ribohexopyranosyl)-oxy]-6-0-methyl-3-oxo-12,11-(oxycarbonyl-[(4-(2-phenyl-5-thiazolyl)butyl)-imino))-erythromycin.
References Cited (Backward Citations)
US4742049A
Cited
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