US5561118A
Expired / Lapsed
US
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Erythromycin compounds
Assignee: Aventis Pharma SA
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Filing: 1994-03-31
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Granted: 1996-10-01
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Expires: 2014-03-31
Abstract
Abstract Compounds of the formula ##STR1## wherein X and X' form C═O or C═NOR, R is selected from the group consisting of hydrogen, heterocycle, alkyl, alkenyl, alkynyl, all optionally substituted, or X is ##STR2## R a and R b are hydrogen or a hydrocarbon group or form together with the nitrogen a heterocycle, or with A forms a 9-N, 11-0 ring, and X' is hydrogen, --Y and Y' have the same definition as X and X', B is hydrogen or OR 4 , R 4 is hydrogen or forms together with A a carbonate or a carbamate, A forms with C a double bond or A is OR' 4 , R' 4 is hydrogen or forms together with B a carbonate or A is ##STR3## R 2 is alkyl or --CONH 2 , --CONHCOR 11 or --CONHSO 2 R 11 , R 11 is a hydrocarbon up to 18 carbon atoms, R 3 is hydrogen, ##STR4## and Z is hydrogen or a carboxylic acid remainder and their non-toxic, pharmaceutically acceptable acid addition salts, their preparation and intermediates useful as antibiotics.
Inventors
- 👤 Constantin Agouridas
- 👤 Yannick Benedetti
- 👤 Jean-Francois Chantot
- 👤 Alexis Denis
- 👤 Claude Fromentin
- 👤 Odile Le Martret
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 12:40
CPC Classifications
C; C07; C07H; C07H17/00; C07H17/04; C07H17/08; A; A61; A61P; A61P31/00; A61P31/04; A61P31/12
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
435 words
A compound of the formula ##STR44## wherein X and X' together with the carbon atom to which they are attached is --C=0 or --C═NOR, R is ##STR45## wherein R' 1 and R' 2 are individually selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl and alkynyl of up to 18 carbon atoms, phenyl, naphthyl and phenylalkyl of 1 to 4 alkyl carbon atoms, each of R' 1 and R' 2 being optionally substituted by at least one member of the group consisting of hydroxy, amino, monoalkylamino of up to 4 carbon atoms, dialkylamino of up to 8 carbon atoms, cyano, acyl and carbamoyl of up to 8 carbon atoms, Y and Y' together with the carbon atom are C=0, B is hydrogen or 0R 4 , R 4 is hydrogen or forms with A a carbonate or carbamate, A forms with the carbon which carries it and the carbon in position 10 a double bond, or A is --0R' 4 , R' 4 is hydrogen, or forms with B a carbonate, or A is ##STR46## , R' 5 is ═C=0 forming with B a carbamate group, R' 6 is hydrogen or alkyl, --C 6 H 5 --(CH 2 ) a -- or alkoxy of up to 12 carbon atoms, a is 1, 2, 3 or 4 or ##STR47## R 7 and R 8 are individually hydrogen or alkyl or --C 6 H 5 --(CH 2 ) a -- of up to 18 carbon atoms, q is an integer between 1 and 6, or A is ##STR48## R 9 and R 10 are hydrogen or alkyl of 1 to 8 carbon atoms, n is an integer between 1 and 6, R 2 is selected from the group consisting of alkyl of 1 to 8 carbon atoms, --C0NH 2 , --CONHCOR 11 and --CONHS0 2 R 11 , R 11 is a hydrocarbon of 1 to 18 carbon atoms optionally containing at least one heteroatom, R 3 in α or β position is selected from the group consisting of a) hydrogen, b) alkyl of 1 to 8 carbon atoms, c) ##STR49## R 12 and R 13 are selected from the group consisting of hydrogen and alkyl of 1 to 8 carbon atoms, and d) ##STR50## R 14 and R 15 are individually hydrogen or alkyl of 1 to 8 carbon atoms, Z is hydrogen or the remainder of a carboxylic acid of 1 to 18 carbon atoms, the oximes that can be represented by X and X' or Y and Y' can be of syn or anti configuration or its non-toxic, pharmaceutically acceptable acid addition salt.
Claim 2
Dependent Claim
435 words
A compound of the formula ##STR44## wherein X and X' together with the carbon atom to which they are attached is --C=0 or --C═NOR, R is ##STR45## wherein R' 1 and R' 2 are individually selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl and alkynyl of up to 18 carbon atoms, phenyl, naphthyl and phenylalkyl of 1 to 4 alkyl carbon atoms, each of R' 1 and R' 2 being optionally substituted by at least one member of the group consisting of hydroxy, amino, monoalkylamino of up to 4 carbon atoms, dialkylamino of up to 8 carbon atoms, cyano, acyl and carbamoyl of up to 8 carbon atoms, Y and Y' together with the carbon atom are C=0, B is hydrogen or 0R 4 , R 4 is hydrogen or forms with A a carbonate or carbamate, A forms with the carbon which carries it and the carbon in position 10 a double bond, or A is --0R' 4 , R' 4 is hydrogen, or forms with B a carbonate, or A is ##STR46## , R' 5 is ═C=0 forming with B a carbamate group, R' 6 is hydrogen or alkyl, --C 6 H 5 --(CH 2 ) a -- or alkoxy of up to 12 carbon atoms, a is 1, 2, 3 or 4 or ##STR47## R 7 and R 8 are individually hydrogen or alkyl or --C 6 H 5 --(CH 2 ) a -- of up to 18 carbon atoms, q is an integer between 1 and 6, or A is ##STR48## R 9 and R 10 are hydrogen or alkyl of 1 to 8 carbon atoms, n is an integer between 1 and 6, R 2 is selected from the group consisting of alkyl of 1 to 8 carbon atoms, --C0NH 2 , --CONHCOR 11 and --CONHS0 2 R 11 , R 11 is a hydrocarbon of 1 to 18 carbon atoms optionally containing at least one heteroatom, R 3 in α or β position is selected from the group consisting of a) hydrogen, b) alkyl of 1 to 8 carbon atoms, c) ##STR49## R 12 and R 13 are selected from the group consisting of hydrogen and alkyl of 1 to 8 carbon atoms, and d) ##STR50## R 14 and R 15 are individually hydrogen or alkyl of 1 to 8 carbon atoms, Z is hydrogen or the remainder of a carboxylic acid of 1 to 18 carbon atoms, the oximes that can be represented by X and X' or Y and Y' can be of syn or anti configuration or its non-toxic, pharmaceutically acceptable acid addition salt.
Claim 3
Dependent Claim
19 words
A compound of claim 1 wherein X and X' together with carbon to which they are attached form >C═NOR.
Claim 4
Dependent Claim
22 words
A compound of claim 1 wherein X and X 1 ' together with the carbon to which they are attached are >C═O.
Claim 5
Dependent Claim
24 words
A compound of claim 1 wherein X and X' and Y and Y' together with the carbon to which they are attached are >C═O.
Claim 6
Dependent Claim
16 words
A compound of claim 1 wherein R 2 is alkyl of 1 to 4 carbon atoms.
Claim 7
Dependent Claim
10 words
A compound of claim 1 wherein R 2 is methyl.
Claim 8
Dependent Claim
13 words
A compound of claim 1 wherein R 3 is a β- or α-hydrogen.
Claim 9
Dependent Claim
9 words
A compound of claim 1 wherein A is --OH.
Claim 10
Dependent Claim
9 words
A compound of claim 1 wherein B is --OH.
Claim 11
Dependent Claim
13 words
A compound of claim 1 wherein A and B form a cyclic 11,12-carbonate.
Claim 12
Dependent Claim
60 words
A compound of claim 1 wherein A and B are ##STR51## R' 6 is selected from the group consisting of hydrogen, alkyl, alkoxy and aralkyl of up to 12 carbon atoms and ##STR52## q is an integer of 1 to 6 and R' 7 and R' 8 are individually hydrogen or alkyl or phenylalkyl of up to 18 carbon atoms.
Claim 13
Dependent Claim
16 words
A compound of claim 11 wherein R' 6 is phenylalkyl of up to 12 carbon atoms.
Claim 14
Dependent Claim
18 words
A compound of claim 11 wherein R' 6 is (CH 2 ) 4 --C 6 H 5 .
Claim 15
Dependent Claim
9 words
A compound of claim 1 wherein Z is hydrogen.
Claim 16
Dependent Claim
45 words
A compound of claim 1 selected from the group consisting of 9-[O-[2-(dimethylamino)-ethyl]-oxime] of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl-3-oxo erythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl-3-oxo-12,11-[oxycarbonyl-[(4-phenylbutyl)-imino]] erythromycin, 9-[O-[(2-methoxy-ethoxy)-methyl]-oxime] of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo erythromycin, 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo erythromycin, cyclic 11,12-carbonate of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo erythromycin, (E) 9-O-[2-[[2-(1-pyrrolidinyl-ethyl]-amino]-ethyl]-oxime of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo-erythromycin 9-O-(3-piperidinyl)-oxime of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl-3-oxo-erythromycin, and (E) 9-O-[2-(dimethylamino)-ethyl]-oxime of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-11-deoxy-10,11-didehydro-6-O-methyl 3-oxo-erythromycin.
Claim 17
Dependent Claim
21 words
An antibacterial composition comprising an antibactericidally efective amount of at least one compound of claim 1 and an inert pharmaceutical carrier.
Claim 18
Dependent Claim
22 words
A composition of claim 16 wherein in the compound X and X' together with carbon to which they are attached form >C═NOR.
Claim 19
Dependent Claim
23 words
A composition of claim 16 wherein in the compound X and X' together with the carbon to which they are attached form >C═O.
Claim 20
Dependent Claim
26 words
A method of treating bacterial infections in warm-blooded animals comprising administering to warm-blooded animals an antibactericidally effective amount of at least one compound of claim 1.
Claim 21
Dependent Claim
22 words
A method of claim 19 wherein in the compound X and X' together with carbon to which they are attached form >C═NOR.
Claim 22
Dependent Claim
23 words
A method of claim 19 wherein in the compound X and X' together with the carbon to which they are attached form >C═O.
Claim 23
Dependent Claim
50 words
The method of claim 19 wherein the active compound is selected from the group consisting of 9-[O-[2-(dimethylamino)-ethyl]]-oxime] of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl-3-oxoerythromycin, 11,12-dideoxy-3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl-3-oxo-12,11-[oxycarbonyl-[(4-phenylbutyl)-imino]] erythromycin, 9-[O-[(2-methoxy-ethoxy)-methyl]-oxime] of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo erythromycin, 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo erythromycin, cyclic 11,12-carbonate of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo erythromycin, (E) 9-O-[2-[[2-(1-pyrrolidinyl-ethyl]-amino]-ethyl]-oxime of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl 3-oxo erythromycin, 9-O-(3-piperidinyl)-oxime of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-6-O-methyl-3-oxo-erythromycin, and (E) 9-O-[2-(dimethylamino)-ethyl]-oxime of 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)-oxy]-11-deoxy-10,11-didehydro-6-O-methyl 3-oxo-erythromycin.
References Cited (Backward Citations)
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Cited
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Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-10-01 | 2000-04-01 | 2000-10-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-10-01 | 2004-04-01 | 2004-10-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-10-01 | 2008-04-01 | 2008-10-01 | $7700.00 | Window Closed / Lapsed |