Patent US4044123A successfully refreshed from Google Patents.
US4044123A
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6'-N-alkyl-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols, methods for their use as antibacterial agents and compositions useful therefor
Assignee: Merck Sharp & Dohme LLC
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Filing: 1976-03-15
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Granted: 1977-08-23
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Expires: 1996-03-15
Abstract
Abstract Described are 6'-N-alkyl derivatives of antibacterially active 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols having a primary carbinamine at C-5' of which a preferred group are 6'-N-alkyl derivatives having 2 to 4 carbon atoms of 4-O-aminoglycosyl-6-O-garosaminyl-2-deoxystreptamines having a primary carbinamine at C-5', a particularly preferred compound being 6'-N-ethylsisomicin.
Inventors
- 👤 Peter J. L. Daniels
- 👤 William N. Turner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 04:28
CPC Classifications
C; C07; C07H; C07H15/00; C07H15/20; C07H15/22; C07H15/222; C07H15/226; C07H15/234; C07H15/236
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
127 words
A 6'-N-alkylaminoglycoside derivative selected from the group consisting of 6'-N-X-sisomicin, 6'-N-X-Antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, 6'-n-x-antibiotic Mu-1, 6'-N-X-antibiotic Mu-2, 6'-N-X-Antibiotic Mu-4, 6'-N-X-Antibiotic Mu-5, and the 5-epi-, 5-epi-amino-5-deoxy-, and the 5-epi-azido-5-deoxy-analogs of the following: 6'-N-X-gentamicin C 1a 6'-N-X-gentamicin B, 6'-n-x-antibiotic JI-20A, 6'-n-x-antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, and 6'-N-X-sisomicin, wherein X is a substituent selected from the group consisting of alkyl, cycloalkylalkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl and alkylaminohydroxyalkyl, said substituent having two to eight carbon atoms, the carbon in said substituent adjacent to the aminoglycoside nitrogen being primary or secondary and unsubstituted by hydroxyl or amino functions, and when said substituent is substituted by both hydroxyl and amino functions only one of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof.
Claim 2
Dependent Claim
127 words
A 6'-N-alkylaminoglycoside derivative selected from the group consisting of 6'-N-X-sisomicin, 6'-N-X-Antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, 6'-n-x-antibiotic Mu-1, 6'-N-X-antibiotic Mu-2, 6'-N-X-Antibiotic Mu-4, 6'-N-X-Antibiotic Mu-5, and the 5-epi-, 5-epi-amino-5-deoxy-, and the 5-epi-azido-5-deoxy-analogs of the following: 6'-N-X-gentamicin C 1a 6'-N-X-gentamicin B, 6'-n-x-antibiotic JI-20A, 6'-n-x-antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, and 6'-N-X-sisomicin, wherein X is a substituent selected from the group consisting of alkyl, cycloalkylalkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl and alkylaminohydroxyalkyl, said substituent having two to eight carbon atoms, the carbon in said substituent adjacent to the aminoglycoside nitrogen being primary or secondary and unsubstituted by hydroxyl or amino functions, and when said substituent is substituted by both hydroxyl and amino functions only one of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof.
Claim 3
Dependent Claim
15 words
A compound of claim 1 wherein the substituent X has 2 to 4 carbon atoms.
Claim 4
Dependent Claim
9 words
A compound of claim 2 wherein X is ethyl.
Claim 5
Dependent Claim
8 words
A compound of claim 2 which is 6'-N-X-sisomicin.
Claim 6
Dependent Claim
8 words
A compound of claim 4 which is 6'-N-ethylsisomicin.
Claim 7
Dependent Claim
8 words
A compound of claim 4 which is 6'-N-isopropylsisomicin.
Claim 8
Dependent Claim
8 words
A compound of claim 4 which is 6'-(δ-aminobutyl)-sisomicin.
Claim 9
Dependent Claim
49 words
A 6'-N-X-aminoglycoside of claim 1 having all amino functions other than at 6' protected by a protecting group, Z, wherein X is as defined in claim 1 and Z is a member selected from the group consisting of a hydrocarboncarbonyl having up to 8 carbon atoms, benzyloxycarbonyl, and tert.-butoxycarbonyl.
Claim 10
Dependent Claim
13 words
A compound of claim 8 wherein X is ethyl and Z is acetyl.
Claim 11
Dependent Claim
50 words
A per-N-protected aminoglycoside selected from the group consisting of 1,3,2',3"-tetra-N-Z-6'-N-Y-sisomicin, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40B, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40D, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic Mu-1, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic Mu-2, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic Mu-4, 1,3,5,2',3"-penta-N-Z-6'-N-Y-Antibiotic Mu-5, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-gentamicin C 1a , 1,3,5,3"-tetra-N-Z-6'-N-Y-5-epi-amino-5-deoxy-gentamicin B, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-amino-5-deoxy-Antibiotic JI-20A, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-sisomicin, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-Antibiotic 66-40B, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-Antibiotic 66-40D; and the 5-epi- and 5-epi-azido-5-deoxy analogs of the following: 1,3,2',3"-tetra-N-Z-6'-N-Y-gentamicin C 1a , 1,3,3"-tri-N-Z-6'-N-Y-gentamicin B,
Claim 12
Dependent Claim
50 words
A per-N-protected aminoglycoside selected from the group consisting of 1,3,2',3"-tetra-N-Z-6'-N-Y-sisomicin, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40B, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40D, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic Mu-1, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic Mu-2, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic Mu-4, 1,3,5,2',3"-penta-N-Z-6'-N-Y-Antibiotic Mu-5, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-gentamicin C 1a , 1,3,5,3"-tetra-N-Z-6'-N-Y-5-epi-amino-5-deoxy-gentamicin B, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-amino-5-deoxy-Antibiotic JI-20A, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-sisomicin, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-Antibiotic 66-40B, 1,3,5,2',3"-penta-N-Z-6'-N-Y-5-epi-amino-5-deoxy-Antibiotic 66-40D; and the 5-epi- and 5-epi-azido-5-deoxy analogs of the following: 1,3,2',3"-tetra-N-Z-6'-N-Y-gentamicin C 1a , 1,3,3"-tri-N-Z-6'-N-Y-gentamicin B,
Claim 13
Dependent Claim
72 words
3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic JI-20A, 1,3,2',3"-tetra-N-Z-6'-N-Y-sisomicin, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40B, and 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40D, wherein Y is a member selected from the group consisting of trifluoroacetyl, benzyloxycarbonyl and tert.-butoxy-carbonyl; Z is a member selected from the group consisting of a hydrocarboncarbonyl having up to 8 carbon atoms, benzyloxycarbonyl, and tert.-betoxycarbonyl with the proviso that in a given compound Y and Z are different, with Z being a group which remains intact under conditions in which Y is removed.
Claim 14
Dependent Claim
72 words
3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic JI-20A, 1,3,2',3"-tetra-N-Z-6'-N-Y-sisomicin, 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40B, and 1,3,2',3"-tetra-N-Z-6'-N-Y-Antibiotic 66-40D, wherein Y is a member selected from the group consisting of trifluoroacetyl, benzyloxycarbonyl and tert.-butoxy-carbonyl; Z is a member selected from the group consisting of a hydrocarboncarbonyl having up to 8 carbon atoms, benzyloxycarbonyl, and tert.-betoxycarbonyl with the proviso that in a given compound Y and Z are different, with Z being a group which remains intact under conditions in which Y is removed.
Claim 15
Dependent Claim
13 words
A compound of claim 10 wherein Y is trifluoroacetyl and Z is acetyl.
Claim 16
Dependent Claim
28 words
A 6'-N-unsubstituted-poly-N-protected aminoglycoside selected from the group consisting of 1,3,2',3"-tetra-N-Z-sisomicin, 1,3,2',3"-tetra-N-Z-Antibiotic 66-40B, 1,3,2',3"-tetra-N-Z-Antibiotic 66-40D, 1,3,2',3"-tetra-N-Z-Antibiotic Mu-1, 1,3,2',3"-tetra-N-Z-Antibiotic Mu-2, 1,3,2',3"-tetra-N-Z-Antibiotic Mu-4, 1,3,5,2',3"-penta-N-Z-Antibiotic Mu-5, 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxygentamicin C 1a , 1,3,5,3"-tetra-N-Z-5-epi-amino-5-deoxygentamicin B,
Claim 17
Dependent Claim
28 words
A 6'-N-unsubstituted-poly-N-protected aminoglycoside selected from the group consisting of 1,3,2',3"-tetra-N-Z-sisomicin, 1,3,2',3"-tetra-N-Z-Antibiotic 66-40B, 1,3,2',3"-tetra-N-Z-Antibiotic 66-40D, 1,3,2',3"-tetra-N-Z-Antibiotic Mu-1, 1,3,2',3"-tetra-N-Z-Antibiotic Mu-2, 1,3,2',3"-tetra-N-Z-Antibiotic Mu-4, 1,3,5,2',3"-penta-N-Z-Antibiotic Mu-5, 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxygentamicin C 1a , 1,3,5,3"-tetra-N-Z-5-epi-amino-5-deoxygentamicin B,
Claim 18
Dependent Claim
44 words
3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxy-Antibiotic JI-20A, 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxysisomicin, 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxy-Antibiotic 66-40B, and 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxy-Antibiotic 66-40D; the 5-epi- and 5-epi-azido-5-deoxy- analogs of the following: 1,3,2',3"-tetra-N-Z-gentamicin C 1a , 1,3,3"-tri-N-Z-gentamicin B, 1,3,2',3"-tetra-N-Z-Antibiotic JI-20A, 1,3,2',3"-tetra-N-Z-sisomicin, 1,3,2',3"-tetra-N-Z-Antibiotic 66-40B, and 1,3,2',3"-tetra-N-Z-Antibiotic 66-40D, wherein Z is a hydrocarboncarbonyl having up to 8 carbon atoms, benzyloxycarbonyl, or tert.-butoxycarbonyl.
Claim 19
Dependent Claim
44 words
3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxy-Antibiotic JI-20A, 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxysisomicin, 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxy-Antibiotic 66-40B, and 1,3,5,2',3"-penta-N-Z-5-epi-amino-5-deoxy-Antibiotic 66-40D; the 5-epi- and 5-epi-azido-5-deoxy- analogs of the following: 1,3,2',3"-tetra-N-Z-gentamicin C 1a , 1,3,3"-tri-N-Z-gentamicin B, 1,3,2',3"-tetra-N-Z-Antibiotic JI-20A, 1,3,2',3"-tetra-N-Z-sisomicin, 1,3,2',3"-tetra-N-Z-Antibiotic 66-40B, and 1,3,2',3"-tetra-N-Z-Antibiotic 66-40D, wherein Z is a hydrocarboncarbonyl having up to 8 carbon atoms, benzyloxycarbonyl, or tert.-butoxycarbonyl.
Claim 20
Dependent Claim
9 words
A compound of claim 12 wherein Z is acetyl.
Claim 21
Independent Claim
165 words
The method of eliciting an antibacterial response in a warm-blooded animal having a susceptible bacterial infection, which comprises administering to said animal a non-toxic, antibacterially effective amount of a member selected from the group consisting of a 6'-N-alkylaminoglycoside derivative selected from the group consisting of ' -N-X-sisomicin, 6'-N-X-Antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, 6'-n-x-antibiotic Mu-1, 6'-N-X-Antibiotic Mu-2, 6'-N-X-Antibiotic Mu-4, 6'-N-X-Antibiotic Mu-5, and the 5-epi-, 5-epi-amino-5-deoxy-, and the 5-epi-azido-5-deoxy- analogs of the following: 6'-N-X-gentamicin C 1a 6'-N-X-gentamicin B, 6'-n-x-antibiotic JI-20A, 6'-n-x-antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, and 6'-N-X-sisomicin, wherein X is a substituent selected from the group consisting of alkyl, cycloalkylalkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl and alkylaminohydroxyalkyl, said substituent having two to eight carbon atoms, the carbon in said substituent adjacent to the aminoglycoside nitrogen being primary or secondary and unsubstituted by hydroxyl or amino functions, and when said substituent is substituted by both hydroxyl and amino functions only one of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof.
Claim 22
Independent Claim
165 words
The method of eliciting an antibacterial response in a warm-blooded animal having a susceptible bacterial infection, which comprises administering to said animal a non-toxic, antibacterially effective amount of a member selected from the group consisting of a 6'-N-alkylaminoglycoside derivative selected from the group consisting of ' -N-X-sisomicin, 6'-N-X-Antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, 6'-n-x-antibiotic Mu-1, 6'-N-X-Antibiotic Mu-2, 6'-N-X-Antibiotic Mu-4, 6'-N-X-Antibiotic Mu-5, and the 5-epi-, 5-epi-amino-5-deoxy-, and the 5-epi-azido-5-deoxy- analogs of the following: 6'-N-X-gentamicin C 1a 6'-N-X-gentamicin B, 6'-n-x-antibiotic JI-20A, 6'-n-x-antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, and 6'-N-X-sisomicin, wherein X is a substituent selected from the group consisting of alkyl, cycloalkylalkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl and alkylaminohydroxyalkyl, said substituent having two to eight carbon atoms, the carbon in said substituent adjacent to the aminoglycoside nitrogen being primary or secondary and unsubstituted by hydroxyl or amino functions, and when said substituent is substituted by both hydroxyl and amino functions only one of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof.
Claim 23
Dependent Claim
143 words
A pharmaceutical composition comprising an antibacterially effective amount of a compound selected from the group consisting of 6'-N-X-sisomicin, 6'-N-X-Antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, 6'-n-x-antibiotic Mu-1, 6'-N-X-Antibiotic Mu-2, 6'-N-X-Antibiotic Mu-4, 6'-N-X-Antibiotic Mu-5, and the 5-epi-, 5-epi-amino-5-deoxy-, and the 5-epi-azido-5-deoxy- analogs of the following: 6'-N-X-gentamicin C 1a 6'-N-X-gentamicin B, 6'-n-x-antibiotic JI-20A, 6'-n-x-antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, and 6'-N-X-sisomicin, wherein x is a substituent selected from the group consisting of alkyl, cycloalkylalkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl and alkylaminohydroxyalkyl, said substituent having two to eight carbon atoms, the carbon in said substituent adjacent to the aminoglycoside nitrogen being primary or secondary and unsubstituted by hydroxyl or amino functions, and when said substituent is substituted by both hydroxyl and amino functions only one of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof, together with a non-toxic pharmaceutically acceptable carrier.
Claim 24
Dependent Claim
143 words
A pharmaceutical composition comprising an antibacterially effective amount of a compound selected from the group consisting of 6'-N-X-sisomicin, 6'-N-X-Antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, 6'-n-x-antibiotic Mu-1, 6'-N-X-Antibiotic Mu-2, 6'-N-X-Antibiotic Mu-4, 6'-N-X-Antibiotic Mu-5, and the 5-epi-, 5-epi-amino-5-deoxy-, and the 5-epi-azido-5-deoxy- analogs of the following: 6'-N-X-gentamicin C 1a 6'-N-X-gentamicin B, 6'-n-x-antibiotic JI-20A, 6'-n-x-antibiotic 66-40B, 6'-n-x-antibiotic 66-40D, and 6'-N-X-sisomicin, wherein x is a substituent selected from the group consisting of alkyl, cycloalkylalkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, aminohydroxyalkyl and alkylaminohydroxyalkyl, said substituent having two to eight carbon atoms, the carbon in said substituent adjacent to the aminoglycoside nitrogen being primary or secondary and unsubstituted by hydroxyl or amino functions, and when said substituent is substituted by both hydroxyl and amino functions only one of said functions can be attached at any one carbon atom; and the pharmaceutically acceptable acid addition salts thereof, together with a non-toxic pharmaceutically acceptable carrier.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-08-22 | 1981-02-21 | 1981-08-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-08-22 | 1985-02-21 | 1985-08-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-08-22 | 1989-02-21 | 1989-08-23 | $7700.00 | Window Closed / Lapsed |