US4468513A
Expired / Lapsed
US
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2'-N-Acylated and 2'-N-alkylated derivatives of 4-O-substituted-2-deoxystreptamine aminoglycosides
Assignee: Eli Lilly and Co
•
Filing: 1982-09-07
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Granted: 1984-08-28
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Expires: 2002-09-07
Abstract
Abstract Nickel salts are used to effect the regio-selective acylation and alkylation of the 2'-amino group of 4-O-substituted-2-deoxystreptamine containing aminoglycosides. The 2'-N-substituted derivatives of apramycin, certain α or β-(lower alkyl)aprosaminides and certain α or β-(substituted lower alkyl)aprosaminides are new. The 2'-N-substituted-4-O-substituted-2-deoxystreptamine aminoglycosides produced by the process of this invention are antibacterial agents.
Inventors
- 👤 Herbert A. Kirst
- 👤 Brenda A. Truedell
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 03:41
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/30; C07D207/34; C07D207/36; C07D207/40; C07D207/416; C07H; C07H15/00; C07H15/20; C07H15/22; C07H15/222; C07H15/224
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
128 words
A 2'-N-acylated or 2'-N-alkylated derivative of a 4-0-substituted-2-deoxystreptamine aminoglycoside selected from the group consisting of: apramycin, α or β-(C 1 to C 6 alkyl)aprosaminide, α or β-(C 2 to C 6 hydroxyalkyl)aprosaminide, α or β-(C 2 to C 6 aminoalkyl)aprosaminide, α or β-(C 2 to C 6 protected aminoalkyl)aprosaminide, α or β-(C 3 to C 6 aminohydroxyalkyl)aprosaminide, α or β-(C 3 to C 6 (protected amino)hydroxyalkyl)aprosaminide, and the pharmaceutically acceptable acid addition salts thereof; wherein the acyl or alkyl substituent group is selected from the group consisting of γ-amino-α-hydroxybutyryl, γ-protected amino-α-hydroxybutyryl, β-amino-α-hydroxypropionyl, β-protected amino-α-hydroxypropionyl, glycyl, N-protected glycyl, 3-hydroxypyrrolidine-3-carbonyl, N-protected 3-hydroxypyrrolidine-3-carbonyl, 3-hydroxyazetidine-3-carbonyl, N-protected 3-hydroxyazetidine-3-carbonyl, 2-hydroxy-2-(azetidin-3-yl)acetyl, N-protected 2-hydroxy-2-(azetidin-3-yl)acetyl, 4-amino-2-hydroxybutyl, 3-amino-2-hydroxypropyl, 2-aminoethyl, 3-hydroxypyrrolidine-3-methylene, 3-hydroxyazetidine-3-methylene, 2-hydroxy-2-(azetidin-3-yl)ethyl, C 2 to C 4 alkyl, C 3 to C 5 allyl, benzyl and substituted benzyl.
Claim 2
Dependent Claim
128 words
A 2'-N-acylated or 2'-N-alkylated derivative of a 4-0-substituted-2-deoxystreptamine aminoglycoside selected from the group consisting of: apramycin, α or β-(C 1 to C 6 alkyl)aprosaminide, α or β-(C 2 to C 6 hydroxyalkyl)aprosaminide, α or β-(C 2 to C 6 aminoalkyl)aprosaminide, α or β-(C 2 to C 6 protected aminoalkyl)aprosaminide, α or β-(C 3 to C 6 aminohydroxyalkyl)aprosaminide, α or β-(C 3 to C 6 (protected amino)hydroxyalkyl)aprosaminide, and the pharmaceutically acceptable acid addition salts thereof; wherein the acyl or alkyl substituent group is selected from the group consisting of γ-amino-α-hydroxybutyryl, γ-protected amino-α-hydroxybutyryl, β-amino-α-hydroxypropionyl, β-protected amino-α-hydroxypropionyl, glycyl, N-protected glycyl, 3-hydroxypyrrolidine-3-carbonyl, N-protected 3-hydroxypyrrolidine-3-carbonyl, 3-hydroxyazetidine-3-carbonyl, N-protected 3-hydroxyazetidine-3-carbonyl, 2-hydroxy-2-(azetidin-3-yl)acetyl, N-protected 2-hydroxy-2-(azetidin-3-yl)acetyl, 4-amino-2-hydroxybutyl, 3-amino-2-hydroxypropyl, 2-aminoethyl, 3-hydroxypyrrolidine-3-methylene, 3-hydroxyazetidine-3-methylene, 2-hydroxy-2-(azetidin-3-yl)ethyl, C 2 to C 4 alkyl, C 3 to C 5 allyl, benzyl and substituted benzyl.
Claim 3
Dependent Claim
21 words
The compound of claim 1, wherein the alkyl substituent group on the 2'-amino group is C 2 to C 4 alkyl.
Claim 4
Dependent Claim
16 words
The compound of claim 2, wherein the alkyl substituent group on the 2'-amino group is n-butyl.
Claim 5
Dependent Claim
16 words
The compound of claim 2, wherein the alkyl substituent group on the 2'-amino group is ethyl.
Claim 6
Dependent Claim
21 words
The compound of claim 1, wherein the alkyl substituent group on the 2'-amino group is C 3 to C 5 allyl.
Claim 7
Dependent Claim
16 words
The compound of claim 5, wherein the alkyl substituent group on the 2'-amino group is allyl.
Claim 8
Dependent Claim
16 words
The compound of claim 1, wherein the alkyl substituent group on the 2'-amino group is benzyl.
Claim 9
Dependent Claim
16 words
The compound of claim 1, wherein the acyl substituent group on the 2'-amino group is glycyl.
Claim 10
Dependent Claim
16 words
The compound of claim 1, wherein the acyl substituent group on the 2'-amino group is N-benzyloxycarbonylglycyl.
Claim 11
Dependent Claim
16 words
The compound of claim 1, wherein the acyl substituent group on the 2'-amino group is S-γ-amino-α-hydroxybutyryl.
Claim 12
Dependent Claim
16 words
The compound of claim 1, wherein the acyl substituent group on the 2'-amino group is RS-γ-amino-α-hydroxybutyryl.
Claim 13
Dependent Claim
16 words
The compound of claim 1, wherein the acyl substituent group on the 2'-amino group is RS-γ-benzyloxycarbonylamino-α-hydroxybutyryl.
Claim 14
Dependent Claim
16 words
The compound of claim 1, wherein the acyl substituent group on the 2'-amino group is S-γ-benzyloxycarbonylamino-α-hydroxybutyryl.
Claim 15
Dependent Claim
16 words
The compound of claim 1, wherein the 4-O-substituted-2-deoxystreptamine aminoglycoside is β-(C 1 to C 6 alkyl)aprosaminide.
Claim 16
Dependent Claim
16 words
The compound of claim 1, wherein the 4-O-substituted-2-deoxystreptamine aminoglycoside is β-(C 2 to C 6 hydroxyalkyl)aprosaminide.
Claim 17
Dependent Claim
16 words
The compound of claim 1, wherein the 4-O-substituted-2-deoxystreptamine aminoglycoside is β-(C 2 to C 6 aminoalkyl)aprosaminide.
Claim 18
Dependent Claim
17 words
The compound of claim 1, wherein the 4-O-substituted-2-deoxystreptamine aminoglycoside is β-(C 2 to C 6 protected aminoalkyl)aprosaminide.
Claim 19
Dependent Claim
16 words
The compound of claim 1, wherein the 4-O-substituted-2-deoxystreptamine aminoglycoside is β-(C 3 to C 6 aminohydroxyalkyl)aprosaminide.
Claim 20
Dependent Claim
17 words
The compound of claim 1, wherein the 4-O-substituted-2-deoxystreptamine aminoglycoside is β-(C 3 to C 6 (protected amino)hydroxyalkyl)aprosaminide.
Claim 21
Dependent Claim
10 words
The compound of claim 1, wherein the 4-O-substituted-2-deoxystreptamine is apramycin.
Claim 22
Dependent Claim
16 words
The compound of claim 20, wherein the acyl substituent group on the 2'-amino group is glycyl.
Claim 23
Dependent Claim
16 words
The compound of claim 20, wherein the acyl substituent group on the 2'-amino group is N-benzyloxycarbonylglycyl.
Claim 24
Dependent Claim
16 words
The compound of claim 20, wherein the acyl substituent group on the 2'-amino group is S-γ-amino-α-hydroxybutyryl.
Claim 25
Dependent Claim
16 words
The compound of claim 20, wherein the acyl substituent group on the 2'-amino group is RS-γ-amino-α-hydroxybutyryl.
Claim 26
Dependent Claim
16 words
The compound of claim 20, wherein the acyl substituent group on the 2'-amino group is S-γ-benzyloxycarbonylamino-α-hydroxybutyryl.
Claim 27
Dependent Claim
16 words
The compound of claim 20, wherein the acyl substituent group on the 2'-amino group is RS-γ-benzyloxycarbonylamino-α-hydroxybutyryl.
Claim 28
Dependent Claim
21 words
The compound of claim 20, wherein the alkyl substituent group on the 2'-amino group is C 2 to C 4 alkyl.
Claim 29
Dependent Claim
16 words
The compound of claim 27, wherein the alkyl substituent group on the 2'-amino group is ethyl.
Claim 30
Dependent Claim
17 words
The compound of claim 27, wherein the alkyl substituent group on the 240 -amino group is n-butyl.
Claim 31
Dependent Claim
21 words
The compound of claim 20, wherein the alkyl substituent group on the 2'-amino group is C 3 to C 5 allyl.
Claim 32
Dependent Claim
16 words
The compound of claim 30, wherein the alkyl substituent group on the 2'-amino group is allyl.
Claim 33
Dependent Claim
16 words
The compound of claim 20, wherein the alkyl substituent group on the 2'-amino group is benzyl.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-08-28 | 1988-02-27 | 1988-08-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-08-28 | 1992-02-27 | 1992-08-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-08-28 | 1996-02-27 | 1996-08-28 | $7700.00 | Window Closed / Lapsed |