US4421760A
Expired / Lapsed
US
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β-Lactam antibiotic, its preparation and use
Assignee: Beecham Group PLC
•
Filing: 1981-06-17
•
Granted: 1983-12-20
•
Expires: 2001-06-17
Abstract
Abstract The compound of the formula (VI): ##STR1## pharmaceutically acceptable salts and pharmaceutically acceptable esters thereof, are useful for their antibacterial activity and for their β-lactamase inhibitory activity. They may be combined in a synergistically effective amount with a penicillin or cephalosporin for the treatment of bacterial infections in humans and animals.
Inventors
- 👤 Stephen J. Box
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 08:18
CPC Classifications
C; C07; C07D; C07D477/00; C07D477/10; C07D477/12; C07D477/16; C07D477/20; A; A61; A61P; A61P31/00; A61P31/04; C12; C12N; C12N1/00; C12N1/20; C12N1/205; C12P; C12P17/00; C12P17/18; C12P17/182; C12P17/184; C12R; C12R2001/00; C12R2001/01; C12R2001/465; C12R2001/58
Claims Analysis
Total Claims: 77
Claim 1
Independent Claim
40 words
A compound of the formula (VI): ##STR8## a pharmaceutically acceptable salt, the lithium salt or a pharmaceutically acceptable ester thereof, said ester being one which is convertible to the free acid or salt thereof by biological methods or chemical methods.
Claim 2
Dependent Claim
40 words
A compound of the formula (VI): ##STR8## a pharmaceutically acceptable salt, the lithium salt or a pharmaceutically acceptable ester thereof, said ester being one which is convertible to the free acid or salt thereof by biological methods or chemical methods.
Claim 3
Dependent Claim
14 words
A compound according to claim 1 in the form of a pharmaceutically acceptable salt.
Claim 4
Dependent Claim
15 words
A compound according to claim 2 in the form of a di-sodium or di-potassium salt.
Claim 5
Dependent Claim
13 words
A compound according to claim 1 in the form of the p-nitrobenzyl ester.
Claim 6
Dependent Claim
28 words
A compound according to claim 1 in the form of a pharmaceutically acceptable salt selected from the group consisting of alkali metal salts and alkaline earth metal salts.
Claim 7
Dependent Claim
30 words
A compound according to claim 1 in the form of a pharmaceutically acceptable salt wherein said salt is the sodium, potassium, calcium, magnesium, ammonium, trimethylammonium, dimethylammonium, tetramethylammonium or pyrrolidine salt.
Claim 8
Dependent Claim
25 words
A compound according to claim 1 in the form of a pharmaceutically acceptable salt wherein the salt is the mono- or di-sodium or potassium salt.
Claim 9
Dependent Claim
89 words
A compound according to claim 1 in the form of an ester wherein the ester is an alkyl of up to 6 carbon atoms, an alkenyl of up to 6 carbon atoms, an alkynyl of up to 6 carbon atoms, phenyl or phenylalkyl of up to 6 carbon atoms in the alkyl moiety unsubstituted or substituted by halo, alkoxy of 1-6 carbon atoms, alkanoyl of 1-6 carbon atoms, hydroxy, alkanoyloxy of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms or di-alkylamino of 1-6 carbon atoms in each alkyl moiety.
Claim 10
Dependent Claim
236 words
A compound according to claim 1 in the form of an ester wherein the ester moiety is of the formula: ##STR9## wherein A 1 is hydrogen, alkanoyl of 1-6 carbon atoms or alkyl of 1-6 carbon atoms unsubstituted or substituted by alkoxy of 1-7 carbon atoms, carboxylic acyloxy of 1-7 carbon atoms, alkenyl of up to 5 carbon atoms or alkynyl of up to 5 carbon atoms; A 2 is hydrogen or methyl; A 3 is phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro alkyl of 1-3 carbon atoms or alkoxy of 1-3 carbon atoms; A 4 is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro alkyl of 1-3 carbon atoms or alkoxy of 1-3 carbon atoms; A 5 is hydrogen or methyl; A 6 is alkyl of 1-6 carbon atoms, phenyl, phenoxy, phenyl alkyl of 1-3 carbon atoms in the alkyl moiety, phenyl alkoxy of 1-3 carbon atoms in the alkoxy moiety or alkoxy of 1-6 carbon atoms or A 5 is joined to A 6 to form a phthalidyl, dimethylphthalidyl or dimethoxyphthalidyl moiety; A 7 is alkyl of 1-4 carbon atoms, phenyl, chlorophenyl or nitrophenyl; A 8 is alkyl of 1-4 carbon atoms or phenyl; A 9 is alkyl of 1-4 carbon atoms or phenyl; A 10 is alkyl of 1-4 carbon atoms; A 11 is alkyl of 1-4 carbon atoms; or CHA 1 A 2 is phenacyl or bromophenacyl.
Claim 11
Dependent Claim
64 words
An ester according to claim 9 wherein A 1 is hydrogen, methyl, ethyl, vinyl or ethenyl; A 2 is hydrogen; A 3 is phenyl, p-bromophenyl, p-methoxyphenyl or p-nitrophenyl; A 4 is hydrogen; A 5 is hydrogen; A 6 is methyl, t-butyl or ethoxy or A 6 is joined to A 5 to form a phthalidyl, di-methylphthalidyl or di-methoxythalidyl moiety; and A 7 is methyl.
Claim 12
Dependent Claim
14 words
An ester according to claim 9 which is the methyl, ethyl or acetonyl ester.
Claim 13
Dependent Claim
13 words
An ester according to claim 9 which is the benzyl or p-nitrobenzyl ester.
Claim 14
Dependent Claim
28 words
An ester according to claim 10 wherein A 5 is hydrogen and A 6 is methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, phenyl, benzyl, methoxy, ethoxy, n-propyloxy or iso-propyloxy.
Claim 15
Dependent Claim
11 words
An ester according to claim 13 wherein A 6 is tert-butyl.
Claim 16
Dependent Claim
17 words
An ester according to claim 9 which is the acetoxymethyl, pivaloyloxymethyl, ethoxycarbonyloxymethyl, phthalidyl, α-ethoxycarbonyloxyethyl or α-acetoxyethyl ester.
Claim 17
Dependent Claim
11 words
An ester according to claim 9 which is the methoxymethyl ester.
Claim 18
Dependent Claim
14 words
An ester according to claim 9 which is the trimethylsilyl, tert-butyldimethylsilyl or tert-butyldiphenylsilyl ester.
Claim 19
Dependent Claim
11 words
An ester according to claim 9 which is the p-methoxycarbonylbenzyl ester.
Claim 20
Dependent Claim
13 words
An ester according to claim 9 which is the p-nitrobenzyl or phthalidyl ester.
Claim 21
Dependent Claim
23 words
A compound according to claim 1 in the form of an ester wherein the ester is an alkyl ester of 1-6 carbon atoms.
Claim 22
Dependent Claim
13 words
An ester according to claim 20 which is the methyl or ethyl ester.
Claim 23
Dependent Claim
16 words
A compound according to claim 1 or a salt or ester thereof in substantially pure form.
Claim 24
Dependent Claim
57 words
A pharmaceutical composition useful for treating bacterial infections in humans and animals and for effecting β-lactamase inhibition in humans and animals which comprises an antibacterially effective amount or a β-lactamase inhibitory amount of a compound of the formula (VI): ##STR10## or a pharmaceutically acceptable salt or pharmaceutically acceptable ester thereof, in combination with a pharmaceutically acceptable carrier.
Claim 25
Dependent Claim
57 words
A pharmaceutical composition useful for treating bacterial infections in humans and animals and for effecting β-lactamase inhibition in humans and animals which comprises an antibacterially effective amount or a β-lactamase inhibitory amount of a compound of the formula (VI): ##STR10## or a pharmaceutically acceptable salt or pharmaceutically acceptable ester thereof, in combination with a pharmaceutically acceptable carrier.
Claim 26
Independent Claim
50 words
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 a compound of the formula (VI): ##STR11## or a pharmaceutically acceptable salt or pharmaceutically acceptable ester thereof, in combination with a pharmaceutically acceptable carrier.
Claim 27
Independent Claim
50 words
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 a compound of the formula (VI): ##STR11## or a pharmaceutically acceptable salt or pharmaceutically acceptable ester thereof, in combination with a pharmaceutically acceptable carrier.
Claim 28
Dependent Claim
18 words
A composition according to claim 23 wherein the compound is in the form of a pharmaceutically acceptable salt.
Claim 29
Dependent Claim
19 words
A composition according to claim 25 wherein the compound is in the form of a di-sodium or di-potassium salt.
Claim 30
Dependent Claim
17 words
A composition according to claim 23 wherein the compound is in the form of the p-nitrobenzyl ester.
Claim 31
Dependent Claim
32 words
A composition according to claim 23 wherein the compound is in the form of a pharmaceutically acceptable salt selected from the group consisting of alkali metal salts and alkaline earth metal salts.
Claim 32
Dependent Claim
34 words
A composition according to claim 23 wherein the compound is in the form of a pharmaceutically acceptable salt wherein said salt is the sodium, potassium, calcium, magnesium, ammonium, trimethylammonium, dimethylammonium, tetramethylammonium or pyrrolidine salt.
Claim 33
Dependent Claim
29 words
A composition according to claim 23 wherein the compound is in the form of a pharmaceutically acceptable salt wherein the said is the mono- or di-sodium or potassium salt.
Claim 34
Dependent Claim
36 words
A composition according to claim 23 wherein the compound is in the form of an ester, said ester being one which is convertible to the free acid or salt thereof by biological methods or chemical methods.
Claim 35
Dependent Claim
93 words
A composition according to claim 23 wherein the compound is in the form of an ester wherein the ester is an alkyl of up to 6 carbon atoms, an alkenyl of up to 6 carbon atoms, an alkynyl of up to 6 carbon atoms, phenyl or phenylalkyl of up to 6 carbon atoms in the alkyl moiety unsubstituted or substituted by halo, alkoxy of 1-6 carbon atoms, alkanoyl of 1-6 carbon atoms, hydroxy, alkanoyloxy of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms or di-alkylamino of 1-6 carbon atoms in each alkyl moiety.
Claim 36
Dependent Claim
240 words
A composition according to claim 23 wherein the compound is in the form of an ester wherein the ester moiety is of the formula: ##STR12## wherein A 1 is hydrogen, alkanoyl of 1-6 carbon atoms or alkyl of 1-6 carbon atoms unsubstituted or substituted by alkoxy of 1-7 carbon atoms, carboxylic acyloxy of 1-7 carbon atoms, alkenyl of up to 5 carbon atoms or alkynyl of up to 5 carbon atoms; A 2 is hydrogen or methyl; A 3 is phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro alkyl of 1-3 carbon atoms or alkoxy of 1-3 carbon atoms; A 4 is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro alkyl of 1-3 carbon atoms or alkoxy of 1-3 carbon atoms; A 5 is hydrogen or methyl; A 6 is alkyl of 1-6 carbon atoms, phenyl, phenoxy, phenyl alkyl of 1-3 carbon atoms in the alkyl moiety, phenyl alkoxy of 1-3 carbon atoms in the alkoxy moiety or alkoxy of 1-6 carbon atoms or A 5 is joined to A 6 to form a phthalidyl, dimethylphthalidyl or dimethoxyphthalidyl moiety; A 7 is alkyl of 1-4 carbon atoms, phenyl, chlorophenyl or nitrophenyl; A 8 is alkyl of 1-4 carbon atoms or phenyl; A 9 is alkyl of 1-4 carbon atoms or phenyl; A 10 is alkyl of 1-4 carbon atoms; A 11 is alkyl of 1-4 carbon atoms; or CHA 1 A 2 is phenacyl or bromophenacyl.
Claim 37
Dependent Claim
64 words
A composition according to claim 33 wherein A 1 is hydrogen, methyl, ethyl, vinyl or ethenyl; A 2 is hydrogen; A 3 is phenyl, p-bromophenyl, p-methoxyphenyl or p-nitrophenyl; A 4 is hydrogen; A 5 is hydrogen, A 6 is methyl, t-butyl or ethoxy or A 6 is joined to A 5 to form a phthalidyl, di-methylphthalidyl or di-dimethoxyphthalidyl moiety; and A 7 is methyl.
Claim 38
Dependent Claim
16 words
A composition according to claim 33 wherein the ester is the methyl, ethyl or acetonyl ester.
Claim 39
Dependent Claim
15 words
A composition according to claim 33 wherein the ester is the benzyl or p-nitrobenzyl ester.
Claim 40
Dependent Claim
28 words
A composition according to claim 34 wherein A 5 is hydrogen and A 6 is methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, phenyl, benzyl, methoxy, ethoxy, n-propyloxy or iso-propyloxy.
Claim 41
Dependent Claim
11 words
A composition according to claim 37 wherein A 6 is tert-butyl.
Claim 42
Dependent Claim
19 words
A composition according to claim 33 wherein the ester is the acetoxymethyl, pivaloyloxymethyl, ethoxycarbonyloxymethyl, phthalidyl, α-ethoxycarbonyloxyethyl or α-acetoxyethyl ester.
Claim 43
Dependent Claim
13 words
A composition according to claim 33 wherein the ester is the methoxymethyl ester.
Claim 44
Dependent Claim
16 words
A composition according to claim 33 wherein the ester is the trimethylsilyl, tert-butyldimethylsilyl or tert-butyldiphenylsilyl ester.
Claim 45
Dependent Claim
13 words
A composition according to claim 33 wherein the ester is the p-methoxycarbonylbenzyl ester.
Claim 46
Dependent Claim
16 words
A composition according to claim 33 wherein the ester is the p-nitrobe zyl or phthalidyl ester.
Claim 47
Dependent Claim
27 words
A composition according to claim 23 wherein the compound is in the form of an ester wherein the ester is an alkyl ester of 1-6 carbon atoms.
Claim 48
Dependent Claim
15 words
A composition according to claim 44 wherein the ester is the methyl or ethyl ester.
Claim 49
Dependent Claim
23 words
A composition according to claim 23 wherein the compound, pharmaceutically acceptable salt thereof or pharmaceutically acceptable ester thereof is in substantially pure form.
Claim 50
Dependent Claim
10 words
A composition according to claim 23 in oral administration form.
Claim 51
Dependent Claim
10 words
A composition according to claim 23 in parenteral administration form.
Claim 52
Dependent Claim
10 words
A composition according to claim 23 in topical administration form.
Claim 53
Dependent Claim
18 words
A method according to claim 24 wherein the compound is in the form of a pharmaceutically acceptable salt.
Claim 54
Dependent Claim
19 words
A method according to claim 50 wherein the compound is in the form of a di-sodium or di-potassium salt.
Claim 55
Dependent Claim
17 words
A method according to claim 24 wherein the compound is in the form of the p-nitrobenzyl ester.
Claim 56
Dependent Claim
32 words
A method according to claim 24 wherein the compound is in the form of a pharmaceutically acceptable salt selected from the group consisting of alkali metal salts and alkaline earth metal salts.
Claim 57
Dependent Claim
34 words
A method according to claim 24 wherein the compound is in the form of a pharmaceutically acceptable salt wherein said salt is the sodium, potassium, calcium, magnesium, ammonium, trimethylammonium, dimethylammonium, tetramethylammonium or pyrrolidine salt.
Claim 58
Dependent Claim
29 words
A method according to claim 24 wherein the compound is in the form of a pharmaceutically acceptable salt wherein the salt is the mono- or di-sodium or potassium salt.
Claim 59
Dependent Claim
36 words
A method according to claim 24 wherein the compound is in the form of an ester, said ester being one which is convertible to the free acid or salt thereof by biological methods or chemical methods.
Claim 60
Dependent Claim
93 words
A method according to claim 24 wherein the compound is in the form of an ester wherein the ester is an alkyl of up to 6 carbon atoms, an alkenyl of up to 6 carbon atoms, an alkynyl of up to 6 carbon atoms, phenyl or phenylalkyl of up to 6 carbon atoms in the alkyl moiety unsubstituted or substituted by halo, alkoxy of 1-6 carbon atoms, alkanoyl of 1-6 carbon atoms, hydroxy, alkanoyloxy of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms or di-alkylamino of 1-6 carbon atoms in each alkyl moiety.
Claim 61
Dependent Claim
240 words
A method according to claim 24 wherein the compound is in the form of an ester wherein the ester moiety is of the formula: ##STR13## wherein A 1 is hydrogen, alkanoyl of 1-6 carbon atoms or alkyl of 1-6 carbon atoms unsubstituted or substituted by alkoxy of 1-7 carbon atoms, carboxylic acyloxy of 1-7 carbon atoms, alkenyl of up to 5 carbon atoms or alkynyl of up to 5 carbon atoms; A 2 is hydrogen or methyl; A 3 is phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro alkyl of 1-3 carbon atoms or alkoxy of 1-3 carbon atoms; A 4 is hydrogen or phenyl unsubstituted or substituted by fluoro, chloro, bromo, nitro alkyl of 1-3 carbon atoms or alkoxy of 1-3 carbon atoms; A 5 is hydrogen or methyl; A 6 is alkyl of 1-6 carbon atoms, phenyl, phenoxy, phenyl alkyl of 1-3 carbon atoms in the alkyl moiety, phenyl alkoxy of 1-3 carbon atoms in the alkoxy moiety or alkoxy of 1-6 carbon atoms or A 5 is joined to A 6 to form a phthalidyl, dimethylphthalidyl or dimethoxyphthalidyl moiety; A 7 is alkyl of 1-4 carbon atoms, phenyl, chlorophenyl or nitrophenyl; A 8 is alkyl of 1-4 carbon atoms or phenyl; A 9 is alkyl of 1-4 carbon atoms or phenyl; A 10 is alkyl of 1-4 carbon atoms; A 11 is alkyl of 1-4 carbon atoms; or CHA 1 A 2 is phenacyl or bromophenacyl.
Claim 62
Dependent Claim
64 words
A method according to claim 58 wherein A 1 is hydrogen, methyl, ethyl, vinyl or ethenyl; A 2 is hydrogen; A 3 is phenyl, p-bromophenyl, p-methoxyphenyl or p-nitrophenyl; A 4 is hydrogen; A 5 is hydrogen; A 6 is methyl, t-butyl or ethoxy or A 6 is joined to A 5 to form a phthalidyl, di-methylphthalidyl or di-methoxyphthalidyl moiety; and A 7 is methyl.
Claim 63
Dependent Claim
16 words
A method according to claim 58 wherein the ester is the methyl, ethyl or acetonyl ester.
Claim 64
Dependent Claim
15 words
A method according to claim 58 wherein the ester is the benzyl or p-nitrobenzyl ester.
Claim 65
Dependent Claim
28 words
A method according to claim 59 wherein A 5 is hydrogen and A 6 is methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, phenyl, benzyl, methoxy, ethoxy, n-propyloxy or iso-propyloxy.
Claim 66
Dependent Claim
11 words
A method according to claim 62 wherein A 6 is tert-butyl.
Claim 67
Dependent Claim
19 words
A method according to claim 58 wherein the ester is the acetoxymethyl, pivaloyloxymethyl, ethoxycarbonyloxymethyl, phthalidyl, α-ethoxycarbonyloxyethyl or α-acetoxyethyl ester.
Claim 68
Dependent Claim
13 words
A method according to claim 58 wherein the ester is the methoxymethyl ester.
Claim 69
Dependent Claim
16 words
A method according to claim 58 wherein the ester is the trimethylsilyl, tert-butyldimethylsilyl or tert-butyldiphenylsilyl ester.
Claim 70
Dependent Claim
13 words
A method according to claim 58 wherein the ester is the p-methoxycarbonylbenzyl ester.
Claim 71
Dependent Claim
16 words
A method according to claim 58 wherein the ester is the p-nitrobe zyl or phthalidyl ester.
Claim 72
Dependent Claim
27 words
A method according to claim 24 wherein the compound is in the form of an ester wherein the ester is an alkyl ester of 1-6 carbon atoms.
Claim 73
Dependent Claim
15 words
A method according to claim 69 wherein the ester is the methyl or ethyl ester.
Claim 74
Dependent Claim
23 words
A method according to claim 24 wherein the compound, pharmaceutically acceptable salt thereof or pharmaceutically acceptable ester thereof is in substantially pure form.
Claim 75
Dependent Claim
11 words
A method according to claim 24 wherein the administration is oral.
Claim 76
Dependent Claim
11 words
A method according to claim 24 wherein the administration is parenteral.
Claim 77
Dependent Claim
11 words
A method according to claim 24 wherein the administration is topical.
References Cited (Backward Citations)
US4113856A
Cited
US4146610A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-12-19 | 1987-06-20 | 1987-12-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-12-19 | 1991-06-20 | 1991-12-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-12-19 | 1995-06-20 | 1995-12-20 | $7700.00 | Window Closed / Lapsed |