Patent US4452796A successfully refreshed from Google Patents.
US4452796A
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6-Aminoalkylpenicillanic acid 1,1-dioxides as beta-lactamase inhibitors
Assignee: Pfizer Inc
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Filing: 1982-10-21
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Granted: 1984-06-05
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Expires: 2002-10-21
Abstract
Abstract Beta-lactamase inhibitors which are 6-alpha- and 6-beta-(aminomethyl) and (1-aminoethyl)pencillanic acid 1,1-dioxides; pharmaceutically-acceptable salts thereof; conventional esters thereof which are hydrolyzable in vivo; bis-methanediol esters thereof; or mixed methanediol esters with said beta-lactamase inhibitors and sulbactam. Pharmaceutical compositions comprising said beta-lactamase inhibitors and a conventional beta-lactam antibiotic, used in the treatment of bacterial infections. Compounds useful as intermediates in the synthesis of said beta-lactamase inhibitors. Antibacterial mixed bis-methanediol esters of said aminoalkyl penicillanic acid 1,1-dioxides and ampicillin or amoxicillin, also used in the treatment of bacterial infections; and intermediates therefor.
Inventors
- 👤 Wayne E. Barth
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 20:20
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/41; A61K31/425; A61K31/429; A61K31/43; A61K31/54; A61K31/542; A61K31/545; C; C07; C07D; C07D499/00
Claims Analysis
Total Claims: 60
Claim 1
Independent Claim
62 words
A compound having the stereochemical formula ##STR12## wherein R is hydrogen or methyl; and n is 1 and R 1 is hydrogen, a radical group forming an ester hydrolyzable under physiological conditions, or 1,1-dioxopenicillanoyloxymethyl; or n is 2 and R 1 is --CH 2 --; a pharmaceutically-acceptable acid addition salt thereof or a pharmaceutically-acceptable cationic salt thereof when R 1 is hydrogen.
Claim 2
Dependent Claim
62 words
A compound having the stereochemical formula ##STR12## wherein R is hydrogen or methyl; and n is 1 and R 1 is hydrogen, a radical group forming an ester hydrolyzable under physiological conditions, or 1,1-dioxopenicillanoyloxymethyl; or n is 2 and R 1 is --CH 2 --; a pharmaceutically-acceptable acid addition salt thereof or a pharmaceutically-acceptable cationic salt thereof when R 1 is hydrogen.
Claim 3
Dependent Claim
41 words
A compound of claim 1 wherein n is 1 and R 1 is: gamma-butyrolacton-4-yl, --CHR 2 OCOR 3 , or --CHR 2 OCOOR 3 , wherein R 2 is hydrogen or methyl and R 3 is (C 1 -C 6 )alkyl.
Claim 4
Dependent Claim
10 words
A compound of claim 2 wherein R 1 is 1-ethoxycarbonyloxyethyl.
Claim 5
Dependent Claim
10 words
A compound of claim 2 wherein R 1 is pivaloyloxymethyl.
Claim 6
Dependent Claim
9 words
A compound of claim 4 wherein R is hydrogen.
Claim 7
Dependent Claim
9 words
The compound of claim 5 having the formula (II).
Claim 8
Dependent Claim
16 words
The compound of claim 6 which is in the form of its p-toluenesulfonic acid addition salt.
Claim 9
Dependent Claim
14 words
A compound of claim 1 wherein n is 1 and R 1 is hydrogen.
Claim 10
Dependent Claim
10 words
A compound of claim 8 having the stereochemical formula (I).
Claim 11
Dependent Claim
10 words
A compound of claim 8 having the stereochemical formula (II).
Claim 12
Dependent Claim
9 words
A compound of claim 8 wherein R is hydrogen.
Claim 13
Dependent Claim
9 words
A compound of claim 8 wherein R is methyl.
Claim 14
Dependent Claim
12 words
A compound of claim 8 wherein the aminoalkyl side chain is 1S-aminoethyl.
Claim 15
Dependent Claim
12 words
A compound of claim 8 wherein the aminoalkyl side chain is 1R-aminoethyl.
Claim 16
Dependent Claim
14 words
A compound of claim 1 wherein n is 1 and R 1 is 1,1-dioxopenicillanoyloxymethyl.
Claim 17
Dependent Claim
9 words
A compound of claim 15 wherein R is hydrogen.
Claim 18
Dependent Claim
9 words
The compound of claim 16 having the formula (II).
Claim 19
Dependent Claim
16 words
A compound of claim 1 wherein n is 2 and R 1 is --CH 2 --.
Claim 20
Dependent Claim
9 words
A compound of claim 18 wherein R is hydrogen.
Claim 21
Dependent Claim
9 words
The compound of claim 19 having the formula (II).
Claim 22
Dependent Claim
31 words
A pharmaceutical composition for treating bacterial infections which comprises an antibacterially effective amount of a compound of claim 1 and a beta-lactam antibiotic in a weight ratio of 1:3 to 3:1.
Claim 23
Dependent Claim
74 words
A pharmaceutical composition of claim 21 wherein the beta-lactam antibiotic is amoxicillin, ampicillin, azlocillin, bacampicillin, carbenicillin, carbenicillin indanyl, carbenicillin phenyl, cefaclor, cefadroxil, cefaloram, cefamandole, cefamandole nafate, cefaparole, cefatrizine, cefazolin, cefmenoxime cefonicid cefodizime cefoperazone, ceforanide, cefotaxime, cefoxitin, cefsulodin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cephacetrile, cephalexin, cephaloglycin, cephaloridine, cephalothin, cephapirin, cephradine, cyclacillin, epicillin, hetacillin, levopropylcillin, mecillinam, mezlocillin, penicillin G, penicillin V, phenethicillin, piperacillin, pirbenicillin, pivampicillin, sarmoxicillin, sarpicillin, suncillin, talampicillin or ticarcillin; or a pharmaceutically acceptable salt thereof.
Claim 24
Dependent Claim
15 words
A pharmaceutical composition of claim 22 wherein n is 1 and R 1 is hydrogen.
Claim 25
Dependent Claim
42 words
A pharmaceutical composition of claim 22 wherein n is 1 and R 1 is: gamma-butyrolacton-4-yl, --CHR 2 OCOR 3 , or --CHR 2 OCOOR 3 , wherein R 2 is hydrogen or methyl and R 3 is (C 1 -C 6 )alkyl.
Claim 26
Dependent Claim
11 words
A pharmaceutical composition of claim 24 wherein R 1 is pivaloyloxymethyl.
Claim 27
Dependent Claim
15 words
A pharmaceutical composition of claim 22 wherein n is 1 and R 1 is 1,1-dioxopenicillanoyloxymethyl.
Claim 28
Dependent Claim
17 words
A pharmaceutical composition of claim 22 wherein n is 2 and R 1 is --CH 2 --.
Claim 29
Dependent Claim
10 words
A pharmaceutical composition of claim 22 wherein R is hydrogen.
Claim 30
Dependent Claim
10 words
A pharmaceutical composition of claim 22 wherein R is methyl.
Claim 31
Dependent Claim
17 words
A pharmaceutical composition of claim 22 wherein the beta-lactam antibiotic is ampicillin, hetacillin, pivampicillin, bacampicillin or talampicillin.
Claim 32
Dependent Claim
15 words
A pharmaceutical composition of claim 22 wherein the beta-lactam antibiotic is amoxicillin, sarmoxicillin or sarpicillin.
Claim 33
Dependent Claim
12 words
A pharmaceutical composition of claim 22 wherein the beta-lactam antibiotic is cefoperazone.
Claim 34
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 22.
Claim 35
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 23.
Claim 36
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 24.
Claim 37
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 25.
Claim 38
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 36.
Claim 39
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 27.
Claim 40
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 28.
Claim 41
Dependent Claim
27 words
A method of treaing a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 29.
Claim 42
Dependent Claim
50 words
A compound having the stereochemical formula ##STR13## wherein R is hydrogen or methyl and R 4 is ##STR14## wherein Y is hydrogen, hydroxy, (C 2 -C 7 )-alkanoyloxy, (C 2 -C 7 )-alkoxycarbonyloxy, benzoyloxy, or benzoyloxy monosubstituted with (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or halo.
Claim 43
Dependent Claim
50 words
A compound having the stereochemical formula ##STR13## wherein R is hydrogen or methyl and R 4 is ##STR14## wherein Y is hydrogen, hydroxy, (C 2 -C 7 )-alkanoyloxy, (C 2 -C 7 )-alkoxycarbonyloxy, benzoyloxy, or benzoyloxy monosubstituted with (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or halo.
Claim 44
Dependent Claim
9 words
A compound of claim 41 wherein Y is hydrogen.
Claim 45
Dependent Claim
9 words
A compound of claim 41 wherein Y is hydroxy.
Claim 46
Dependent Claim
9 words
A compound of claim 42 wherein R is hydrogen.
Claim 47
Dependent Claim
9 words
A compound of claim 42 wherein R is methyl.
Claim 48
Dependent Claim
24 words
A pharmaceutical composition suitable for treating a bacterial infection in a mammal which comprises an antibacterially effective amount of a compound of claim 41.
Claim 49
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 46.
Claim 50
Dependent Claim
19 words
A compound of the stereochemical formula ##STR15## wherein R is hydrogen or methyl, and A is ##STR16## or S.
Claim 51
Dependent Claim
19 words
A compound of the stereochemical formula ##STR15## wherein R is hydrogen or methyl, and A is ##STR16## or S.
Claim 52
Dependent Claim
21 words
A compound of the stereochemical formula ##STR17## wherein R is hydrogen or methyl and Y' is benzyloxycarbonylamino, amino, azido, or trifluoromethanesulfonyloxy.
Claim 53
Dependent Claim
21 words
A compound of the stereochemical formula ##STR17## wherein R is hydrogen or methyl and Y' is benzyloxycarbonylamino, amino, azido, or trifluoromethanesulfonyloxy.
Claim 54
Dependent Claim
19 words
A compound having the stereochemical formula ##STR18## wherein R is hydrogen or methyl and X is chloro or iodo.
Claim 55
Dependent Claim
19 words
A compound having the stereochemical formula ##STR18## wherein R is hydrogen or methyl and X is chloro or iodo.
Claim 56
Dependent Claim
9 words
The compound of claim 10 wherein R is hydrogen.
Claim 57
Dependent Claim
17 words
A pharmaceutical composition of claim 23 wherein the compound has the formula (II) and R is hydrogen.
Claim 58
Dependent Claim
17 words
A pharmaceutical composition of claim 25 wherein the compound has the formula (II) and R is hydrogen.
Claim 59
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 52.
Claim 60
Dependent Claim
27 words
A method of treating a bacterial infection in a mammal which comprises administering to said mammal an antibacterially effective amount of a pharmaceutical composition of claim 53.
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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) | 1987-06-05 | 1987-12-05 | 1988-06-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-06-05 | 1991-12-05 | 1992-06-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-06-05 | 1995-12-05 | 1996-06-05 | $7700.00 | Window Closed / Lapsed |