US4138486A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Arylmalonamido-1-oxadethiacephalosporins
Assignee: Shionogi and Co Ltd
•
Filing: 1977-03-22
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Granted: 1979-02-06
•
Expires: 1997-03-22
Abstract
Abstract Antibacterial 1-oxadethiacephalosporins of the formula: ##STR1## [wherein Ar is ##STR2## (in which Acyl is organic or inorganic acyl); COB 1 and COB 2 each is carboxy or protected carboxy; Het is ##STR3## (in which COB 3 is carboxy or protected carboxy); AND Y is hydrogen or methoxy; And when COB 1 , COB 2 , and/or COB 3 is carboxy, pharmaceutically acceptable salts thereof are included, But with a proviso that when Y is methoxy, Het is ##STR4## a pharmaceutical or veterinary composition comprising the said 1-oxadethiacephalosporins and pharmaceutical carrier, and a method for treating or preventing human or veterinary infectious diseases comprising administering the said 1-oxadethiacephalosporin.
Inventors
- 👤 Masayuki Narisada
- 👤 Wataru Nagata
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 08:28
CPC Classifications
C; C07; C07D; C07D498/00; C07D498/02; C07D498/04; A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/535; A61P; A61P31/00; A61P31/04; C07D205/00; C07D265/00; C07D505/00
Claims Analysis
Total Claims: 46
Claim 1
Independent Claim
139 words
A compound selected from the group consisting of (a) a compound of the formula ##STR27## wherein Ar is ##STR28## in which Acyl is alkanoyl containing 1 to 5 carbon atoms, carbamoyl, N-alkylcarbamoyl containing 2 to 6 carbon atoms, or ureidocarbonyl; Cob 1 and COB 2 each is carboxy, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, t-butoxycarbonyl, pentyloxycarbonyl, cyclopropylmethoxycarbonyl, monohydroxy-t-butoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, chloromethoxycarbonyl, cyanomethoxycarbonyl, methanesulfonylethoxycarbonyl, acetylmethoxycarbonyl, acetoxymethoxycarbonyl, acetoxyethoxycarbonyl, propionyloxymethoxycarbonyl, propionyloxyethoxycarbonyl, pivaloyloxymethoxycarbonyl, benzoyloxymethoxycarbonyl, methoxymethoxycarbonyl, phenoxymethoxycarbonyl, methylthiomethoxycarbonyl, phenylthiomethoxycarbonyl, α,α-dimethylpropargyloxycarbonyl, methoxycarbonyloxyethoxycarbonyl, ethoxycarbonylethoxycarbonyl, methoxycarbonyloxypropoxycarbonyl, allyloxycarbonyl, benzyloxycarbonyl, phenethyloxycarbonyl, tolylmethoxycarbonyl, dimethylbenzyloxycarbonyl, nitrobenzyloxycarbonyl, halobenzyloxycarbonyl, methoxybenzyloxycarbonyl, p-hydroxy-di-t-butylbenzyloxycarbonyl, diphenylmethoxycarbonyl, trityloxycarbonyl, phenacyloxycarbonyl, chlorophenacyloxycarbonyl, bromophenacyloxycarbonyl, nitrophenacyloxycarbonyl, methylphenacyloxycarbonyl, trimethylsilyloxycarbonyl, dimethylmethoxysilyloxycarbonyl, trimethylstannyloxycarbonyl, phenoxycarbonyl, naphthyloxycarbonyl, tolyloxycarbonyl, dimethylphenoxycarbonyl, nitrophenoxycarbonyl, methoxyphenoxycarbonyl, methanesulfonylphenoxycarbonyl, chlorophenoxycarbonyl, pentachlorophenoxycarbonyl, indanyloxycarbonyl, sodiooxycarbonyl, potassiooxycarbonyl, magnesiooxycarbonyl calciooxycarbonyl, or a salt of carboxy group with procain, xylocain, triethylamine, or dicyclohexylamine; and (b) when at least one of COB 1 and COB 2 is carboxy, a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
139 words
A compound selected from the group consisting of (a) a compound of the formula ##STR27## wherein Ar is ##STR28## in which Acyl is alkanoyl containing 1 to 5 carbon atoms, carbamoyl, N-alkylcarbamoyl containing 2 to 6 carbon atoms, or ureidocarbonyl; Cob 1 and COB 2 each is carboxy, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, t-butoxycarbonyl, pentyloxycarbonyl, cyclopropylmethoxycarbonyl, monohydroxy-t-butoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, chloromethoxycarbonyl, cyanomethoxycarbonyl, methanesulfonylethoxycarbonyl, acetylmethoxycarbonyl, acetoxymethoxycarbonyl, acetoxyethoxycarbonyl, propionyloxymethoxycarbonyl, propionyloxyethoxycarbonyl, pivaloyloxymethoxycarbonyl, benzoyloxymethoxycarbonyl, methoxymethoxycarbonyl, phenoxymethoxycarbonyl, methylthiomethoxycarbonyl, phenylthiomethoxycarbonyl, α,α-dimethylpropargyloxycarbonyl, methoxycarbonyloxyethoxycarbonyl, ethoxycarbonylethoxycarbonyl, methoxycarbonyloxypropoxycarbonyl, allyloxycarbonyl, benzyloxycarbonyl, phenethyloxycarbonyl, tolylmethoxycarbonyl, dimethylbenzyloxycarbonyl, nitrobenzyloxycarbonyl, halobenzyloxycarbonyl, methoxybenzyloxycarbonyl, p-hydroxy-di-t-butylbenzyloxycarbonyl, diphenylmethoxycarbonyl, trityloxycarbonyl, phenacyloxycarbonyl, chlorophenacyloxycarbonyl, bromophenacyloxycarbonyl, nitrophenacyloxycarbonyl, methylphenacyloxycarbonyl, trimethylsilyloxycarbonyl, dimethylmethoxysilyloxycarbonyl, trimethylstannyloxycarbonyl, phenoxycarbonyl, naphthyloxycarbonyl, tolyloxycarbonyl, dimethylphenoxycarbonyl, nitrophenoxycarbonyl, methoxyphenoxycarbonyl, methanesulfonylphenoxycarbonyl, chlorophenoxycarbonyl, pentachlorophenoxycarbonyl, indanyloxycarbonyl, sodiooxycarbonyl, potassiooxycarbonyl, magnesiooxycarbonyl calciooxycarbonyl, or a salt of carboxy group with procain, xylocain, triethylamine, or dicyclohexylamine; and (b) when at least one of COB 1 and COB 2 is carboxy, a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
56 words
A compound selected from the group consisting of (a) a compound according to claim 1, wherein each of COB 1 and COB 2 is carboxy, acetoxymethoxycarbonyl, pivaloyloxymethoxycarbonyl, acetoxyethoxycarbonyl, propionyloxyethoxycarbonyl, indanyloxycarbonyl, phenoxycarbonyl, tolyloxycarbonyl, dimethylphenoxycarbonyl, methoxyphenoxycarbonyl, methoxycarbonyloxyethoxycarbonyl, ethoxycarbonyloxymethoxycarbonyl, or phenacyloxycarbonyl, and (b) when at least one COB 1 or COB 2 is carboxy, a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
17 words
A compound selected from the group consisting of 7β-(α-phenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 5
Dependent Claim
17 words
A compound selected from the group consisting of 7β-(α-phenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 6
Dependent Claim
10 words
A compound according to claim 1 wherein Ar is p-hydroxyphenyl.
Claim 7
Dependent Claim
47 words
A compound selected from the group consisting of (a) a compound according to claim 1 wherein COB 1 is carboxy, acetoxymethoxycarbonyl, pivaloyloxymethoxycarbonyl, acetoxyethoxycarbonyl, propionyloxyethoxycarbonyl, indanyloxycarbonyl, phenoxycarbonyl, tolyloxycarbonyl, dimethylphenoxycarbonyl, methoxyphenoxycarbonyl, methoxycarbonyloxyethoxycarbonyl, ethoxycarbonyloxymethoxycarbonyl or phenacyloxycarbonyl, and (b) when COB 1 is carboxy, a pharmaceutically acceptable salt of the compound.
Claim 8
Dependent Claim
27 words
A compound selected from the group consisting of (a) a compound according to claim 5 wherein COB 2 is carboxy and (b) a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
10 words
A compound according to claim 1 that is 7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyl-tetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 10
Dependent Claim
13 words
A compound according to claim 1 that is sodium salt of 7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 11
Dependent Claim
13 words
A compound according to claim 1 that is potassium salt of 7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 12
Dependent Claim
11 words
A compound according to claim 1 that is 7β- [α-p-hydroxyphenyl-α-(5-indanyloxy)carbonylacetamido]-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 13
Dependent Claim
13 words
A compound according to claim 1 that is sodium salt of 7β-[α-p-hydroxyphenyl-α-(5-indanyloxy)carbonylacetamido]-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 14
Dependent Claim
10 words
A compound according to claim 1 wherein Ar is p-acyloxyphenyl.
Claim 15
Dependent Claim
10 words
A compound according to claim 12 wherein Ar is carbamoyloxyphenyl.
Claim 16
Dependent Claim
10 words
A compound according to claim 13 that is 7β-(α-p-carbamoyloxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyl-tetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 17
Dependent Claim
13 words
A compound according to claim 13 that is sodium salt of 7β-(α-p-carbamoyloxyphenyl-α-carboxylacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 18
Dependent Claim
13 words
A compound according to claim 13 that is potassium salt of 7β-(α-p-carbamoyloxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 19
Dependent Claim
19 words
A compound selected from the group consisting of the compound 7β-(α-p-acetoxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyl-tetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 20
Dependent Claim
19 words
A compound selected from the group consisting of the compound 7β-(α-p-acetoxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyl-tetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 21
Dependent Claim
19 words
A compound selected from the group consisting of the compound 7β-(α-p-N-methylcarbamoyloxyphenyl-α-carboxyacetamido-7.alpha.-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 22
Dependent Claim
19 words
A compound selected from the group consisting of the compound 7β-(α-p-N-methylcarbamoyloxyphenyl-α-carboxyacetamido-7.alpha.-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 23
Dependent Claim
19 words
A compound selected from the group consisting of the compound 7β-(α-p-ureidocarbonyloxyphenyl-α-carboxyacetamido)-7.alpha.-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 24
Dependent Claim
19 words
A compound selected from the group consisting of the compound 7β-(α-p-ureidocarbonyloxyphenyl-α-carboxyacetamido)-7.alpha.-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid and a sodium or potassium salt thereof.
Claim 25
Dependent Claim
20 words
A bactericidal composition comprising a bactericidally effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.
Claim 26
Dependent Claim
14 words
A composition according to claim 20 containing 0.01% to 99% of the active compound.
Claim 27
Dependent Claim
10 words
A composition according to claim 21 in dosage unit form.
Claim 28
Dependent Claim
9 words
A composition according to claim 22 suitable for injection.
Claim 29
Dependent Claim
17 words
A composition according to claim 23 in a form suitable for injection in an ampule or vial.
Claim 30
Dependent Claim
18 words
A composition according to claim 23 in the form of powder, crystals, microcrystals or lypholizate in a vial.
Claim 31
Dependent Claim
30 words
A composition according to claim 23 wherein Ar is p-hydroxyphenyl, or p-carbamoyloxyphenyl and COB 1 and COB 2 each is carboxy in the form of the sodium or potassium salt.
Claim 32
Dependent Claim
18 words
A composition according to claim 23 wherein the compound is the sodium or potassium salt of 7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 33
Dependent Claim
18 words
A composition according to claim 23 wherein the compound is the sodium or potassium salt of 7β-(α-p-carbamoyloxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 34
Dependent Claim
10 words
A composition according to claim 22 suitable for enteral administration.
Claim 35
Dependent Claim
15 words
A composition according to claim 29 in the form of capsule, tablet or dry syrup.
Claim 36
Dependent Claim
30 words
A composition according to claim 29 wherein Ar is p-hydroxyphenyl or carbamoyloxyphenyl; COB 1 is indanyl, phenyl, or dimethylphenyl; COB 2 is carboxy or a sodium or potassium salt thereof.
Claim 37
Dependent Claim
26 words
A method for treating human or veterinary bacterial infection comprising the administration to a patient a bactericidally effective amount of a compound according to claim 1.
Claim 38
Dependent Claim
61 words
A method according to claim 32 for treating human or veterinary bacterial infection selected from the group consisting of pneumonia, bronchitis, pneumonitis, empyema, nasopharyngitis, tonsillitis, rhinitis, dermatitis, pustulosis, ulceration, absess, wound and soft tissue infection, ear infections, osteomyelitis, septicemia, gastroenteritis, enteritis, urinary tract infections, and pyelonephritis, when caused by bacteria sensitive to the active compound or for preventing post operative infection.
Claim 39
Dependent Claim
31 words
A method according to claim 32 wherein the compound is administered at a daily dose of 0.05 to 50 mg per kilogram body weight when the compound is given by injection.
Claim 40
Dependent Claim
31 words
A method according to claim 32 wherein the compound is administered at a daily dose of 0.5 to 200 mg per kilogram of body weight when the compound is administered orally.
Claim 41
Dependent Claim
27 words
A method according to claim 32 wherein the compound is administered at a daily dose of 1 μg to 1 mg when the compound is given topically.
Claim 42
Dependent Claim
34 words
A method according to claim 32 wherein Ar is p-hydroxyphenyl, or p-carbamoyloxyphenyl and COB 1 and COB 2 each is carboxy in the form of the free acid or a pharmaceutically acceptable salt thereof.
Claim 43
Dependent Claim
18 words
A method according to claim 32 wherein the compound is the sodium or potassium salt of 7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 44
Dependent Claim
18 words
A method according to claim 32 wherein the compound is the sodium or potassium salt of 7β-(α-p-carbamoyloxyphenyl-α-carboxyacetamido)-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid.
Claim 45
Dependent Claim
36 words
A method according to claim 32 wherein Ar is p-hydroxyphenyl, or p-carbamoyloxyphenyl; COB 1 is phenoxycarbonyl, dimethylphenoxycarbonyl, or indanyloxycarbonyl; COB 2 is carboxy; in the form of the free acid or a pharmaceutically acceptable salt thereof.
Claim 46
Dependent Claim
17 words
A method according to claim 40 wherein the compound is 7β-[α-p-hydroxyphenyl-α-(5-indanyloxy)carbonylacetamido]-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-1-oxadethia-3-cephem-4-carboxylic acid or a sodium salt thereof.
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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) | 1982-02-05 | 1982-08-07 | 1983-02-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1986-02-05 | 1986-08-07 | 1987-02-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1990-02-05 | 1990-08-07 | 1991-02-06 | $7700.00 | Window Closed / Lapsed |