US4201782A
Expired / Lapsed
US
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Thiadiazolyl cephalosporin analogs
Assignee: Shionogi and Co Ltd
•
Filing: 1978-08-24
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Granted: 1980-05-06
•
Expires: 1998-08-24
Abstract
Abstract Antibacterial 7β-arylmalonamido-7α-methoxy-3-optionally alkylated thiadiazolylthiomethyl-1-oxadothiacephalosporins of the following formula: ##STR1## (wherein Ar is 2-thienyl, 3-thienyl, phenyl, p-hydroxyphenyl, p-acyloxyphenyl or p-protected hydroxyphenyl; COB 1 and COB 2 each is carboxy, protected carboxy or a carboxylate salt; and R is hydrogen or lower alkyl), processes for preparing said compounds, a pharmaceutical or veterinary composition comprising the said compounds and pharmaceutical carrier and a method for treating or preventing human or veterinary infectious diseases comprising administering the said compound.
Inventors
- 👤 Masayuki Narisada
- 👤 Wataru Nagata
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 02:37
CPC Classifications
C; C07; C07D; C07D505/00; A; A61; A61P; A61P31/00; A61P31/04
Claims Analysis
Total Claims: 63
Claim 1
Independent Claim
45 words
A compound of the formula: ##STR11## wherein Ar is phenyl, p-hydroxyphenyl, p-1-5C alkanoyloxyphenyl, p-benzyloxyphenyl, p-dimethylbenzyloxyphenyl, p-methoxybenzyloxyphenyl, p-nitrobenzyloxyphenyl, p-tetrahydropyranyloxyphenyl, p-3-8C trialkylsilyloxyphenyl, 3-thienyl or 2-thienyl; R is hydrogen or 1-3C alkyl; and COB 1 and COB 2 each is carboxy, protected carboxy or a carboxylate salt group.
Claim 2
Dependent Claim
45 words
A compound of the formula: ##STR11## wherein Ar is phenyl, p-hydroxyphenyl, p-1-5C alkanoyloxyphenyl, p-benzyloxyphenyl, p-dimethylbenzyloxyphenyl, p-methoxybenzyloxyphenyl, p-nitrobenzyloxyphenyl, p-tetrahydropyranyloxyphenyl, p-3-8C trialkylsilyloxyphenyl, 3-thienyl or 2-thienyl; R is hydrogen or 1-3C alkyl; and COB 1 and COB 2 each is carboxy, protected carboxy or a carboxylate salt group.
Claim 3
Dependent Claim
13 words
A compound as claimed in claim 1, wherein Ar is p-hydroxyphenyl or 3-thienyl.
Claim 4
Dependent Claim
13 words
A compound as claimed in claim 1, wherein R is hydrogen or methyl.
Claim 5
Dependent Claim
34 words
A compound as claimed in claim 1, wherein Ar is p-hydroxyphenyl or 3-thienyl; R is hydrogen or methyl; and COB 1 and COB 2 each is carboxy, protected carboxy or a carboxylate salt group.
Claim 6
Dependent Claim
11 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid.
Claim 7
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid sodium salt.
Claim 8
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid potassium salt.
Claim 9
Dependent Claim
11 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid.
Claim 10
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid sodium salt.
Claim 11
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid potassium salt.
Claim 12
Dependent Claim
11 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-[α-(3-thienyl)-α-carboxyacetamido]-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid.
Claim 13
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-[α-(3-thienyl)-α-carboxyacetamido]-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid sodium salt.
Claim 14
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-[α-(3-thienyl)-α-carboxyacetamido]-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid potassium salt.
Claim 15
Dependent Claim
11 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-[α-(3-thienyl)-α-carboxyacetamido]-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid.
Claim 16
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-[α-(3-thienyl)-α-carboxyacetamido]-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid sodium salt.
Claim 17
Dependent Claim
13 words
The compound as claimed in claim 4, that is 7α-methoxy-7β-[α-(3-thienyl)-α-carboxyacetamido]-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid potassium salt.
Claim 18
Dependent Claim
35 words
A compound as claimed in claim 1, wherein Ar is p-1 to 5C alkanoyloxyphenyl; R is hydrogen or methyl; and COB 1 and COB 2 each is carboxy, protected carboxy or a carboxylate salt group.
Claim 19
Dependent Claim
17 words
A compound as claimed in claim 17, that is 7α-methoxy-7β-(α-p-acetoxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 20
Dependent Claim
17 words
A compound as claimed in claim 17, that is 7α-methoxy-7β-(α-p-acetoxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 21
Dependent Claim
17 words
A compound as claimed in claim 17, that is 7α-methoxy-7β-(α-p-propionyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 22
Dependent Claim
17 words
A compound as claimed in claim 17, that is 7α-methoxy-7β-(α-p-propionyloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 23
Dependent Claim
17 words
A compound as claimed in claim 17, that is 7α-methoxy-7β-(α-p-butyryloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 24
Dependent Claim
17 words
A compound as claimed in claim 17, that is 7α-methoxy-7β-(α-p-butyryloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 25
Dependent Claim
40 words
A compound as claimed in claim 1, wherein Ar is p-hydroxyphenyl or 3-thienyl; R is hydrogen, methyl or propyl; COB 1 is a pharmaceutically acceptable carboxylate ester group; and COB 2 is carboxy, protected carboxy or a carboxylate salt group.
Claim 26
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-[α-p-hydroxyphenyl-α-(5-indanyl)oxycarbonylacetamido]-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 27
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-[α-p-hydroxyphenyl-α-(5-indanyl)oxycarbonylacetamido]-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 28
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-pivaloyloxymethoxycarbonylacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 29
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-acetoxymethoxycarbonylacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 30
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-phenoxycarbonylacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 31
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-phenoxycarbonylacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 32
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-(α-p-hydroxyphenyl-α-tolyloxycarbonylacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 33
Dependent Claim
17 words
A compound as claimed in claim 24, that is 7α-methoxy-7β-[α-(3-thienyl)-α-phenoxycarbonylacetamido]-3-(2-ethyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 34
Dependent Claim
17 words
A compound as claimed in claim 1, that is 7α-methoxy-7β-(α-phenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 35
Dependent Claim
17 words
A compound as claimed in claim 1, that is 7α-methoxy-7β-(α-phenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 36
Dependent Claim
17 words
A compound as claimed in claim 1, that is 7α-methoxy-7β-[α-(2-thienyl)-α-carboxyacetamido]-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 37
Dependent Claim
17 words
A compound as claimed in claim 1, that is 7α-methoxy-7β-[α-(2-thienyl)-α-carboxyacetamido]-3-(2-propyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its sodium or potassium salt.
Claim 38
Dependent Claim
40 words
A compound as claimed in claim 1, wherein Ar is p-benzyloxyphenyl, p-dimethylbenzyloxyphenyl, p-methoxybenzyloxyphenyl, p-nitrobenzyloxyphenyl, p-tetrahydropyranyloxyphenyl or p-3 to 8C-trialkylsilyloxyphenyl; R is hydrogen or methyl; and COB 1 and COB 2 each is carboxy, protected carboxy or a carboxylate salt group.
Claim 39
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-benzyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 40
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-benzyloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 41
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-methoxybenzyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 42
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-methoxybenzyloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 43
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-butoxycarbonyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 44
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-butoxycarbonyloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 45
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-tetrahydropyranyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 46
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-tetrahydropyranyloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 47
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-trimethylsilyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 48
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-triethylsilyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 49
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-triethylsilyloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 50
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-t-butyldimethylsilyloxyphenyl-α-carboxyacetamido)-3-(1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 51
Dependent Claim
18 words
A compound as claimed in claim 37, that is 7α-methoxy-7β-(α-p-t-butyldimethylsilyloxyphenyl-α-carboxyacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid or its benzyl, p-methoxybenzyl or diphenylmethyl ester.
Claim 52
Dependent Claim
32 words
A pharmaceutical or veterinary formulation which comprises a bactericidally effective amount of a compound as claimed in claim 1 together with a pharmaceutically acceptable or veterinarily acceptable, respectively, diluent, carrier or excipient.
Claim 53
Dependent Claim
24 words
A pharmaceutical or veterinary composition consisting of 0.01 to 99% of a compound according to claim 1 and a pharmaceutically or veterinarily acceptable carrier.
Claim 54
Dependent Claim
22 words
A pharmaceutical or veterinary composition as claimed in claim 51 in the form of an injectable composition in an ampoule or vial.
Claim 55
Dependent Claim
18 words
A pharmaceutical or veterinary composition as claimed in claim 53 in the form of sterilized microcrystals or lyophilizate.
Claim 56
Dependent Claim
11 words
A composition as claimed in claim 51 in unit dosage form.
Claim 57
Dependent Claim
65 words
A pharmaceutical or veterinary composition as claimed in claim 51, wherein the compound is that having p-hydroxyphenyl, p-1 to 5C alkanoyloxyphenyl, 2-thienyl or 3-thienyl as Ar; hydrogen or methyl as R; carboxy, a pharmaceutical or veterinarily acceptable carboxylate salt group or pharmaceutically or veterinarily acceptable ester group as COB 1 ; and carboxy or a pharmaceutically or veterinarily acceptable salt group as COB 2 .
Claim 58
Dependent Claim
39 words
A pharmaceutical or veterinary composition as claimed in claim 51, wherein the compound has p-hydroxyphenyl or 3-thienyl as Ar; carboxy or sodium or potassium carboxylate salt groups as COB 1 and COB 2 and hydrogen or methyl as R.
Claim 59
Dependent Claim
35 words
A method for the prevention or cure of a bacterial disease in a human or animal subject, which comprises administering to the subject a bactericidally effective amount of a compound as claimed in claim 1.
Claim 60
Independent Claim
51 words
A method as claimed in clam 58, wherein the disease is bacterial infectious disease selected from pneumonia, bronchitis, pneumonitis, empyema, nasopharyngitis, tonsillitis, rhinitis, dermatitis, pustulosis, ulceration, abses, wound and soft tissue infections, ear infections, osteomyelitis, septicemia, gastroenteritis, enteritis, urinary tract infections and pyelonephritis when caused by bacteria sensitive to the compound.
Claim 61
Dependent Claim
46 words
A method as claimed in claim 58, wherein the compound is administered at a daily dose of 0.05 to 50 mg per kilogram body weight for injection; 0.05 to 100 mg per body weight for oral administration; or 1 μg to 1 mg for topical application.
Claim 62
Dependent Claim
14 words
A method as claimed in claim 58 when effected by intravenous injection or drip.
Claim 63
Dependent Claim
37 words
A method as claimed in claim 58, wherein the compound has p-hydroxyphenyl or 3-thienyl as Ar; carboxys or sodium or potassium carboxylate salt groups as COB 1 and COB 2 ; and hydrogen or methyl as R.
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) | 1983-05-06 | 1983-11-05 | 1984-05-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-05-06 | 1987-11-05 | 1988-05-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-05-06 | 1991-11-05 | 1992-05-06 | $7700.00 | Window Closed / Lapsed |