US4092474A
Expired / Lapsed
US
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Cephalosporins having a metaloxy group in 3-substituent
Assignee: Shionogi and Co Ltd
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Filing: 1975-12-03
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Granted: 1978-05-30
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Expires: 1995-12-03
Abstract
Abstract Antibacterial cephalosporins of the formula ##STR1## wherein Acyl is an acyl group; R is a hydrogen or methoxy, R 1 is a hydrocarbyl group containing 1 to 8 carbon atoms; R 2 is a hydrogen, alkali metal, alkaline earth metal, halo-alkaline earth metal group or acyl group containing 1 to 12 carbon atoms; R 3 is a hydrogen, pharmaceutically acceptable cation, or ester residue; or when R 2 and R 3 are both hydrogens, they can be combined to form a lactone ring; the broken line shows a double bond at position 2 or 3; and n is zero or one, and processes for preparing them by the reaction of the compound shown by above formula in which R 1 and R 2 combined to show a bond, with a Grignard type or organometallic reagent to introduce R 1 , followed by acylation, oxidation, reduction, double bond migration, or other reactions.
Inventors
- 👤 Mitsuru Yoshioka
- 👤 Yuji Sendo
- 👤 Masayuki Murakami
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 02:06
CPC Classifications
C; C07; C07D; C07D501/00; C07D501/02; C07D501/04; C07D501/14; C07D501/16; C07D501/18; C07D501/20; C07D501/24
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
190 words
A compound of the formula: ##STR3## wherein Acyl is selected from a group of acyls consisting of formyl, acetyl, butyryl, pivaloyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cyclohexylacetyl, cycloheptylacetyl, dihydrophenylacetyl, crotonyl, methoxyacetyl, methylthioacetyl, isopropenylthioacetyl, phenoxyacetyl, phenylthioacetyl, benzyloxyacetyl, benzoyl, xylol, naphthoyl, phthaloyl, tetrahydronaphthoyl, nicotinoyl, pyrazinoyl, 2-methyl-5-phenylisoxazol-5-ylcarbonyl, phenylacetyl, phenylpropionyl, tolylacetyl, naphthylacetyl, tetrahydronaphthylacetyl, tetrazolylacetyl, thienylacetyl, thienylpropionyl, furylacetyl, pyrimidylacetyl, pyrrylacetyl, isoxazolylacetyl, benzoisothiazolylacetyl, benzoxazolylacetyl, cyclohexyloxycarbonyl, cycloheptyloxycarbonyl, benzyloxycarbonyl, phenoxycarbonyl, naphthyloxycarbonyl, pyridylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl and cyclopropylethoxycarbonyl; R is hydrogen or methoxy; R 1 is alkyl of 1 to 8 carbon atoms, cycloalkyl of up to 8 carbon atoms, phenylalkyl of up to 8 carbon atoms, or phenyl; R 2 is lithium, sodium, potassium, magnesium, cadmium, zinc, chloromagnesium, bromomagnesium, iodomagnesium, bromozinc or bromocadmium; R 3 is hydrogen, a pharmaceutically acceptable cation, or an ester residue selected from the group of methyl, ethyl, t-butyl, cyclohexyl, propenyl, methoxymethyl, ethoxymethyl, methylthioethyl, phenoxymethyl, phenylthiomethyl, tolylmethyl, chloromethyl, bromomethyl, trichloroethyl, cyanomethyl, nitrophenylthiomethyl, chlorophenoxymethyl, chlorophenacyl, nitrophenacyl, dimethylaminoethyl, diethylaminoethyl, phenyl, xylyl, naphthyl, pentachlorophenyl, trichlorophenyl, p-methanesulfonylphenyl, p-phenylazophenyl, dinitrophenyl, pyridyl, quinolyl, benzyl, phenethyl, nitrobenzyl, chlorobenzyl, trimethoxybenzyl, benzhydryl, p,p'-dimethoxydiphenylmethyl, pentachlorobenzyl, 4-oxy-3,5-di-tertiary butylbenzyl, pyridylmethyl, quinolylmethyl, and vinyl; the broken line shows a double bond at position 2 or 3; and n is zero or one.
Claim 2
Dependent Claim
190 words
A compound of the formula: ##STR3## wherein Acyl is selected from a group of acyls consisting of formyl, acetyl, butyryl, pivaloyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cyclohexylacetyl, cycloheptylacetyl, dihydrophenylacetyl, crotonyl, methoxyacetyl, methylthioacetyl, isopropenylthioacetyl, phenoxyacetyl, phenylthioacetyl, benzyloxyacetyl, benzoyl, xylol, naphthoyl, phthaloyl, tetrahydronaphthoyl, nicotinoyl, pyrazinoyl, 2-methyl-5-phenylisoxazol-5-ylcarbonyl, phenylacetyl, phenylpropionyl, tolylacetyl, naphthylacetyl, tetrahydronaphthylacetyl, tetrazolylacetyl, thienylacetyl, thienylpropionyl, furylacetyl, pyrimidylacetyl, pyrrylacetyl, isoxazolylacetyl, benzoisothiazolylacetyl, benzoxazolylacetyl, cyclohexyloxycarbonyl, cycloheptyloxycarbonyl, benzyloxycarbonyl, phenoxycarbonyl, naphthyloxycarbonyl, pyridylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl and cyclopropylethoxycarbonyl; R is hydrogen or methoxy; R 1 is alkyl of 1 to 8 carbon atoms, cycloalkyl of up to 8 carbon atoms, phenylalkyl of up to 8 carbon atoms, or phenyl; R 2 is lithium, sodium, potassium, magnesium, cadmium, zinc, chloromagnesium, bromomagnesium, iodomagnesium, bromozinc or bromocadmium; R 3 is hydrogen, a pharmaceutically acceptable cation, or an ester residue selected from the group of methyl, ethyl, t-butyl, cyclohexyl, propenyl, methoxymethyl, ethoxymethyl, methylthioethyl, phenoxymethyl, phenylthiomethyl, tolylmethyl, chloromethyl, bromomethyl, trichloroethyl, cyanomethyl, nitrophenylthiomethyl, chlorophenoxymethyl, chlorophenacyl, nitrophenacyl, dimethylaminoethyl, diethylaminoethyl, phenyl, xylyl, naphthyl, pentachlorophenyl, trichlorophenyl, p-methanesulfonylphenyl, p-phenylazophenyl, dinitrophenyl, pyridyl, quinolyl, benzyl, phenethyl, nitrobenzyl, chlorobenzyl, trimethoxybenzyl, benzhydryl, p,p'-dimethoxydiphenylmethyl, pentachlorobenzyl, 4-oxy-3,5-di-tertiary butylbenzyl, pyridylmethyl, quinolylmethyl, and vinyl; the broken line shows a double bond at position 2 or 3; and n is zero or one.
Claim 3
Dependent Claim
20 words
A compound claimed in claim 1 wherein R 1 is an alkyl containing 1 to 8 carbon atoms or phenyl.
Claim 4
Dependent Claim
17 words
A compound claimed in claim 1 wherein R 2 is lithium or a half mole of magnesium.
Claim 5
Dependent Claim
13 words
A compound claimed in claim 1 wherein R 2 is a halomagnesio group.
Claim 6
Dependent Claim
16 words
A compound claimed in claim 1 wherein R 3 is a hydrogen, sodium, diphenylmethyl, or p-nitrobenzyl.
Claim 7
Dependent Claim
13 words
A compound claimed in claim 1 wherein Acyl is a 2-thienylacetyl or phenoxyacetyl.
Claim 8
Dependent Claim
10 words
A compound claimed in claim 1 wherein n is zero.
Claim 9
Dependent Claim
19 words
A compound claimed in claim 1 wherein n is one and S O bond represents α or β configuration.
Claim 10
Dependent Claim
20 words
A compound claimed in claim 1 wherein the broken line represents the presence of a double bond at position 2.
Claim 11
Dependent Claim
20 words
A compound claimed in claim 1 wherein the broken line represents the presence or a double bond at position 3.
Claim 12
Dependent Claim
27 words
A compound selected from the following compounds: methyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-3-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-3-cephem-4-carboxylate 1-oxide, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-lithiooxyethyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(α-bromomagnesiooxybenzyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(α-bromomagnesiooxybenzyl)-3-cephem-4-carboxylate, p-nitrobenzyl 7β-phenoxyacetamido-3-(1-bromomagnesiooxyethyl)-2-cephem-4-carboxylate, and p-nitrobenzyl 7β-phenoxyacetamido-3-(1-magnesiooxybutyl)-3-cephem-4-carboxylate.
Claim 13
Dependent Claim
27 words
A compound selected from the following compounds: methyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-3-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-iodomagnesiooxyethyl)-3-cephem-4-carboxylate 1-oxide, diphenylmethyl 7β-(2-thienylacetamido)-3-(1-lithiooxyethyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(α-bromomagnesiooxybenzyl)-2-cephem-4-carboxylate, diphenylmethyl 7β-(2-thienylacetamido)-3-(α-bromomagnesiooxybenzyl)-3-cephem-4-carboxylate, p-nitrobenzyl 7β-phenoxyacetamido-3-(1-bromomagnesiooxyethyl)-2-cephem-4-carboxylate, and p-nitrobenzyl 7β-phenoxyacetamido-3-(1-magnesiooxybutyl)-3-cephem-4-carboxylate.
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) | 1981-05-29 | 1981-11-28 | 1982-05-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-05-29 | 1985-11-28 | 1986-05-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-05-29 | 1989-11-28 | 1990-05-30 | $7700.00 | Window Closed / Lapsed |