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US4012380A Expired / Lapsed US ⏱️ 0.0 years remaining

7-Acylamino-3-acyl-2(or 3)cephems

Assignee: Eli Lilly and Co
•
Filing: 1974-12-10
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Granted: 1977-03-15
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Expires: 1994-12-10
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Abstract

Abstract Intermediate C-3 1-hydroxyalkyl or 1-hydroxyarylalkyl cephems, prepared by reacting Grignard reagents at low temperature with 3-formyl-2-cephem compounds, are oxidized to the corresponding 7-acylamino-3-acyl-2(or 3)cephem-4-carboxylic acids and esters thereof, which are useful as antibiotics or as intermediates in preparing antibiotic substances.

Inventors

  • 👤 Douglas O. Spry

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-29 21:00
CPC Classifications
C; C07; C07D; C07D501/00; C07D501/14

Claims Analysis

Total Claims: 16
Claim 1
Independent Claim 244 words
The compound of the formula ##STR35##wherein Z is a group of the formula ##STR36##wherein R is a group of the formula --OR 5 wherein R 5 is hydrogen or a carboxylic acid protecting ester forming group; R 4 taken together with Y forms a carbon-oxygen double bond; and R 3 is C 1 -C 6 alkyl, vinyl, allyl, ethynyl, benzyl, or phenyl; and R 1 is an acyl group of the formula ##STR37##wherein R' is (a) C 1 -C 6 alkyl, C 3 -C 7 alkenyl, cyanomethyl, halomethyl, 4-amino-4-carboxybutyl, 4-protected amino-4-protected carboxybutyl; or (b) benzyloxy, 4-nitrobenzyloxy or 4-methoxybenzyloxy; or (c) the group -R" wherein R" is 1,4-cyclohexadienyl, phenyl or substituted phenyl wherein the substituents are 1-3 halogens, hydroxy, nitro, cyano, trifluoromethyl, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, carboxy, carboxymethyl, hydroxymethyl, aminomethyl or protected aminomethyl; or (d) an arylalkyl group of the formula R"--(Y).sub.m --CH.sub.2 -- wherein R" is as defined above, Y is O or S, and m is 0 or 1; or (e) a substituted arylalkyl group of the formula ##STR38## wherein R'" is R" as defined above, 2-thienyl or 3-thienyl, W is hydroxy or protected hydroxy, carboxy or protected carboxy, amino or protected amino; or (f) a heteroarylmethyl group of the formula R""--CH.sub.2 -- wherein R"" is 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-thiazolyl, 5-tetrazolyl or 1-tetrazolyl; and R 2 is hydrogen or methoxy; and when R 5 is hydrogen, the pharmaceutically acceptable non-toxic salts of the acids represented thereby.
Claim 2
Dependent Claim 244 words
The compound of the formula ##STR35##wherein Z is a group of the formula ##STR36##wherein R is a group of the formula --OR 5 wherein R 5 is hydrogen or a carboxylic acid protecting ester forming group; R 4 taken together with Y forms a carbon-oxygen double bond; and R 3 is C 1 -C 6 alkyl, vinyl, allyl, ethynyl, benzyl, or phenyl; and R 1 is an acyl group of the formula ##STR37##wherein R' is (a) C 1 -C 6 alkyl, C 3 -C 7 alkenyl, cyanomethyl, halomethyl, 4-amino-4-carboxybutyl, 4-protected amino-4-protected carboxybutyl; or (b) benzyloxy, 4-nitrobenzyloxy or 4-methoxybenzyloxy; or (c) the group -R" wherein R" is 1,4-cyclohexadienyl, phenyl or substituted phenyl wherein the substituents are 1-3 halogens, hydroxy, nitro, cyano, trifluoromethyl, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, carboxy, carboxymethyl, hydroxymethyl, aminomethyl or protected aminomethyl; or (d) an arylalkyl group of the formula R"--(Y).sub.m --CH.sub.2 -- wherein R" is as defined above, Y is O or S, and m is 0 or 1; or (e) a substituted arylalkyl group of the formula ##STR38## wherein R'" is R" as defined above, 2-thienyl or 3-thienyl, W is hydroxy or protected hydroxy, carboxy or protected carboxy, amino or protected amino; or (f) a heteroarylmethyl group of the formula R""--CH.sub.2 -- wherein R"" is 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-thiazolyl, 5-tetrazolyl or 1-tetrazolyl; and R 2 is hydrogen or methoxy; and when R 5 is hydrogen, the pharmaceutically acceptable non-toxic salts of the acids represented thereby.
Claim 3
Dependent Claim 27 words
The compound of claim 1 wherein R 5 is hydrogen, tert-butyl, benzyl, 4-methoxybenzyl, C 2 -C 6 alkanoyloxymethyl, 2-iodoethyl, 4-nitrobenzyl, diphenylmethyl (benzhydryl), phenacyl, p-halophenacyl, dimethylallyl or 2,2,2-trichloroethyl.
Claim 4
Dependent Claim 10 words
The compound of claim 2 wherein R 5 is hydrogen.
Claim 5
Dependent Claim 17 words
The compound of claim 1 wherein R 3 is C 1 -C 3 alkyl, benzyl or phenyl.
Claim 6
Dependent Claim 10 words
The compound of claim 4 wherein R 5 is hydrogen.
Claim 7
Dependent Claim 19 words
The compound of claim 4 wherein R' is an arylalkyl group of the formula R"--(Y) m --CH 2 --.
Claim 8
Dependent Claim 17 words
The compound of claim 4 wherein R' is a heteroarylalkyl group of the formula R""CH 2 --.
Claim 9
Dependent Claim 9 words
The compound of claim 7 wherein R' is 2-thienylmethyl.
Claim 10
Dependent Claim 10 words
The compound of claim 8 said compound being 7-(2-thienylacetamido)-3-propionyl-3-cephem-4-carboxylic acid.
Claim 11
Dependent Claim 10 words
The compound of claim 8 said compound being 7-(2-thienylacetamido)-3-benzoyl-3-cephem-4-carboxylic acid.
Claim 12
Dependent Claim 10 words
The compound of claim 8 said compound being 7-(2-thienylacetamido)-7-methoxy-3-acetyl-3-cephem-4-carboxylic acid.
Claim 13
Dependent Claim 16 words
The compound of claim 4 wherein R' is a substituted arylalkyl group of the formula ##STR39##
Claim 14
Dependent Claim 46 words
The compound of claim 12 wherein W is hydroxy, or hydroxy derived formyloxy, chloroacetoxy, benzyloxy, benzhydryloxy, trityloxy, 4-nitrobenzyloxy, 4-methoxybenzyloxy, trimethylsilyloxy; carboxy, or carboxy derived tert-butoxycarbonyl, benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-iodoethoxycarbonyl, 4-nitrobenzyloxycarbonyl, benzhydryloxycarbonyl, phenacyloxycarbonyl, p-halophenacyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, dimethylallyloxycarbonyl; or amino, or amino derived tert-butoxycarbonylamino, benzyloxycarbonylamino, 4-methoxybenzyloxycarbonylamino, 4-nitrobenzyloxycarbonylamino, 2,2,2-trichloroethoxycarbonylamino, or 1-carbomethoxy-2-propenylamino.
Claim 15
Dependent Claim 10 words
The compound of claim 13 said compound being 7-(2-formyloxy-2-phenylacetamido)-3-acetyl-3-cephem-4-carboxylic acid.
Claim 16
Dependent Claim 10 words
The compound of claim 13 wherein R 2 is methoxy.

References Cited (Backward Citations)

US3707540A Cited
US3488729A Cited
US3647786A Cited
US3714154A Cited
US3905967A Cited
ZA718229B Cited
US3947413A Cited
US3897424A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1980-03-14 1980-09-13 1981-03-15 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1984-03-14 1984-09-13 1985-03-15 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1988-03-14 1988-09-13 1989-03-15 $7700.00 Window Closed / Lapsed

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