US4226866A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Novel antibiotic analogues of cephalosporins
Assignee: Merck and Co Inc
•
Filing: 1979-06-08
•
Granted: 1980-10-07
•
Expires: 1999-06-08
Abstract
Abstract Novel antibiotics of the formula: <IMAGE> and its salts, esters and amides wherein R is acyl; B is H, OMe, Me or SR wherein R is lower alkyl or aryl; A1 is hydrogen, hydroxy, or an organic group; and, X is a divalent radical selected from -O-, -CH2-, or -NY- where Y is hydrogen or lower alkyl of from 1 to 6 carbon atoms such as methyl, ethyl, i-propyl, n-butyl, n-pentyl, n-hexyl and the like, formyl or benzyl. This invention is directed to novel antibiotics, novel intermediates useful in their preparation, and processes for preparing the novel antibiotics. The novel antibiotics are effective against gram-negative bacteria including Proteus vulgaris, E. coli and Salmonella schottmulleri, and gram-positive bacteria including Staphylococcus aureus and Bacillus subtilis and are useful in combatting bacterial infections in animals or humans in addition to various industrial applications.
Inventors
- 👤 Burton G. Christensen
- 👤 Ronald W. Ratcliffe
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 16:47
CPC Classifications
C; C07; C07F; C07F9/00; C07F9/02; C07F9/28; C07F9/38; C07F9/40; C07F9/4003; C07F9/4006; C07C; C07C45/00; C07C45/44; C07C51/00; C07C51/58; C07C51/60; C07D; C07D205/00; C07D205/02; C07D205/06; C07D205/08; C07D205/085; C07D205/09; C07D205/095; C07D265/00; C07D265/04; C07D265/06; C07D265/08; C07D317/00; C07D317/08; C07D317/10; C07D317/14; C07D317/18; C07D317/24; C07D317/28; C07D505/00
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
85 words
A compound of the formula: ##STR173## and its isomers wherein R is a carboxylic acyl radical; B is H, OCH 3 , CH 3 or SR" wherein R" is lower alkyl of 1-6 carbons and phenyl; A is azido, halo, cyano, quaternary ammonium, hydroxy, carbamoyloxy, N-lower alkyl carbamoyloxy, N,N-di-lower alkyl carbamoyloxy, amino mercapto, lower alkylthio, lowe alkanoyloxy, aroyloxy or a 5-membered heterocyclic thio radical selected from the group consisting of 1-methyltetrazolylthio and 2-methyl-1,3,4-thiadiazolylthio; X is --O-- and non-toxic pharmacologically acceptable salts, esters and amides thereof.
Claim 2
Dependent Claim
85 words
A compound of the formula: ##STR173## and its isomers wherein R is a carboxylic acyl radical; B is H, OCH 3 , CH 3 or SR" wherein R" is lower alkyl of 1-6 carbons and phenyl; A is azido, halo, cyano, quaternary ammonium, hydroxy, carbamoyloxy, N-lower alkyl carbamoyloxy, N,N-di-lower alkyl carbamoyloxy, amino mercapto, lower alkylthio, lowe alkanoyloxy, aroyloxy or a 5-membered heterocyclic thio radical selected from the group consisting of 1-methyltetrazolylthio and 2-methyl-1,3,4-thiadiazolylthio; X is --O-- and non-toxic pharmacologically acceptable salts, esters and amides thereof.
Claim 3
Dependent Claim
38 words
The compound according to claim 1 wherein R is of the formula: ##STR174## wherein R 3 is phenyl, thienyl, furyl, tetrazolyl, or ##STR175## and R 2 is hydrogen, halo, amino, guanidino, phosphono, hydroxy, tetrazolyl, carboxyl, sulfo or sulfamino.
Claim 4
Dependent Claim
33 words
A compound accroding to claim 2 wherein R 2 is hydrogen, amino or carboxyl; R 3 is phenyl, thienyl, furyl or tetrazolyl; and A is lower alkanoyloxy, carbamoyloxy, pyridinium, 1-methyl tetrazolylthio, or 2-methyl-1,3,4-thiadiazolylthio.
Claim 5
Dependent Claim
29 words
A compound according to claim 2 wherein the radical ##STR176## is 2-thienylacetyl, 2-furylacetyl, 3-thienylacetyl, 1-tetrazolylacetyl, D-phenylglycyl, phenylmalonyl, 3-thienylmalonyl, or α-hydroxyphenylacetyl; and A is acetoxy, carbamoyloxy, 1-methyltetrazolylthio, 2-methyl-1,3,4-thiadiazolylthio, or pyridinium.
Claim 6
Dependent Claim
9 words
A compound of claim 4 which is d,1-7α-methoxy-7-(2-thienylacetamido)-1-oxadethia-cephalosporanic acid.
Claim 7
Dependent Claim
8 words
A compoundof claim 4 which is d,1-7α-methoxy-7-(2-thienylacetamido)-3-carbamoyloxymethyl-1-oxa-dethiaceph-3-em-4-carboxylic acid.
Claim 8
Dependent Claim
9 words
A compound of claim 4 which is sodium 7β-(2'-thienylacetamido)-1-oxa-1-dethiacephalosporanate.
Claim 9
Dependent Claim
10 words
A compound of claim 4 which is 7β- (2-thienylacetamido)-1-oxadethiacephalosporanic acid.
Claim 10
Dependent Claim
10 words
A compound of claim 2 which is 7β- (2-tetrazolylacetamido)-3-(2-methyl-1,3,4-thiadiazolyl-5-thiomethyl)-1-oxadethiacephalosporanic acid.
Claim 11
Dependent Claim
138 words
A process for preparing a compound of the formula: ##STR177## wherein R is a carboxylic acyl radical; B is H, CH 3 , OCH 3 or SR wherein R is lower alkyl of 1-6 carbon atoms or phenyl; R 1 is hydrogen or a protecting group; A is azido, halo, cyano, quaternary ammonium, hydroxy, carbamoyloxy, N-loweralkyl carbamoyloxy, N,N-di-lower alkyl carbamoyloxy, amino, mercapto, lower alkylthio, lower alkanoyloxy, aroyloxy or a 5-membered heterocyclic thio radical selected from the group consisting of 1-methyltetrazolylthio and 2-methyl-1,3,4-thiadiazolylthio; and X is --O-- which comprises treating a compound of the formula: ##STR178## wherein X and A are as defined above; R 1' is a blocking group; R 4 is hydrogen or both R 4 are joined to form a benzylidene with an acylating agent; and removal of said blocking group to form the free acid.
Claim 12
Dependent Claim
138 words
A process for preparing a compound of the formula: ##STR177## wherein R is a carboxylic acyl radical; B is H, CH 3 , OCH 3 or SR wherein R is lower alkyl of 1-6 carbon atoms or phenyl; R 1 is hydrogen or a protecting group; A is azido, halo, cyano, quaternary ammonium, hydroxy, carbamoyloxy, N-loweralkyl carbamoyloxy, N,N-di-lower alkyl carbamoyloxy, amino, mercapto, lower alkylthio, lower alkanoyloxy, aroyloxy or a 5-membered heterocyclic thio radical selected from the group consisting of 1-methyltetrazolylthio and 2-methyl-1,3,4-thiadiazolylthio; and X is --O-- which comprises treating a compound of the formula: ##STR178## wherein X and A are as defined above; R 1' is a blocking group; R 4 is hydrogen or both R 4 are joined to form a benzylidene with an acylating agent; and removal of said blocking group to form the free acid.
Claim 13
Dependent Claim
85 words
A compound of the formula: ##STR179## wherein B is H, CH 3 , OCH 3 or SR wherein R is lower alkyl of 1-6 carbon atoms or phenyl; A 1 is azido, halo, cyano, quaternary ammonium, hydroxy, carbamoyloxy, N-loweralkyl carbamoyloxy, N,N-di-lower aljyl carbamoyloxy, amino, mercapto, lower alkylthio, lower alkyanoyloxy, aroyloxy or a 5-membered heterocyclic thio radical selected from the group consisting of 1-methyltetrazolylthio andd 2-methyl-1,3,4-thiadiazolylthio; R 1' is H or a protecting group; X is --O--,; and R 6 is azido, amino, or a benzaldimino.
Claim 14
Dependent Claim
85 words
A compound of the formula: ##STR179## wherein B is H, CH 3 , OCH 3 or SR wherein R is lower alkyl of 1-6 carbon atoms or phenyl; A 1 is azido, halo, cyano, quaternary ammonium, hydroxy, carbamoyloxy, N-loweralkyl carbamoyloxy, N,N-di-lower aljyl carbamoyloxy, amino, mercapto, lower alkylthio, lower alkyanoyloxy, aroyloxy or a 5-membered heterocyclic thio radical selected from the group consisting of 1-methyltetrazolylthio andd 2-methyl-1,3,4-thiadiazolylthio; R 1' is H or a protecting group; X is --O--,; and R 6 is azido, amino, or a benzaldimino.
Claim 15
Dependent Claim
11 words
A compound according to claim 11 wherein R 6 is 7β-amino.
Claim 16
Dependent Claim
12 words
A compound accroding to claim 12 wherein B is -CH 3 .
Claim 17
Dependent Claim
11 words
Acompound according to claim 12 wherein B is --OCH 3 .
Claim 18
Dependent Claim
68 words
A compound according to claims 1 and 18 wherein R is: ##STR180## wherein R'" is selected from the group consisting of amino, hydroxy, azido, carbamoyl, guanidino, halo, sulfamino, tetrazolyl, sulfo, carboxy, and carbalkoxy; and R" is substituted and unsubstituted aryl wherein the aryl is phenyl and wherein the substituent is selected from the group consisting of OH, SH, halo, cyano, carboxy, sulfamino, carbamoyl, sulfonyl, azido, amino and guanidino.
Claim 19
Dependent Claim
17 words
A method of treatment comprising administering an antibiotically effective amount of a compound according to claim 1.
Claim 20
Dependent Claim
21 words
An antibiotic pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.
Claim 21
Dependent Claim
12 words
A compound according to claim 1 wherein B is --OCH 3 .
Claim 22
Dependent Claim
9 words
A compound of claim 4 which is 7β-(D-2-phenyl-2-hydroxyacetamido)-3-(5-(1-methyl-1,2,3,4-tetrazolyl)thio)methyl-1-oxadethio-decephalosporanic acid.
References Cited (Backward Citations)
DE1914366A1
Cited
US3795672A
Cited
US3948927A
Cited
US3852277A
Cited
DE2355209A1
Cited
DE2355210A1
Cited
DE2355206A1
Cited
BE832174A
Cited
US4013653A
Cited
US4011216A
Cited
US4013648A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-10-07 | 1984-04-07 | 1984-10-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-10-07 | 1988-04-07 | 1988-10-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-10-07 | 1992-04-07 | 1992-10-07 | $7700.00 | Window Closed / Lapsed |