GB1433141A - Antibiotics - Google Patents

Antibiotics

Info

Publication number
GB1433141A
GB1433141A GB3200472A GB3200472A GB1433141A GB 1433141 A GB1433141 A GB 1433141A GB 3200472 A GB3200472 A GB 3200472A GB 3200472 A GB3200472 A GB 3200472A GB 1433141 A GB1433141 A GB 1433141A
Authority
GB
United Kingdom
Prior art keywords
acid
prepared
thien
compound
hydroxyimino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB3200472A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Glaxo Laboratories Ltd
Original Assignee
Glaxo Laboratories Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Laboratories Ltd filed Critical Glaxo Laboratories Ltd
Priority to GB3200472A priority Critical patent/GB1433141A/en
Priority to PH13759A priority patent/PH11435A/en
Priority to ES416646A priority patent/ES416646A2/en
Priority to FR7324943A priority patent/FR2191883B2/fr
Priority to AU57851/73A priority patent/AU490918B2/en
Priority to BE133186A priority patent/BE801997R/en
Priority to IE114573A priority patent/IE39743B1/en
Priority to LU67955D priority patent/LU67955A1/xx
Priority to ZA734593A priority patent/ZA734593B/en
Priority to US466780A priority patent/US3926957A/en
Priority to US05/554,014 priority patent/US4024134A/en
Priority to US05/612,262 priority patent/US3991046A/en
Publication of GB1433141A publication Critical patent/GB1433141A/en
Expired legal-status Critical Current

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  • Cephalosporin Compounds (AREA)

Abstract

1433141 Antibiotics GLAXO LABORATORIES Ltd 14 June 1973 [7 July 1972] 32004/72 Heading C2C The invention is directed to compounds which are selected from the group consisting of (a) 7#-acylamido -3-acetoxymethylceph-3- em-4-carboxylic acids (syn-isomers) in which the 7#-acylamido group is 2-hydroxyimino-2- (thien - 3 - yl)acetamido; 2 - hydroxyimino- 2- furylacetamido; 2 - ethoxycarbonyloxyimino - 2 - (thien - 2 - yl)acetamido; 2- acetoxyimino - 2(thien - 2 - yl)acetamido; 2 - (2- chloroethylcarbamoyloxyimino - 2 - (thien - 2- yl)acetamido; or 2 - hydroxyimino - 2 - (pyrid- 4 - yl)acetamido, (b) 3 - (substituted methyl)- 7# - [2 - hydroxyimino - 2 - (thien - 2 - yl)- acetamido ceph - 3 - em - 4 - carboxylic acids (syn-isomers) in which the group at the 3- position is acetylthiomethyl, crotonyloxymethyl, 1 - phenyltetrazol - 5 - ylthiomethyl, 1 - methyl tetrazol - 5 - ylthiomethyl, or 5- phenyl - 1,3,4 - oxa - diazol - 2 - ylthiomethyl, (c) 3 - (substituted methyl) - 7# - [2 - hydroxyimino - 2(furyl) - acetamido]ceph - 3 - em - 4- carboxylic acid (syn-isomers) in which the group at the 3-position is 4-carbamoylpyridinium-methyl, 1-methyl tetrazol-5-ylthiomethyl or 5 - methyl - 1,3,4 - thia - diazol - 2 - ylthiomethyl and (d) 6#-acylamido-2,2-dimethylpenam - 3α - carboxylic acids (syn - isomers) in which the 6#-acylamido group is 2-hydroxyimino - 2 - (thienyl) acetamido, or 2 - hydroxyimino - 2 - (furyl) acetamido and non - toxic salts and esters thereof. The above compounds have the Formula I wherein R<SP>α</SP> and X have appropriate meanings corresponding to those embraced by (a)-(d) above, and may be prepared by either (A) condensing a compound of formula wherein B is > S or > S # O, X has the abovedefined meaning, R<SP>1</SP> is H or a carboxyl blocking group, and the dotted line indicates that the compound may be a ceph-2-em or ceph-3-em compound or an acid addition salt thereof with an acylating agent which is the syn-isomer corresponding to the acid R<SP>α</SP>.OH wherein R<SP>α</SP> has the above-defined meanings, or with an acylating agent corresponding to an acid which is a precursor for the acid R<SP>α</SP>.OH or (B) reacting a compound of formula or of formula with R<SP>α</SP>, OH or a percursor therefor (which acid does not contain a free hydroxy imino group; or (C) reacting a compound of formula wherein Acyl is R<SP>α</SP> or a precursor thereof and X<SP>1</SP> is a replaceable residue of a nucleophile, with a nucleophile whereafter in each instance, any of the following (D) are carried out: (i) conversion of a precursor for the desired R<SP>α</SP> group into that said group, (ii) conversion of a #<SP>2</SP> isomer into a #<SP>3</SP> isomer, (iii) removal of any carboxyl blocking groups, (iv) reduction of a compound in which B is > S # O to form the compound in which B is > S and (E) recovering the desired compound of Formula (I) or a non-toxic salt or ester thereof, if necessary, after separation of isomer. The acylation may be carried out at -50‹ to +50‹ C., in the presence of an acidbinding agent (e.g. a tertiary amine, inorganic base or oxirane) and a condensation agent (e.g. a carbodiimide, a carbonyl compound or an isoxazolinium salt). Acylation may be effected with an acid halide or an amide-forming derivative of the acid. The Specification also describes the following compounds and their preparation (1) ethyl thien-3-ylglyoxylate which is prepared by adding 3-bromothiophene to nbutyl lithium in ether and reacting the resulting slurry with diethyl oxalate in ether, (2) thien- 3-ylgloxylic acid which is prepared by reacting methanol with a mixture of sodium hydroxide and ethyl thien-3-yl glyoxylate, (3) 2-hydroxyimino-2-(thien-3-yl)-acetic acid, prepared by adding to hydroxylamine hydrochloride in methanol a methanolic solution of sodium methoxide, and adding thien-3-yl-gloxylic acid to the resulting mixture, (4) 2-dichloroacetoxyimino - 2 - (thienyl - 3 - yl) acetyl chloride (syn-isomer), prepared by mixing 2-hydroxyimino-2-(thien-3-yl) acetic acid with dichloroacetyl chloride in dry methylene chloride and then mixing with phosphorous pentachloride in dry methylene chloride, (5) 2-hydroxyimino- 2-(fur-2-yl) acetic acids, prepared by mixing methanolic solutions of hydroxylamine, sodium methoxide and fur-2-yl glyoxylic acid, (6) 2- diohloroacetoxyimino - 2 - (fur - 2 - yl)acetyl chloride (syn-isomer) prepared by mixing dichloroacetyl chloride and 2-hydroxyimino-2- (fur-2-yl) acetic acid and then mixing with phosphorous pentachloride, (7) 2-dichloroacetoxyimino -2 - (thien - 2 - yl) acetyl chloride (syn-isomer) prepared from the corresponding acid in the manner indicated in (4) above, (8) diphenyl - 3 - acetylthiomethyl - 7# - formamidoceph - 3 - em - 4 - carboxylate - 1# - oxide prepared by reacting diphenyl 3-bromomethyl- 7 - # - formamidoceph - 3 - em - 4 - carboxylate- 1 #-oxide with ethane thiolic acid, (9) diphenylmethyl 3 -acetylthiomethyl-7#-formamidoceph- 3-em-4-carboxylate, prepared by reacting compound (8) with potassium iodide, acetylchloride and sodium metabisulphite, (10) diphenylmethyl - 3 - (1 - methyltetrazol - 5 - ylthiomethyl) - 7# - (2 - thienylacetamido - ceph - 3 - em- 4-carboxylate prepared by mixing diphenylmethyl 3 - bromomethyl - 7# - (2 - thienylacetamido) - ceph - 3 - em - 4 - carboxylate, 5 - mercapto - 1 - methyltetrazole and triethylamine, (11) diphenylmethyl - 7# - amino- 3 - (1 - methyltetrazol - 5 - yl - thiomethyl)- ceph - 3 - em - 4 - carboxylate prepared by reacting compound (10) with phosphorous pentachloride, and (12) diphenylmethyl-7#- amino - 3(5 - phenyl, - 1,3,4 - oxadiazol - 2- ylthiomethyl) - ceph - 3 - em - 4 - carboxylate hydrochloride prepared by mixing diphenylmethyl - 3 - bromomethyl - 7# - formamidoceph- 3 - em - 4 - carboxylate - 1# - oxide with triethyl amine and 5-mercapto-2-phenyl-1,3,4- oxadiazole, followed by treatment with phosphorous tribromide and sodium bicarbonate in methylene dichloride to give the carboxylate which is then treated with phosphorous oxychloride to give compound (12) Pharmaceutical compositions comprising the above novel compounds and a carrier therefor are described in usual forms and having antibiotic activity.
GB3200472A 1971-01-29 1972-07-07 Antibiotics Expired GB1433141A (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
GB3200472A GB1433141A (en) 1972-07-07 1972-07-07 Antibiotics
PH13759A PH11435A (en) 1972-07-07 1972-07-28 7 b-acylamidoceph-3em-4-carboxylic acid derivatives and pharmaceutical compositions containing same
ES416646A ES416646A2 (en) 1972-07-07 1973-07-06 Antibiotics
FR7324943A FR2191883B2 (en) 1972-07-07 1973-07-06
AU57851/73A AU490918B2 (en) 1972-07-07 1973-07-06 Improvements in or relating to antibiotics
BE133186A BE801997R (en) 1972-07-07 1973-07-06 IMPROVEMENTS TO ANTIBIOTICS OF THE CEPHALOSPORIN AND PENICILLIN SERIES
IE114573A IE39743B1 (en) 1972-07-07 1973-07-06 Improvements in or relating to cephalsoporing an penicillin derivatives
LU67955D LU67955A1 (en) 1972-07-07 1973-07-06
ZA734593A ZA734593B (en) 1972-07-07 1973-07-06 Improvements in or relating to antibiotics
US466780A US3926957A (en) 1971-01-29 1974-05-03 Penicillin antibiotics
US05/554,014 US4024134A (en) 1971-01-29 1975-02-28 Syn isomers of cephalosporins having α-hydroximino- or α-acyloxyiminoacylamido groups at position-7
US05/612,262 US3991046A (en) 1972-07-07 1975-09-11 Penicillin antibiotics

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB3200472A GB1433141A (en) 1972-07-07 1972-07-07 Antibiotics

Publications (1)

Publication Number Publication Date
GB1433141A true GB1433141A (en) 1976-04-22

Family

ID=10331586

Family Applications (1)

Application Number Title Priority Date Filing Date
GB3200472A Expired GB1433141A (en) 1971-01-29 1972-07-07 Antibiotics

Country Status (8)

Country Link
BE (1) BE801997R (en)
ES (1) ES416646A2 (en)
FR (1) FR2191883B2 (en)
GB (1) GB1433141A (en)
IE (1) IE39743B1 (en)
LU (1) LU67955A1 (en)
PH (1) PH11435A (en)
ZA (1) ZA734593B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1472534A (en) * 1973-07-06 1977-05-04 Glaxo Lab Ltd 7beta-hydroxyiminoacylamido-cephalosporins
GB9104238D0 (en) * 1990-03-16 1991-04-17 Ici Pharma 3-tetrazolylthiomethyl cephalosporin antibiotics

Also Published As

Publication number Publication date
ZA734593B (en) 1974-06-26
FR2191883B2 (en) 1976-12-17
IE39743L (en) 1974-01-07
ES416646A2 (en) 1977-05-16
AU5785173A (en) 1975-01-09
BE801997R (en) 1974-01-07
LU67955A1 (en) 1973-09-11
PH11435A (en) 1978-02-01
IE39743B1 (en) 1978-12-20
FR2191883A2 (en) 1974-02-08

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Legal Events

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PS Patent sealed
PCNP Patent ceased through non-payment of renewal fee