Abstract: Antibiotic compositions comprising a 1-oxa .beta.-lactam antibiotic compound of the formula ##STR1## or pharmaceutically acceptable salts thereof and either tobramycin, amikacin or piperacillin exhibit synergistic activity against multiple-antibiotic-resistant organisms. The 1-oxa compound can be used in conjunction with tobramycin, amikacin or piperacillin in a method of treating infections caused by resistant organisms.
Abstract: Antibiotic albicidin, a non-peptide antibiotic, is produced by culturing chlorosis-inducing strains of Xanthomonas albilineans isolated from diseased sugarcane, and mutants thereof. The antibiotic is isolated from the culture medium by adsorption on resin and is purified by gel filtration and HPLC.
Abstract: 7.beta.-Acylamino-3-azido-3-cephem-4-carboxylic acid esters are obtained with the corresponding 3-halo or 3-sulfonyloxy-3-cephem esters and an alkali metal azide. The 3-azido compounds as the free acids or salts are antibacterial agents while in esterified form react with alcohols and phenols to provide 2-alkoxy (or 2-phenoxy)-3amino-3-cephem esters and isomeric ring expanded 4,7-bicyclo .beta.-lactam compounds, namely [2R-(2.alpha.,7.alpha.,8.beta.)-4-alkoxy (or 4-phenoxy)-9-oxo-8-acylamino-6-thia-1,3-diazabicyclo[5.2.0]non-3-ene-2-car boxylic acids and esters and the corresponding 3-alkoxy (or 3-phenoxy) 1,4-diazabicyclo[5.2.0]non-3-ene-2-carboxylic acids and esters. These reaction products obtained with the azide possess antibacterial properties.
Abstract: Angiotensin I converting enzyme inhibitors A-58365 factors A, B, and C are produced by culturing Streptomyces chromofuscus NRRL 15098 under submerged aerobic fermentation conditions and are isolated and purified from the acidic filtered fermentation broth via chromatography, in particular HPLC. The factors are useful hypotensive agents.
Abstract: Cephalosporin compounds substituted in the 7-position by a 2-(5- or 6-membered heterocyclic)-2-oximinoacetylamino group and in the 3-position with a thienopyridinium methyl group or a furopyridinium methyl group are broad spectrum antibiotics highly effective in combating bacterial infections of gram-negative and gram-positive microorganisms. The cephalosporins are best prepared by reacting a silylated 7-[2-(heterocyclic)-2-oximinoacetylamino-3-iodomethyl-3-cephem-4-carboxyli c acid with the thienopyridine or the furopyridine. Pharmaceutical formulations comprising a compound of the invention and a method for treating bacterial infections comprising their use are also provided.
Abstract: 7.beta.-[2-Amino-2-(benzothien-4,5,6, and 7-yl)acetylamino]-3-substituted-3-cepham-4-carboxylic acids and 7.beta.-[2-amino-2-(2,3-dihydrobenzothien-4,5,6, and 7 yl)acetylamino]-3H- or 3-substituted-3-cephem-4-carboxylic acids (1), e.g. 7.beta.-[2-amino-2-(benzothien-4-yl)acetylamino]-3-methyl-3-cephem-4-carbo xylic acid, are orally effective antibiotics. Also provided are benzothienyl oximino compounds, the corresponding 2,3-dihydro compounds (2) useful as intermediates to (1) and as antibiotics, as well as 7.beta.-(2,2-dialkyl-5-oxo-4-benzothienyl-1-imidazolidinyl)-3H-(3-substitu ted)-3-cephem-4-carboxylic acids and the corresponding 2,3-dihydro compounds (3) useful as antibiotics, and prepared with (1) by condensation with ketones. Pharmaceutical formulations of antibiotic compounds (1), (2), and (3) are provided.
Abstract: 4-Fluoroazetidinone antibacterial agents are provided by a process comprising the reaction of an azetidinone-4-sulfinic acid, or a salt thereof, with perchloryl fluoride (FClO.sub.3) at -80.degree. C. to -25.degree. C., e.g., p-nitrobenzyl 3-methyl-2-(2-oxo-4-sulfino-3-phenoxyacetamido-1-azetidinyl-3-butenoate is reacted with FClO.sub.3 to provide corresponding 4-fluoroazetidinone. The latter is isomerized with a tertiary amine to corresponding 2-butenoate which a carboxy group deprotection provides an antibacterial compound.
Type:
Grant
Filed:
December 27, 1982
Date of Patent:
February 19, 1985
Assignee:
Eli Lilly and Company
Inventors:
Wayne A. Spitzer, Theodore Goodson, Jr.
Abstract: Actaplanin antibiotics (A4696) designated as C.sub.2a, D.sub.1, D.sub.2, K, L, M, N, and O are obtained by the partial acidic hydrolysis of known actaplanins at about pH 1.85 for 2.5 hours at about 90.degree. C. The new actaplanins, like the known actaplanins, are glycopeptides which possess antibacterial activity and, either alone or as a mixture with other actaplanins, improve the feed efficiency in ruminants, swine and poultry.
Abstract: Glycopeptide antibiotic A-4696G is produced by culturing Actinoplanes missouriensis mutant strain ATCC 31681 under submerged aerobic fermentation conditions, and is recovered from the fermentation broth by resin adsorption and chromatographic purification. A-4696G inhibits the growth of bacteria pathogenic to man and animals and also enhances the growth of ruminants by increasing feed utilization.
Type:
Grant
Filed:
September 29, 1982
Date of Patent:
July 24, 1984
Assignee:
Eli Lilly and Company
Inventors:
Charles L. Hershberger, Kurt E. Merkel, Robert E. Weeks, Gene M. Wild
Abstract: An azetidin-2-one-4-sulfinic acid represented by the formula ##STR1## is reacted with Pb(OAc).sub.4 in liquid SO.sub.2 containing CuII ion to provide isomeric cyclization products of the formulas ##STR2## wherein R is e.g. benzyl, phenoxymethyl, benzyloxy, diphenylmethoxy, and R.sub.1 is a carboxy-protecting group. The products of the process are useful intermediates for 1-oxa-.beta.-lactam antibacterials.
Abstract: Antibiotic A-39183 complex, comprising microbiologically active, related factors A, B, C, D, and E, is produced by submerged, aerobic fermentation of a new microorganism Streptomyces sp., NRRL 12049. The A-39183 antibiotics are closely related antibiotics. The individual A-39183 factors are separated by chromatography. The A-39183 factors are antibacterial agents which have activity against Staphylococcus and Streptococcus species that are penicillin resistant. The A-39183 factors are also active against both gram-positive and gram-negative anaerobic bacteria, and are ionophores.
Abstract: Antibiotic compositions comprising a 1-oxa .beta.-lactam antibiotic compound of the formula ##STR1## or pharmaceutically acceptable salts thereof and either tobramycin, amikacin or piperacillin exhibit synergistic activity against multiple-antibiotic-resistant organisms. The 1-oxa compound can be used in conjunction with tobramycin, amikacin or piperacillin in a method of treating infections caused by resistant organisms.
Abstract: Broad spectrum cephalosporin betaine antibiotics represented by the formula ##STR1## wherein Q is an oximino-substituted pyridinium, quinolinium or isoquinolinium group of the formulas ##STR2## wherein R.sub.1 and R.sub.2 are hydrogen or C.sub.1 -C.sub.3 alkyl; and R' is an amino-substituted 5- or 6-membered heterocyclic, e.g., 2-aminothiazol-4-yl; and R" is C.sub.1 -C.sub.4 alkyl, an N-substituted carbamoyl group, or a carboxy-substituted alkyl or cycloalkyl group; have potent activity vs. G.sup.- organisms. Pharmaceutical formulations and a method for treating infectious disease with above compounds are provided.
Abstract: Cephalosporin broad spectrum antibiotics possessing a 7.beta.-[2-[(2-aminooxazol)-4-yl]-2-(substituted oximino)]acetamido side chain and a variety of substituents at the 3-position of the cephalosporins are claimed. Also claimed are intermediates in the synthesis of the above cephalosporin antibiotics.
Abstract: Broad spectrum cephalosporin antibiotics represented by the betaine structure of the formula ##STR1## wherein R is a 5-membered amino-substituted heterocyclic containing oxygen and nitrogen; R' is e.g., hydrogen or C.sub.1 -C.sub.4 alkyl; and bicyclicpyridinium is a thienopyridinium or a furopyridinium group; are prepared by reacting a silylated 3-iodomethyl cephalosporin with a thienopyridine, e.g., thieno[2,3-b]pyridine or a furopyridine. The compounds are potent antibacterials against gram-positive and gram-negative organisms. Pharmaceutical compositions and a method for treating bacterial infections are also provided.
Abstract: Angiotensin I converting enzyme inhibitor A-58365 factor B is provided in greater abundance than coproduced Factor A by culturing Streptomyces chromofuscus NRRL 15098 under submerged aerobic fermentation conditions in an aqueous nutrient culture medium supplement with the amino acids proline and lysine.
Abstract: Angiotensin I converting enzyme inhibitor A-58365 factor A is produced in enhanced yields by culturing Streptomyces chromofuscus NRRL 15098 under submerged aerobic fermentation conditions in a proline supplemented aqueous nutrient culture medium containing assimilable sources of carbon, nitrogen and inorganic salts.
Type:
Grant
Filed:
August 19, 1982
Date of Patent:
September 13, 1983
Assignee:
Eli Lilly and Company
Inventors:
Sean C. O'Connor, Walter M. Nakatsukasa
Abstract: Broad spectrum cephalosporin betaine antibiotics represented by the formula ##STR1## wherein Q is an oximino-substituted pyridinium, quinolinium or isoquinolinium group of the formulas ##STR2## wherein R.sub.1 and R.sub.2 are hydrogen or C.sub.1 -C.sub.3 alkyl; and R' is an amino-substituted 5- or 6-membered heterocyclic, eg., 2-aminothiazol-4-yl; and R" is C.sub.1 -C.sub.4 alkyl, an N-substituted carbamoyl group, or a carboxy-substituted alkyl or cycloalkyl group; have potent activity vs. G.sup.- organisms. Pharmaceutical formulations and a method for treating infectious disease with above compounds are provided.
Abstract: Cephalosporin broad spectrum antibiotics represented by the formula ##STR1## wherein R' is an amino-substituted 5- or 6-membered nitrogen heterocyclic ring, eg. 2-aminothiazol-4-yl and 3-aminopyridin-1-yl; R" is hydrogen, C.sub.1 -C.sub.4 alkyl, a carboxy-substituted alkyl or cycloalkyl group, or a carbamoyl or substituted carbamoyl group; and R.sub.1 and R.sub.2 are hydrogen, C.sub.1 -C.sub.4 alkyl, mono or di(C.sub.1 -C.sub.4 alkyl)amino, mono or di(hydroxy-substituted C.sub.2 -C.sub.4 alkyl)amino; are provided. These betaine cephalosporins are provided in antibiotic formulations and are useful in a method for treating infections.