Abstract: Sodium 7-(D-2-hydroxy-2-phenylacetamido)-3-(1-methyl-1H-tetrazole-5-ylthiomethyl) -3-cephem-4-carboxylate is obtained as a pharmaceutically acceptable crystalline anhydrate via crystalline methanolate or crystalline monohydrate forms.

Abstract: 6-Alkoxylated-6-acylamidopenicillanic acids and 7-alkoxylated-7-acylamidocephalosporin acids and esters thereof, are provided by reacting a 6-acylamidopenicillanic acid ester or a 7-acylamidocephalosporin ester under anhydrous conditions at -90.degree. C. to -15.degree. C. with an alkali metal salt of a lower alkyl alcohol in the presence of an excess of the corresponding alcohol to produce, in situ, the anionic form of the antibiotic which on halogenation with a positive halogen compound, e.g. t-butyl hypochlorite, yields the compound of the invention. Compounds of the invention, e.g. 6-methoxy-6-phenoxy-acetamidopenicillanic acid and 7-methoxy-7-[2-(2-thienyl)acetamido]cephalosporanic acid are useful antibiotics.

Abstract: Cephalosporin sulfoxides are reduced to the corresponding cephalosporin with acyl bromides, e.g., acetyl bromide, in the presence of a bromine scavenger, e.g., an olefin, acetylene, phenol, phenol ether, or an organophosphite. For example, p-nitrobenzyl 7-phenoxyacetamido-3-methyl-3-cephem-4-carboxylate sulfoxide is reduced with acetyl bromide in the presence of amylene to p-nitrobenzyl 7-phenoxyacetamido-3-methyl-3-cephem-4-carboxylate.

Abstract: 7-Acylamino-7-methoxycephalosporins substituted in the 3-position with an acetoxymethyl, halomethyl or 3-thio-substituted-methyl substituent are reduced electrolytically to provide the corresponding 3-exomethylenecepham compound. For example, 7-(2-thienylacetamido)-7-methoxy-3-acetoxymethyl-3-cephem-4-carboxylic acid is electrolytically reduced to provide 7-(2-thienylacetamido)-7-methoxy-3-exomethylenecepham-4-carboxylic acid and a lesser amount of the corresponding 3-methylcephalosporin compound.

Abstract: 7-[.alpha.-(guanyl-1-ureido)phenylacetamido]-3-(1-methyl-1H-tetrazol-5-ylth iomethyl)-3-cephem-4-carboxylic acid, 7-[.alpha.-(3-guanyl-1-ureido)phenylacetamido]-3-(5-methyl-1,3,4-thiadiazo l-2-ylthiomethyl)-3-cephem-4-carboxylic acid and related compounds, the pharmaceutically acceptable non-toxic salts and certain esters thereof are valuable broad spectrum antibiotics demonstrating high levels of activity against Pseudomonas species.

Abstract: Bis-trimethylsilyl cefamandole is useful for regenerating cefamandole of excellent purity.

Abstract: 7-Acylamido-3-exomethylenecepham ester sulfoxides are reacted with ozone to provide the corresponding 3-hydroxy-3-cephem ester sulfoxides, intermediates for 3-methoxy and 3-halo substituted cephalosporin antibiotics; e.g., p-nitrobenzyl 7-phenoxyacetamido-3-exomethylenecepham-4-carboxylate-1-oxide provides the corresponding 3-hydroxy-3-cephem ester sulfoxide.

Abstract: Novel quinoxaline derivatives, useful as immune regulatory agents capable of altering the immune response in mammals.

Abstract: 7-Amino-(or 7-acylamido)-3-(disubstituted-amino)-3-cephem-4-carboxylic acid esters are prepared with the corresponding 3-chloro-3-cephem ester or 3-alkyl-(or aryl)-sulfonyloxy-3-cephem esters and a secondary amine, e.g., diphenylmethyl 7-[2-(2-thienyl)acetamido] -3-morpholino-3-cephem-4-carboxylate is prepared with the corresponding 3-methyl-sulfonyloxy ester and morpholine. The 3-amino-substituted cephem esters are useful intermediates undergoing reduction with diborane to the corresponding 3H-3-cephem esters, or, alternatively, they are reacted with Grignard reagents, e.g., phenylmagnesium bromide to provide, for example, the 3-phenyl-3-cephem ester.

Abstract: 6-acylamido-6-methoxypenicillanic acids are obtained by reacting a 6-acylamidopenicillanic acid with mercuric acetate in methanol to yield a methyl .alpha.-methoxypenicilloate. Esterification of the latter with isobutylene affords the methyl, t-butyl diester of the methoxypenicilloic acid which undergoes selective hydrolysis in base to provide the free .alpha.-carboxylic acid half t-butyl ester of the penicilloic acid. The latter on reaction with dicyclohexylcarbodiimide affords an oxazolone-thiazolidine of the formula ##STR1## WHICH WITH 98% FORMIC ACID PROVIDES A COMPOUND OF THE INVENTION.

Abstract: 7-Acylamino-3-methyl-3-cephem-4-carboxylic acids and esters are prepared via the reductive cleavage of a 3-thio substituted 2-cephem-4-carboxylic acid or ester with hydrogen and Raney nickel or zinc in formic acid and DMF to provide reduction product mixtures of the corresponding 7-substituted 3-methyl-2-cephem-4-acid or ester (I) and 3-exomethylenecepham-4-acid or ester (II). Reduction product mixtures are separable via chromatography and individual I and II are isomerized to 3-methyl-3-cephem antibiotics.

Abstract: This invention relates to certain 3-amino-5,6-diaryl-1,2,4-triazines useful as anti-inflammatory agents and a method of treating inflammation.

Abstract: The cephalosporin antibiotic, sodium 7-(D-.alpha.-formyloxy-.alpha.-phenylacetamido)-3-(1-methyl-1H-tetrazol-5- ylthiomethyl)-3-cephem-4-carboxylate, is provided in a stable, non-solvated anhydrate crystalline form designated as the gamma crystalline form.

Abstract: Benzimidazo[2,1-b]quinazolin-12(6H)ones, immunosuppressives and agents for treatment of auto-immune diseases, are prepared via (1) reacting a 2-chlorobenzimidazole with an anthranilic acid or ester; (2) reacting a 2-aminobenzimidazole with an anthranilic acid or ester in the presence of trifluoroacetic acid or (3) reacting a 2-methylmercaptobenzimidazole with an anthraniloyl halide hydrohalide.

Abstract: 6-Alkoxylated-6-acylamidopenicillanic acids and 7-alkoxylated-7-acylamidocephalosporin acids and esters thereof, are provided by reacting a 6-acylamidopenicillanic acid ester or a 7-acylamidocephalosporin ester under anhydrous conditions at -90.degree. C. to -15.degree. C. with an alkali metal salt of a lower alkyl alcohol in the presence of an excess of the corresponding alcohol to produce, in situ, the anionic form of the antibiotic which on halogenation with a positive halogen compound, e.g. t-butyl hypochlorite, yields the compound of the invention. Compounds of the invention, e.g. 6-methoxy-6-phenoxyacetamidopenicillanic acid and 7-methoxy-7-[2-(2-thienyl)acetamido]cephalosporanic acid are useful antibiotics.

Abstract: 7-Acylamido-3-cephem-4-carboxylic acid antibiotics directly substituted in the 3-position of the cephem ring system with a sulfur atom bonded to a 5- or 6-membered heterocyclic ring, a lower alkyl group, or a phenyl or substituted phenyl group are prepared with the corresponding 3-halo-3-cephem esters. For example, p-nitrobenzyl 7-[2-(2-thienyl)acetamido]-3-chloro-3-cephem-4-carboxylate reacts with 1-methyl-1H-tetrazol-5-ylthiol to provide p-nitrobenzyl 7-[2-(2-thienyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thio]-3-cephem-4- carboxylate. The p-nitrobenzyl ester group is removed by catalytic hydrogenolysis to provide the antibiotic carboxylic acid compound. Alternatively, the antibiotics are prepared by reacting a 3-alkylsulfonyloxy, or 3-arylsulfonyloxy-3-cephem, for example, 3-methanesulfonyloxy-3-cephem, or a 3-p-toluenesulfonyloxy-3-cephem with the heterocyclic thiol, the phenyl or substituted phenylthiol, or with the lower alkylthiol.

Abstract: 6-APA, 7-ACA and 7-ADCA esters are reacted with benzaldehyde, acetophenone or substituted derivatives thereof providing imines which react in the presence of a strong base such as sodium hydride or lithium diisopropyl amide with a C.sub.2 -C.sub.5 alkanoyl halide, 2,2,2-trichloroethoxycarbonyl chloride, a benzoyl halide, a C.sub.1 -C.sub.4 alkoxycarbonyl chloride or a methoxymethyl halide to afford C.sub.6 and C.sub.7 substituted .beta.-lactam imines via acylation or methoxymethylation. The .beta.-lactam substituted imines are reacted with a carbonyl reagent, e.g. Girard's reagent T to provide a C.sub.6 substituted 6-APA ester or a C.sub.7 substituted 7-ACA or 7-ADCA ester which is acylated to provide a 6-acylamido-6-substituted penicillin or a 7-acyl-amide-7-substituted cephalosporin.

Abstract: N-Mono or dihydroxyphenylalkyl dopamine derivatives and salts thereof are inotropic agents useful in a method for treatment of acutely depressed cardiac insufficiency.

Abstract: 7-Acylamido-3-alkylsulfonyloxy (and phenyl or substituted phenylsulfonyloxy)-3-cephem-4-carboxylic acids and esters thereof are provided via sulfonation of 3-hydroxy-3-cephem esters. The 3-cephem-3-sulfonate esters are useful antibacterial compounds.

Abstract: A method for enhancing the contractile force of mammalian heart muscle which comprises administering an effective amount of antibiotic A-23187, a divalent cation ionophore.