Alfa Farmaceutici S.p.a.

Mediolanum Farmaceutici, S.r.l.

Alpha Farmaceutici S.p.a.

Giuseppe Mascellani

Valerio Borzatta

Mauro Morotti

Manlio Cristofori

Patrizia Terni

Arnaldo Fravolini

Guido Guerra

Egidio Marchi

Mario Brufani

Carlo Buitar

Renato Andrisano

Pierfranco Bellomo

A new class of antimicrobial pyrido-benzothiazine compounds and processes for their preparation are described. The compounds have the general formula: ##STR1##

Anti-bacterial pyrido-benzothiazine derivative and pharmaceutical

Pyrido-benzothiazine compounds having anti-microbial activity are prepared by (a) reacting 3-chloro-4-fluoroaniline with potassium thiocyanate and bromine to produce 2-amino-6-fluoro-7-chlorobenzothiazole, (b) reacting 2-amino-6-fluoro-7-chlorobenzothiazole with sodium hydroxide to produce the disulfide of 2-amino-5-fluoro 6-chlorothiophenol, (c) reacting the disulfide with sodium monochloroacetate to produce 7-fluoro-8-chloro-2H-1,4-benzothiazin-3(4H)-one, (d) reducing 7-fluoro-8-chloro-2H-1,4-benzothiazin-3(4H)-one to produce 7-fluoro-8-chloro-3,4-dihydro-2H-1,4-benzothiazone, (e) reacting 7-fluoro-8-chloro-3,4-dihydro-2-H-1,4-benzothiazone with ethyl ethoxymethylenemalonate and cyclyzing the intermediate formed with polyphosphoric acid to produce ethyl 9-fluoro-10-chloro-7-oxo-2,3-dihydro-7H-pyrido[1,2,3 de] [1,4]-benzothiazine-6-carboxylate and (f) hydrolyizing the ethyl carboxylate to produce the corresponding carboxylic acid.

Derivatives of pyrido-benzothiazine with high anti-microbial activity

Derivatives of benzoylphenoxyalkanoic acids corresponding to the formula: ##STR1## wherein: X represents for example a halogen, R.sup.1 and R.sup.2 represent for example alkyl groups, R represents for example an aminoacid; and the salts thereof are new products showing antilipaemic and anticholesterolemic pharmacological activity.

Derivatives of benzoylphenoxyalkanoic acids having normolipemizing

New compounds being derivatives of 3-carboxyrifamycin S and SV are prepared by oxidation of cyanohydrin of 3-formylrifamycin S to 3-(cyanocarbonyl)rifamycin S, condensation with a compound of formula HR (an alcohol, an amine or an substituted hydrazine) and, optionally, reduction of the derivative of 3-carboxyrifamycin S so obtained to the corresponding SV form. Alternatively 3-(cyanocarbonyl)rifamycin S may be converted to the SV form before condensing with the compound HR.

Derivatives of 3-carboxyrifamycin S and SV and process for their

A process for the recovery of cephalosporin C from an aqueous medium, including the steps of treating the medium with a sulphonyl chloride of formula R--SO.sub.2 Cl, in which R is a substituted or unsubstituted alkyl group having from 4 to 10 carbon atoms, or a substituted or unsubstituted aryl group, to convert the cephalosporin C to the corresponding sulphonamide and extracting the sulphonamide with an essentially water immiscible solvent. The sulphonyl chloride may be toluene-p-sulphonyl chloride, p-isopropylbenzenesulphonyl chloride or .beta.-naphthalenesulphonyl chloride. The molar ratio of sulphonyl chloride to cephalosporin C present in the aqueous medium is from 3 to 10. The temperature of the reaction of sulphonyl chloride with cephalosporin C is maintained in the range from 10.degree. to 20.degree. C. The water immiscible solvent is selected from ethyl acetate, n-butanol and methylisobutylketone. The pH of the reaction medium is maintained at a value of from 7.5 to 9.5 by means of a buffering agent. The extraction of the sulphonamide of cephalosporin C is carried out at a pH of from 1 to 4.

Process for the recovery of cephalosporin C and derivatives thereof

Novel cephalosporin derivatives, for example N-acetoacetylcephalosporin C, N-decanoylcephalosporin C, N-dodecanoylcephalosporin C and N-hendecenoylcephalosporin C, are useful as readily-recoverable intermediates in the isolation of cephalosporin C value from fermentation broths and in the preparation of 7-aminocephalosporanic acid. They are prepared by treating an aqueous solution containing cephalosporin C, such as a fermentation broth, with diketene or an acid chloride such as decanoyl chloride, dodecanoyl chloride or hendecenoyl chloride, followed by solvent extraction. They are converted into 7-aminocephalosporanic acid by successively forming the silyl di-ester, halogenating to the imino-halide, converting the imino-ether and hydrolysing to 7-ACA.

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Bologna, Italy

Giuseppe Mascellani