Archifar Industrie Chimiche Del Trentino S.p.a.

Archifar Laboratori Chimico Farmacologici S.p.a.

Rifar S.r.l.

Farmitalia Carlo Erba S.p.a.

Dobfar S.p.a.

Archifar Laboratori Chimico Farmachologici S.p.a.

Archifar Laboratori Chimice Farmacologici S.p.a.

Leonardo Marsili

Carmine Pasqualucci

Vittorio Rossetti

Giovanni Franceschi

Aurora Sanfilippo

Marco Falciani

Sergio Vioglio

Renato Broggi

Pietro Cesti

The invention relates to a substantially anhydrous crystalline cefadroxil having a water content between about 0.8% and 3.9%. Such cefadroxil is obtained slurrying a cefadroxil solvate of dimethylacetamide, or of N-methyl-2-pyrrolidone or of monomethylformamide, with isopropyl alcohol with up to 4% of water and preferably in the presence of methanol in an amount lower than 60%, at a temperature of about +45.degree. C. to +55.degree. C. and then filtering the so obtained compound.

Substantially anhydrous crystalline cefadroxil and method for producing

The invention relates to a novel crystalline cefadroxyl hemihydrate having a K.F. between about 3.5 and 2.0%: such compound is more stable than other cefadroxyl molecules. The novel cefadroxyl is obtained preparing and isolating a novel cefadroxil solvate of dimethylacetamide, or of N-methyl-2-pyrrolidone or of monomethylformamide, slurrying and solvate with a mixture methanol/isporpyl alcohol 30:70 to 50:50 by volume at a temperature of about +45.degree. C. to +55.degree. C. and then filtering the so obtained compound.

Cefadroxil solvates

The invention relates to a novel crystalline cefadroxyl hemihydrate having a K.F. between about 3.5 and 2.0%: such compound is more stable than other cefadroxyl molecules. The novel cefadroxyl is obtained preparing and isolating a novel cefadroxil solvate of dimethylacetamide, or of N-methyl-2-pyrrolidone or of monomethylformamide, slurrying said solvate with a mixture methanol/isopropyl alcohol 30:70 to 50:50 by volume at a temperature of about +45.degree. C. to +55.degree. C. and then filtering the so obtained compound.

Solvate of cefadroxyl

The invention relates to a method for producing crystalline cefadroxil hemihydrate. According to the method a cefadroxil solvate is slurried with a mixture methanol:isopropyl alcohol 30:70 to 70:30 by volume containing from 5% to 12% of water, a temperature from +45.degree. C. to +55.degree. C. and then isolating the so obtained crystalline compound.

Method for producing crystalline cefadroxil hemihydrate

The invention relates to a method for preparing crystalline cefadroxil monohydrate. According to such a method a cefadroxil solvate is slurried with isopropyl alcohol containing less 6% to 18% of water at a temperature between +45.degree. to +55.degree. C.: the crystalline cefadroxil monohydrate is isolated by filtration. Some of the cefadroxil solvates which can be used are novel: they are prepared by adding dimethylacetamide, N-methyl-2-pyrrolidone or monomethylformamide to an aqueous solution of cefadroxil at a pH between 5.5 and 6.

Method for preparing crystalline cefadroxil monohydrate

There are provided 3-azinomethyl rifamycins of the formula I: ##STR1## wherein R represents hydrogen or acetyl;

3-azinomethyl rifamycins

There are provided azino rifamycin compounds of the formula (I): ##STR1## Y.dbd.H or CH.sub.3 CO; R.sub.1 linear or branched C.sub.1 -C.sub.7 alkyl or C.sub.3 -C.sub.4 alkenyl- R.sub.2 =linear or branched C.sub.1 -C.sub.7 alkyl, C.sub.2 -C.sub.4 chloroalkyl, C.sub.3 -C.sub.4 alkenyl, Cycloalkyl having 3 to 7 C atoms in the ring, cycloalkyl alkyl having 3 to 6 C atoms in the ring, phenyl, or C.sub.7 -C.sub.8 aralkyl, unsubstituted or mono-substituted by a halogen atom in the aryl group; or NR.sub.1 R.sub.2 =a cyclic moiety having 5 to 8 C atoms, unsubstituted or substituted by 1 or 2 CH.sub.3 groups, morpholino. The compounds inhibit the growth of gram positive bacteria and Mycobacterium tuberculosis. Oxidized compounds, preparative methods and pharmaceutical compositions are also described and claimed.

Azino rifamycins

Novel 3-amidino rifamycins having the formula: ##STR1## wherein Y is --H or --COCH.sub.3 ; R.sub.1 and R.sub.2 may be linear or branched alkyl having from 1 to 7 carbon atoms and alkenyl having 3 or 4 atoms and R.sub.2 may be also chloroalkyl having from 2 to 4 carbon atoms, cycloalkyl having from 3 to 7 carbon atoms in the ring, cycloalkylalkyl having from 3 to 6 carbon atoms in the ring, phenyl, bornyl, arylalkyl hydrocarbon having 7 or 8 carbon atoms which may be substituted with one halogen atom in the aryl group; and R.sub.1 and R.sub.2 along with the N atom to which they are bonded form an unsubstituted cyclic moiety having from 5 to 8 carbon atoms, a cyclic moiety having from 5 to 8 carbon atoms substituted with 1 or 2 methyl radicals, 4-alkylpiperazine, morpholine, 1,2,3,4-tetrahydroisoquinoline. These novel compounds are from grey to dark solids having high antibacterial activity which are obtained by reacting 3-amino rifamycin S or SV with a chloroformiminio chloride.

3-Amidino ansamycins

Novel rifamycin derivatives having the formula: ##STR1## wherein Y is --H or --COCH.sub.3 ; R.sub.1 and R.sub.2 may be linear or branched alkyl having from 1 to 7 carbon atoms and alkenyl having 3 or 4 carbon atoms R.sub.2 may be also chloroalkyl having from 2 to 4 carbon atoms, cycloalkyl having from 3 to 7 carbon atoms in the ring, cycloalkylalkyl having from 3 to 6 carbon atoms in the ring, phenyl, bornyl, arylalkyl hydrocarbon having 7 or 8 carbon atoms which may be substituted with one halogen atom in the aryl group; and R.sub.1 and R.sub.2 along with the N atom to which they are bonded form an unsubstituted cyclic moiety having from 5 to 8 carbon atoms, a cyclic moiety having from 5 to 8 carbon atoms substituted with 1 or 2 methyl radicals, 4-alkylpiperazine, morpholine, 1,2,3,4-tetrahydroisoquinoline. These novel compounds are yellow-orange solids having high antibacterical activity which are obtained by reacting 3-amino-4-deoxo-4-imino rifamycin S with a chloroformiminium chloride.

Rifamycin XII derivatives, their preparation and anti-bacterial

Method of producing derivatives of 6-.beta.-amidinopenicillanic acid, according to which a derivative of 6-aminopenicillanic acid is condensed with a reactive derivative of disubstituted amide in an inert anhydrous solvent and in the presence of a tertiary amine. In such a reaction, the reactive derivative of the disubstituted amide comprises a complex of an amide of carboxylic acid.

Method of producing derivatives of 6-.beta.-amidinopenicillanic acid

Novel rifamycin compounds of high antibiotic activity. Such compounds are obtained by reacting 3-amino-4-deoxo-4-imino-rifamycin S with aldehydes.

Novel rifamycin compounds of high antibiotic activity

Oxidized rifamycin compounds having high antibiotic activity as obtained by reacting 3-amino-4-deoxo-4-imino-rifamycin S or related compounds with a ketone.

Rifamycin compounds

3-nitro-rifamycins S and SV useful as starting compounds for the production of antibiotic substances. Such compounds are obtained by reaction of a 3-bromo-rifamycin S with sodium nitrite in a dipolar aprotic solvent at a temperature from room temperature to +40.degree. C.

3-Nitro-rifamycins S and SV

Method of preparing 3-amino-rifamycins S and SV having antibiotic activity. According to such a method a 3-bromo-rifamycin S is reacted with sodium nitrite to give 3-nitro-rifamycin S which is reduced with zinc powder to give the 3-amino-rifamycin SV from which the 3-amino-rifamycin S can be obtained by treatment with an oxidating agent.

Process for producing 3-amino-rifamycins S and SV

Rifamycin compounds having high antibacterial activity, consisting of powder colored from yellow to orange. Such compounds are provided by reacting 3-amino-rifamycin S with an aldehyde of formula X--CHO in the presence of a reducing agent and in an organic solvent.

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Milan, Italy

Leonardo Marsili