Pliva, Farmaceutska, Kemijska, Prehrambena I Kozmeticka Industrija,

Pliva Farmaceutska

Pliva and Pliva Handels Gmbh

Irena Lukic

Jure J Herak

Mice Kovacevic

Mirjana Tomic

Zinka Brkic

Zora Mandiec

Zora Mandic

The invention relates to novel 2-bromo- and 2-nitroxy derivatives of 3-,bromo- and 3-dibromo-4-oxo-azetidines, to processes for the preparation thereof and to the use thereof. According to the invention 2-bromo- and 2-nitroxy derivatives of 3-bromo- and 3-dibromo-4-oxo-azetidines are prepared by reacting derivatives of protected penicillanic lanic acid 1,1-dioxides with DBN reactant (1,5-diazabicyclo/3.4.0/non-5-ene) and then the obtained DBN salt of sulfinic acid or isolated sulfinic acid is treated with thionyl chloride and, after eliminating thionyl chloride by evaporation, the obtained residue is passed through a silica gel column with methylene chloride or some other solvent as eluant or the obtained residue is dissolved in tetrahydrofuran or some other suitable solvent and treated with tetrabutyl ammonium bromide and after the treatment a derivative of 2-bromo, 3-bromo or 2-bromo-3,3-dibromo-4oxo-azetidine is isolated, which derivative may be subjected to a reaction with silver nitrate in 2-propanol and, after the treatment of the reaction mixture, derivatives of 2-nitroxy-, 3-bromo- or 2-nitroxy-3,3-dibromo-4-oxo-azetidine are isolated. The obtained substances are useful intermediates in the syntheses of beta lactam analogons or as components in formulations having antibacterial, inhibitory, anti-tumour or antagonistic action.

Process for the preparation of 2-bromo- and 2-nitroxy derivatives of

Novel 2-bromo- and 2-nitroxy derivatives of 3-bromo- and 3-dibromo-4-oxo-azetidines, to processes for the preparation thereof and to the use thereof are provided. The azetidines of the present invention have the formula I ##STR1## wherein R.sup.1 is hydrogen or bromine,

2-bromo-and derivatives of 3-bromo-and 3,3-dibromo-4-oxo-azetidines,

3-Bromo- and 3,3-dibromo-4-oxo-1-azetidines of the formula I ##STR1## wherein R.sub.1 is hydrogen or bromo, R.sub.2 is hydrogen or bromo, R.sub.3 is hydrogen, ##STR2## wherein R.sub.4 is hydrogen, methyl, benzyl or some other protective group, R.sub.5 is hydrogen, alkyl, alkylaryl, a heterocyclic ring, Y is a halo atom, X is a halo atom, alkoxy group, nitroxy group are provided along with processes for the preparation thereof and the use thereof. The 3-bromo- and 3,3-dibromo-4-oxo-1-azetidines can be prepared by reacting 2-sulfinic acid derivatives, with various halogenating agents, and after treating the reaction mixture, 2-halo derivatives of 3-bromo- and 2,2-dibromo-4-oxo-azetidines are isolated and are subjected to a reaction with silver tetrafluoroborate and alcohols to give the corresponding 2-alkoxy derivatives of 3-bromo- and 3,3-dibromo-4-oxo azetidines, or 2-halo derivatives of 3-bromo- and 3-3-dibromo-4-oxo azetidines are subjected to a reaction with silver nitrate in 2-propanol to give, after treating the reaction mixture, 2-nitroxy derivatives of 3-bromo and 3,3-dibromo-4-oxo-1-azetidines. Some newly prepared compounds are deprotected and derivatives having a free carboxy group are obtained. The prepared compounds are components in pharmaceutical compositions effective in antibacterial or antirumour therapy.

Derivatives of 3-bromo- and 3,3-dibromo-4-oxo-1-azetidines, processes

The azetidines of the present invention have the formula I ##STR1## wherein R.sup.1 is hydrogen or bromine,

2-bromo- and 2-nitroxy derivatives of 3-bromo- and

Formulations exhibiting antibacterial inhibitory or antitumor action containing an effective amount of 2-bromo-and 2-nitroxy derivatives of 3-bromo and 3,3-dibromo-4-oxo-azetidine, and a method of use of the formulations are provided.

Preparations containing 2-bromo- and 2-nitroxy derivatives of 3-bromo-

The invention relates to the novel 4-oxo-azetidine-2-sulfonic acid amides and their salts of the formula I ##STR1## wherein the radicals have the meanings: R.sup.1 =hydrogen, halogen;

Amides of 4-oxo-azetidine-2-sulfonic acids and salts thereof, processes

5-Thia-1,4-diazabicyclo[4.2.0]octane-3,8-dioxo analogs of .beta.-lactam, processes for the preparation thereof and the use thereof Disclosed are novel 5-thia-1,4-diazabicyclo[4.2.0]octane-3,8-dioxo .beta.-lactam analogs of the general formula I ##STR1## wherein R.sup.1 is hydrogen or halo;

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Zagreb, Croatia

Irena Lukic