Hoffmann-la Roche Inc.

The United States of America

Manfred Weigele

Willy Leimgruber

Dennis D Keith

Chung-Chen Wei

Emanuel Grunberg

Roy Cleeland, Jr

Harry A Albrecht

John E Heveran

Sidney Teitel

Steve Yik-Kai Tam

Antonino Focella

Silvano DeBernardo

Ka-kong Chan

Donna Mary Huryn

Hiroaki Mitsuya

Magdalena U Gomez

Pamela Loreen Rossman

Harvey Gurien

Frederick M Konzelmann

Rudolf L Then

John P Tengi

Roxana Yang

Samuel Broger

Silvano De Bernardo

There are presented antibacterial cephalosporine having broad antimicrobial activity, having the formula ##STR1## wherein R is hydrogen or a carboxylic acid-protecting group: R.sub.1 represents a substituted piperazinyl group of formula ##STR2## or a substituted pyrrolidinylamino group of formula ##STR3## or a substituted pyrrolidinylmethylamino group of formula ##STR4## where the piperazinyl or pyrrolidinyl group may be optionally substituted with one or more lower alkyl groups, and where Q represents a substituted quinolinyl or naphthyridinyl group: R.sub.2 is selected from the group consisting of hydrogen, lower alkoxy, lower alkylthio and amido; R.sub.3 is hydrogen or an acyl group: and m is 0, 1 or 2, but preferably 0; as well as the corresponding readily hydrolyzable esters. pharmaceutically acceptable salts and hydrates of these compounds.

Antibacterial cephalosporin compounds

There are presented antibacterial cephalosporins having broad antimicrobial activity as well as intermediates for their formation, such compounds having the formula ##STR1## wherein R is hydrogen or a carboxylic acid-protecting group; R.sub.1 is a substituted piperazinium group of the formula ##STR2## in which Q represents a substituted quinolinyl or naphthyridinyl group and the piperazine nucleus may be optionally substituted with one or more lower alkyl groups; R.sub.2 is selected from the group consisting of hydrogen, lower alkoxy, lower alkylthio and amido; R.sub.3 is hydrogen or an acyl group; and m is 0, 1 or 2, preferably 0; as well as the corresponding readily hydrolyzable esters, pharmaceutically acceptable salts and hydrates of these compounds.

There are presented anti-bacterial cephalosporins having broad antimicrobial activity of the formula ##STR1## wherein R.sub.1 is an antibiotically active quinolonyl; R.sub.2 is selected from the group consisting of hydrogen, lower alkoxy, amino, lower alkylthio and amido; R.sub.3 is selected from the group consisting of hydrogen, and acyl group, and m is 0, 1 or 2 and the readily hydrolysable esters or salts of these compounds and hydrates of the compounds of formula I or of their esters or salts.

Anti-bacterial cephalosporin compounds

Isomeric derivatives of 2',3'-dideoxyadenosine and 2',3'-dideoxyguanosine wherein the adenine or guanine base is attached to the 1' position of the iso-dideoxysugar residue by the 9-N position, the novel intermediates used in the synthesis of these compounds, and a method for treating a subject infected with a retrovirus by administering the compounds of the invention.

Isomeric dideoxynuclesides

A-B-C wherein A and C are each independently 2',3' dideoxynucleosides and B is a linking group; and a method of treating or preventing a retroviral injection in a subject by administering the compounds of the invention.

Anti-retroviral compounds

There are presented compounds of the formula ##STR1## wherein R.sub.2, R.sub.3, R.sub.4 and m are as described herein.

Methylene penam and derivatives thereof

A novel enantiomeric systhesis from ascorbic acid of (3S,4S)-3-amino-4-carbamoyloxymethyl-2-azetidinone-1-sulfate, an intermediate for an antibiotic compound.

4-hydroxy-l-threoninamides

6-Amidinopenicillanic acid derivatives wherein one of the nitrogen atoms of the amidino group is part of a heterocyclic ring having on a side chain an unsubstituted heterocyclic ring containing 2 to 3 nitrogen atoms, and being useful as an antibiotic.

Imidazole derivatives

A novel enantiomeric synthesis from ascorbic acid of (3S,4S)-3-amino-4-carbamoyloxymethyl-2-azetidinone-1-sulfate, an intermediate for an antibiotic compound.

Enantiomeric synthesis of

A process for the Raney nickel desulfurization of penicillins is described. In the process of the invention, amino penicillanic acid or derivatives thereof are reacted with Raney nickel under controlled conditions of temperature and time to yield azetidinones which are useful as intermediates for the synthesis of monocyclic beta-lactam antibiotics.

Desulfurization of penicillins to prepare azetidinones

Penicillanic acid derivatives

A .beta.-lactamase inhibitor of the formula ##STR1## and the pharmaceutically acceptable salts thereof are presented. Also presented are intermediates and synthetic processes for the manufacture of the formula I compound. The compound inhibits the activity of enzymes which inactivate certain .beta.lactam antibiotics.

.beta.-Lactamase inhibitors

Aminoaryl esters and amino-lower alkyl amides of carboxy substituted barbiturates are linked via an amide linkage to carboxylated latex polymers to form reagents which are useful in a sensitive diagnostic test to detect the presence of barbiturates in body fluids.

Diagnostic test for barbiturates

The amino acid 2-amino-4-(2-aminoethoxy)-trans-but-3-enoic acid can be conveniently prepared via novel intermediates from a 2,2'-disubstituted diethyl ether and a dialkyl N-protected amidomalonate starting material using a multi-step process. Preferred starting materials are bis-2-chloroethyl ether and diethyl acetamidomalonate. The process, in a preferred embodiment, proceeds through the key intermediate ethyl-2-acetamido-4-[2-(2-phthalimido)ethoxy]-but-2-enoate.

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North Caldwell, NJ, United States of America

Manfred Weigele