Eli Lilly and Company

William J Wheeler

William H Lunn

David T Wong

Edward Louis Mattiuz

John-Michael Sauer

The present invention provides compounds and methods for the inhibition of monoamine uptake in mammals.

Inhibitor of monoamine uptake

7.beta.-[2'-triazepinone-2'-(oximine ether) acetamido] cephalosporin antibiotics are claimed. Also claimed are the 2'-triazepinone-2'-(oxime ether) acetic acid intermediates and the esters, salts and halides thereof.

1,3,5-triazepinones

7.beta.-[2'-Triazepinone-2'-(oxime ether) acetamido] cephalosporin antibiotics are claimed. Also claimed are the 2'-triazepinone-2'-(oxime ether) acetic acid intermediates and the esters, salts and halides thereof.

7.beta.-(2'-(1',3',5'-Triazepin-4'-one)-2'-(oxime

Cephalosporin broad spectrum antibiotics possessing a 7.beta.-[2-[(2-aminooxazol)-4-yl]-2-(substituted oximino)]acetamido side chain and a variety of substituents at the 3-position of the cephalosporins are claimed. Also claimed are intermediates in the synthesis of the above cephalosporin antibiotics.

7-[2-(2-Aminooxazol-4-yl)-2-(oximino)acetamido cephalosporin antibiotics

Cephalosporin broad spectrum antibiotics possessing a 7.beta.-[2-[(2-aminooxazol)-4-yl]-2-(substituted oximino)acetamido side chain and a variety of substituents at the 3-position of the cephalosporins are claimed. Also claimed are intermediates in the synthesis of the above cephalosporin antibiotics.

7-[2-(2-Aminooxazol-4-yl)-2-(oximino)acetamido]cephalosporin antibiotics

Broad spectrum cephalosporin antibiotics represented by the formula, ##STR1## pharmaceutical compositions of the antibiotics, and a method for treating infections are provided. In the formula, R is 2-aminooxazol-4-yl, 5-amino-1,2,4-oxadiazol-3-yl or 5-aminoisoxazol-3-yl; R' is eg. C.sub.1 -C.sub.4 alkyl; R.sub.1 is H, NH.sub.2, chloro, C.sub.1 -C.sub.4 NH--, (C.sub.1 -C.sub.4).sub.2 N--, etc. The antibiotics are best prepared by reacting a pyrazine with a 3-iodomethyl cephalosporin.

Amino-substituted oxazole, oxadiazole and isoxazole-substituted

Broad spectrum cephalosporin antibiotics represented by the formula ##STR1## are provided. In the formula, R represents a 2-aminooxazol-4-yl, 5-amino-1,2,4-oxadiazol-3-yl, or 5-aminoisoxazol-3-yl heterocyclic group; R' is hydrogen, C.sub.1 -C.sub.4 alkyl, a carboxy-substituted alkyl or cycloalkyl group or a C.sub.1 -C.sub.4 alkyl ester or carboxy-protecting ester derivative thereof; or an N-substituted carbamoyl group; and R.sub.1 and R.sub.2 are independently hydrogen or a substituent group, eg. halo, hydroxy, amino, carbamoyl, alkyl, or trifluoromethyl. The antibiotics are useful in a method for treating bacterial infections and can be formulated into pharmaceutical formulations for such use.

3'-Substituted quinolinium cephalosporins

Broad spectrum cephalosporin antibiotics represented by the formula ##STR1## wherein R is a 3-aminoisoxazol-5-yl, 2-aminooxazol-4-yl, or a 5-amino-1,2,4-oxadiazol-3-yl group; R.sub.1 is isoquinolinium or substituted isoquinolinium; and R' is C.sub.1 -C.sub.4 alkyl, an N-substituted carbamoyl group, or a carboxy-substituted alkyl or cycloalkyl group; and the pharmaceutically acceptable non-toxic salts thereof; are prepared by the reaction of a 3-iodomethyl cephalosporin, having the above 2-(amino-substituted heterocyclic)-2-oximinoacetyl side chain, with isoquinoline or a substituted isoquinoline. Pharmaceutical formulations of the antibiotics and a method for treating bacterial infections with the antibiotics are provided.

Isoquinolinium substituted cephalosporins

Broad spectrum cephalosporin antibiotics represented by the formula ##STR1## wherein R is an amino-substituted oxazole, oxadiazol, or isoxazole heterocyclic, R' is C.sub.1 -C.sub.4 alkyl, a carboxysubstituted alkyl or cycloalkyl group, etc., and .sup..sym. R.sub.1 is an oximino-substituted pyridinium, quinolinium or isoquinolinium group, e.g., .sup..sym. R.sub.1 is a 3- or 4-formylpyridinium oxime group; pharmaceutical compositions comprising the antibiotic, and a method for treating antibacterial infections are provided.

Oximino-substituted cephalosporin compounds

The crystalline D-sesquisodium salt of the diacid of the formula ##STR1## and process for its preparation via acetone dilution of an aqueous solution of non-crystalline D,L-diacid and D,L-disodium salt.

Crystallization process

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

Bis-trimethylsilyl cefamandole and process therefor

Acyloxymethyl esters of 7-D-mandelamido-3-(1-methyl-1,2,3,4-tetrazole-5-thiomethyl)-3-cephem-4-car boxylic acid are orally active broad spectrum antibiotics.

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Indianapolis, IN, United States of America

William J Wheeler