E. R. Squibb Sons, Inc.

Squibb & Sons, Inc.

Slusarchyk, William A.

Dejneka, Tamara

Gordon, Eric M.

Koster, William H.

Ermann, Peter H.

Sundeen, Joseph E.

Treuner, Uwe D.

Straub, Henner

William H Koster

William A Slusarchyk

Robert Zahler

Christopher M Cimarusti

Joseph E Sundeen

Uwe D Treuner

Eric M Gordon

Gregory S Bisacchi

Richard B Sykes

Peter H Ermann

Sailesh A Varia

Henner Straub

Kent Amsberry

Michael Fakes

Hermann Breuer

David R Kronenthal

Joseph Edward Dolfini

William L Parker

Joseph E Dolfini

Spencer David Kimball

Jack Bernstein

Jerome L Moniot

Tamara Dejneka

Rita T Fox

Glenn A Jacobs

Alan W Fritz

Paula L Kuester

Edward M Cohen

W Lawrence Parker

Antibacterial activity is exhibited by novel compounds having the formula ##STR1## where R.sub.1, R.sub.2, and M are as defined herein and X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring.

Hereroaryl derivatives of monocyclic beta-lactam antibiotics

Antibacterial activity is exhibited by novel compounds having the formula ##STR1## where R.sub.1, R.sub.2, and M are as defined herein and X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring. Also described are various intermediates for the preparation of compounds of formula 1.

Intermediates for the preparation of heteroaryl derivatives of

Heteroaryl derivatives of monocyclic beta-lactam antibiotics

Antibacterial activity is exhibited by .beta.-lactams having a sulfonic acid salt substituent in the 1-position and an amino or acylamino substituent in the 3-position.

2-oxo-1-azetidinesulfonic acid salts

In accordance with the present invention an orally active monosulfactam antibiotics having a crystalline structure and thereby improved stability are disclosed. The antibiotics comprise the dierythromycin (M.sup..sym.=erythromycin.H.sup..sym.) salt or the dicholine (M.sup..sym. =HOCH.sub.2 CH.sub.2 N.sup..sym. (CH.sub.3).sub.3) salt of the acid (M.sup..sym. =H.sup..sym.) having the formula ##STR1## that is, [3S(Z)]-2[[[1-(2-amino-4-thiazolyl)-2-[[2,2-dimethyl-4-oxo-1-(sulfooxy)-3- azetidinyl]-amino]-2-oxoethylidene]amino]oxy]acetic acid.

Crystalline salts of

Antibacterial activity is exhibited by 2-azetidinones having a 3-acylamino substituent and having an activating group in the 1-position of the formula ##STR1##

2-oxo-1-[[(substituted sulfonyl)amino]carbonyl]azetidines

Antibacterial activity is exhibited by 2-azetidinones having an acylamino substituent in the 3-position and having an activating group in the 1-position of the formula ##STR1##

1-(substituted phosphorous)-azetidinone antibacterials

Antimicrobial activity is exhibited by .beta.-lactams having a ##STR1## substituent in the 1-position and an acylamino substituent in the 3-position, or a pharmaceutically acceptable salt thereof; wherein Y is oxygen or sulfur and R.sub.5 is hydroxyl, alkyl, substituted alkyl, phenyl, substituted phenyl, alkoxy, alkylthio, (substituted alkyl)oxy, (substituted alkyl)thio, phenyloxy, phenylthio, (substituted phenyl)oxy or (substituted phenyl)thio.

3-acylamino-2-oxo-1-azetidinyl esters of phosphonic acids, phosphoric

Antibacterial activity is exhibited by compounds having the formula and pharmaceutically acceptable salts thereof.

O-sulfated spiro .beta.-lactam hydroxamic acids

Antibacterial activity is exhibited by .beta.-lactams having a 3-acylamino substituent and in the 1-position a substituent having the formula ##STR1## wherein R.sub.5 and R.sub.6 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, phenyl, substituted phenyl, cycloalkyl or a 4,5,6 or 7-membered heterocycle, or R.sub.5 and R.sub.6 together with the carbon atom to which they are attached are cycloalkyl or a 4,5,6 or 7-membered heterocycle, or one of R.sub.5 and R.sub.6 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, alkenyl, alkynyl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, --CH.sub.2 X.sub.1, --S--X.sub.2, --O--X.sub.2, or ##STR2## R.sub.7 is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, 1-(ethoxycarbonyloxy)ethyl, 1,3-dihydro-3-oxo-1-isobenzofuranyl, ##STR3## wherein R' is hydrogen or alkyl, R' is alkyl or phenyl, R'' is hydrogen, methyl or phenyl, and R.sup.iv is hydrogen or together with R'' is --(CH.sub.2).sub.3 -- or --(CH.sub.2).sub.5 --; and

((3-Acylamino-2-oxo-1-azetidinyl)oxy)methyl)phosphinic acids

Antimicrobial activity is exhibited by compounds having the formula ##STR1## wherein R.sub.1 is hydrogen or aryl;

Acetylenic antibiotics

Antibacterial activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof.

Pharmaceutically acceptable salts of [3S(Z)]-2-[[[1-(2-amino-4-thiazolyl)-2-[[2,2-dimethyl-4-oxo-1-(sulfooxy)-3 -azetidinyl]amino]-2-oxoethylidene]amino]oxy] acetic acid and a process useful in the preparation of such salts are disclosed herein.

[3S(Z)]-2-[[[1-(2-amino-4-thiazolyl)-2-[[2,2-dimethyl-4-oxo-1-(sulfoo

A compound having the formula ##STR1## can be prepared by heating an anion having the formula ##STR2## with a cation having the formula ##STR3## or a cation having the formula ##STR4##

Desulfonation process for preparing 2-azetidinones

Growing community of inventors

Pennington, NJ, United States of America

William H Koster