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US 5,686,441 AGranted
Penam sulfones as .beta.-lactamase inhibitors
AssigneesSyphar Laboratories, Inc., Taiho Pharmaceutical Co., Ltd.
InventorsSamarendra Nath Maiti, Oludotun Adebayo Phillips, Andhe Venkat Narender Reddy, Eduardo Luis Setti, Ronald George Micetich, Chieko Kunugita, Fusahiro Higashitani, Akio Hyodo
Life of this patent
Estimating the term…
Abstract
Novel 3-(substituted)-3-methyl-4-thia-1-azabicyclo3.2.0!heptane-2-carboxylate, 4,4-dioxides which are of value for use in combination with .beta.-lactam antibiotics to increase the effectiveness of the antibiotics.
Claims14
A compound of formula I or Ia ##STR8## wherein R.sub.1 is the residue of a carboxy protecting group;
- R.sub.a is hydrogen or a pharmaceutically-acceptable salt forming agent or a pharmaceutically acceptable ester residue readily hydrolyzable in vivo;
- R.sub.2 is OR.sub.3 or NR.sub.4 R.sub.5,
- wherein R.sub.3 is selected from the group consisting of:
- (a) hydrogen;
- (b) straight or branched chain alkyl having from 1 to 20 carbon atoms;
- (c) alkenyl having from 2 to 20 carbon atoms;
- (d) alkynyl having from 2 to 20 carbon atoms;
- (e) cycloalkyl having from 3 to 8 carbon atoms;
- (f) cycloalkenyl having from 5 to 8 carbon atoms;
- (g) benzyl and (h) a heterocyclic alkyl wherein the heterocyclic group means a 5-(or 6-) membered ring containing from 1 to 4 of any one or more of the heteroatoms selected from O, S and N;
- (b) to (h) can be unsubstituted or substituted by radicals selected from the group consisting of alkyl, hydroxy, alkoxy, alkanoyloxy, halo, cyano, azido, nitro, carboxy, alkoxycarbonyl, alkanoyl, amino, substituted amino, amidino, guanidino, carboxamido, substituted carboxamido, mercapto, sulfinyl, sulfonyl, diethoxyphosphinylalkyl, dihydroxyphosphinylalkyl, a heteroarylthio, a heteroaryl group bonded via carbon, or!and a nitrogen containing heterocyclic group bonded via nitrogen;
- wherein R.sub.4 is selected from the group consisting of:
- (a) hydrogen;
- (b) straight or branched chain lower alkyl;
- (c) cycloalkyl;
- (d) alkanoyl;
- (e) benzoyl;
- (f) amido;
- (g) thioamido;
- (h) amidino;
- (i) benzyloxycarbonyl;
- and (j) trichloroethyloxycarbonyl;
- R.sub.5 is hydrogen or any of the groups (b) to (j) defined for R.sub.4 ;
- and R.sub.4 and R.sub.5 may join together and form part of the!a heterocyclic group ##STR9## which may contain one or more additional heteroatoms selected from N, S or O;
- and the pharmaceutically-acceptable salts thereof and the pharmaceutically-acceptable and readily hydrolyzable esters thereof.
22 more elements
A compound of formula Ia ##STR14## wherein R.sub.a is hydrogen or a pharmaceutically-acceptable salt forming agent or a pharmaceutically acceptable ester residue readily hydrolyzable in vivo;
- R.sub.2 is OR.sub.3 or NR.sub.4 R.sub.5,
- wherein R.sub.3 is selected from the group consisting of:
- (a) hydrogen;
- (b) straight or branched chain alkyl having from 1 to 20 carbon atoms;
- (c) alkenyl having from 2 to 20 carbon atoms;
- (d) alkynyl having from 2 to 20 carbon atoms;
- (e) cycloalkyl having from 3 to 8 carbon atoms;
- (f) cycloalkenyl having from 5 to 8 carbon atoms;
- (g) benzyl and (h) a heterocyclic alkyl wherein the heterocyclic group means a 5-(or 6-) membered ring containing from 1 to 4 of any one or more of the heteroatoms selected from O, S and N;
- (b) to (h) can be unsubstituted or substituted by radicals selected from the group consisting of alkyl, hydroxy, alkoxy, alkanoyloxy, halo, cyano, azido, nitro, carboxy, alkoxycarbonyl, alkanoyl, amino, substituted amino, amidino, guanidino, carboxamido, substituted carboxamido, mercapto, sulfinyl, sulfonyl, diethoxyphosphinylalkyl, dihydroxyphosphinylalkyl, a heteroarylthio, a heteroaryl group bonded via carbon, or a nitrogen containing heterocyclic group bonded via nitrogen;
- wherein R.sub.4 is selected from the group consisting of:
- (a) hydrogen;
- (b) straight or branched chain lower alkyl;
- (c) cycloalkyl;
- (d) alkanoyl;
- (e) benzoyl;
- (f) amido;
- (g) thioamido;
- (h) amidino;
- (i) benzyloxycarbonyl;
- and (j)trichloroethyloxycarbonyl;
- R.sub.5 is hydrogen or any of the groups (b) to (j) defined for R.sub.4 ;
- and R.sub.4 and R.sub.5 may join together and form part of the heterocyclic group ##STR15## which may contain one or more additional heteroatoms selected from N, S or O;
- and the pharmaceutically-acceptable salts thereof and the pharmaceutically-acceptable and readily hydrolyzable esters thereof,
- which compound contains variable amounts of water.
22 more elements
Dependencies are inferred from the claim text.