Claims
- 1. A compound of the formula: ##STR127## wherein: (A) Z is oxygen;
- (B) R.sub.0 is hydrogen, (C.sub.1 -C.sub.2)alkyl, CH.sub.2 OR.sub.4, CH.sub.2 NHR.sub.5, CH(OR.sub.4)CH.sub.3, CHFCH.sub.3 or CH(NHR.sub.5)CH.sub.3 ; wherein
- (i) R.sub.4 is selected from hydrogen, and moieties of the formulae: ##STR128## (ii) R.sub.5 is selected from hydrogen, and moieties of the formulae: ##STR129## (iii) R.sub.6 is selected from a straight, branched or substituted (C.sub.1 -C.sub.18)alkyl, (C.sub.2 -C.sub.18)alkenyl, unsubstituted or substituted (C.sub.3 -C.sub.7)monocyclo (C.sub.1 -C.sub.10) alkyl, unsubstituted or substituted (C.sub.5 -C.sub.10) bicyclo (C.sub.1 -C.sub.10)alkyl, aryl or substituted aryl, heteroaryl or substituted heteroaryl, heterocyclyl or substituted heterocyclyl; wherein the heterocyclyl moiety is a monocyclic or bicyclic group having 1-10 carbon atoms and 1-4 heteroatoms selected from oxygen, nitrogen or sulfur atoms and each ring of the heterocycle is comprised of 4 to 7 atoms, the heteroaryl group is an aromatic monocyclic or bicyclic heterocyclic group of 5-12 atoms wherein the heteroatom or heteroatoms are selected from 1-4 oxygen, nitrogen or sulfur atoms; the substitution for the alkyl, monocycloalkyl and bicycloalkyl moieties are selected from trifluoromethyl, pentafluoroethyl, amino, mono(C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, hydroxy, (C.sub.1 -C.sub.6)alkoxy, (C.sub.3 -C.sub.8)cycloalkoxy, carboxy, (C.sub.2 -C.sub.10)carboalkoxy, cyano and (C.sub.1 -C.sub.10)carboxamido; the substitution for the aryl, heteroaryl and heterocyclyl moieties is selected from (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)mono-, di- or polyfluoroalkyl, hydroxy, (C.sub.1 -C.sub.6)alkoxy, (C.sub.3 -C.sub.8) cycloalkoxy, amino, mono(C.sub.1 -C.sub.6)alkylamino, di-(C.sub.1 -C.sub.6)alkylamino, carboxy, (C.sub.2 -C.sub.10)carboalkoxy, cyano and (C.sub.1 -C.sub.10)carboxamido;
- (C) R.sub.1 is straight or branched (C.sub.1 -C.sub.8)alkyl, straight or branched (C.sub.2 -C.sub.8)alkenyl, (C.sub.3 -C.sub.8)cycloalkyl; or (CH.sub.2).sub.n' R; wherein n' is an integer of from 1-6; R is selected from CF.sub.3, C.sub.2 F.sub.5, fluorine, chlorine, bromine, hydroxy, alkoxy, nitrile, azido, amidino, formamidino, guanidino and NR'R"; wherein
- (i) R' and R" are independently selected from hydrogen, straight or branched (C.sub.1 -C.sub.6)alkyl, straight or branched (C.sub.1 -C.sub.6)alkoxy, 2-hydroxyethyl, 2-azidoethyl and 2-aminoethyl;
- (ii) and when R' is hydrogen or straight or branched (C.sub.1 -C.sub.6)alkyl, R" may also be selected from amino, hydroxy, mono (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkyl-amino, acyl, benzoyl, dihydroxybenzoyl, an acyl residue of an amino acid or peptide said amino acid selected from the group consisting of alanine, glycine, arginine, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, aminopimelic acid and threonine, and straight or branched substituted (C.sub.1 -C.sub.6)alkyl wherein said alkyl substituent is selected from hydroxy, (C.sub.1 -C.sub.6)alkoxy, azido, amino, mono(C.sub.1 -C.sub.6)alkylamino, di- (C.sub.1 -C.sub.6)alkylamino, guanidino, nitrile, carboxy, formimidoyl and phenyl; or
- (iii) R' and R" taken together with the associated nitrogen is an unsubstituted or substituted monocyclic or bicyclic heterocyclic ring having up to four (4) heteroatoms in each ring independently selected from oxygen, nitrogen and sulfur, wherein said substituent is selected from straight or branched (C.sub.1 -C.sub.6)alkyl, straight or branched (C.sub.1 -C.sub.6)alkoxy, (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.3 -C.sub.8)cycloalkoxy, trifluoromethyl, hydroxy, halogen (selected from bromine, chlorine, fluorine and iodine), amino, nitrile, carboxy, carbamido, carbamoyl, straight or branched mono(C.sub.1 -C.sub.6)alkylamino, straight or branched di(C.sub.1 -C.sub.6)alkylamino, and amino (C.sub.1 -C.sub.6)alkyl;
- (D) n is an integer from 1-3;
- (E) R.sub.2 is:
- (i) --OCOCH.sub.3, --OCOCF.sub.3, --OSO.sub.2 Ph, azido;
- (ii) a moiety of the formula:
- --S(O).sub.n" R.sup.a
- wherein n" is an integer from 0-2; and R.sup.a is
- (a) hydrogen or an
- (b) organic group bonded via a carbon atom selected from substituted or unsubstituted (C.sub.1 -C.sub.6)alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaryl (C.sub.1 -C.sub.6)alkyl, substituted or unsubstituted heterocyclyl; said substitution is selected from (C.sub.1 -C.sub.6)alkyl, hydroxy (C.sub.1 -C.sub.6) alkoxy, phenyl, heterocyclyl, amino, amidino, guanidino, carboxamido, carbamoyl (C.sub.1 -C.sub.6)alkanoylamino, mono- and di(C.sub.1 -C.sub.6)alkylamino;
- (iii) or R.sub.2 is selected from hydroxy, --OR.sup.a, --OC(O)R.sup.a, --OC(O)OR.sup.a, --OC(O)NR.sup.a R.sup.a or ##STR130## wherein R.sup.a is independently selected and is as hereinabove defined; (iv) or R.sub.2 is an organic residue bonded via a nitrogen atom, selected from:
- (a) NO.sub.2 and NR.sup.h R.sup.j wherein R.sup.h and R.sup.j are independently selected from hydrogen, amino, substituted amino, substituted or unsubstituted (C.sub.1 -C.sub.8)alkyl, aryl, wherein the substituents in the above mentioned substituted alkyl and amino are selected from the group consisting of amino, mono-, di- and tri(C.sub.1 -C.sub.6)alkylamino, hydroxyl, oxo, carboxyl, alkoxyl, chloro, fluoro, bromo, nitro, --SO.sub.2 NH.sub.2, phenyl, benzyl, acyloxy, alkoxylcarbonyloxy, cycloalkoxycarbonyloxy and carboxamido;
- (b) moieties of the formulae: ##STR131## wherein R.sup.h and R.sup.j are as hereinabove defined; (c) acylamino moieties of the formula: ##STR132## wherein R.sup.h and R.sup.j are as hereinabove defined; (d) an amino moiety containing an acyl residue of an amino acid or peptide represented by the formula: ##STR133## wherein R.sup.h is as hereinabove defined; R.sup.m is hydrogen or an acyl residue of an amino acid or peptide said amino acid selected from the group consisting of alanine, glycine, arginine, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, prolite, aminopimelic acid and threonine; and R.sup.t is hydrogen, benzyl, and straight or branched (C.sub.1 -C.sub.6)alkyl optionally substituted with halo, hydroxy, amino, guanidinyl, carboxy, phenyl, aminocarbonyl, alkylthio, hydroxyphenyl or heterocyclyl;
- (e) an acylcic quaternary ammonio moiety of the formula: ##STR134## wherein R.sub.7, R.sub.8 and R.sub.9 are the same or different and are selected from hydrogen, a straight or branched (C.sub.1 -C.sub.6) alkyl, and substituted (C.sub.1 -C.sub.6)alkyl, wherein the substitution is selected from hydroxy, (C.sub.1 -C.sub.6)alkoxy, azido, amino, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)-alkylamino, guanidino, nitrile, carboxy, formimidoyl and phenyl; alternatively, R.sub.7 and R.sub.8 taken together are --(CH.sub.2).sub.2 X(CH.sub.2).sub.2 --, wherein X is (CH.sub.2).sub.w, wherein w is an integer from 0 to 2 oxygen, sulfur NH, NR.sup.h, NOH and NOR.sup.h wherein R.sup.h is as hereinabove defined and B.sup.- is a physiologically acceptable anion;
- (f) a quaternized heteroaryl wherein the heteroaryl moiety must contain at least one positively charged nitrogen atom in association with a physiologically acceptable anion, wherein the quaternized heteroaryl is optionally substituted by R.sup.a as hereinabove defined;
- (v) or R.sub.2 is --CHR.sup.h R.sup.j wherein R.sup.h and R.sup.j are as hereinabove defined, provided that when R.sub.2 is --CHR.sup.h R.sup.j then R.sup.h and R.sup.j cannot both be hydrogen;
- (F) R.sub.3 is selected from hydrogen; a straight or branched (C.sub.1 -C.sub.4)alkyl group; a (C.sub.1 -C.sub.4)alkoxymethyl group; a straight or branched 1-(C.sub.1 -C.sub.5)aliphatic acyloxy-ethyl or methyl group; a straight, branched or cyclic 1-(C.sub.1 -C.sub.6)alkoxycarbonyloxyethyl or methyl group; a phthalidyl group; and water soluble cations selected from the group consisting of lithium, sodium, potassium, ammonium and tetra (C.sub.1 -C.sub.6)alkyl ammonium or a pharmaceutically acceptable salt thereof.
- 2. The compound according to claim 1 wherein:
- n is 1.
- 3. The compound according to claim 1: wherein:
- (A) Z is oxygen;
- (B) R.sub.0 is CH(OR.sub.4)CH.sub.3 ; wherein
- (i) R.sub.4 is hydrogen, and moieties of the formulae: ##STR135## R.sub.6 is selected from a straight, branched or substituted (C.sub.1 -C.sub.18)alkyl and unsubstituted or substituted (C.sub.3 -C.sub.7)monocyclo (C.sub.1 -C.sub.10)alkyl;
- (C) R.sub.1 is straight or branched (C.sub.1 -C.sub.8)alkyl, straight or branched (C.sub.2 -C.sub.8)alkenyl, and (C.sub.3 -C.sub.8)cycloalkyl;
- (D) n is 1;
- (E) R.sub.2 is:
- (i) --OCOCH.sub.3, --OCOCF.sub.3, azido,
- (ii) or R.sub.2 is selected from hydroxy, --OC(O)R.sup.a, --OC(O)OR.sup.a, --OC(O)NR.sup.a R.sup.a or ##STR136## and R.sup.a is (a) hydrogen or an
- (b) organic group bonded via a carbon atom selected from substituted or unsubstituted (C.sub.1 -C.sub.6)alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl; said substitution is selected from (C.sub.1 -C.sub.6)alkyl, hydroxy (C.sub.1 -C.sub.6)alkoxy, phenyl, heterocyclyl, amino, amidino, guanidino, carboxamido, carbamoyl, (C.sub.1 -C.sub.6)alkanoylamino, mono- and di(C.sub.1 -C.sub.6)alkylamino;
- (iii) or R.sub.2 is an organic residue bonded via a nitrogen atom, selected from:
- (a) NO.sub.2 and NR.sup.h R.sup.J wherein R.sup.h and R.sup.J are independently selected from hydrogen, amino, substituted amino, substituted or unsubstituted (C.sub.1 -C.sub.8)alkyl, aryl, wherein the substituents in the above mentioned substituted alkyl and amino are selected from the group consisting of amino, mono-, di- and tri(C.sub.1 -C.sub.6)alkylamino, hydroxyl, oxo, carboxyl, alkoxyl, chloro, fluoro, bromo, nitro, --SO.sub.2 NH.sub.2, phenyl, benzyl, acyloxy, alkoxylcarbonyloxy, cycloalkoxycarbonyloxy and carboxamido;
- (b) moieties of the formulae: ##STR137## wherein R.sup.h and R.sup.J are as hereinabove defined; (c) acylamino moieties of the formula: ##STR138## wherein R.sup.h and R.sup.J are as hereinabove defined; (d) an amino moiety containing an acyl residue of an amino acid or peptide represented by the formula: ##STR139## wherein R.sup.h is as hereinabove defined; R.sup.m is hydrogen or an acyl residue of an amino acid or peptide said amino acid selected from the group consisting of alanine, glycine, arginine, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, aminopimelic acid and threonine; and R.sup.t is hydrogen, benzyl, and straight or branched (C.sub.1 -C.sub.6)alkyl optionally substituted with halo, hydroxy, amino, guanidinyl, carboxy, phenyl, aminocarbonyl, alkylthio, hydroxyphenyl or heterocyclyl;
- (e) an acyclic quaternary ammonio moiety of the formula: ##STR140## wherein R.sub.7, R.sub.8 and R.sub.9 are the same or different and are selected from hydrogen, a straight or branched (C.sub.1 -C.sub.6) alkyl, and substituted (C.sub.1 -C.sub.6)alkyl, wherein the substitution is selected from hydroxy, (C.sub.1 -C.sub.6)alkoxy, azido, amino, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, guanidino, nitrile, carboxy, formimidoyl and phenyl; alternatively, R.sub.7 and R.sub.8 taken together are --(CH.sub.2).sub.2 X(CH.sub.2).sub.2 --, wherein X is (CH.sub.2).sub.w wherein w is an integer from 0 to 2, oxygen, sulfur, NH, NR.sup.h, NOH and NOR.sup.h wherein R.sup.h is as hereinabove defined and B.sup.- is a physiologically acceptable anion,
- (f) a quaternized heteroaryl wherein the heteroaryl moiety must contain at least one positively charged nitrogen atom in association with a physiologically acceptable anion, wherein the quaternized heteroaryl is optionally substituted by R.sup.a as hereinabove defined; and
- (F) R.sub.3 is selected from hydrogen; a straight or branched (C.sub.1 -C.sub.4)alkyl group; a (C.sub.1 -C.sub.4)alkoxymethyl group; a straight or branched 1-(C.sub.1 -C.sub.5)aliphatic acyloxy-ethyl or methyl group; a straight, branched or cyclic 1-(C.sub.1 -C.sub.6)alkoxycarbonyloxyethyl or methyl group; a phthalidyl group; and water soluble cations selected from the group consisting of lithium, sodium, potassium, ammonium and tetra (C.sub.1 -C.sub.4)alkyl ammonium or a pharmaceutically acceptable salt thereof.
- 4. A compound according to claim 1 wherein Z is oxygen; R.sub.0 is --CH(OR.sub.4)CH.sub.3 ; R.sub.4 is hydrogen; R.sub.1 is straight (C.sub.1 -C.sub.3)-alkyl;
- R.sub.2 is selected from the group consisting of:
- (a) --OCOCH.sub.3, --OCOCF.sub.3, azido;
- (b) hydroxy, --OC(O)R.sup.a, --OC(O)OR.sup.a, --OC(O)NR.sup.a R.sup.a, or --OC(O)--C(NH.sub.2)R.sup.a wherein R.sup.a is hydrogen, substituted or unsubstituted (C.sub.1 -C.sub.4)alkyl, substituted or unsubstituted phenyl, wherein the substituent in said substituted alkyl or phenyl group is selected from (C.sub.1 -C.sub.4)alkyl, hydroxy, (C.sub.1 -C.sub.4)alkoxy, amino, amidino, guanidino, carboxamido, and carbamoyl;
- (c) moieties of the formulae: ##STR141## wherein R.sup.h and R.sup.J are independently selected from hydrogen; substituted or unsubstituted (C.sub.1 -C.sub.4)alkyl, phenyl or substituted phenyl wherein the substituents are selected from the group consisting of amino, mono-, di- and tri(C.sub.1 -C.sub.4) alkylamino, hydroxyl, oxo, carboxyl, alkoxyl, chloro, fluoro, bromo, nitro, --SO.sub.2 NH.sub.2, phenyl, benzyl, acyloxy, alkoxylcarbonyloxy, cycloalkoxycarbonyloxy and carboxamido; R.sup.m is hydrogen or an acyl residue of an amino acid or peptide said amino acid selected from the group consisting of alanine, clycine, arginine, cysteine, isoleucine, leucine, lysine, methionine, phenylalaine, proline, aminopimelic acid and threonine and R.sup.t is hydrogen, benzyl, and straight or branched (C.sub.1 -C.sub.6) alkyl optionally substituted with halo, hydroxy, amino, guanidinyl, carboxy, phenyl, aminocarbonyl, alkylthio, hydroxyphenyl or heterocyclyl;
- R.sub.3 is hydrogen; a straight or branched (C.sub.1 -C.sub.4)alkyl group; a (C.sub.1 -C.sub.4)alkoxymethyl group; a straight or branched 1-(C.sub.1 -C.sub.5)aliphatic acyloxy-ethyl or methyl group; a straight, branched or cyclic 1-(C.sub.1 -C.sub.6)alkoxycarbonyloxyethyl or methyl group; a phthalidyl group; and water soluble cations selected from lithium, sodium, potassium, ammonium and tetra(C.sub.1 -C.sub.4)alkyl ammonium or a pharmaceutically acceptable salt thereof.
- 5. The compound according to claim 1, [3-[4R-[4.alpha., 5.beta., 6.beta.(R*)]]]-2,5-Anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-1-(methylamino)-3-thio-D-threo-pentitol.
- 6. A compound according to claim 1, [4R-[3(3R*,5R* and 3S*,5S*),4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-4-methyl-7-oxo-3-[[tetrahydro-5-(hydroxymethyl)-3-furanyl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 7. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-4-methyl-7-oxo-3-[[tetrahydro-5-(hydroxymethyl)-3-furanyl]thio]-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid monosodium salt.
- 8. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-3-[[5-[[(Aminocarbonyl)oxy]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 9. A compound according to claim 1, [4R-[3(3R*,5R* and 3S*,5S*)4alpha,5beta,6beta(R*)]]-3-[[5-[[(Aminocarbonyl)oxy]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 10. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-3-[[5-(Aminomethyl)tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.
- 11. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-4-methyl-7-oxo-3-[[tetrahydro-5-[[(1-iminoethyl)amino]methyl]-3-furanyl]thio]-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid.
- 12. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-3-[[tetrahydro-5-(iminomethyl)amino]methyl]-3-furanyl]thio]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.
- 13. A compound according to claim 1, [4R-[3(2R*,4S* and 2S*,4R*)4alpha,5beta,6beta(R*)]]-4-[[2-Carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]thio]tetrahydro-N,N,N-trimethyl-2-furanmethanaminium hydroxide, inner salt.
- 14. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-3-[[5-[[(2-Amino-6-carboxy-1-oxohexyl)amino]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxethyl-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 15. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-3-[[5-[[(2-Amino-3-chloro-1-oxopropyl)amino]methyl]-tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.
- 16. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-3-[[5-[[(Hexahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid monosodium salt.
- 17. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-4-methyl-7-oxo-3-[[tetrahydro-5-[[[(methylamino)acetyl]amino]methyl]-3-furanyl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.
- 18. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-4-methyl-7-oxo-3-[[tetrahydro-5-(phenoxymethyl)-3-furanyl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 19. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-3-[[5-[[(4-Fluorophenoxy)methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo-[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 20. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)5beta,6beta(R*)]]-3-[[5-[[(4-Fluorophenyl)thio]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo-[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 21. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-4-methyl-7-oxo-3-[[tetrahydro-5-[(2-naphthalenyloxy)methyl]3-furanyl]thio]-1-azabicyclo-[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 22. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*)4alpha,5beta,6beta(R*)]]-3-[[5-[[(4-Fluorophenyl)sulfonyl]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt.
- 23. A compound according to claim 1, [4R-[3(3R*,5R* and 3S*,5S*)4alpha,5beta,6beta(R*)]]-3-[[5-(Aminomethyl)tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid.
- 24. A compound according to claim 1, [4R-[3(3R*,5R* and 3S*,5S*)4alpha,5beta,6beta(R*)]]-6-(1-Hydroxyethyl)-3-[[5-(iminomethyl)amino]methyl]tetrahydro-3-furanyl]thio]-4-methyl-7-oxo-1-azabicyclo-[3.2.0]hept-2-ene-2-carboxylic acid.
- 25. A compound according to claim 1, [4R-[4.alpha.,5.beta.,6b(R*)]]-5-Amino-1,4-anhydro-2-S-(2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0.]hept-2-en-3-yl)-3,5-dideoxy-2-thio-D-erythropentitol.
- 26. A compound according to claim 1, [4R-[4.alpha.,5.beta.,6.beta.(R*)]]-1-Amino-2,5-anhydro-4-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,3-dideoxy-4-thio-L-threopentitol.
- 27. A compound according to claim 1, [4R-[4.alpha.,5.beta.,6.beta.(R*)]]-2,5-Anhydro-1,3-dideoxy-1-(dimethylamino)-4-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-4-thio-L-threo-pentitol.
- 28. A compound according to claim 1, [4R-[3(3R*,5R* and 3S*,5S*),4.alpha.,5.beta.,6.beta.(R*)]]-3-[(5-[[Ethylamino)methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]-hept-2-ene-carboxylic acid.
- 29. A compound according to claim 1, [4R-[3(3R*,5S* and 3S*,5R*),4.alpha.,5.beta.,6.beta.(R*)]]-3-[(5-[[Ethylamino)methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-carboxylic acid.
- 30. A compound according to claim 1, [4R-[4.alpha.,5.beta.,6.beta.(R*)]-1-Amino-2,5-anhydro-4-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,3-dideoxy-4-thio-D-threo-pentitol.
- 31. A compound according to claim 1, [4R-[4.alpha.,5.beta.,6.beta.(R*)]-1-Amino-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 32. A compound according to claim 1, 4R-[4.alpha.,5.beta.,6.beta.(R*)]-2,5-Anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-1-[(iminomethyl)amino]-3-thio-D-threo-pentitol.
- 33. A compound according to claim 1, 3-[[5-(Azidomethyl)tetrahydro-3-furanyl]thio]-4-methyl-6-[1-[[(2-methylpropoxy)carbonyl]oxy]ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (4-nitrophenyl)methyl ester.
- 34. A compound according to claim 1, 3-[[5-(Aminomethyl)tetrahydro-3-furanyl]thio]-4-methyl-6-[1-[[(2-methylpropoxy)carbonyl]oxy]ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.
- 35. A compound according to claim 1, [4R-[4.alpha.,5.beta.,6.beta.(R*)]]-5-Amino-1,4-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-2,5-dideoxy-3-thio-D-erythro-pentitol.
- 36. A compound according to claim 1, [3-S-[4R-[4.alpha.,5.beta.,6.beta.(R*)]]]-1-[(Aminoacetyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0.]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 37. A compound according to claim 1, [3-S-[4R-[1-(S*),4.alpha.,5.beta.,6.beta.(R*)]]]-1-[(2-Amino-1-oxopropyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 38. A compound according to claim 1, [3-S-[4R-[1-(S*),4.alpha.,5.beta.,6.beta.(R*)]]]-1-[(2-Amino-1-oxo-3-phenylpropyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]-hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 39. A compound according to claim 1, [3-S-[4R-[4.alpha.,5.beta.,6.beta.(R*)]]]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]-hept-2-en-3-yl]-1,4-dideoxy-1-[(N-L-phenylalanyl-L-phenylalanyl)amino-3-thio-D-threo-pentitol.
- 40. A compound according to claim 1, [3-S-[4R-[1(S*),4alpha,5beta,6beta(R*)]]]-1-[(2-Amino-4-methyl-1-oxopentyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 41. A compound according to claim 1, [3-S-[4R-[4.alpha.,5.beta.,6.beta.(R*)]]]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]- hept-2-en-3-yl]-1,4-dideoxy-1-[N-L-leucyl-L-leucyl)amino-3-thio-D-threo-pentitol.
- 42. A compound according to the claim 1, [4R-[3(2S*),4alpha,5beta,6beta(R*)]]-1-[(2-Amino-1-oxobutyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-(hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 43. A compound according to claim 1, [3-S[4R-[1(S*),4alpha,5beta,6beta(R*)]]]-1-[(2-Amino-3-methyl-1-oxobutyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo-[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 44. A compound according to claim 1, [3-S[4R-[1(S*,S*),4alpha,5beta,6beta(R*)]]]-1-[(2-Amino-3-methyl-1-oxopentyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 45. A compound according to claim 1, [3-[4R-[4alpha,5beta,6beta(R*)]]]-1-[[[1-(Acetyloxy)ethoxy]carbonyl]amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol monosodium Salt.
- 46. A compound according to claim 1, [3-[4R-[4alpha,5beta,6beta(R*)]]]-1-[[1-(Acetyloxy)-ethoxy]carbonyl]amino]-2,5-anhydro-3-S-[2-[[1[[(cyclohexyloxy)carbonyl]oxy]ethoxy]-carbonyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 47. A compound according to claim 1, [3-[4R-[3(2S*),4alpha,5beta,6beta(R*)]]]-1-[(2-Amino-1-oxopropyl)methylamino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo-[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol.
- 48. A compound according to claim 1, [3-[4R-[4alpha,5beta,6beta(R*)]]]-1-[[[1-(Acetyloxy)ethoxy]carbonyl]amino]-2,5-anhydro-1,4-dideoxy-3-S-[2-[[(2,2-dimethyl-1-oxopropoxy)methoxy]carbonyl]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-thio-D-threo-pentitol.
- 49. A compound according to claim 1, 4R-[3(R*, 5R* and 3S*, 5S*), 4alpha, 5beta, 6beta(R*)]]-3-[[5-[[Aminocarbonyl)oxy]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0.]hept-2-ene-2-carboxylic acid (2,2-Dimethyl-1-oxopropoxy)methyl ester.
- 50. A compound according to claim 1, [4R-[3(3R*, 5S* and 3S*, 5R*), 4alpha, 5beta, 6beta(R*)]]-3-[[5-[[(Aminocarbonyl)oxy]methyl]tetrahydro-3-furanyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (2,2-Dimethyl-1-oxopropoxy)methyl ester.
- 51. A pharmaceutical composition of matter comprising an antibacterial effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.
- 52. A pharmaceutical composition comprising an antibacterial effective amount of a compound according to claim 1, a dipeptidase inhibitor and a pharmaceutically acceptable carrier.
- 53. A method of treating bacterial infections in mammals which comprises administering an effective anitibacterial amount of a compound according to claim 1.
Parent Case Info
This is a continuation-in-part of application Ser. No. 08/033,684 filed on Mar. 16, 1993 abandoned.
US Referenced Citations (10)
Foreign Referenced Citations (2)
Number |
Date |
Country |
010317 |
Dec 1983 |
EPX |
126587 |
Nov 1984 |
EPX |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
33684 |
Mar 1993 |
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