Claims
- 1. A process for making a compound of the formula
- (Q--L.sup.1)--L--(L.sup.2 --B)
- the method comprising the steps of:
- (1) coupling a compound having a structure according to Formula (III) ##STR34## wherein (A)
- (1) A.sup.1, A.sub.2 or A.sub.3 is N C(R.sup.7), C(R.sup.2), or C(R.sup.5); where
- (a) R.sup.5 is hydrogen
- (b) R.sup.2 is R.sup.5 or halogen
- (c) R.sup.7 is R.sup.2, hydroxy, alkoxy, nitro, cyano, alkyl, or --N(R.sup.8)(R.sup.9), and
- (d) R.sup.8 and R.sup.9 are, independently, hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R.sup.8 and R.sup.9 together form a heterocyclic ring including the nitrogen to which they are bonded;
- (2) R.sup.1 is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or --N(R.sup.8)(R.sup.9);
- (3) R.sup.3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring;
- (4) R.sup.4 is hydroxy;
- (5) R.sup.6 is hydrogen, halogen, nitro or --N(R.sup.8)(R.sup.9); and
- (6) X is a leaving group
- (B) and
- (1) when A.sup.2 is C(R.sup.2), R.sup.2 and R.sup.3 may together form --O--(CH.sub.2).sub.n --O--, where n is from 1 to 4;
- (2) when A.sup.3 is C(R.sup.5), R.sup.4 and R.sup.5 may together form a heterocyclic ring; and
- (3) when A.sup.1 is C(R.sup.7), R.sup.7 and R.sup.3 may together form a heterocyclic ring including A.sup.1 and the carbon atom to which R.sup.3 is bonded;
- or a protected form, salt, ester, or solvate thereof;
- with a lactam-containing compound having a structure according to Formula (II), to form an intermediate compound; and
- (2) cyclizing the intermediate compound by reaction with an organosilicon compound to give a compound of the formula (Q--L.sup.1)--L--(L.sup.2 --B);
- wherein
- (I) Q has a structure according to Formula (I) ##STR35## wherein (A)
- (1) A.sup.1, A.sup.2 or A.sup.3 is N or C(R.sup.7) C(R.sup.2) or C(R.sup.5); where
- (a) R5 is hydrogen,
- (b) R2 is R5 or halogen,
- (c) R.sup.7 is, R2 or, hydroxy, alkoxy, nitro, cyano, alkyl, or --N(R.sup.8)(R.sup.9), and
- (d) R.sup.8 and R.sup.9 are, independently, R.sup.8a where R.sup.8a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R.sup.8 and R.sup.9 together form a heterocyclic ring including the nitrogen to which they are bonded;
- (2) R.sup.1 is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or --N(R.sup.8)(R.sup.9);
- (3) R.sup.3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring;
- (4) R.sup.4 is hydroxy; and
- (5) R.sup.6 is hydrogen, halogen, nitro or --N(R.sup.8)(R.sup.9);
- (B) and
- (1) when A.sup.2 is C(R.sup.2), R.sup.2 and R.sup.3 may together form --O--(CH.sub.2).sub.n --O--, where n is from 1 to 4;
- (2) when A.sup.3 is C(R.sup.5), R.sup.4 and R.sup.5 may together form a heterocyclic ring; and
- (3) when A.sup.1 is C(R.sup.7), R.sup.7 and R.sup.3 may together form a heterocyclic ring including A.sup.1 and the carbon atom to which R.sup.3 is bonded;
- (C) and provided that one of R.sup.1, R.sup.3, or R.sup.6 is a covalent bond to L.sup.1 ;
- (II) B has a structure according to Formula (II): ##STR36## wherein (A) R.sup.10 is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R.sup.8 --O--, R.sup.8 CH.dbd.N--, (R.sup.8)(R.sup.9)N--, R.sup.17 --C(.dbd.CHR.sup.20)--C(.dbd.O)NH--, R.sup.17 --C(.dbd.NO--R.sup.19)--C(.dbd.O)NH--, or R.sup.18 --(CH.sub.2).sub.m --C(.dbd.O)NH--; where
- (1) m is an integer from 0 to 9;
- (2) R.sup.17 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring;
- (3) R.sup.18 is R.sup.17, --Y.sup.1, or --CH(Y.sup.2)(R.sup.17);
- (4) R.sup.19 is R.sup.17, arylalkyl, heteroarylalkyl, --C(R.sup.22)(R.sup.23)--COOH, --C(.dbd.O)O--R.sup.17, or --C(.dbd.O)NH--R.sup.17, where R.sup.22 and R.sup.23 are, independently, R.sup.17 or together form a carbocyclic ring or a heterocyclic ring including the carbon atom to which R.sup.22 and R.sup.23 are bonded;
- (5) R.sup.20 is R.sup.19, halogen, --Y.sup.1, or --CH(Y.sup.2)(R.sup.17);
- (6) Y.sup.1 is --C(.dbd.O)OR.sup.21, --C(.dbd.O)R.sup.21, --N(R.sup.24)R.sup.21, --S(O).sub.p R.sup.29, or --OR.sup.29 ; and Y.sup.2 is Y.sup.1 or --OH, --SH, or --SO.sub.3 H;
- (a) p is an integer from 0 to 2;
- (b) R.sup.24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroalkenyl; a carbocyclic ring; a heterocyclic ring; --SO.sub.3 H; --C(.dbd.O)R.sup.25 ; or, when R.sup.18 is --CH(N(R.sup.24)R.sup.21)(R.sup.17), R.sup.24 may form a moiety bonded to R.sup.21 to form a heterocyclic ring; and
- (c) R.sup.25 is R.sup.17, NH(R.sup.17), N(R.sup.17)(R.sup.26), O(R.sup.26), or S(R.sup.26); where R.sup.26 is alkyl, alkenyl, a carbocyclic ring, a heterocyclic ring, or when R.sup.25 is --N(R.sup.17)(R.sup.26), R.sup.26 may be a moiety bonded to R.sup.17 to form a heterocyclic ring; and
- (7) R.sup.21 is R.sup.29 or hydrogen; where R.sup.29 is alkyl; alkenyl; arylalkyl; heteroalkyl; heteroalkenyl; heteroarylalkyl; a carbocyclic ring; a heterocyclic ring; or, when Y.sup.1 or Y.sup.2 is --N(R.sup.24)R.sup.21 and R.sup.21 is R.sup.29, R.sup.21 and R.sup.24 may together form a heterocyclic ring including the nitrogen atom to which R.sup.24 is bonded;
- (B) R.sup.11 is hydrogen, halogen, alkoxy, or R.sup.27 C(.dbd.O)NH--, where R.sup.27 is hydrogen or alkyl;
- (C) bond "a" is a single bond or is nil; and bond "b" is a single bond, a double bond, or is nil; except bond "a" and bond "b" are not both nil;
- (D) R.sup.12 is --C(R.sup.8)--, or --CH.sub.2 --R.sup.28 --; where R.sup.28 is --C(R.sup.8), --O--, or --N--, and R.sup.28 is directly bonded to N" in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then R.sup.12 is
- (1) --C(R.sup.8)(X.sup.1)--, where
- (a) X.sup.1 is --R.sup.21 ; --OR.sup.30 ; --S(O).sub.r R.sup.30, where r is an integer from 0 to 2; --OC(.dbd.O)R.sup.30 ; or --N(R.sup.30)R.sup.31 ; and
- (b) R.sup.30 and R.sup.31 are, independently, alkyl, alkenyl, a carbocyclic ring or a heterocyclic ring; or R.sup.30 and R.sup.31 together form a heterocyclic ring including the nitrogen atom to which R.sup.30 and R.sup.31 are bonded; or
- (2) --CH.sub.2 --R.sup.32 --; where R.sup.32 is --C(R.sup.8)(R.sup.21), --O--, or --NR.sup.8, and R.sup.32 is directly bonded to N" in Formula (II) to form a 5-membered ring;
- (E)
- (1) if bond "b" is a single bond, R.sup.13 is --CH(R.sup.33); or, --C(O)NHSO.sub.2 --, if bond "a" is nil; or --C*(R.sup.33)-- if R.sup.14 contains a R.sup.36 moiety; where R.sup.33 is hydrogen or COOR.sup.46 where R.sup.46 is hydrogen, alkyl or alkenyl, and C* is linked to R.sup.36 to form a 3-membered ring;
- (2) if bond "b" is a double bond, R.sup.13 is --C(R.sup.33).dbd.; or
- (3) if bond "b" is nil, R.sup.13 is hydrogen, --SO.sub.3 H, --PO(OR.sup.34)OH, --C(O)NHSO.sub.2 N(R.sup.34)(R.sup.35), --OSO.sub.3 H, --CH(R.sup.35)COOH, or --OCH(R.sup.34)--COOH; where R.sup.34 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R.sup.35 is hydrogen, alkyl, alkenyl, or --NHR.sup.8 ; or, if R.sup.13 is --C(O)NH--SO.sub.2 N--(R.sup.34)(R.sup.35), R.sup.34 and R.sup.35 may together comprise a heterocyclic ring including the nitrogen to which R.sup.34 and R.sup.35 are bonded; and
- (F)
- (1) if bond "a" or bond "b" is nil, then R.sup.14 is a covalent bond;
- (2) if bond "a" and "b" are single bonds, R.sup.14 is --W--C'".dbd.C(R.sup.8)--R.sup.37 --, or --W--C'"(R.sup.36)--R.sup.37 --; or
- (3) if bond "a" is a single bond and bond "b" is a double bond, R.sup.14 is --C(R.sup.8)(R.sup.38)--W--C'"--R.sup.37 --; --W--C(R.sup.8)--(R.sup.38)--C'"--R.sup.37 --; or --W--C'"--R.sup.37 --;
- (4) where
- (a) W is O; S(O).sub.s, where s is an integer from 0 to 2; or C(R.sup.38), where R.sup.38 is hydrogen, alkyl or alkoxy;
- (b) R.sup.36 is hydrogen; alkyl; alkenyl; --COOH; or, if R.sup.13 is --C*(R.sup.33), R.sup.36 may be linked to C* to form a 3-membered carbocyclic ring;
- (c) R.sup.37 is covalent bond, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and
- (d) C'" is directly bonded to R.sup.13 to form a 5- or 6-membered ring; and
- (III)
- (A) L is --C(.dbd.Z)--; --S(O).sub.v --; --N(R.sup.44)--; --N.sup.+ (R.sup.44)(R.sup.45)--; --N(R.sup.44)--N(R.sup.44)--; --O--; .dbd.N--; or a covalent bond; and L is bonded to L.sup.3 and L.sup.4 ; where
- (1) Z is O, S, or .sup.+ N(H).sub.2 ;
- (2) v is 0, 1 or 2;
- (3) R.sup.44 is hydrogen, substituted or unsubstituted lower alkyl, aryl, acyl, hydroxy, alkoxy, aryloxy, or acyloxy; and
- (4) R.sup.45 is hydrogen, unsubstituted or substituted lower alkyl, or substituted or unsubstituted aryl;
- (B) L.sup.1 is L.sup.3 or R.sup.15 L.sup.3 ; where
- (1) when L is --C(.dbd.Z)--, L.sup.3 is a covalent bond, oxygen, sulfur, or nitrogen; and when L is other than --C(.dbd.Z)--, L.sup.3 is a covalent bond;
- (2) R.sup.15 is alkyl, alkenyl, heteroalkyl, a heterocyclic ring, a carbocyclic ring, or R.sup.15 together with L.sup.3 is a heteroalkyl or a heterocyclic ring; and
- (3) L.sup.1 is bonded to Q at the point of attachment of R.sup.1, R.sup.3 or R.sup.6, whichever is a covalent bond;
- (C) L.sup.2 is L.sup.4, --X.sup.2.sub.t --R.sup.39 --L.sup.4, or --X.sup.3.sub.t --R.sup.39 --L.sup.4 ; where
- (1) when L is --C(.dbd.Z)--, L.sup.4 is a covalent bond, oxygen, sulfur, or nitrogen; and when L is other than --C(.dbd.Z)--, L.sup.4 is a covalent bond;
- (2) X.sup.2 is oxygen, or S(O).sub.v, where v is 0, 1, or 2;
- (3) X.sup.3 is nitrogen; --N(R.sup.40)--; --N.sup.+ (R.sup.41)(R.sup.42)--; or R.sup.43 --N(R.sup.41); and is linked to R.sup.14 by a single or double bond; or, if R.sup.14 is covalent bond, X.sup.3 is linked to B by a single or double bond; where
- (a) R.sup.40 is R.sup.8 ; --OR.sup.8 ; or --C(.dbd.O)R.sup.8 ;
- (b) R.sup.41 and R.sup.42 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings; heterocyclic rings; or, if R.sup.6 is R.sup.16 X, then R.sup.41 and R.sup.42 together with "Q" may form a heterocyclic ring as R.sup.16 ;
- (c) R.sup.43 is N(R.sup.41), oxygen or sulfur;
- (4) t is 0 or 1;
- (5) R.sup.39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; and
- (6)
- (a) if bond "a" or bond "b" is nil, then L.sup.2 is bonded directly to R.sup.12 or R.sup.13 ; or
- (b) if bond "a" and bond "b" are not nil, then L.sup.2 is bonded to R.sup.14 ;
- (D) provided that if L.sup.1, L.sup.2 and R.sup.37 are each a covalent bond, then L cannot be a covalent bond;
- or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof.
- 2. The process according to claim 1, wherein the coupling step comprises adding a solution containing the lactam-containing compound to a solution containing the compound of Formula (III).
- 3. The process according to claim 1, wherein the coupling step is carried out in a halocarbon solvent, an ether solvent, an aromatic solvent, a dialkylamide solvent, or a mixture thereof.
- 4. The process according to claim 3, wherein the solvent is methylene chloride, chloroform, dichloroethane, diethyl ether, tetrahydrofuran, benzene, toluene; N,N-dimethylformamide; or a mixture thereof.
- 5. The process according to claim 1, wherein the coupling step is performed at a temperature from about -78.degree. C. to about 50.degree. C.
- 6. The process according to claim 5, wherein the coupling step is performed at a temperature of from about -50.degree. C. to about 25.degree. C.
- 7. The process according to claim 1, wherein the process further comprises an organosilicon compound reacted with a compound of Formula (III) prior to the coupling step.
- 8. The process according to claim 7, wherein the coupling step is performed at a temperature of less than about 0.degree. C.
- 9. The process according to claim 8, wherein the coupling step is performed at a temperature of from about -78.degree. C. to about -15.degree. C.
- 10. The process according to claim 1, wherein R.sup.14 is --W--C'"--R.sup.37 -- or --W--C(R.sup.8)(R.sup.38)--C'"--R.sup.37 --.
- 11. The process according to claim 10, wherein W is S(O).sub.s, where s is 0; or W is C(R.sup.38).
- 12. The process according to claim 1, wherein A.sup.1 is C(R.sup.7), A.sup.2 is C(R.sup.2), and A.sup.3 is C(R.sup.5); or A.sup.1 is nitrogen, A.sup.2 is C(R.sup.2), and A.sup.3 is C(R.sup.5).
- 13. The process according to claim 12, wherein A.sup.1 is C(R.sup.7), A.sup.2 is C(R.sup.2), and A.sup.3 is C(R.sup.5).
- 14. The process of claim 12, wherein R.sup.1 is alkyl, aryl, cycloalkyl, or alkylamino.
- 15. The process of claim 14, wherein R.sup.7 is hydrogen or halogen.
- 16. The process of claim 12, wherein R.sup.3 is a heterocyclic ring.
- 17. The process of claim 16, wherein R.sup.3 is a substituted or unsubstituted pyrrolidine or a substituted or unsubstituted piperazine.
- 18. The process according to claim 1, wherein R.sup.3 is a covalent bond to L.sup.1.
- 19. The process according to claim 1, wherein R.sup.6 is a covalent bond to L.sup.1.
- 20. The process according to claim 1, wherein L is --C(.dbd.Z)--, where Z is O; and wherein L.sup.3 is nitrogen.
- 21. The process according to claim 1, wherein L is --N(R.sup.44)--, where R.sup.44 is hydrogen or unsubstituted or substituted lower alkyl.
- 22. The process according to claim 1, wherein the quinolone moiety, Q, is:
- 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazinyl-quinoline-3-carboxylic acid;
- 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazinyl-quinoline-3-carboxylic acid allyl ester;
- 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazinyl-quinoline-3-carboxylic acid diphenylmethyl ester;
- 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazinyl-quinoline-3-carboxylic acid t-butyl ester;
- 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazinyl-quinoline-3-carboxylic acid 2,2,2-trichloroethyl ester;
- 7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid;
- 7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid allyl ester;
- 7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid allyl ester;
- 5-Amino-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid allyl ester;
- 5-Amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-piperazinyl)-4-oxo-quinoline-3-carboxylic acid;
- 7-(3-Amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid allyl ester; or
- 7-�3-(t-Butyloxycarbonyl)amino-1-pyrrolidinyl!-1-cyclopropyl-6,8-difluoro-1,4-dihydro-5-hydrazino-4-oxo-quinoline-3-carboxylic acid allyl ester.
- 23. A process, according to claim 1, wherein the lactam moiety, B, is:
- �5R-�5a,6a!!-6-�(R)-1-(t-butyldimethylsilyloxy)ethyl!-3-hydroxymethyl-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid allyl ester;
- �5R-�5a,6a!!-6-�(R)-1-�(allyloxycarbonyl)oxy!ethyl!-3-hydroxymethyl-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid allyl ester;
- �5R-�5a,6a!!-6-�(R)-1-�(2,2,2-trichloroethyloxycarbonyl)oxy!ethyl!-3-hydroxymethyl-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid 2,2,2-trichloroethyl ester;
- �5R-�5a,6a!!-6-�(R)-1-(t-butyldimethylsilyloxy)ethyl!-3-hydroxymethyl-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid diphenylmethyl ester;
- �5R-�5a,6a!!-6-�(R)-1-(t-butyldimethylsilyloxy)ethyl!-3-hydroxymethyl-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid t-butyl ester;
- �5R-�4b,5a,6a!!-6-�(R)-1-(t-butyldimethylsilyloxy)ethyl!-3-hydroxymethyl-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid allyl ester;
- �5R-�5a,6a!!-6-�(R)-1-(t-butyldimethylsilyloxy)ethyl!-3-(2-hydroxyethylthio)-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid allyl ester; or
- �5R-�4b,5a,6a!!-6-�(R)-1-(t-butyldimethylsilyloxy)ethyl!-3-(2-hydroxyethylthio)-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic acid allyl ester.
- 24. A process, according to claim 1, wherein said compound is:
- �5R-�5a,6a!!-3-���4-(3-Carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl!carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�4b,5a,6a!!-3-���4-(3-Carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl!carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�5a,6a!!-3-����4-(3-Carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-quinolinyl)-(S)-3-pyrrolidinyl!amino!-carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�4b,5a,6a!!-3-����4-(3-Carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-quinolinyl)-(S)-3-pyrrolidinyl!amino!-carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�5a,6a!!-3-����4-�3-Carboxy-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridin-1-yl!-(S)-3-pyrrolidinyl!amino!-carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�4b,5a,6a!!-3-����4-�3-Carboxy-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridin-1-yl!-(S)-3-pyrrolidinyl!amino!-carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�5a,6a!!-3-���4-(5-Amino-3-carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo7-quinolinyl)-2,6-dimethyl-4-piperazinyl!carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�4b,5a,6a!!-3-���4-(5-Amino-3-carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-quinolinyl)-2,6-dimethyl-4-piperazinyl!carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�5a,6a!!-3-���2-�7-((S)-3-Amino-1-pyrrolidinyl)-3-carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-5-quinolinyl!-1-hydrazino!-carbonyloxy!methyl!-6-�(R)-hydroxyethyl!-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�4b,5a,6a!!-3-���2-�7-((S)-3-Amino-1-pyrrolidinyl)-3-carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-5-quinolinyl!-1-hydrazino!-carbonyloxy!methyl!-6-�(R)-1-hydroxyethyl!-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �4R-�4.alpha.,5.beta.,6.beta.(R*)!!-3-���4-(3-Carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl!carbonyloxy!methyl!-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium salt;
- �6R-�6.alpha.,7.beta.!!-3-���4-(3-Carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl!carbonyloxy!methyl!-8-oxo-7-�(2-thienylacetyl)amino!-5-thia-1-azabicyclo�4.2.0!oct-2-ene-2-carboxylic Acid, Disodium Salt;
- �6R-�6.alpha.,7.beta.!!-3-���4-�3-Carboxy-1-(1,1-dimethylethyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-napthyridin-7-yl!-1-piperazinyl!carbonyloxy!-methyl!-8-oxo-7-�(2-thienylacetyl)amino!-1-azabicyclo�4.2.0!oct-2-ene-2-carboxylic Acid, Disodium Salt;
- �5R-�5.alpha.,6.alpha.(R*)!!-3-��4-(3-Carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl!methyl!-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium Salt;
- �6R-�6.alpha.,7.beta.!!-3-��4-(3-Carboxy-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl!!methyl!-8-oxo-7-�2-(phenoxyacetyl)amino!-1-azabicyclo�4.2.0!oct-2-ene-2-carboxylic Acid, Disodium Salt;
- �4S-�3(R*),4.alpha.,5.beta.,6.beta.(S*)!!-3-���1-�3-Carboxy-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-napthyridin-7-yl!-3-pyrrolidinyl!amino!methyl!-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo�3.2.0!hept-2-ene-2-carboxylic Acid, Disodium salt; or
- �6R-�3(S*),6.alpha.,7.beta.!!-3-���1-�3-Carboxy-1-(1,1-dimethylethyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-napthyridin-7-yl!-3-pyrrolidinyl!amino!methyl!-8-oxo-7-�(2-thienylacetyl)amino!-5-thia-1-azabicyclo�4.2.0!oct-2-ene-2-carboxylic Acid.
Parent Case Info
This is a continuation of application Ser. No. 08/284,771, filed on Aug. 2, 1994 abandoned.
US Referenced Citations (13)
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 181 521 A1 |
May 1986 |
EPX |
Continuations (1)
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Number |
Date |
Country |
Parent |
284771 |
Aug 1994 |
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