ANTIMICROBIAL QUINOLONYL LACTAMS

Abstract: Antimicrobial quinolonyl lactam compounds comprising a lactam-containing moiety linked to a quinolone moiety, of formula (I), wherein (1) A<1>, A<2>, A<3>, R<1>, and R<4> generally form any of a variety of quinolone, naphthyridine or related cyclic moieties known in the art to have antimicrobial activity; and (2) R<6> is part of a linking moiety, linking hte quinolone moiety to a lactam-containing moiety having formula (II), wherein (3) R<10>, R<11>, R<12>, R<13>, and R<14>, together with bonds ''a'' and ''b'', form any of a variety of lactam-containing moieties known in the art to have antimicrobial activity; and (4) the linking moiety includes (for example) carbamate, dithiocarbamate, urea, thiourea, isouronium, isothiouronium, guanidine, carbonate, trithiocarbonate, reversed carbamate, xanthate, reversed isouronium, reversed dithiocarbamate, reversed isothiouronium, amine, imine, ammonium, heteroarylium, ether, thioether, ester, thioester, amide, and hydrazide groups.

Description: ANTIMICROBIAL QUIN0L0NYL LACTAMS BACKGROUND OF THE INVENTION This invention relates to novel antimicrobial compounds and compositions. The compounds of this invention contain, as integral substituents, a quinolone moiety and a lactam-containing moiety. The chemical and medical literature describes a myriad of compounds that are said to be antimicrobial, i.e., capable of destroying or suppressing the growth or reproduction of microorganisms, such as bacteria. In particular, antibacterials include a large variety of naturally-occurring (antibiotic), synthetic, or semi-synthetic compounds. They may be classified (for example) as the aminoglycosides, ansamacrolides, beta-lacta s (including penicillins ana cephalosporins) , lincos- aminides, macrolides, nitrofurans, nucleosides, oligosaccharides, peptides and polypeptides, phenazines, polyenes, polyethers, quinolones, tetracycl ines, and sulfonamides. Such antibacterials and other antimicrobials are described in Antibiotics. Chemotherapeutics, and Antibacterial Agents for Disease Control (M. Grayson, editor, 1982), and E. Gale et al . , The Molecular Basis of Antibiotic Action 2d edition (1981), both incorporated by reference herein. The mechanism of action of these antibacterials vary. However, each can be generally classified as functioning in one or more of four ways: by inhibiting cell wall synthesis or repair; by altering cell wall permeability; by inhibiting protein synthesis; or by inhibiting synthesis of nucleic acids. For example, beta-lactam antibacterials act through inhibiting the essential penicillin binding proteins (PBPs) in bacteria, which are responsible for cell wall synthesis. On the other hand, quinolones act by inhibiting synthesis of bacterial DNA, thus preventing the bacteria from replicating. Not surprisingly, the pharmacological characteristics of antibacterials and other antimicrobials, and their suitability for any given clinical use, also vary considerably. For example, the classes of antimicrobials (and members within a class) may vary in their relative efficacy against different types of microorganisms, and their susceptibility to development of microbial resistance. These antimicrobials may also differ in their pharmacological characteristics, such as their bioavailability, and biodistribution. Accordingly, selection of an appropriate antibacterial (or other antimicrobial) in any given clinical situation can be a complicated analysis of many factors, including the type of organism involved, the desired method of administration, and the location of the infection to be treated. The development of microbial resistance is one factor in the selection of an appropriate antimicrobial (particularly anti¬ bacterials), which is of increasing concern in medical science. This "resistance" can be defined as existence of organisms, within a population of a given microbial species, that are less susceptible to the action of a given antimicrobial agent. Such resistant strains may subvert the mechanism of action of a particular antimicrobial, or chemically degrade the antimicrobial before it can act. For example, bacterial resistance to beta-lactam antibacterials has arisen through development of bacterial strains that produce beta-lactamase enzymes, which degrade the antibacterial. In part as a result of the intense use of antibacterials over extended periods of time, many highly resistant strains of bacteria have evolved. This is of partirular ronrprn in environments such as hospitals and nursing homes, which are characterized by relatively high rates of infection and intense use of antibacterials. See, e.g., . Sanders, Jr. et al., "Inductible Beta-lactamases: Clinical and Epidemiologi Implications for Use of Newer Cephalosporins", 10 Reviews of Infectious Diseases 830 (1988). Indeed, the development of resistant bacterial strains has led to a concern that pathogenic bacteria may be produced that are essentially resistant to even the newest developed antibacterial agents. The literature describes many attempts to enhance the efficacy of antimicrobials, and to overcome the development of microbial resistance. Many such attempts involve the combination of antimicrobials. For example, Thabaut et al . , 16 Presse Med. 2167 (1987) describes combinations of pefloxacin (a quinolone) with the beta-lactams cefotaxime and cefsulodin. Lenoc et al., 36 Path. Bio! . 762 (1988), describes combined use of cephems with a inoglycosides, and with quinolones. Japanese Patent Publication 60/06,617, published January 14, 1985, also describes compositions " containing beta-lactams and quinolones. O'Callaghan et al., 10 Antimicrobial Agents and Chemotherapy 245 (1976), describes a mercapto pyridine-substituted cephem, which is said to liberate an active antimicrobial agent when the cephalosporin is hydrolyzed by beta-lactamase. Mobashery et al., 108 J__ American Chemical Society 1684 (1986), presents a theory of employing bacterial beta-lactamase jjn situ to release an antibacterially-active leaving group from the 10-position of a cephem. However, many such attempts to produce improved antimicrobials yield equivocal results. Indeed, few antimicrobials are produced that are truly clinically-acceptable in terms of their spectrum of antimicrobial activity, avoidance of microbial resistance, and pharmacology. SUMMARY OF THE INVENTION The present invention provides compounds of the general structure Q - L - B wherein Q, L and B are defined as follows: (I) Q is a structure according to Formula (I) wherein R 1 (A) (1) Al is N or C(R 7 ); where (i) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or N(R8)(R9), and (ii . ) R 8 and R 9 are, independently, Rδa where R 8a is hydrogen, alkyl, alkenyl, carbocyclic ring, or heterocyclic ring; or R 8 and R9 together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A 2 is N or C(R 2 ); where R is hydrogen or halogen; (3) A 3 is N or C(R 5 ); where R 5 is hydrogen; (4) Rl is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or N(R8)(R9); (5) R 3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R* is hydroxy; and (7) R 6 is R 15 or R 16 X; where R 15 is a substituent moiety of L and is nil, alkyl, heteroalkyl, or alkenyl; R δ is a substituent moiety of L and is alkyl, alkenyl, a carbocyclic ring or a heterocyclic ring; and X is alkyl, heteroalkyl, alkenyl, oxygen, sulfur, or NH; (8) except that (1) when Al is C(R 7 ), Rl and R 7 may together comprise a heterocyclic ring including N' and Al; (2) when A 2 is C(R 2 ), R 2 and R 3 may together comprise -0-(CH2)n-0-, where n is an integer from 1 to 4; (3) when A is C(R 5 ), R 4 and R** 5 may together comprise heterocyclic ring including the carbon atoms to whic R 4 and R 5 are bonded and the carbon atom of Formula (I to which said carbon atoms are bonded; and (4) when A 3 is C(R 5 ), and R 5 may together comprise heterocyclic ring including N' and the adjacent carbo to which R5 is bonded; (II) B is a structure according to Formula (II), where L i bonded to R : wherein (A) Rl° is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R β a-o-, R8acH-N-, (R8)(R9)N-, Rl -C(=CHR20)-C(=0)NH-, Rl 7 -C(«NO-Rl9)-C(-»0)NH-, or where (1) m is an integer from 0 to 9; (2) Rl 7 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl , a carbocyclic ring, or a heterocyclic ring; (3) Rl8 is Rl- 7 , -Yl, or -CH(Y )(Rl 7 ); (4) Rl 9 is Rl 7 , arylalkyl, heteroarylalkyl , _C(R22)( 23)C00H, -C(=0)0-Rl 7 , or -C(«0)NH-Rl 7 , where R2 and R23 are, independently, Rl 7 or together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R 22 and R 23 are bonded; (5) R 20 is Rl9, halogen, -γl, or -CH(Y 2 )(Rl 7 ) ; -o- (6) γl is -C(=0)0R21, -C(=0)R21, -N(R24) R 21, - S (0) p R29, or -0R29; and Y 2 is γl or -OH, -SH, or -SO3H; (a) p is an integer from 0 to 2; (b) R 4 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroal enyl ; a carbocyclic ring; a heterocycli ring; -SO3H; -C(=0)R25 ; orj wπen R18 i -CH(N(R2 )R21)(R!7), R24 may comprise a moiet bonded to R 1 to form a heterocyclic ring; and (c) R25 is Rl 7 , NH(Rl 7 ), N(Rl )(R26), 0(R26), O S(R26); where R 2 6 is alkyl, alkenyl, a carbocycli --•ring, a heterocyclic ring, or when R25 i N(R1 7 )(R26), R26 may be a moiety bonded to Rl 7 t form a heterocyclic ring; and (7) R21 is R 29 or hydrogen; where R29 is alkyl; alkenyl arylalkyl; heteroalkyl; heteroalkenyl; heteroarylal yl a carbocyclic ring; a heterocyclic ring; or, when γl i N(R 24 )R 2 1 and R 2 1 is R 29 , R 2 1 and R 24 may togethe comprise a heterocyclic ring including the nitroge atom to which R 24 is bonded; (B) Rl! is hydrogen, halogen, alkoxy, or R 2 C(=0)NH- , wher R 27 is hydrogen or alkyl; (C) bond "a" is a single bond or is nil; and bond "b" is single bond, a double bond, or is nil; except bond "a" an bond "b" are not both nil; (D) Rl 2 is -C(R8a)-, or -CH2-R 28 -; where R 2 8 is -C(R8a), -0-, o -N-, and R 8 is directly bonded to N" in Formula (II) t form a 5-membered ring; except, if bond "a" is nil, then Rl 2 is (1) -C(R8a)(χl)-, where (i) χl is -R 2 1; -0R 3 0; -S(0) r R 3 0, where r is integer from 0 to 2; -0(C=0)R 0; or N(R30)R31 ; a (ii) R 30 and R 31 - are, independently, alkyl, alkenyl carbocyclic ring or heterocyclic ri substituents; or R 30 and R 3 1 together comprise heterocyclic ring including the nitrogen atom which R 3 0 and R 1 are bonded; or (2) -CH2-R 32 -; where R 32 is -C(R8aj (R21) , -0-, or -NR 8a , . and R 32 i s directly bonded to N" in Formula (II) to form a 5-membered ring; (E) (1) if bond "b" is a single bond, Rl3 is -CH(R 33 )-; or, -C(0)NHS02-, if bond "a" is nil; or -C*(R 33 )- if R 14 contains a R ^ moiety; where R 33 is hydrogen or COOH, and C* is linked to R 36 to form a 3-membered ring; (2) if bond "b" is a double bond, Rl3 is -C(R 33 )=; or (3) if bond "b" is nil, Rl 3 is hydrogen, -SO3H, -P0(0R 3 )0H, -C(0)NHS02N(R 34 )(R 3 5), -OSO3H, -CH(R 3 5)C00H, or -0CH(R 34 )C00H; where R 34 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R 35 is hydrogen, alkyl, alkenyl, or -NHR 8a ; or, if R 13 is -C(0)NHS02N(R 34 ) (R 3 5) , R 34 and R 3 $ may together comprise a heterocyclic ring including the nitrogen to which R 34 and R 3 5 are bonded; and (F) (1) if bond "a" or bond "b" is nil, then Rl 4 is nil and L is bonded directly to R 2 or Rl 3 ; (2) if bond "a" and "b" are single bonds, Rl 4 is -W-C"'=C(R8a)-R37. ) or . W . C »' (R36).R37. ; or (3) if bond "a" is a single bond and bond "b" is a double bond, Rl is -C(R8a)(R38)- -C"-R 37 -; - -C(R8a)(R 3 8)-C"'-R 3 7-; or -W-C"'-R 37 -; where (a) is 0; S(0) s , where s is an integer from 0 to 2; or C(R 3 8), where R 38 is hydrogen, alkyl or alkoxy; (b) R 35 hydrogen; alkyl; alkenyl; -COOH; or, if R i3 is -C*(R 33 ), R 3 6 may be linked to C* to form a 3-membered carbocyclic ring; (c) R 37 is nil, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and (d) C" is directly bonded to Rl to form a 5- or 6-membered ring, and (III) L links Q to B; and L is L\ -χ2 t _R39.[ t or _χ3 t -R39-|_\ where L' is Q', -X 2 -Q", or -X 3 -Q", -X t-C(=Y U )-Z-Q" ; (1) t and u are, independently, 0 or 1; (2) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; (3) X 2 is oxygen, or S(0) v , where v is an integer from 0 to 2; (4) X 3 is nitrogen; N(R 0); N+(R 4 1)(R 42 ) ; or R 3 -N(R 1); and is linked to 4 by a single or double bond; or, if Rl 4 is nil, X 3 is linked to B by a single or double bond; where (a) R 0 is R 8a ; -0R8a ; 0 r -C(=0)Rδa ; (b) R 4 1 and R 42 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings; heterocyclic rings; or, if R 6 is Rl6χ, then R 4 1 and R 42 together with Q" may comprise a heterocyclic ring as Rl β ; (c) R 43 is N(R41) , oxygen or sulfur; (5) X 4 is oxygen, sulfur, NR 0, or R 3 -NR 1; (6) Y 3 is oxygen, sulfur, NR- ϋr N+(R41)(R42) ; (7) Y 4 is oxygen or NR 1; (8) Z is nil, oxygen, sulfur, nitrogen, NR 40 , or N(R41).R43 ; (9) Q' is said R 6 substituent of Q; and (10) Q" is Q'; or together with χ2, X 3 , or Z, is said R 6 substituent of Q; and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof. It has been found that the compounds of this invention, and compositions containing these compounds, are effective antimicrobial agents against a broad range of pathogeni microorganisms. These compounds provide advantages versus antimicrobial agents among those known in ths art, including (fo example) the spectrum of antimicrobial activity, potency, th avoidance of microbial resistance, reduced toxicity, and improved pharmacology. DESCRIPTION OF THE INVENTION c The present invention encompasses certain novel lactam- quinolones, methods for their manufacture, dosage forms, and methods of administering the lactam-quinolones to a human or other animal subject. Specific compounds and compositions to be used in the invention must, accordingly, be pharmaceutically 10 acceptable. As used herein, such a "pharmaceutically-acceptable" component is one that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio. ,-. Quinolonyl Lactams The compounds of this invention, herein referred to as "quinolonyl lactams", encompass any of a variety of lactam moieties linked, by a linking moiety, to a quinolone moiety at the 5-position of the quinolone. These compounds include those 0 having the general formula Q - L - B wherein Q, L and B are defined as follows: 5 (I) Q is a structure according to Formula (I) 5 wherein R (A) (1) Al is N or C(R 7 ); -vnere (i) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or N(R 8 )(R 9 ) (preferably hydrogen or halogen), and (ii) R 8 and R 9 are, independently, R 8a , where R 8a is hydrogen, alkyl, alkenyl, carbocyclic ring, o heterocyclic ring substituents; or R 8 and R together comprise a heterocyclic ring includin the nitrogen to which they are bonded; {2) A 2 is N or C(R 2 ) (preferably C(R 2 )); where R 2 i hydrogen or halogen; (3) A 3 is N or (preferably) C(R 5 ); where R 5 is hydrogen; (4) Rl is hydrogen, alkyl, a carbocyclic ring, heterocyclic ring, alkoxy, hydroxy, alkenyl arylalkyl, or N(R 8 )(R 9 ) (preferably alkyl or carbocyclic ring); (5) R 3 is hydrogen, halogen, alkyl, a carbocyclic ring, o a heterocyclic ring (preferably a heterocyclic ring); (6) R 4 is hydroxy; and (7) R 5 is Rl5 or RI^X; where Rl5 i s a substituent moiety o L and is nil, alkyl, heteroalkyl, or alkenyl; Rl* 5 is substituent moiety of L and is alkyl, alkenyl, carbocyclic ring or a heterocyclic ring; and X i alkyl, heteroalkyl, alkenyl, oxygen, sulfur, or NH; (B) except that (1) when Al is C(R 7 ), Rl and R 7 may together comprise heterocyclic ring including N' and Al; (2) when A 2 is C(R 2 ), R 2 and R 3 may together compris -0-(CH )n-0-> where n is an integer from 1 to 4; (3) when A 3 is C(R5), R 4 and R5 may together comprise heterocyclic ring including the carbon atoms to whi R 4 and R5 are bonded and the carbon atom of Formula ( to which said carbon atoms are bended; and (4) when A 3 is C(R5), Rl and R5 may together comprise heterocyclic ring including N' and the adjacent carb to which R5 is bonded; (II) B is a structure according to Formula (II), where L is bonded to Rl : where (A) RlO is hydrogen, halogen, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R 8a -0-, R 8a CH=N-, (R 8 )(R 9 )N-, Rl 7 -C(=CHR20)-C(=0)NH-. or (preferably) alkyl, alkenyl, Rl7-C(=NO-Rl9)-C(=0)NH-, or Rl8-(CH 2 ) -C(-=0)NH- ; where (1) m is an integer from 0 to 9 (preferably from 0 to 3); (2) Rl 7 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocycl ic ring (preferably alkyl, a carbocyclic ring, or a heterocycl ic ring) ; (3) Rl 8 is Rl* 7 , -Yl, or -CH(γ2) (Rl7) • ( ) R 19 is Rl , arylalkyl, heteroarylalkyl , -C(R22)(R23)C00H, -C(=0)0-Rl 7 , or -C(=0)NH-Rl 7 , where R22 and R2 are, independently, Rl- 7 or together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R22 and R 23 are bonded (preferably Rl 7 or -C(R22)(R23)C00H) (5) R20 is Rl9, halogen, -γl, or -CH(γ2)(Rl 7 ) (preferably Rl9 or halogen) ; (6) Yl is -C(=0)0R21, -C(-0)R21, -N(R24)R21, 0 r -S(0) p R2 9 or -0R29; and γ is l or -OH, -SH, or -SO3H; (a) p is an integer from 0 to 2 (preferably 0); (b) R 24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroalkenyl; a carbocyclic ring; a heterocyclic ring; -SO3H; -C(=0)R 2 *5; or, when Rl 8 is -CH(N(R 2 )R21)(Rl7), R24 may comprise a moiety bonded to R21 to form a heterocyclic ring; and (c) R25 is R 17, NH(Rl 7 ), N(R17)(R26), 0(R26), 0 r S(R26) (preferably Rl- 7 , NH(Rl7) or N(Rl 7 )(R26)) ; where R 25 is alkyl, alkenyl, a carbocyclic ring, a heterocyclic ring or (preferably) when R 2 5 is N(Rl )(R 26 ), R 26 may comprise a moiety bonded to Rl7 to form a heterocyclic ring; and (7) R 2 1 is R 29 or hydrogen; where R 29 is alkyl; alkenyl; arylalkyl; heteroalkyl; heteroalkenyl; heteroarylalkyl ; a carbocyclic ring; a heterocyclic ring; or, when γl is N(R 2 )R 2 1 and R 2 1 is R 29 , R 2 1 and R 24 may together compritse a heterocyclic ring including the nitrogen atom to which R 24 is bonded (preferably hydrogen, alkyl, a carbocyclic ring or a heterocyclic ring); (B) Rll is hydrogen, halogen, alkoxy, or R 27 C(=0)NH- (preferably hydrogen or alkoxy), where R 27 is hydrogen or alkyl (preferably hydrogen); (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) Rl 2 is -C(R 8a )-, or -CH2-R 28 - (preferably -C(R 8 )-); where R 28 is -C(R 8a ), -0-, or -N-, and R 28 is directly bonded to N" in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then Rl 2 is (1) (preferably) -C(R 8a )(Xl)-, where (i) Xl is -R 2 1; -0R 3 °; -S(0) r R 30 , where r is an integer from 0 to 2 (preferably 0); -0(C*0)R 3 0; or N(R 3 0)R 3 1; and (ii) R 30 and R 3 1 are, independently, alkyl, alkenyl, carbocyclic ring or heterocyclic ring substituents; or R 30 and R 3 1 together comprise a heterocyclic ring including the nitrogen atom to which R 30 and R 3 1 are bonded; or (2) -CH2-R 32 -; where R 32 is -C(R8a)(R21), -o-, or -NRδa, and R 32 is directly bonded to N" in Formula (II) to form a 5-membered ring; (E) (1) if bond "b" is a single bond, Rl 3 is preferably -CH(R 33 )-; or, -C(0)NHS02-, if bond "a" is nil; or -C*(R 33 )-, if Rl contains a R 35 moiety; where R 33 is hydrogen or COOH (preferably COOH), and C* is linked to R 35 to .form a 3-membered ring; (2) if bond "b" is a double bond, Rl 3 is -C(R 33 )=; or (3) if bond "b" is nil, Rl 3 is hydrogen, -S03H, -P0(0R 34 )0H, -C(0)NHS02N(R 3 )(R 3 5), -OSO3H, -CH(R 3 5)C00H, or -0CH(R 34 )C00H (preferably -SO3H, or -C(0)NHSθ2N(R 34 )(R 35 ); where R 34 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R 3 5 is hydrogen, alkyl, alkenyl, or -NHR8a ; or (preferably), if R i3 is -C(0)NHS02N(R 34 )(R 3 5) , R 34 and R 35 may together comprise a heterocyclic ring including the nitrogen to which R 34 and R 35 are bonded; and (F) (1) if bond "a" or bond "b" is nil, then Rl 4 is nil and L is bonded directly to Rl2 or Rl 3 ; (2) if bond "a" and "b" are single bonds, Rl is -W-C"'=C(R8a)-R37- r or -W-C" (R 3 6)-R 3 7. ; 0. r (3) (preferably) if bond "a" is a single bond and bond "b" is a double bond, Rl 4 is -C(R 8 a)(R 38 )-W-C"'-R 37 -; 0 r (preferably) -W-C(R 8a ) (R 38 )-C"'-R 37 -, or -w-C" -RJ'-; where (a) W is 0; S(0) s , where s is an integer from 0 to 2 (preferably 0); or C(R 38 ), where R 38 is hydrogen, alkyl or alkoxy; (b) R 36 hydrogen; alkyl; alkenyl; -COOH; or, if Rl 3 is -C*(R 33 ), R 3( 5 may be linked to C* to form a 3-membered carbocyclic ring; (c) R 37 is nil, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and (d) C" is directly bonded to Rl 3 to form a 5- or 6-membered ring, and (III) L links Q to B; and L is L\ -χ2 t - 9 -L', or -X fK 3 2-L ' , where L' is Q', -X 2 -Q", -χ3-Q", or -X 4 t-C(*Y 3 U )-Z-Q" (preferably -X -Q", -X3-Q", -X4 t -C(=Y3 U )-Z-Q"); (1) t and u are, independently, 0 or 1; ( 2 ) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring (preferably alkyl or alkenyl) ; (3) X 2 is oxygen, or S(0) , where v is an integer from 0 to 2 (preferably 0); (4) X 3 is nitrogen; N(R °); N+(R 1)(R 42 ) ; or R 43 -N(R 4 1); and is linked to Rl 4 by a single or double bond; or, if Rl is nil, X 3 is linked to B by a single or double bond (preferably X 3 is nitrogen, N(R 40 ) or N+(R 4 1)(R 42 )); where (a) R 4 0 is R 8a ; -0R 8a ; or -C(-0)R 8a ; (preferably R 8a ) (b) R 4 1 and R 42 are, independently, hydrogen; alkyl alkenyl; carbocyclic rings; heterocyclic rings or, if R 6 is Rl6χ, then R 1 and R 42 together with Q", may comprise a heterocyclic ring as Rlδ; (c) R 43 is N(R 4 1), oxygen or sulfur; (5) X 4 is oxygen, sulfur, NR 0, or R 3 -NR 1 (preferably oxygen, sulfur or NR 40 ); (6) Y 3 is oxygen, sulfur, NR 4 0 or N + (R 1)(R 42 ) ; (7) Y 4 is oxygen or NR 4 1 (preferably oxygen); (8) Z is nil, oxygen, sulfur, nitrogen, NR 40 , or N(R 4 1)-R 43 (preferably oxygen, sulfur, nitrogen or NR 0); (9) Q' is said ≠ substituent of Q; and (10) Q" is Q'; or together with X 2 , X 3 , Z or V . is said Rδ substituent of Q; and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof. Definitions and Usage of Terms: The following is a list of definitions for terms used herein. "Heteroato " is a nitrogen, sulfur or oxygen atom. Groups containing one or more heteroatoms may contain different heteroatoms. "Alkyl" is an unsubstituted or substituted saturated hydrocarbon chain radical having from 1 to 8 carbon atoms, preferably from 1 to 4 carbon atoms. Preferred alkyl groups include (for example) methyl, ethyl, propyl , isopropyl, and butyl . "Heteroalkyl" is an unsubstituted or substituted saturated chain radical having from 3 to 8 members comprising carbon atoms and one or two heteroatoms. "Alkenyl" is an unsubstituted or substituted hydrocarbon chain radical having from 2 to 8 carbon atoms, preferably from 2 to 4 carbon atoms, and having at least one olefinic double bond. "Carbocyclic ring" is an unsubstituted or substituted, saturated, unsaturated or aromatic, hydrocarbon ring radical. Carbocyclic rings are monocyclic or are fused, bridged or spiro polycyclic ring systems. Monocyclic rings contain from 3 to 9 atoms, preferably 3 to 6 atoms. Polycyclic rings contain from 7 to 17 atoms, preferably from 7 to 13 atoms. "Cycloalkyl" is a saturated carbocyclic ring radical. Preferred cycloalkyl groups include (for example) cyclopropyl, cyclobutyl and cyclohexyl. "Heterocyclic ring" is an unsubstituted or substituted, saturated, unsaturated or aromatic ring radical comprised of carbon atoms and one or more heteroatoms in the ring. Heterocyclic rings are monocyclic or are fused, bridged or spiro polycyclic ring systems. Monocyclic rings contain from 3 to 9 atoms, preferably 3 to 6 atoms. Polycyclic rings contain from 7 to 17 atoms, preferably from 7 to 13 atoms. "Aryl" is an aromatic carbocyclic ring radical. Preferred aryl groups include (for s mple) phenyl , tolyl, xylyl, cumenyl and naphthyl . "Heteroaryl" is an aromatic heterocyclic ring radical. Preferred heteroaryl groups include (for example) thienyl, furyl , pyrrolyl, pyridinyl, pyrazinyl, thiazolyl, quinolinyl, pyri idinyl and tetrazolyl. "Alkoxy" is an oxygen radical having a hydrocarbon chain substituent, where the hydrocarbon chain is an alkyl or alkenyl (i.e., -0-alkyl or -0-alkenyl). Preferred alkoxy groups include (for example) ethoxy, ethoxy, propoxy and allyloxy. "Alkylamino" is an amino radical having one or two alkyl substituents (i.e., -N-alkyl). "Arylalkyl" is an alkyl radical substituted with an aryl group. Preferred arylalkyl groups include benzyl and phenylethyl . "Arylamino" is an amine radical substituted with an aryl group (i.e., -NH-aryl). "Aryloxy" is an oxygen radical having a aryl substituen (i.e., -0-aryl). "Acyl" or "carboπyl" is a radical formed by removal of th hydroxy from an carboxylic acid (i.e., R-C(=0)-). Preferre alkylacyl groups include (for example) acetyl , for yl , an propionyl . "Acyloxy" is an oxygen radical having an acyl substituen (i.e., -0-acyl); for example, -0-C(=0)-alkyl . "Acylamino" is an amino radical having an acyl substituen (i.e., -N-acyl); for example, -NH-C(-O)-alkyl . "Halo", "halogen", or "halide" is a chloro, bro o, fluoro o iodo atom radical. Chloro and fluoro are preferred ha!ides. Also, as referred to herein, a "lower" hydrocarbon moiet (e.g., "lower" alkyl) is a hydrocarbon chain comprised of from to 6, preferably from 1 to 4, carbon atoms. A "pharmaceutically-acceptable salt" is a cationic sal formed at any acidic (e.g., carboxyl) group, or an anionic sal formed at any basic (e.g., amino) group. Many such salts ar known in the art, as described in World Patent Publicatio 87/05297, Johnston et al . , published September 11, 198 (incorporated by reference herein). Preferred cationic salt include the alkali metal salts (such as sodium and potassium) and alkaline earth metal salts (such as magnesium and calcium) Preferred anionic salts include the halides (such as chloride salts) . A "biohydrolyzable ester" is an ester of a quinolonyl lactam that does not essentially interfere with the antimicrobial activity of the compounds, or that are readily metabolized by a human or lower animal subject to yield an antimicrobially-active quinolonyl lactam. Such esters include those that do not inter¬ fere with the biological activity of quinolone antimicrobials or beta-lactam antimicrobials (cephems, for example). Many such esters are known in the art, as described in World Patent Publication 87/05297, Johnston et al . , published September 11, 1987, (incorporated by reference herein). Such esters include lower alkyl esters, lower acyloxy-alkyl esters (such as acetoxymethyl , acetoxyethyl , aminocarbonyloxymethyl , pivaloylox- y ethyl and pivaloyloxyethyl esters), lactonyl esters (such as phthalidyl and thiophthal idyl esters), lower alkoxyacyloxyalkyl esters (such as methoxycarbonyloxymethyl , ethoxycarbonyloxyethyl and isopropoxycarbonyloxyethyl esters), alkoxyalkyl esters, choline esters and alkyl acylamino alkyl esters (such as acetamido ethyl esters). As defined above and as used herein, substituent groups may themselves be substituted. Such substitution may be with one or more substituents. Such substituents include (for example) those listed in C. Hansch and A. Leo, Substituent Constants for Correlation Analysis in Chemistry and Biology (1979), incorporated by reference herein. Preferred substituents include (for example) alkyl, alkenyl, alkoxy, hydroxy, oxo, nitro, amino, a inoalkyl (e.g., amiπomethyl, etc.), cyano, halo, carboxy, alkoxyaceyl (e.g., carboethoxy, etc.), thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl (e.g., piperidinyl, morpholinyl, pyrrolidinyl , etc.), imino, thioxo, hydroxyalkyl, aryloxy, arylalkyl, and combinations thereof. Also, as used in defining the structure of the compounds of this invention, a particular radical may be defined for use as a substituent in multiple locations. For example, the R 8a substituent is defined as a potential substituent of R 7 , but is also incorporated into the definition of other substituents (such as Rδ. Rl2, R32 an d '). AS used herein, such a radical is independently selected each time it is used (e.g., R8a neec j no t be alkyl in all occurrences in defining a given compound of this invention) . Lactam-containing moiety: Groups Rl2, Rl 3 , and Rl , together with bonds "a" and "b" of formula (I), form any of a variety of lactam-containing moieties known in the art to have antimicrobial activity. Such moieties wherein either bond "a" or bond "b" are nil (i.e., do not exist) are mono-cyclic; if both bonds exist, the structures are bi-cyclic. Preferably, bond "a" is a single bond and bond "b" is a double bond. Preferred lactam moieties include the cephems, oxacephems and carbacephems of the representative formula: COOH wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a double bond; Rl 2 is -C(R 8 a)., where R 8a is hydrogen; Rl 3 is -CH(R 33 ), where R 33 is COOH; and R i4 is -W-C(R8a)(R38)- C '"-R37, where R 8a and R 38 are hydrogen, R 37 is methylene, and W is S (for cephems), 0 (for oxacephems) or C(R 38 ) (for carbacephems). Other preferred lactam moieties include the isocepheπ"*: and iso-oxacephems of the representative formula: COOH wherein, referring to formula II, bond "a" is a single bond; bond "b" is a double bond; R 12 is -C(R 8a ) where R 8a is hydrogen; Rl 3 is -C(R 33 )=, where R 33 is COOH; and R* 4 is -C(R8aj (R38)-W-C"'-R 37 where R 8a and R 38 are each hydrogen, R 37 is methylene, and W is S (for isocephems) or 0 (for iso-oxacephems) . Other preferred lactam-containing moieties include the penems, carbapene s and clavems, of the representative formula: COOH wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a double bond; Rl 2 is -C(R 8a ), where R 8a is hydrogen; Rl is -C(R 33 )«, where R 33 is COOH; and Rl 4 is -W-C'-R 37 , where R 37 is methylene, and W is S (for penems), C(R 38 ) (for carbapenems), or 0 (for clavems). Such lactam moieties are described in the following articles, all incorporated by reference herein: R. Wise, "In Vitro and Pharmacokinetic Properties of the Carbapenems", 30 Antimicrobial Agents and Chemotherapy 343 (1986); and S. McCombie et al . , "Synthesis and In Vitro Activity of the Penem Antibiotics", 8 Medicinal Research Reviews 393 (1988). Other preferred lactam-containing moieties of this invention include the penicillins of the representative formula: wherein, referring to formula II, bond "a" is a single bond, bond "b" is a single bond; Rl 2 is -C(R8a)-, where R8a -j S hydrogen; Rl 3 is -CH(R 33 )- where R 33 is COOH; and Rl 4 is -W-C M ' (R 6)-R 37 - where R 36 is methyl, R 37 is methylene, and W is S. Other preferred lactam-containing moieties include the monocyclic beta-lactams, of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond "b" is nil; Rl 2 is -C(R8a)-, where R8a i s hydrogen; Rl 4 is nil; and Rl 3 is -SO3H (for a monobactaπ!}, -P0(0R 34 )0H (for a monophospham); -C(0)NHS02N(R 34 )(R 5) (for a monocarbam), -OSO3H (for a onosulfactam), -CH(R 35 )COOH (for nocardicins) , or -OCH(R 34 )COOH. Such lactam moieties are described in C. Ci arusti et al., "Monocyclic 8- actam Antibiotics", 4 Medicinal Research Reviews 1 (1984), incorporated by reference herein. Other preferred lactam moieties include the monocyclic beta-lactams of the representative formula: wherein referring to formula II, bond "a" is nil, bond "b" is a single bond; Rl2 is -C(R8a)(R29). w h ere both R8a and R 29 are hydrogen; and Rl 4 is nil. Other preferred lactam moieties include the clavams of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a single bond; R 2 is -C(R 8 a)-, where R 8 a is hydrogen; Rl 3 is -CH(R 33 )-, where R 33 is COOH; and Rl is W-C"'=C-(R8a)-R 7 > where R 8 a is hydrogen and R 37 is methylene, and W is 0. Other preferred lactam moieties include the 2,3-methyleno- penams and -carbapenams of the representative formula: COOH wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a single bond; Rl 2 is -C(R8a). j w ere R 8 i s hydrogen; Rl 3 is -C*(R 33 ), where R 33 is COOH; and R i4 is W-C H, (R 36 )-R 37 , where R 37 is nil, R 36 is linked to C* to form a 3-membered carbocyclic ring, and W is C(R 38 ) or sulfur. Lactam moieties of this invention also include the lactivicin analogs of the representative formula: wherein, referring to formula (II), bond "a" is nil; bond "b" is a single bond; Rl 2 is -CH2-R 32 , where R 32 is 0; Rl is -CH(R 33 )-, where R 33 is COOH; and Rl 4 is nil. Other lactam moieties include the pyrazolidinones of the representative formula: wherein, referring to formula (I), bond "a" is a single bond; bond "b" is a double bond; R i2 is -CH2-R 28 -, where R28 is -N-; Rl3 is -C(R 33 )-, where R 33 is COOH; and RI 4 is W-C"'-R 37 -, where R 37 is methylene, and W is C(R 38 ). Other lactam moieties include the gamma-lactams of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond H b M is nil; Rl2 is -CH2-R 28 -, where R28 i S -C(R8a) and R 8 a is hydrogen; Rl 3 is -SO3H, -PO(OR 34 )OH, -C(0)NHSθ2N(R 34 )(R 3 5) , -OSO3H, -CH(R 5)COOH, or -0CH(R )C0OH; and Rl is nil. Preferred lactam-containing moieties include cephems, isocephems, iso-oxacephe s, oxacephems, carbacephems, penicillins, penems, carbapenems, and monocyclic beta-lactams. Particularly preferred are cephems, penems, ca apcπεmi and monocyclic beta-lactams. RlO, in formula (II) " , is any radical that may be substituted at the active stereoisomeric position of the carbon adjacent to the lactam carbonyl of an antimicrobially-active lactam. (As used herein, the term "antimicrobially-active lactam" refers to a lactam-containing compound, without a quinolonyl substituent moiety, which has antimicrobial activity.) This "active" position is beta (i.e., 7-beta) for cephems, oxacephems and carbacephems (for example). The active position is alpha for penems, carbapenems, clavems and clavams. Appropriate Rl groups will be apparent to one of ordinary skill in the art. Many such RlO groups are known in the art, as described in the following documents (all of which are incorporated by reference herein): Cephalosporins and Penicillins: Chemistry and Biology (E. Flynn, editor, 1972); Chemistry and Biolooy of b-Lactam Antibiotics (R. Morin et al . , editors, 1987); "The Cephalosporin Antibiotics: Seminar-in-Print", 34 Drugs (Supp. 2) 1 (J. Williams, editor, 1987); New Beta-Lactam Antibiotics: A Review from Chemistry of Clinical Efficacy of the New Cephalosporins (H. Neu, editor, 1982); M. Sassiver et al . , in Structure Activity Relationships among the Semi -synthetic Antibiotics (D. Perlman, editor, 1977). W. Durckheimer et al . , "Recent Developments in the Field of Beta-Lactam Antibiotics", 24 Angew. Chem. Int. Ed. Engl . 180 (1985); G. Rolinson, "Beta-Lactam Antibiotics", 17 __, Antimicrobial Chemotherapy 5 (1986); European Patent Publication 187,456, Jung, published July 16, 1986; and World Patent Publication 87/05297, Johnston et al . , published September 11, 1987. For penems, carbapenems, clavems and clavams, Rl is preferably lower alkyl, or hydroxy-substituted lower alkyl. Particularly preferred Rl groups include hydrogen, hydroxymethyl , ethyl, [l(R)-hydroxyethyl] , [l(R)-[(hydroxysul- fonyl)oxyethyl]], and [1-methyl-l-hydroxyethyl]. Except for penems, carbapenems, clavems and clavams, preferred R i0 groups are amides, such as: acetylamino, preferably substituted with aryl, heteroaryl, aryloxy, heteroarylthio and lower alkylthio substituents; arylglycylamino, preferably N-substituted with heteroarylcarbonyl and cycloheteroalkylcarbonyl substituents; arylcarbonylamino; heteroarylcarbonylamino; and lower alkoxyiminoacetylamiπo, preferably substituted with aryl and heteroaryl substituents. Particularly preferred RlO groups include amides of the general formula and Rl 8 is Rl 7 . Examples of such preferred RlO groups include: [(2-amino-5-halo-4-thiazolyl)acetyl]amino; [(4-aminopyridin-2-yl)acetyl ]amino; [[(3,5-dichloro-4-oxo-l(4H)-pyridinyl)acetyl]amino]; [[[2-(aminomethyl)phenyl]acetyl]amino]; [(lH-tetrazol -1-ylacetyl )amino] ; [(cyanoacetyl)amino] ; [(2-thienylacetyl )amino]; [[(2-amino-4-thiazoyl)acetyl]amino3; and sydnoηe, 3-[-2-amino]-2-oxoethyl . The following are other such preferred Rl groups. HCONH- When RlO is and Rl 8 is -Yl, preferred RlO groups include the following: [sulfamoylphenylacetyl ]amino; [[(4-pyridiny!thio)acetyl]aπiir-ύl; [[[(cyanomethyl)thio]acetyl ]amino] ; (S)-[[[(2-amino-2-carboxyethyl)thio]acetyl]amino] ; [[[(trifluoromethyl)thio]acetyl]amino] ; and (E)-[[[(2-aminocarbonyl-2-fluoroetheny1)thio]acetyl]amino] . The following are other such preferred RlO groups. n HH - F When RlO is and Rl 8 is -CH(γ2)(R 17 ) , preferred Rl groups include the following: [carboxypheny1acetyl]amino; [(phenoxycarbonyl)phenylacetyl]amino; [4-methyl-2,3-dioxo-1-piperazinecarbonyl-D-phenylglycyl]- amino; [[[3-(2-furyl ethyleneamino)-2-oxo-l-imidazolidinyl]- carbonyl]amino]phenyl]acetyl ]amino; (R)-[(aminophenylacetyl )amino]; (R)-[[amino(4-hydroxyphenyl )acetyl]amino] ; (R)-[(amino-1,4-cyclohexadien-l-ylacetyl)amino]; [(hydroxyphenylacetyl )amino]; (R)-[[[[(Met yl-2,3-dioxo-1-piperazinyl)carbonyl]amino]- (4-hydroxyphenyl)acetyl]amino] ; (R)-[[[[(5-carboxy-lH-imidazol-4-yl)carbonyl]amino]phenyl- acetyl]amino]; (R)-[[[[(4-hydroxy-6-methy1-3-pyridinyl)carbonyl]amino](4- hydroxyphenyl )acetyl ]amino] ; (R)-[(phenylsulfoacetyl)amino] ; (2R,3S)-[[2-[[(4-ethyl-2,3-dioxo-l-piperazinyl)carbonyl]- amiπo]-3-hydroxy-l-oxobutyl ]amino] ; [[carboxy(4-hydroxyphenyl)acetyl]amino]; (R)-[[amino[3-[(ethylsulfonyl)amino]phenyl]acetyl]amino]; (R)-[[amino(benzo[b]thien-3-yl )acetyl]amino]; (R)-[[amino(2-naphthyl)acetyl]amino]; (R)-[[amino(2-amino-4-thiazolyl)acetyl]amino]; [[[[(6,7-dihydroxy-4-oxo-4H-l-benzopyran-3-yl)carbonyl]- amino](4-hydroxyphenyl)acetyl]amino]; (R,R)-[[2-[4-[2-amino-2-carboxyethyloxycarbonyl]aminophen- yl]-2-hydroxyacetyl]aππno]; and (S)-[[(5-hydroxy-4-oxo-l(4H)-pyridin-2-yl)carbonylamino(2- amino-4-thiazolyl)acetyl]amino]. The following are other such preferred Rl groups. 10 Another preferred R 10 group is R1 -C(=CHR20)-C(=0)NH- Such groups include (for example) the following structures. Another class of preferred RlO groups (for lactam-containing moieties other than penems, carbapenems, clavems and clavams) include those of the formula: Rl 7 -C(=N0-Rl9)-C(=0)NH-. Examples of this preferred class of Rl° groups include: 2-phenyl-2-hydroxyiminoacetyl ; 2-thienyl-2-methoxyiminoacetyl ; and 2-[4-(gamma-D-glutamyloxy)phenyl]-2-hydroxyiminoacetyl . (Z)[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]; [[(2-furanyl(methoxyimino)acetyl]amino]; (Z)-[[(2-amino-4-thiazolyl)[(l-carboxy-l-methyl)ethoxyim- ino]acetyl ]amino] ; (Z)-[[(2-amino-4-thiazolyl ) (l-carboxymethoxyimino)acetyl]am- ino]; [[(2-amino-4-thiazolyl)[(lH-imidazol-4-ylmeιhoxy)imino]acet¬ yl]amino]; (Z)-[[(2-amino-4-thiazolyl-3-oxide)(methoxyimino)acetyl]am¬ ino]; and (S,Z)-[[(2-amino-4-thiazolyl)[carboxy(3,4-dihydroxyphen- yl)methoxyimino]acetyl]amino] . Other preferred Rl° groups include the following structures (where "SS H is HC0NH-). 35 1 35 The following are other preferred RlO groups. Suitable RH groups are among those well-known in the art, including those defined in the following documents (all incorporated by reference herein). W. Durckheimer et al., "Recent Developments in the Field of Beta- c m Antibiotics 8 , 24 Anoew. Chem. Int. Ed. Enql . 180 (1985); G. Rolinson, "Beta-Lactam Antibiotics", 17 J. Antimicrobial Chemotherapy (1986); and European Patent Publication 187,456, Jung, publishe July 16, 1986. Preferred RU groups include hydrogen, methoxy ethoxy, propoxy, thiomethyl, halogen, cyano, for yl and formyla ino. Particularly preferred Rll groups include hydrogen, methoxy, halogen, and formylamino. Quinolone Moieties: Groups Al, A 2 , A 3 , Rl, R 3 , and R 4 of formula I form a moiety (herein, "core quinolone moiety") present in any of a variety of quinolone, naphthyridine or related heterocyclic moieties known in the art to have antimicrobial activity. Such heterocyclic moieties are well known in the art, as described in the following articles, all incorporated by reference herein: J. Wolfson et al., "The Fluoroquinolones: Structures, Mechanisms of Action and Resistance, and Spectra of Activity In Vitro", 28 Antimicrobial Agents and Chemotherapy 581 (1985); and T. Rosen et al . , 31 vL. Med Chem. 1586 (1988); T. Rosen et al . , 31 J. Med. Chem. 1598 (1988); G. Klopman et al . , 31 Antimicrob. Agents Che other. 1831 (1987); 31:1831-1840; J. P. Sanchez et al . , 31 J. Med. Chem. 983 (1988); J. M. Do agala et al . , 31 J. Med. Chem. 991 (1988); M. P. Wentland et al., in 20 Ann. Rep. Med. Chem. 145 (D. M. Baily, editor, 1986); J. B. Cornett et al., in 21 Ann. Rep. Med. Chem. 139 (D. M. Bailey, editor, 1986); P. B. Fernandes et al . , in 22 Ann. Reo. Med. Chem. 117 (D. M. Bailey, editor, 1987); R. Albrecht, 21 Proα. Drug Research 9 (1977); and P. B. Fernandes et al., in 23 Ann. Reo. Med. Chem. (R. C. Allen, editor, 1987). Preferred quinolone moieties include those where Al is C(R 7 ), A 2 is C(R 2 ), and A 3 is C(R5) (i.e., quinolones); Al is nitrogen, A 2 is C(R 2 ), and A 3 is C(R 5 ) (i.e., naphthyridines) ; Al is C(R 7 ), A 2 is C(R 2 ), and A 3 is nitrogen (i.e., cinnoline acid derivatives); and where A is nitrogen, A 2 is nitrogen, and A 3 is C(R5) (i.e., pyridopyrimidine derivatives). More preferred quinolone moieties are those where A is C(R 7 ), A 2 is C(R 2 ), and A 3 is C(R5) (i.e., quinolones); and where A is nitrogen, A 2 is C(R 2 ), and A 3 is C(R~) (i.e., naphthyridines). Particularly preferred quinolone moieties are where Al is C(R 7 ), A 2 is C(R 2 ), and A 3 is C(R5) (i.e., quinolones). Rl is preferably alkyl, aryl, cycloalkyl and alkylamino. More preferably, Rl is ethyl, 2-fluoroethyl , 2-hydroxyethyl , t-butyl, 4-fluorophenyl , 2,4-difluorophenyl , methylamino and cyclopropyl. Cyclopropyl is a particularly preferred R group. Preferred quinolone moieties also include those where Al is C(R 7 ) and Rl and R 7 together comprise a 6-membered heterocyclic ring containing an oxygen or sulfur atom. R 2 is preferably hydrogen or halo. More preferably R 2 is chlorine or fluorine. Fluorine is a particularly preferred R 2 group. Preferred R 3 groups include nitrogen-containing heterocyclic rings. Particularly preferred are nitrogen-containing heterocyclic rings having from 5 to 8 members. The heterocyclic ring may contain additional heteroatoms, such as oxygen, sulfur, or nitrogen, preferably nitrogen. Such heterocyclic groups are described in U.S. Patent 4,599,334, Petersen et al., issued July 8, 1986; and U.S. Patent 4,670,444, Grohe et al . , issued June 2, 1987 (both incorporated by reference herein). Preferred R 3 groups include unsubstituted or substituted pyridine, piperi- dine, morpholine, diazabicyclo[3.1.1]heptane, diazabicy- clo[2.2.1]heptane, di zabicyclo[3.2.1]octane, diazabicyclo[2.2.2] octane, thiazolidine, imidazolidine, pyrrole and thiamorpholine, as well as the following particularly preferred R 3 groups include piperazine, 3-methylpiperazine, 3-aminopyrrolidine, 3-aminomethylpyrrolidine, N,N-dimethylaminomethylpyrrolidine, N-methylaminomethylpyrrolidine, N-ethylaminomethylpyrrolidine, pyridine, N-methylpiperazine, and 3,5-dimethylpiperazine. Linking Moieties: Group L, together with the R-*-* substituent, form a variety of linking moieties between the lactam-containing structure (B) and the quinolone structure (Q) of the quinolonyl lactams. Linking moieties include the following general classes. (1) Carbamate linking moieties, wherein L is -X t-C(=Y 2 U )-Z-Q"; t is 1 and u is 1; X 4 is oxygen; Y 2 is oxygen; and Z is nitrogen. (2) Dithiocarbamate linking moieties, wherein L is -X t-C(=Υ U )-Z-Q"; t is 1 and u is 1; X 4 is sulfur; Y 2 is sulfur; and Z is NR 4 1, where R 4 ** is hydrogen. (3) Urea linking moieties wherein L is -X t-C(=Y 2 U )-Z-Q" ; t is 1 and u is 1; X 4 is NR 40 , where R 40 is hydrogen; Y 2 is oxygen; and Z is nitrogen. (4) Thiourea linking moieties wherein L is -X 4 t-C(=Y 2 U )-Z-Q" ; t is 1 and u is 1; X 4 is NR 40 , where R 40 is hydrogen; Y 2 is sulfur; and Z is nitrogen. (5) Isouronium linking moieties wherein L is -X t-C(=Y 2 U )-Z-Q"; t is 1 and u is 1; X 4 is oxygen; Y 2 is N+(R 4 1)(R 4 2) , where R 1 and R 4 2 are hydrogen; and Z is nitrogen. (6) Isothiouronium linking moieties wherein L is t is 1 and u is 1; X 4 is sulfur; γ is N+(R 4 1)(R 42 ), where R and R 4 2 are hydrogen; and Z is nitrogen. (7) Guanidinium linking moieties wherein L is t is 1 and u is 1; X 4 is NR 0, where R 4 0 is hydrogen; γ2 is N+(R 4 1)(R 42 ), where R i and R 42 are hydrogen; and Z is nitrogen. (8) Carbonate linking moieties wherein L is t is 1 and u is 1; X 4 is oxygen; γ2 is oxygen; and Z is oxygen. (9) Trithiocarbonate linking moieties wherein L is t is 1 and u is 1; X 4 is sulfur; γ2 is sulfur; and Z is sulfur. (10) Reversed carbamate linking moieties wherein L is t is 1 and u is 1; X 4 is NR 40 , R 40 is hydrogen; γ2 is oxygen; and Z is oxygen. (11) Xanthate linking moieties wherein L is -χ4 t -C(=Y 2 u )-Z-Q"; t is 1 and u is 1; X 4 is NR 40 , where R 4 0 i s hydrogen; Y 2 is N + (R 4 1)(R 42 ), where R 42 and R 42 are hydrogen; and Z is oxygen. (12) Reversed dithiocarbamate linking moieties wherein L is -X t-C(=Y 2 U )-Z-Q"; t is 1 and u is 1; X 4 is NR 0, where R 40 is hydrogen; Y 2 is sulfur; and Z is sulfur. (13) Reversed isothiouronium linking moieties wherein L is -X t-C(=Y 2 U )-Z-Q"; t is 1 and u is 1; X 4 is NR 0, where R 40 is hydrogen; Y 2 is N+(R 41 )(R 42 ), where R 4 1 and R 42 are both hydrogen; and Z is sulfur. (14) Amine linking moieties wherein L is -X 3 -Q"; and X 3 is nitrogen. (15) Imine linking moieties wherein L is -X 3 -Q"; X 3 is nitrogen, and is linked to R i4 by a double bond. (16) Ammonium linking moieties wherein L is -X 3 -Q"; and X 3 is N+(R 4 1)(R 42 ). (17) Heteroaryl ium linking moieties wherein L is -X 3 -Q"; and X 3 is nitrogen. (18) Ether linking moieties wherein L is -X 2 -Q"; and X 2 is oxygen. (19) Thioether, sulfoxide and sulfone linking moieties wherein L is -X 2 -Q"; and X 2 is S(0)t, where t=0 (thioether), t=l (sulfoxide) or t=2 (sulfone). (20) Ester or thioester linking moiety wherein L is -X 4 t-C(=Y 2 U )-Z-Q"; t is 1 and u is 1; X 4 is oxygen (for an ester) or sulfur (for a thioester); Y 2 is oxygen; and Z is nil. (21) Amide or hydrazide linking moiety wherein -X 4 t-C(=Y u )-Z-Q" ; t is 1 and u is 1; X 4 is N(R 4 0), where R 4 ° is hydrogen (for an amide), or X 2 is R 43 -NR 1 (for a hydrazide), where R 4 1 is hydrogen and R 43 is NR 4 *, and R 4 is hydrogen; Y 2 is oxygen; and Z is nil. Preferred linking moieties include carbamate, dithiocar¬ bamate, urea, thiourea, isothiouronium, amine, ammonium, ester, amide, and heteroaryl ium containing moieties. Particularly preferred linking moieties include carbamate, dithiocarbamate, and amine linking moieties. The specific physical, chemical, and pharmacological properties of the quinolonyl lactams of this invention may depend upon the particular combination of the integral lactam-containing moiety, quinolone moiety and linking moiety comprising the compound. For example, selection of particular integral moieties may affect the relative susceptibility of the quinolonyl lactam to bacterial resistance mechanisms (e.g., beta-lactamase activity) . Preferred quinolonyl lactams include (for example) the following compounds. -46- 35 35 20 35 Methods of Manufacture The quinolonyl lactams of this invention may be made using any of a variety of synthetic techniques known in the art. Manufacture of quinolonyl lactam generally involves the prepara¬ tion of a lactam-containing moiety, a quinolone moiety and a procedure or set of procedures for linking the lactam-containing and quinolone moieties. Procedures for making a broad variety of lactam-containing moieties and core quinolone moieties are well known in the art. For example, procedures for preparing lactam- containing moieties are described in the following references, all incorporated by reference herein (including articles cited within these references): Cephalosporins and Penicillins: Chemistry and Biology (E. H. Flynn, ed, 1972) Chapters 2, 3, 4, 5, 6, 7, 15 and Appendix I; Recent Advances in the Chemistry of g-Lactam Antibiotics (A.G. Brown and S. M. Roberts, ed., 1985); Topics in Antibiotic Chemistry, Vol. 3, (Part B) and Vol. 4, (P. Som es, ed., 1980); Recent Advances in the Chemistry of β-lacta Antibiotics (J. Elks, ed., 1976); Structure-Activity Relation¬ ships Among the Semisynthetic Antibiotics (D. Perlman, ed, 1977); Chapts. 1, 2, 3, 4; Antibiotics, Chemotheraoeutics and Antibac¬ terial Agents for Disease Control (M. Grayson, ed, 1982); Chemistry and Biology of 3-Lactam Antibiotics, Vols 1-3 (K. B. Morin and M. Gorman, eds, 1982); 4 Medicinal Research Review 1-24 (1984); 8 Medicinal Research Review 393-440 (1988); 2 Anoew. Chem. Int. Ed. Enol. 180-202 (1985); 40 J. Antibiotic 182-189 (1987); European Patent Publication 266,060; 42 J Antibiotics 993 (1989); U.S. Patent 4,742,053; 35 Chem. Phar Bull. 1903-1909 (1987); 32 J. Med. Chem.. 601-604 (1989); U.S Patent 4,791,106; Japanese Patent Publication 62/158291; 31 _ Med. Chem. 1987-1993 (1988); 30 J. Med. Chem.. 514-522 (1987); 2 Tet. Let. 285-288 (1987); 28 Tet. Let. 289-292 (1987); 52 J. Pro Chem. , 40C7-4013 (1937); 40 J. Antibiotics. 370-364 (1987); 40 _ Antibiotics, 1636-1639 (1987); 37 J. Antibiotics. 685-688 (1984) 23 Heterocycles. 2255-2270; 27 Heterocycles. 49-55; 33 Chem Pharm. Bull. 4371-4381 (1985); 28 Tet. Let. 5103-5106 (1987); 5 J. Orα. Chem., 4154-4156 (1988); 39 J. Antibiotics. 1351-135 (1986); 59 Pure and Appl . Chem.. 467-474 (1987); 1987 J.C.S. Chem. Comm.: 44 Tetrahedron. 3231-3240 (1988); 28 Tet. Let., 2883-2886, (1987); 40 J. Antibiotics. 1563-1571 (1987); 33 Chem. Pharm. Bull.. 4382-4394 (1985); 37 J. Antibiotics. 57-62 (1984); U.S. Patent 4,631,150; 34 Chem. Pharm. Bull.. 999-1014 (1986); 52 J. Orα. Chem., 4401-4403 (1987); 39 Tetrahedron, 2505-2513 (1983); 38 J. Antibiotics, 1382-1400 (1985); European Patent Application 053,815; 40 J. Antibiotics. 1563-1571 (1987); 40 vλ. Antibiotics, 1716-1732 (2987); 47 J. Org. Chem., 5160-5167 (1981); U.S. Patent 4,777,252; U.S. Patent 4,762,922; European Patent Publication 287,734; U.S. Patent 4,762,827; European Patent Publication 282,895; European Patent Publication 282,365; and U.S. Patent 4,777,673. The methods of this invention preferably use a core quinolone moiety having a non-hydrogen substituent at the 5-position (at the point of attachment of R^). General procedures for preparing core quinolone moieties useful in the methods of this invention are described in the following references, all incorporated by reference herein (including articles listed within these references); 21 Progress in Drug Research, 9-104 (1977); 31 J. Med. Chem., 503-506 (1988); 32 J___ Med. Chem., 1313-1318 (1989); 1987 Liebiσs Ann. Chem., 871-879 (1987); 14 Drugs Exptl . Cl in. Res., 379-383 (1988); 31 J. Med. Chem., 983-991 (1988); 32 J. Med. Chem., 537-542 (1989); 78 J . Pharm. Sci.. 585-588 (1989); 26 J. Het. Chem., (1989); 24 J. Het. Chem.. 181-185 (1987); U.S. Patent 4,599,334, 35 Chem. Pharm. Bull.. 2281-2285 (1987); 29 J. Med. Chem.. 2363-2369 (1986); 31 J. Med. Chem.. 991-1001 (1988); 25 J. Het. Chem.. 479-485 (1988); European Patent Publication 266,576; European Patent Publication 251,308, 36 Chem. Pharm. Bull., 1223-1228 (1988); European Patent Publication 227,088; European Patent Publication 227,039; European Patent Publication 228,661; 31 J. Med. Chem.. 1586-1590 (1988); 31 J. Med. Chem., 1598-1611 (1988); and 23 J. Med. Chem.. 1358-1363 (1980); A general procedure for preparing 5-substituted quinolones useful in the methods of this invention includes treating an appropriate core quinolone moiety, having a 5-fluoro substituent, with various nucleophiles (for example, amines, thiols, azide, and cyanide) in an inert polar solvent, such as dimethyl formamide (DMF) or dimethyl sulfoxide (DMSO) . Further elaboration of the R6 group, to produce quinolone moieties useful in this invention, may be performed by known procedures for protecting group removal, functional group modification and/or (for example) interconversion or ho ologation. Preparation of core quinolone moieties having a non-hydrogen substituent at the 5-position are (for example) described in the following documents, all of which are incorporated by reference herein: 32 J. Med. Chem. 1313 (1989); European Patent Publication 342,649 (1989); European Patent Publication 309,789 (1988); World Patent Publication 89/06649 (1989); European Patent Publication 310,917 (1989); European Patent Publication 312,085 (1989); European Patent Publication 304,087 (1989); European Patent Publication 305,744 (1989); European Patent Publication 306,860 (1989); European Patent Publication 287,951 (1988); German Offenlegungsschrift 3,711,193 (1983); European Patent Publication 265,230 (1988); European Patent Publication 247,464 (1987); European Patent Publication 255,908 (1988); European Patent Publication 242,789 (1987); European Patent Publication 230,053 (1987); 31 J. Med. Chem. 503 (1988); European Patent Publication 230,946 (1987); European Patent Publication 230,295 (1987); European Patent Publication 221,463 (1987); European Patent Publication 226,961 (1987); European Patent Publication 172,651 (1986); and European Patent Publication 115,334 (1984). Procedures for linking the lactam-containing moiety and quinolone moieties may vary according to the type of linking group desired. For example, the quinolonyl lactams having carbamate linking moiety may be made by the following general reaction, sequence: Lact-CH2θH ---> Lact-CH2θC(=0)-X + HN-Quin ---•> Lact-CH2-0C(=0)N-Quin where X is a reactive leaving group (such as alkoxy, halo, or N-heteroaryl ) , "Lact" represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephe , or carbacephem) and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate lactam carbonate derivative, followed by acylation of a quinolone amino functionality to form a carbamate coupled conjugate of the lactam and quinolone. Alternatively, "reversed" dithiocarbamate conjugates can be prepared by the following sequence. Quin-CH20H ---•> Quin-CH2θC(=0)-X + H2N-CH2-Lact ---> Lact-CH2-NHC(=0)0-CH2-Quin where X is a reactive leaving group (such as alkoxy, halo, or N-heteroaryl), "Lact" represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, oxacephem, or carbacephem) and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate quinolone carbonate derivative, followed by acylation of a lactam amino functionality to form a carbamate coupled conjugate of the lactam and quinolone. Lactam-Quinolones having a dithiocarbamate linking moiety may be made by the following general reaction sequence: CS2 + HN-Quin - - - . M+-SC(=S)N-Quin + Lact-CH2-X ---> Lact-CH 2 -SC(=S)N-Quin where X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality), "Lact" represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem), and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate quinolone dithiocarbamate salt, followed by nucleophilic displacement of the lactam X substituent to form a dithiocarbamate coupled conjugate of the lactam and quinolone. Alternatively, "reversed" dithiocarbamate conjugates can be prepared by the following sequence. Lact-CH2-NH2 + CS2 ---> Lact-CH2-NHC(=S)S-M+ + X-CH2-Quin ---> where X is a reactive leaving group (such as halo, a sulfonate ester, or other activated hydroxyl functionality), "Lact" represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, oxacephem, or carbacephem), and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate lactam dithiocarbamate salt, followed by nucleophilic displacement of the suitable quinolone X substituent to form a "reversed" dithiocarbamate coupled conjugate of the lactam and quinolone. Quinolonyl lactams having a thiourea or urea linking moiety ma be made by the following general reaction sequence: Lact-CH2-X + M+'YCN ---> HN-Quin + Lact-CH2-N»C=Y ---> Lact-CH2-NHC(=Y)N-Quin (thiourea: Y is sulfur; urea: Y is oxygen) where X is a reactive leaving group (such as halo, a sulfonat ester, dichloroacetate, thiobenzoate or other activated hydroxy functionality), and Y is either 0 or S. "Lact" represents a appropriately protected l ctafn-coπtaining structure (such as penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, o carbacephem), and "Quin" represents an appropriately protecte quinolone. The sequence can be envisioned as formation of th intermediate lactam isothiocyanate (Y •*• S) or isocyanate (Y = 0) followed by reaction with the quinolone amino substituent to for a thiourea (Y = S) or urea (Y = 0) coupled conjugate of th lactam and quinolone. Alternatively, the thiourea or urea conjugates can b prepared by the following sequence. Quin-NH + XC(=Y)X - - - > Quin-NC(=Y)X . Lact-CH2NH2 ---> Lact-CH2NHC(=Y)N-Quin (thiourea: Y is sulfur; urea: Y is oxygen) where X is a reactive leaving group such as halo, N-heteroaryl o activated hydroxyl functionality, and Y is either S or 0. "Lact represents an appropriately protected lactam-containing structur (such as penem, carbapenem, cephem, monocyclic beta-lactam oxacephem, or carbacephem), and "Quin" represents an appropri ately protected quinolone. The sequence can be envisioned a formation of the intermediate quinolone activated thio carbamat (Y=S) or carbamate (Y=ϋ), followed by reaction with the lacta amino substituent to form a thiourea (Y=S) or urea (Y=0) couple conjugate of the lactam and quinolone. Quinolonyl lactams having an imine, amine or ammonium linkin moiety may be made by the following general reaction sequence: Lact-CHO + HN-Quin ---> Lact-CH=N-Quin (an imine) ---> Lact-CH2-N-Quin (an amine) ---> Lact-CH2-N+(R)-Quin (a ammonium) "Lact" represents an appropriately protected lactam containing structure (such as a penem, carbapenem, cephem oxacephem, or carbscεphe ), and "Quin" represents an appro priately protected quinolone. The sequence can be envisioned a the condensation of the quinolone amine with the lactam aldehyd to form the imine coupled quinolonyl lactam conjugate. Reductio of the imine yields the corresponding amine coupled lactam quinolone conjugate. Alkylation yields the corresponding quaternary ammonium-coupled quinolonyl lactam conjugate. Alternatively, the quaternary ammonium and amine (R is H) conjugates can be prepared by the following general sequence. Lact-CH2-X -r (R)N-Quin - -- . Lact-CH2-N+(R)-Quin where X is a reactive leaving group (such as halo, a sulfonate ester, or other activated hydroxyl functionality, etc.) This se uence can be envisioned as an alkylation of a quinolone amino group with the lactam starting material to obtain the amine or quaternary ammonium coupled conjugate between the lactam and quinolone. Quinolonyl lactams having an amide linking moiety may be made by the following general reaction sequence: Lact-CH2-NH2 + X-C(=0)-Quin ---> Lact-CH2-NHC(=0)-Quin where X is a reactive leaving group (such as halo, an HOBt ester, mixed anhydride or other activated :arboxyl functionality), "Lact" represents an appropriately protected lactam-containin structure (such as a penem, carbapenem, cephem, oxacephem, o carbacephem),, and "Quin" represents an appropriately protecte quinolone. The reaction can be envisioned as an acylation of th lactam amino substituent with the activated quinolone carboxy group, to form an amide coupled conjugate of the lactam an quinolone. Alternatively, "reversed" amide conjungates can be prepare by the following sequence. La t-COOH ---> LactC(=0)-X 1- HN-Quin ---> Lact-C(=0)N-Quin where X is a reactive leaving group (such as halo, an HOBT ester mixed anhydride or another activated carboxyl functionality) "Lact" represents an appropriately protected lactam-containin structure (such as a penem, carbapenem, cephem, oxacephem or carbacephem), and "Quin" represents an appropriately protected quinolone. The reaction can be envisioned as an acylation of the quinolone amino substituent with the activated lactam carboxyl group to form a "reversed" amide coupled conjungate of the lactam and quinolone. Quinolonyl lactams having a guanidinium linking moiety may be made by the following general reaction sequence: R'C(=0)N=C=S + HN-Quin ---> H2NC(=S)N-Quin ---> RSC(=NH2 + X-)N-Quin - Lact-CH2-NH2 > Lact-CH2-NHC(=NH2 + X")N-Quin where "Lact" represents an appropriately protected lactam-containing structure (such as penem, carbapenem, cephem, oxacephem, or carbacephem) and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate quinolone isothiouronium salt, followed by reaction with the lactam amino substituent to form a guanidinium coupled conjugate of the lactam and quinolone. Quinolonyl lactams having a heteroaryl ium linking moiety may be made by the following general reaction sequence: Lact-CH2-X + NHef uin "> Lact-CH2-N + HefQ*J in where X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality), "Lact" represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacepheπi) and "Quin" represents an appropriately protected quinolone that contains a heteroaromatic nitrogen : containing substituent (for example, pyridine). The sequence can be envisioned as an alkylation of the quinolone heteroaromatic nitrogen containing substituent by the lactam to form the pyridinium-type conjugate. Quinolonyl lactams naving a xanthate linking moiety may be made by the following general reaction sequence: CS2 + HO-Quin --- ■ M + "SC(=S)0-Quin + Lact-CH2-X ---. Lact-CH2-SC(=S)0-Quin where X is a reactive leaving group (such as halo, a sulfonate ester, acetate?, thiobenzoate or other activated hydroxyl functionality), "Lact" represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem), and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate quinolone xanthate salt, followed by nucleophilic displacement of the lactam X substituent to form a xanthate coupled conjugate of the lactam and quinolone. Quinolonyl lactams having a thioether, sulfoxide or sulfone linking moiety may be made by the following general reaction sequence: Lact-CH2-X + HS-Quin ---> Lact-CH2-S-Quin (a thioether) ---> Lact-CH2-S0-Quin (a sulfoxide) ---> Lact-CH2-S02-Quin ( sulfone) where X is a reactive leaving group (such as halo, a sulfonat ester, acetate, thiobenzoate or other activated hydroxy functionality, etc.). "Lact" represents an appropriatel protected lactam-containing structure (such as a penem carbapenem, cephem, monocyclic beta-lactam, oxacephem, o carbacephem), and "Quin" represents an appropriately protecte quinolone. The sequence can be envisioned as nucleophili displacement of the lactam X group with a thio-containin quinolone to form the thioether coupled conjugate of the lactam and the quinolone. Oxidation of the thioether yields the corres¬ ponding sulfoxide conjugate. Further oxidation produces the sulfone quinolonyl lactam conjugate. Quinolonyl lactams having a vinyl -thioether linking moiety may be made bv the following general reaction sequence: where X is a reactive vinyl ic leaving group (such as halo, sulfonate ester, phosphate ester or other activated enolic functionality, etc.) The lactam-containing structure may be a penem, as represented above, or more may be another appropriately protected lactam-containing structure (such as carbapenem, cephem, oxacephem, or carbacephem), and "Quin" represents an appropriately protected quinolone possessing a thiol substituent. The sequence can be envisioned as the displacement of the vinyl ic lactam X substituent to form the corresponding vinyl -thioether coupled conjugate of the lactam and quinolone. Quinolonyl lactams having an isothiouronium linking group may be made by the following general reaction sequence: RC(=0)N=C=S + HN-Quin ---> H2NC(=S)N-Quin + Lact-CH2-X ---> Lact-CH2-SC(=NH2 + X-)N-Quin where X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality). Lact represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem, and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate quinolone thiourea, followed by nucleophilic displacement of the lactam X substituent to form a isothiouronium coupled conjugate of the lactam and quinolone. In the reaction sequences described herein, certain functional groups contained in the Lact and Quin structures, (such as carboxyl, hydroxyl, and amino groups) may need to be blocked in order to prevent undesired competing side reactions from occurring with X. Suitable protecting groups for carboxyl substituents include esters. Protecting groups for hydroxyl substituents include ethers, esters, and carbonates; an protecting groups for amino substituents include carba ates, an amides. If various protecting groups are employed, the appropriate deprotecting chemistry, that will not decompose th coupled conjugate, may be required to obtain antibacteriall active products. Compositions The compositions of this invention comprise: (a) a safe and effective amount of a quinolonyl lactam; an (b) a pharmaceutically-acceptable carrier. A "safe and effective amount" of a quinolonyl lactam is an amoun that is effective, to inhibit microbial growth at the site of a infection to be treated in a human or lower animal subject without undue adverse side effects (such as toxicity, irritation or allergic response), commensurate with a reasonabl benefit/risk ratio when used in the manner of this invention The specific "safe and effective amount" will, obviously, var with such factors as the particular condition being treated, th physical condition of the patient, the duration of treatment, th nature of concurrent therapy (if any), the specific dosage for to be used, the carrier employed, the solubility of th quinolonyl lactam therein, and the dosage regimen desired for th composition. The compositions of this invention are preferably provide in unit dosage form. As used herein, a "unit dosage form" is composition of this invention containing an amount of quinolonyl lactam that is suitable for administration to a human or lower animal subject, in a single dose, according to good medical practice. These compositions preferably contain from about 30 g to about 20,000 g, more preferably from about 50 g (milligrams) to about 7000 mg, more preferaoly from about 500 mg to about 3500 mg, of a quinolonyl lactam. The compositions of this invention may be in any of a variety of forms, suitable (for example) for oral, rectal, topical or parenteral administration. Depending upon the particular route of administration desired, a variety of pharmaceutically-acceptable carriers well-known in the art may be used. These include solid or liquid fillers, diluents, hydrotropes, surface-active agents, and encapsulating substances. Optional pharmaceutically-active materials may be included, which do not substantially interfere with the antimicrobial activity of the quinolonyl lactam. The amount of carrier employed in conjunction with the quinolonyl lactam is sufficient to provide a practical quantity of material for administration per unit dose of the quinolonyl lactam. Techniques and compositions for making dosage forms useful in the methods of this invention are described in the following references, all incorporated by reference herein: 7 Modern Pharmaceutics. Chapters 9 and 10 (Banker & Rhodes, editors, 1979); Lieberman et al., Pharmaceutical Dosage Forms: Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms 2d Edition (1976). In particular, pharmaceutically-acceptable carriers for systemic administration include sugars, starches, cellulose and its derivatives, malt, gelatin, talc, calcium sulfate, vegetable oils, synthetic oils, polyols, alginic acid, phosphate buffer solutions, emulsifiers, isotonic saline, and pyrogen-free water. Preferred carriers for parenteral administration include propylene glycol , ethyl oleate, pyrrclidons, ethanol , and sesame oil. Preferably, the pharmaceutically-acceptable carrier, in compositions for parenteral administration, comprises at least about 90% by weight by the total composition. Various oral dosage forms can be used, including such solid forms as tablets, capsules, granules and bulk powders. These oral forms comprise a safe and effective amount, usually at least about 5%, and preferably from about 25% to about 50%, of the quinolonyl lactam. Tablets can be compressed, tablet triturates, r"teric-coated, sugar-coated, film-coated, or multiple-compressed, containing suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, and melting agents. Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules, and effervescent preparations reconstituted from effervescent granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, melting agents, coloring agents and flavoring agents. Preferred carriers for oral administration- include gelatin, propylene glycol, cottonseed oil and sesame oil. The compositions of this invention can also be administered topically to a subject, i.e., by the direct laying on or spreading of the composition on the epidermal or epithelial tissue of the subject. Such compositions include, for example, lotions, creams, solutions, gels and solids. These topical compositions preferably comprise a safe and effective amount, usually at least about 0.1%, and preferably from about 1% to about 5%, of the quinolonyl lactam. Suitable carriers for topical administration preferably remain in place on the skin as a continuous film, and resist being removed by perspiration or immersion in water. Generally, the carrier is organic in nature and capable of having dispersed or dissolved therein the quinolonyl lactam. The carrier may include pharmaceutically-acceptable emolients, emulsifiers, thickening 2-παr»+ c *-»« 4 * «1 *» « ■ * ■ *■ Methods of Administration This invention also provides methods of treating or preventing an infectious disorder in a human or other animal subject, by administering a safe and effective amount of a quinolonyl lactam to said subject. As used herein, an "infectious disorder" is any disorder characterized by the presence of a microbial infection. Preferred methods of this invention are for the treatment of bacterial infections. Such infectious disorders include (for example) central nervous system infections, external ear infections, infections of the middle ear (such as acute otitis media), infections of the cranial sinuses, eye infections, infections of the oral cavity (such as infections of the teeth, gums and mucosa), upper respiratory tract infections, lower respiratory tract infections, genitourinary infections, gastrointestinal infections, gynecological infections, septicemia, bone and joint infections, skin and skin structure infections, bacterial endocarditis, burns, antibacterial prophylaxis of surgery, and antibacterial prophylaxis in immunosuppressed patients (such as patients receiving cancer chemotherapy, or organ transplant patients). T e quinolonyl lactams and compositions of this invention can be administered topically or systemically. Systemic application includes any method of introducing the quinolonyl lactam into the tissues of the body, e.g., intrathecal, epidural, intramuscular, transdermal , intravenous, intraperitoneal , subcutaneous, sublingual, rectal, and oral administration. The specific dosage of antimicrobial to be administered, as well as the duration of treatment, are mutually dependent. The dosage and treatment regimen will also depend upon such factors as the specific quinolonyl lactam used, the resistance pattern of the infecting organism to the quinolonyl lactam used, the ability of the quinolonyl lactam to reach minimum inhibitory concentrations at the site of the infection, the nature and extent of other infections (if any), the personal attributes of the subject (such a weight), compliance with the treatment regimen, and tne presence and severity of any side effects of the treatment. Typically, for a human adult (weighing approximately 70 kilograms), from about 75 mg to about 30,000 mg, more preferably from about 100 mg to about 20,000 mg, more preferably from about 500 mg to about 3500 mg, of quinolonyl lactam are administered per day. Treatment regimens preferably extend from about 1 to about 55 days, preferably from about 7 to about 28 days, in duration. Prophylactic regimens (such as avoidance of opportunistic infections in immunocompromised patients) may extend 6 months, or longer, according to good medical practice. A preferred method of parenteral administration is through intramuscular injection. As is known and practiced in the art, all formulations for parenteral administration must be sterile. For mammals, especially humans, (assuming an approximate body weight of 70 kijograms) individual doses of from about 100 mg to about 7000 mg, preferably from about 500 mg to about 3500 mg, are acceptable. A preferred method of systemic administration is oral. Individual doses of from about 100 mg to about 2500 mg, preferably from about 250 mg to about 1000 mg are preferred. Topical administration can be used to deliver the quinolonyl lactam systemically, or to treat a local infection. The amounts of quinolonyl lactam to be topically administered depends upo such factors as skin sensitivity, type and location of the tissu to be treated, the composition and carrier (if any) to b administered, the particular quinolonyl lactam to b administered, as well as the particular disorder to be treate and the extent to which systemic (as distinguished from local effects are desired. The following non-limiting examples illustrate th compounds, compositions, processes, and uses of the presen invention. EXAMPLE 1 [6R-[6α, 7β]]-3-[[[[2-[3-Carboxy-l-cyclopropyl-6,8-difluoro-1,4- dihydro-7-(4-methyl-l-piperazinyl)-4-oxo-5-αuinolinyll-l-hydra- zino]thioxomethyl]thio]methyl]-8-oxo-7-(2-thienylacetyl )amino-5- thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium sal is made according to the following general procedure. - 57 - To a mixture of 11.4 gm 1-cyclopropyl -5,6,8-trif1uoro-l,4* dihydro-7-(4-methyl-l-piperazinyl )-4-oxo-quinol ine-3-carboxyl ic acid (Compound I, prepared according to D.B. Moran, et al., 32 s . Med. Chem. 1313-1318 (1989)) and 7.25 gm t-butyl carbazate in 70 ml dimethylsulfoxide at about 35"C with stirring under nitrogen is added 14.1 ml of triethylamine slowly. The reaction is heated at about 90-95 o C for 5 hr and then cooled. Acetonitrile is added and allowed to stir overnight. The resulting precipitate is collected and dried to give 11.34 gm of Compound II. Compound II (10.5 gm) is stirred in approximately 50 ml trifluoroacetic acid for 1 hr at room temperature. The solvent is evaporated, the crude residue dissolved in IN HC1 and precipitated by the addition of acetone. The solid is collected and air-dried to yield 6.05 gm of Compound III as the dihydrochloride salt. Compound III (4.65 gm) is suspended in approximately 10 ml water and 10 ml of 4N NaOH is added, followed by 1.7 gm carbon disul- fide. The reaction is stirred at room temperature for 4 hr, then the addition of acetone precipitates the product which is col¬ lected by filtration. Trituration of this material in acetone then gives 3.1 gm Compound IV. To a solution of 2.6 gm Compound IV in 20 ml water is added a pH 8 (adjusted with sodium carbonate) solution of cephalothin sodium salt (2.4 gm). The solution is heated at about 45 * C for about 15 hr, then concentrated in vacuo and the product is isolated by preparative reverse phase chromatography (C18, acetonitrile/water) to yield 1.49 gm of Compound V. EXAMPLE 2 [5R-[5α,6α]]-3-[[[[[2-[[3-Carboxy-l-cyclopropyl -6,8-difluoro-1,4 dihydro-7-(4-methyl-l-piperazinyl )-4-nχo-5-quinolinyl]thio]-l- ethyl ]amino]carbonyl ]oxy]methyl ]-6-[(R)-1-hydroxyethyl ]-7-oxo-4- thia-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid disodiu salt is made according to the following general procedure. VI: R ' -r TBDMS: R : = aJIyl: R J = H VII: R ! = H: R : = ailyl; R :' = H VIII: R 1 = H: R : = R = Na o 23.0 gm of 1-cyclopropyl -5,6,8-trifluoro-l,4-dihydro-7- (4-methyl-l-piperazinyl )-4-oxo-quinol ine-3-carboxyl ic acid (Co pound I, prepared according to D.B. Moran, et al . , 32 J. Med. Chem- 1313-1318 (1989)) in approximately 600 ml anhydrou methanol is added 14.5 gm thionyl chloride dropwise at abou 5-10'C. The reaction mixture is then refluxed for 18 hr, cooled, and concentrated in vacuo. The residue is taken up in chlorofor and extracted with 10% aqueous sodium carbonate. The organi layer is dried over sodium sulfate and concentrated. The crud solid is recrystallized from acetonitrile to yield 15.1 g Compound II. To 11.8 gm of Compound II and 6.83 gm of N-(2-mercaptoethyl) phthalimide in 400 ml dry 50% THF/DMF is added 1.45 gm NaH (60 in mineral oil) portionwise at about 0-5'C with stirring unde nitrogen. The reaction is stirred for 2 hr and poured into col saturated brine. The aqueous layer is extracted with chloroform The combined organic layers are dried over sodium sulfate an concentrated in vacuo. The residue is trituated i acetone/hexanes and collected. The solid is then chromatographe en silica gel (ethyl acetate/methylene chloride) to yield 7.15 g Compound III. Compound III (7.1 gm) in a mixture of about 250 ml methanol an 250 ml 6N HC1 is refluxed for 4 hr. The reaction is cooled an concentrated to dryness. The crude product is dissolved i minimal aqueous DMF and is precipitated by neutralization wit 10% aqueous sodium bicarbonate solution. The solid is collect and air-dried to yield 4.71 gm of Compound IV. To 4.54 gm of Compound IV in 200 ml 50% DMF/absolute ethanol i added 8 ml of IN hydrazine hydrate in absolute ethanol. T mixture is refluxed for 6 hr and evaporated to dryness. T r p si ue is treated with 25 ml 2N HC1 at about 50 * C for 20 mi then cooled at room temperature for approximately 1 hr. T mixture is filtered and the filtrate is evaporated. The cru product is trituated in acetonitrile, collected and redissolv in water. A 10% sodium bicarbonate solution is added precipate Compound V, which is filtered and dried yielding 2.52 gm. To a solution of 2.27 gm of 3-hydroxymethyl -6-[l-[(l, 1- dimethylethyl )dimethylsilyloxy]ethyl ]-7-oxo-4-thia-l- azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, ally! ester (prepared according to C. Battistini, et al . , US Patent 4,631,150) in 35 ml dry THF at about O'C is added 1,2,2,2- tetrachloroethyl chloroformate (0.88 ml) followed by the dropwise 10 addition of 0.54 ml pyridine over 5 in. The mixture is stirred at about O'C for 60 min and poured into a mixture of Compound V (2.19 gm) in 23 ml water containing 2.6 gm sodium bicarbonate. The resulting mixture is then stirred for 70 min, cooled in an ice bath and diluted with 200 ml of cold 0.2N HC1. The solution 5 is evaporated to dryness and the residue is trituated with ether. The solid is collected and subsequently purified by flash chromatography (silica gel, isopropanol/chlorofor /acetic acid) to yield 0.60 gm Compound VI. 20 To a solution of 0.51 gm Compound VI in 15 ml THF containing 0.33 ml glacial acetic acid at room temperature is added 0.55 gm tetrabutylammonium fluoride trihydrate. The mixture is stirred for 24 hr, the solvent is removed in vacuo, and the crude product is purified by flash chromatography (silica gel, 25 chloroform/methanol/acetic acid) to yield 201 mg Compound VII. To 186 mg of compound VII in 20 ml DMF containing 4 mg bis(tri- phenylphosphine)palladiu (II) cnloride and 25 ml acetic acid is added 0.15 ml tributyltin hydride at about O'C. The reaction is ™ stirred under nitrogen for 30 min and concentrated to 1-2 ml. The residue is diluted with ether to precipitate the crude product. The solvent is decanted and the residue is suspended i 3 ml acetone at about O'C. A cold solution of 42 mg sodium bicarbonate in 1.5 ml water is added. The resultant solution is ^ then diluted with acetone and the precipitated product is collected by filtration, yielding 141 mg of Compound VIII after air-drying. EXAMPLE 3 An antimicrobial composition for parenteral administration, according to this invention, is made comprising: Component Amount compound of Example 1 100 mg/ml carrier Carrier: sodium citrate buffer with (percent by weight of carrier): lecithin 0.48% carboxymethylcellulose 0.53 povidone 0.50 methyl paraben 0.11 propyl paraben 0.011 The above ingredients are mixed, forming a suspension Approximately 2.0 ml of the suspension is systemicall administered, via intramuscular injection, to a human subjec suffering from a lower respiratory tract infection, wit Streptococcus pneumoniae present. This dosage is repeated twic daily, for approximately 14 days. After 4 days, symptoms of th disease subside, indicating that the pathogen has bee substantially eradicated. EXAMPLE 4 An enteric coated antimicrobial composition for ora administration, according to this invention, is made comprisin the following core tablet: Com p onent Amount (mg) compound of Example 2 350.0 starch 30.0 magnesium stearate 5.0 microcrystalline cellulose 100.0 colloidal silicon dioxide 2.5 povidone 12.5 The components are admixed into a bulk mixture. Compressed tablets are formed, using tabletting methods known in the art. The tablet is then coated with a suspension of methacrylic acid/methacryl ic acid ester polymer in isopropanol/acetone. A human subject, having a urinary tract infection with Escherichia col i present, is orally administered two of the tablets, every 8 hours, for 14 days. Symptoms of the disease then subside, indicating substantial eradication of the pathogen.

Claims: CLAIMS : 1. A compound of the general formula Q - L - B wherein Q, L and B are defined as follows: (I) Q is a structure according to Formula (I) R 1 wherein (A) (1) A is N or C(R?); where (i) ? is hydrogen, hydroxy, al oxy, nitro, cyano, halogen, alkyl, or N(R 8 )(R 9 ), and (ii) R 8 and R 9 are, independently, R 8a where R 8a is hydrogen, alkyl, alkenyl, carbocyclic ring, or heterocyclic ring; or R 8 and R together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A 2 is N or C(R 2 ); where R 2 is hydrogen or halogen; (3) A 3 is N or C(R 5 ); where R 5 is hydrogen; (4) Rl is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or N(R 8 )(R 9 ); (5) rR-.1- is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R 4 is hydroxy; and (7) R 6 is Rl 5 or Rl β X; where R i5 is a substituent moiety of L and is nil, alkyl, heteroalkyl, or alkenyl; R i6 is a substituent moiety of L and is alkyl, alkenyl, a carbocyclic ring or a heterocyclic ring; and X is alkyl, heteroalkyl, alkenyl, oxygen, sulfur, or NH; (B) except that (1) when A is CJR* 7 ), Rl and R? may together comprise a heterocyclic ring including N' and Al; (2) when A 2 is C(R 2 ), R 2 and R 3 may together comprise -0-(CH2)n-0-, where n is an integer from 1 to 4; (3) when A 3 is C(R 5 ), R 4 and R 5 may together comprise a heterocyclic ring including the carbon atoms to which R 4 and R 5 are bonded and the carbon atom of Formula (I) to which said carbon atoms are bonded; and (4) when A 3 is C(R5), Rl and R^ may together comprise a heterocyclic ring including N' and the adjacent carbon to which R 5 is bonded; (II) B is a structure according to Formula (II), where L is bonded to Rl 4 : wherein (A) R is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R 8a -0-, R 8a CH=N-, (RS)(R9)N-, R!7-C(=CHR20)-C(=O)NH-, R!- 7 -C(*- G-Rl9)-C(=-0)NH-, or Rl 8 -(CH2)m-C(=0)NH-; where (1) is an integer from 0 to 9; (2) Rl 7 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; (3) R 8 is Rl?, -Yl, or -CH(Y )(Rl7) ; (4) R 19 is R 17 , arylalkyl, heteroarylalkyl, -C(R )(R )C00H, -C(=0)0-Rl7, or -C(=0)NH-Rl 7 , where R 22 and R 23 are, independently, R 17 or together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R 22 and R 23 are bonded; (5) R 20 is l9, halogen, -γl, or -CH(Y 2 )(Rl 7 ); (6) Yl is -C(=0)0R 2 1, -C(=0)R 1, -N(R 2 )R 2 1, -S(0) p R 2 9, or -0R 2 9; and Y 2 is γl or -OH, -SH, or -SO3H; (a) p is an integer from 0 to 2; (b) R 24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroal enyl; a carbocyclic ring; a heterocyclic ring; -SO3H; -C(=0)R 25 ; or, when R 8 is -CH(N(R 24 )R l)(Rl 7 ), R 24 may comprise a moiety bonded to R to form a heterocyclic ring; and (c) R 2 5 is Rl 7 , NH(Rl7), N(Rl 7 )(R 2 6), 0(R 2 6), or S(R 2 6); where R 26 is alkyl, alkenyl, a carbocyclic ring, a heterocyclic ring, or when R 2 ^ is N(Rl 7 )(R 2δ ), R 26 may be a moiety bonded to R 7 to form a heterocyclic ring; and (7) R 2 is R 29 or hydrogen; where R 29 is alkyl; alkenyl; arylal yl ; heteroalkyl ; heteroalkenyl ; heteroarylalkyl ; a carbocyclic ring; a heterocyclic ring; or, when Y is N(R24)R21 and R 2 1 is R 29 , R21 and R 24 may together comprise a heterocyclic ring including the nitrogen atom to which R 24 is bonded; (B) ll is hydrogen, halogen, alkoxy, or R 27 C(=0)NH- , where R 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) Rl 2 is -C(R 8a )-, or -CH2-R 28 -; where R 28 is -C(R 8 ), -0-, or -N-, and R 28 is directly bonded to N" in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then R 2 is (1) -C(R 8a )(Xl)-, where (i) is -R 2 1; -OR 3 0; -S(0) r R 30 , where r is an integer from 0 to 2; -0C=0)R 30 ; or N(R 30 )R 3 1; and (ii) R 30 and R 3i are, independently, alkyl, alkenyl, carbocyclic ring or heterocyclic ring substituents; or R 3 0 and R 3 together comprise a heterocyclic ring including the nitrogen atom to which R 3 and R 1 are bonded; or (2) -CH2-R 32 -; where R 32 is -C(R 8a )(R 2 l), -0-, or -NR 8a , and R 32 is directly bonded to N" in Formula (II) to form a 5-membered ring; (E) (1) if bond "b" is a single bond, Rl 3 is -CH(R 33 )-; or, -C(0)NHS02-, if bond "a" is nil; or -C*(R 33 )- if l 4 contains a R 36 moiety; where R 33 is hydrogen or COOH, and C* is linked to R 36 to form a 3-membered ring; (2) if bond "b" is a double bond, R is -C(R 3 )=; or (3) if bond "b" is nil, Rl 3 is hydrogen, -SO3H, -P0(0R )0H, -C(0)NHS02N(R 34 )(R 5), -OSO3H, -CH(R 3 5)C00H, or -0CH(R 3 )C00H; where R 34 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R 35 is hydrogen, alkyl, alkenyl, or -NHR 8a ; or, if Rl 3 is -C(0)NHS02N(R 34 )(R 5), R 34 and R $ may together comprise a heterocyclic ring including the nitrogen to which R 34 and R 3 -5 are bonded; and (F) (1) if bond "a" or bond "b" is nil, then R 4 is nil and L is bonded directly to R 2 or R 3 ; (2) if bond "a" and "b" are single bonds, R 14 is -W-C"'=C(R 8a )-R 37 -, or -W-C * "(R 36 )-R 37 -; or (3) if bond "a" is a single bond and bond "b" is a double bond, Rl 4 is -C(R 8a )(R 38 )-W-C"'-R 37 -; -W-C(R 8a )(R 38 )-C"'-R 37 -; or -W-C"'-R 37 -; where (a) W is 0; S(0) s , where s is an integer from 0 to 2; or C(R 38 ) , where R 38 is hydrogen, al kyl or al koxy; (b) R 35 hydrogen; al kyl ; al kenyl ; -COOH; or, if Rl 3 is -C*(R 33 ) , R36 may be l inked to C* to form a 3-membered carbocycl ic ring; (c) R 37 is nil , alkyl , alkenyl , a carbocycl ic ring, or a heterocycl ic ring; and (d) C" ' is directly bonded to Rl to form a 5- or 6-membered ring; and (III) L links Q to B; and L is L', -X 2 fR 39 -L', or -X 3 t -R*39-L', where L' is Q', -X 2 -Q", -X 3 -Q\ or -X 4 t-C(=Y 3 U )-Z-Q"; (1) t and u are, independently, 0 or 1; (2) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; (3) X 2 is oxygen, or S(0) v , where v is an integer from 0 to 2 ; (4) X 3 is nitrogen; N(R 4 0); N+(R 4 1)(R 42 ); or R 43 -N(R 4 1); and is linked to R 4 by a single or double bond; or, if R 4 is nil, X 3 is linked to B by a single or double bond; where (a) R 4 0 is R 8 ; -0R 8 ; or -C(=0)R 8 ; (b) R 4i and R 42 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings; heterocyclic rings; or, if R6 is R 6 X, then R 4 and R 42 together with Q" may comprise a heterocyclic ring as R 6 ; (c) R 43 is N(R 4 1), oxygen or sulfur; (5) X 4 is oxygen, sulfur, NR 40 , or R 3 -NR 4 1; (6) Y 3 is oxygen, sulfur, NR 0 or N+(R 4 1)(R 42 ); (7) Y 4 is oxygen or NR 4 1; (8) Z is nil, oxygen, sulfur, nitrogen, NR 40 , or N(R 4 1)-R 43 ; (9) Q' is said R 5 substituent of Q; and (10) Q" is Q'; or together with X 2 , X 3 , Z or Z', is said R 6 substituent of Q; and pharmaceutically-acceptable salts and biohydrolyzable esters thereof, and hydrates thereof. 2. A compound, according to Claim 1, wherein said lactam-containing moiety is selected from the group consisting of cephems, oxacephems, carbacephems, isocephems, iso-oxacephems, penems, carbapenems, clavems, penicillins, clavams, 2,3-methyleno-penems, 2,3-methyleno-carbapenems, and pyrazolidinones; preferably cephems, isocephems, oxacephems, carbacephems, penicillins, and carbapenems. 3. A compound, according to Claim 2, wherein said lactam-containing moiety is selected from the group consisting of cephems, penems, and carbapenems. 4. A compound, according to Claim 1, wherein said lactam-containing moiety is selected from the group consisting of onobactams, monophospha s, onocarbams, monosulfactams, nocardicinε, lactivicin analogs, and gamma-lactams; preferably a monobactam. 5. A compound, according to Claim 2 or Claim 4, wherein Rl is hydrogen or alkoxy; and R i2 is -C(R 8a )-. 6. A compound according to Claim 1, wherein: A is nitrogen or C(R 7 ), preferably nitrogen; A 2 is C(R 2 ); and A 3 is C(R5). 7. A compound according to Claim 6, wherein Q is a 6-fluoroquinolone moiety, a 8-halo-6-fluoroquinolone moiety, a pyridobenzoxazine moiety, a pyridobenthiazine moiety, a isothiazoloquinolinedione, or isoxazoloquinolinedione moiety. 8. A compound, according to Claim 7, wherein R is alkyl, aryl, cycloalkyl or alkylamino, preferably ethyl, 2-fluoroethyl , 2-hydroxyethyl, t-butyl, 4-fluorophenyl , 2,4-difluorophenyl , methylamino or cyclopropyl; and R 2 is hydrogen, chlorine or fluorine. 9. A compound, according to Claim 7 or Claim 8, wherein R 3 is a nitrogen-containing heterocyclic ring, preferably piperazine, 3-methylpiperazine, 3-aminopyrrolidine, 3-aminomethylpyrrolidine, N,N-dimethylaminomethylpyrrolidine, N-methylaminomethylpyrrolidine, N-ethylaminomethylpyrrolidine, pyridine, N-methylpiperazine, or 3,5-dimethylpiperazine. 10. A compound, according to Claim 9, wherein R is cyclopropyl, R 2 is fluorine, and R 3 is piperazine. 11. A compound, according to Claim 1, wherein L comprises a linking moiety selected from the group consisting of carbamate, dithiocarbamate, urea, thiourea, isouronium, isothiouronium, guanidine, carbonate, trithiocarbonate, reversed carbamate, xanthate, reversed isouronium, reversed dithiocarbamate, reversed isothiouronium, amine, imine, ammonium, heteroarylium, ether, thioether, ester, thioester, amide and hydrazide groups; preferably carbamate, dithiocarbamate, urea, thiourea, isothiouronium, amine, ammonium, and heteroarylium groups. 12. A compound, according to Claim 11, wherein L is L', and L' is -X 2 -Q", -X 3 -Q", or X 4 t-C(=Y 3 U )-Z-Q\ preferably X 4 t-C(=Y 3 U )-Z-Q". 13. A compound, according to Claim 12, wherein Q" is said R 6 substituent of Q, or together with X 2 , X 3 , Z or Z', is said R 6 substituent of Q, and wherein said linking moiety is a carbamate or dithiocarbamate group. 14. A composition for treating or preventing an infectious disorder in a human or other animal subject, comprising: (1) a safe and effective amount of a compound of any of Claims 1 through 13; and (2) a pharmaceutically-acceptable carrier. 15. The use, for the manufacture of a medicament for preventing or treating an infectious disorder in a human or other animal subject, of a compound of any of Claims 1 through 13.

Inventors: DEMUTH THOMAS PROSSER JR, WHITE RONALD EUGENE, DEMUTH, THOMAS, PROSSER, JR., WHITE, RONALD, EUGENE
Applicants: NORWICH EATON PHARMA, NORWICH EATON PHARMACEUTICALS, INC.
Application year: 1991
Main classification: C07D501
IPC codes: A61K31, A61P31, C07D401, C07D463, C07D471, C07D477, C07D487, C07D498, C07D499, C07D501, C07D519