Field of the Invention

The present invention relates to new cephalosporin compounds of the formula (I), particularly 3-position of cephem rings substituted with new thione compounds and pharmaceutically acceptable salts thereof, which have broad antibacterial activities against both Gram-positive and Gram-negative bacteria.

Summary of the Invention

An objective of the present invention is to provide new antibiotic cephalosporin compounds of the forraula(I) or pharmaceutically acceptable salts thereof

(1)

wherein

Ri is a Cι-4 alkyl (preferably methyl or ethyl), C3-4 alkenyl(preferably allyl), C3-4 alkynyl (preferably propargyl) group or -C(R ^a )(R ^b )C02H(preferably -C(CH ₃ )2C0 ₂ H or -CH2CO2H), wherein R ^a and R ^b , same or different, are a atom or a Cι- ₄ alkyl group;

R2 is a C1-4 alkyl (preferably methyl or ethyl), C3-4 alkenyl ⁽ preferably allyl),

C3-4 cycloalkyl (preferably cyclopropyl)group or carboxyalkyl (preferably -CH2CO2H)group;

R3 is a 5- or 6-membered heterocyclic compounds-containing 1 or- 2 nitrogen atom(s)

(preferably piperazine, alkylpiperazine-substituted with C1-4 alkyl at N- or

2-position of piperazine, imidazole-substituted or unsubstituted with C1-4 alkyl);

R4 is hydrogen or a carboxylic acid.

Detailed Description of the Invention

The compounds of the formula(I) can be prepared by reacting the compounds of the formular(II) with the new thione compounds of the foπnular (III), as follows:

wherein (I)

Ri is a methyl, allyl, propargyl group or -C(CH3)2C02H; R2 _. R3 and R4 are the same as defined above.

In the preparation of the objective compounds(I), the compounds of the formula(III) are used preferably in an amount of from 1 to 2 equivalent(s) based on 1 equivalent of the compounds of the formula(II).

The reaction for introducing the compounds(III) into the 3-poεition of corapound(II) to prepare compounds(I) is carried out in the presence of a solvent such as water, N,N-dimethylformamide, dimethylsulfoxide, or a mixed agueous solvent of water. An appropriate water-miscible solvent is acetonitrile or acetone.

Also, the reaction may be carried out at 40°C to 100°C, preferably 60°C to 80 ^* C. To stabilize reaction products and their intermediate;;, one or more salts selected from the group consisting of sodium iodide and potassiua iodide can be used as stabilizing agents.

On the other hand, the separation and purification of the compoundsd) can be carried out using a known method such as recrystallization, column chromatography over silica gel or ion-exchange chromatography.

The new thione compounds of the formula(III) can be prepared from quinolone

compounds which prepared by known method, as follows:

(IV) (V)

(VI) (III) wherein

R2 is a methyl cyclopropyl, ethyl or allyl group; R4 is hydrogen; R3 is the same as defined above.

The compounds of the formula(IV) can be prepared by reacting quinolone compounds, sodium borohydride with p-toluenesulfonic acid in the polar solvent, preferably a1cohol.

The compounds of the formula(V) can be prepared by reacting the compounds of the formular(IV) with p-chloranil in the polar solvent, preferably 1,4-dioxane at 50°C to 100°C.

Also, the compounds of the formula(VI) can be prepared by reacting the compounds of the formular(V) with phosphorus pentasulfide in the polar solvent, preferably acetonitrile, and the new thione compounds of the formula(III) can be prepared by substitution of 5- or 6-merabered heterocyclic compounds-containing 1 or 2 nitrogen atom(s)(preferably piperazine, alkylpiperazine-substituted with C1-4 alkyl at N- or 2-position of piperazine, imidazole-substituted or unsubstituted with C1-4 alkyl) at the 7-position of compounds(VI). In case Hi is a carboxylic acid, the compounds of the formula(III) can be prepared from the compounds of the for ula(VII) which prepared by known method, as follows:

wherein (IX)

(III) R ₂ is a cyclopropyl; Hi is a carboxylic acid;

R3 is the same as defined above.

The compounds of the formula(VIII) can be prepared by reacting- with the compounds of the formular(VII) and phosphorus pentasulfide in the polar solvent, preferably acetonitrile. The compounds of the formula(IX) can be prepared b> hydrolysis of the compounds(VI11).

Also, the compounds of the formula(III) can be prepared bv substitution of 5- or 6-membered heterocyclic compounds-containing 1 or 2 nitrogen atom(s) (preferably piperazine, alkylpiperazine-substituted with C1-4 alkyl at N- or- 2-position of piperazine, imidazole-substituted or unsubstituted with C1- ₄ alkyl) at the 7-position of compounds(IX).

The new thione compounds of the formula(III) are shown in Table 1.

(III) Table 1. New Thione Compounds

The new cephalosporin compounds of the formula(I) are shown in Table 2.

(i )

Table 2. New Cephalosporin Compounds

The present invention is described in detail by the following Preparations and Examples:

Preparation 1: Preparation of l-βethyl-6,7-difluoro-l,4-dihydro-4-thioquinoline

A. Preparation of l-meth l-6,7-difluro-l,2,3,4-tetrahydro-4-o;oquinoline l-Methyl-6,7-difluoro-l,4-dihydro-4-oxoquinoline carboxylic cid(7g) was added to methyl alcohol(800ml), and stirred at 0 ^* C. After sodium borohydride(4.3g) and p-toluene sulfonic acid(cat.amount) were added thereto, the reaction mixture was refuluxed for an hour, and the organic solvent was removed under reduced pressure.

To the residue was added chloroform(5ooml), and it was washed twice with water (200ml). The separared organic layer was dehydrated, and concentrated. The residue was solidified with pet. ether, and dried to give the bright.-yellow-above-indicated compound(3.6g). a.p.: 65-67.5°C

Yield: 77% NMR: δ(CDCls) 2.65(t,2H),2.90 ⁽ s,3H),3.40(t,2H),6.40(dd,lH),7.78(m,lH)

B.Preparation of l-methyl-6.7-difluoro-l,4-dihydro-4-oxoquinol ine l-Methyl-6,7-difluoro-l,2,3,4-tetrahydro-4-oxoquinoline(3.19 g) was added to l,4-dioxane(90ml). After p-chloranil(7.5g) was added thereto, the reaction mixture was stirred at 80"C. After 24 hours, the organic solvent was removed under reduced pressure. To the residue was added chloroform(lθθml), and it was washed with lN-sodium hydroxide solution and water. The separated organic layer was dehydrated, and concentrated. The residue was solidified with pentane, and dried to give the white above-indicated compound(1.6g). m.p.: 173.5-175.5°C Yie-ld: 52%

NMR: δ(CDCb) 3.75(S,3H),6.20(d,lH),7.20(ad _l lH),7.50(d,lH),8.2O(dd,lH)

C.Preparation of l-methyl-6,7-difluoro-l,4-dihydro-4-thioquinoline l-Methyl-6,7-difluoro-l,4-dihydro-4-oxoquinoline(1.6g),pho:: phorus pentasulfide

(5.3g), and sodium bicarbonate(4.0g) were added to acetonitril<-(50ml), and stirred at 60 ^C C for 4 hours, cooled to room temperature. The precipi ates were filtered, and dried to give the yellow above-indicated compound(1.36g). m.p.: 198-200°C

Yield: 77%

NMR: δ(CDCl ₃ ) 3.90(s,3H),7,30(d, lH),7.55-7.85(uι,2H),8.50-8.85d d.lH ⁾

Preparation 2- Preparation of l-cyclopropyl-6,7-difluoro-l,4-dilιydro-4-thioquinoline

A.Preparation of l-cyclopropyl-6,7-difluoro-l,2,3,4-tetrahydro- _' l-oxoquinoline

l-Cyclopropyl-6, 7-difluoro-l , 4-dihydro-4-oxoquinol ine car .xylic acid(20g) and sodium borohydridedl . δg) were reacted in the same method as described in

Preparation 1-A to give the yel low above-indicated compound ( 1 ; ) . m. p. : 77.8-80. T Yield: 86%

NMR: δ(CDCl ₃ ) 0.65-1.05(m,4H) , 2.20-2.40(m, lH) , 2.60(t, 2H) , 3.50(t,2H) , 7.05(dd, lH) , 7.70(dd, lH)

B. Preparation of l-cyclopropyl-6,7-difluoro-l,4-dihydro-4-ox iuinoline

1-Cyclopropy1-6,7-difluoro-1,2,3,4-tetrahydro-4-oxoquinol iπe(lOg) and p-chloranil (22g) were reacted in the same method as described in Preparation 1-B to give the white above-indicated compound(8.6g). m.p.: 169.6-172°C

Yield: 87%

NMR: δ(CDC ) 0.95-1.40(m,4H), 3.20-3.45(m,lH), 6.15(d,lH), 7.50-7.80(m,2H), 8.10(dd,lH)

C. Preparation of 1-cyclopropyl-6,7-difluoro-l,4-dihydro-4-thi(<quinoline l-Cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline(4.8g' and phosphorus pentasulfide(14.6g) were reacted in the same method as described in preparation 1-C to give the yellow above-indicated compound(4.98). m.p.: 175-177°C

Yield: 94%

NMR: δ(CDCl ₃ ) 0.90-1.45(m,4H), 3.25-3.60(m,1H), 7.20-7.50(m,2H', 7.60-7.92(dd,lH), 8.55-8.85(dd,lH ⁾

Preparation 3: Preparation of l-ethyl-6,7-difluoro-l,4-dihydro-4-thioquinoline A. Preparation of l-ethyl-6,7-difluoro-l,2,3,4-tetrahydro-4-oχu uinoline l-Ethyl-6,7-difluoro-l,4-dihydro-4-oxoquinoline carboxylic acid(20g) and sodium borohydride(12g) were reacted in the same method as described in Preparation 1-A to give the bright-yellow above-indicated compounddig). m.p.: 82-84°C Yield: 80%

NMR: δ(CDCl ₃ ) 1.15(t,3H),2.70(t,2H),3.40(q,2H),3.50(t,2H),6.50(dd,lH),7.65 (dd,lH)

B. Preparation of l-ethyl-6,7-difluoro-l,4-dihydro-4-oxoquinoline l-Ethyl-6,7-difluoro-l,2,3 _> 4-tetrahydro-5-oxoquinoline( lOg) and p-chloranil

(23g) were reacted in the same method as described in Preparation 1-B to give the white above-indicated compound(6.7g). m.p.: 176-178'C

Yield: 68%

NMR: δ ⁽ CDCl ₃ ) 1.20(t,3H ⁾ ,4.10(q,2H) ,6.20(d,lH),7.70-8.05(m,2H) ,8.20(dd,1H) C. Preparation of ethyl-6,7-difluoro-l,4-dihydro-4-thioquindine

1-Ethyl-6,7-difluoro-l,4-dihydro-4-oxoquirκ>l ine(6.7g) arid phosphorus pentasul- fide(21g) were reacted in the same method as described in Preparation 1-C to give the yellow above-indicated compound(4.4g). m.p.: 174-176°C Yield: 60% NMR: δ(CDCb) 1.40(t,3H),4.40(q,2H),7.30(d,lH),7.95(d,lH),8.15 ⁽ dd,lH),8.65(dd,lH)

Preparation 4: Preparation of l-allyl-6,7-difluoro-l,4-dihydro-4-thioquinoline A. Preparation of l-allyl-6,7-difluoro-1,2,3, ,4-tetrahydro-4-oχoquinoline

1-Ally1-6,7-difluoro-1,4-dihydro-4-oxoquiniline car >oxylic acid(25g) and sodium borohydride(14.2g) were reacted in the same method as described in Preparsation 1-A to give the bright-yellow above-indicated compound(14g). m.p.: 57-59"C Yield: 80%

NMR: δ(CDCb) 2.70(t,2H), 3.55(t,2H), 3.95(d,2H), 5.25(dd,2H), 5.75-5.90(a,1H), 6.50(dd,lH), 7.65(dd,lH),

B. Preparation of l-allyl-6,7-difluoro-l,4-dihydro-4-oxoquinoline

1-A11y1-6,7-dif1uoro-1,2,3,4-tetrahydro-4-oxoquinoline(13 .3g) and ι-chlorani1 (29.3g) were reacted in the same method as described in Preparation 1-B to give the white above-indicated compound(12.3g). m.p.: 172-174°C

Yield: 93%

NMR: δ(CDCb) 4.70(d,2H), 5.18(d,lH), 5.38(d,lH), 5.95-6.10(ιn, 1H), 6.28(d,lH), . 7.25(dd,lH), 7.55(d,lH), 8.25(dd.lH)

C. Preparation of 1-ally1-6,7-difluoro-l,4-dihydro-4-thioquim>line l-Allyl-6,7-difluoro-l,4-dihydro-4-oxoquinoline(12g) and phosphorus pentasul- fide(36g) were reacted in the same method as described in Preparation 1-C to give the yellow above-indicated co pound(lθg) . m.p.: 160-163°C (dec.) Yield: 77%

NMR: δ(CDCb) 5.05(d,2H), 5.15(d,lH), 5.25(d,lH), 5,98-6.lO(π.lH), 7.35(d,lH). 7.95-8.05(m,2H), 8.65(dd,lH)

Preparation 5: Preparation of l-βethyl-β-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline

1-Methy1-6,7-difluoro-1 ,4-dihydro-4-thioquinoline(1.2g) a d piperazine (1.4g)

were added to pyridine(7ml), and stirred at 130°C for an hour. The orqanic solvent was removed under reduced pressure. To the residue was added hloroform(50ml), and it was washed with water. The separated orqanic layer was dehydrated, and concentrated. The residue was solidified with water, and dried to give the yellow above-indicated compound(0.9g). m.p.: 255°C Yield: 54% NMR: δ(DMS0-d _ό ) 2.60-3.10(m,811),3.90(s,3H),7.10-7,65(m.3H),8.4υ(d,lH)

Preparation 6: Preparation of l-»ethyl-6-fluoro-7-(N-Bethylpip(;razinyl)-l,4-dihydro -4-thioquinoline l-Methyl-6,7-difluoro-l,4-thioquinoline(1.2g) and N-met hylpiperazine(1.9ml ) were reacted in the same method as described in Preparation 5 to give the yellow above-indicated compoundd.lg). m.p.: 226-228 ⁰ C(dec.)

Yield: 63%

NMR: δ(DMS0-d ₆ ) 2.38(s,3H),2.60(t,4H),3.30(t,4H),3.75(s,3H),6.58(d,lH),7.05( m,2H), 8.40(d,lH)

Preparation 7: Preparation of l-βethyl-6-fluoro-7-(l-ethylpiper-azinyl)-l,4-dihydτo -4-thioquinoline l-Methyl-6,7-difluoro-l,4-thioquinoline(6g) and l-ethylpiperazine(9.5g) were reacted in the same method as described in Preparation 5 to give the yellow above-indicated compound(4.2g). m.p. : 214-216°C(dec.) Yield: 45%

NMR: δ(DMSOd ₆ ) 1.15(t,3H) .2.30-2.80(m,6H),3.30(t,4H),3.80(s,3H) ,6.60(d,lH), 7.05-7.25(m,2H), 8.50(d,lH)

Preparation 8: Preparation of l-βethyl-6-fluoro-7-(2-βethylpiperazinyl)-l,4- dihydro-4-thioquinoline l-Methyl-6,7-difluoro-l,4-thioquinoline(4.9g) and 2-ιικ -. hy1piperazine(6.8g) were reacted in the same method as described in Preparation 5 to give the yellow above-indicated compound(4.Og). m.p.: 177-179°C Yield: 56%

NMR: δ(DMSO-d _ό ) 1.70(s,3H),2.70-3.30(m,3H),3.40-3.70(m,4H),3.90(s,3H),6.65(d .1H), 7.05-7.30(m,2H),8.50(d,lH)

Preparation 9: Preparation of l-βethyl-6-fluoro-7-iMidazolyl-l,4-dihydro- - thioquinoline l-Methyl-6,7-difluoro-l,4-thioquinoline(2g) and iraidazole .9g) were added to pyridine(20ml ), and stirred at 130°C for 5 hours. The organic solvent was removed under reduced pressure. The residue was solidified with water, and dried to give the yellow above-indicated compound(1.3g). m.p.: 255-257°C(dec.) Yield: 51% NMR: δ(DMSO-dό) 3.90(s,3H),7.15-7.25(m,2H),7.70-8.40(ιn,4H),8.50(d,1H)

Preparation 10: Preparation of l-βethyl-6-fluoro-7-(4-«ethyliBidazolyl)-l,4- dihydro-4-thioquinoline l-Methyl-6,7-difluoro-l,4-thioquinoline(2g) and 4-methylimidazole(2.3g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.4g). m.p.: 278-280"C(dec. ) Yield: 52% NMR: δ(DMS0-d ₆ ) 2.40(s,3H),3.90(s,3H),6.90-8.35(m,5H),8.60(d,1H)

Preparation 11: Preparation of l-cyelopropyl-6-fluoτo-7-piperazinyl-l,4-dihydro-4- thioquinoline 1-Cyclopropyl-6,7-difluoro-1, -thioquinol ine(l.Sg) and ρi|>erazine(1.64g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.lg). m.p.: 205-208. °C

Yield: 55% NMR: δ(DMSO-dό) 0.90-1.40(m,4H),2.65-3.60(m,9H),7.05-7.70(m,3H) ,8.40(d,lH)

Preparation 12: Preparation of l-cyclopropyl-6-fluoro-7-(N-βethylpiperazinyl)-l,4- dihydro-4-thioquinoline

1-Cyclopropyl-6,7-difluoro-l,4-thioquinoline(1.5g) and N-methylpiperazine (2.1ml) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.1 ). m.p.: 181.5-183.7°C

Yield: 52%

NMR: δ(DMSO-dό) 0.95-1.40(m,4H),2.38(s,3H),2.62(t,4H) .3.30U.4H) ,3.40-3.62(m, 1H), 7.00-7.40(m,3H),8.40(d,lH)

Preparation 13: Preparation of l-cyclopropyl-6-fluoro-7-(l-ethylpiperazinyl)-l _> 4- dihydro-4— hioquinoline l-Cyclopropyl-6,7-difluoro-l,4-thioquinoline(5g) and 1-ethylpiperazine 7.3g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(4.Og). m.p.: 178-180^ Yield: 54%

NMR: δ(DMS0-d ₆ ) 0.95-1.40(m,4H),2.30-2.75(m,6H),3.3O(t,4H),3.4O-3.60(m,1H), 7.05-7.40(dd,3H),8.45(d,lH),

Preparation 14: Preparation of l-cyclopropyl-€-fluoro-7-(2-«ethylpiperazinyl)-l,4- dihydro- -thioquinoline l-Cyclopropyl-6,7-difluoro-l,4-thioquinoline(5g) and 2-methylpiperazine(6.4g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(4.8g). m.p.: 132-132°C(dec.)

Yield: 69%

NMR: δ(DMS0-d ₆ ) 0.90-1.40(m,7H),2.40-3.75(a,8H),7.10-7.38(dd,3H),8.50(d,lH)

Preparation 15: Preparation of l-cyclopτopyl-6-fluoro-7-iBidazolyl-l,4-dihydιτ) -4-thio-quinoline l-Cyclopropyl-6,7-difluoro-l,4-thioquinoline(5g) and imidazole(4.3g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(2.8g). m.p.: 205-207"C(dec.) Yield: 45% NMR: δ(DMS0-d ₆ ) 1.10-1.20(m,2H),1.28-1.38(m,2H),3.65-3.85(m,lH),7.25(dd.2H), 7.80(s,1H), 7.95(dd,1H),8.25(ddlH),8.35(d, 1H),8.55(d,1H)

Preparation 18: Preparation of l-cyclopropyl-6-fluoro-7-(4-βethyliBidazolyl)-l,4- dihydro-4-thioquinoline

1-Cyclopropy1-6,7-difluoro-l,4-thioquinoline(2.5g) and 4-ιuethy1piperazine(2.6g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.9g). m.p.: 242-244°C(dec.)

Yield: 58%

NMR: δ(DMS0-i6) 1.00-1.35(m,4H),2.45(s,3H),3.72-3.85(m,lH),6.90(s,lH), 7.25-8.35(m,4H), 8.60(d,lH)

Preparation 17: Preparation of l-cyclopropyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4- dihydrt -4-thioquinoline-3-carboxylic acid

1-Cyclopropyl-6,7-difluoro-l,4-thioquinoline-3-carboxylic acide(l.δg) and 1- ethylpiperazine(2.2g) were reacted in the same method as described in Preparation 9 5 to give the yellow above-indicated compound(1.5g). m.p.: 232-234"C(dec.) Yield: 60%

NMR: δ(DMSCKl6) 1.20(t,3H).1.40( ,2H),2.75-3.40( ,6H),3.60(m,4H) , 7.40(d,lH), 8.40(d,lH ⁾ . 8.85(s,lH)

10 Preparation 18: Preparation of l-cyclopropyl-6-fluoro-7-(2-βethylpiperazinyl)-l,4- dihydro-4-thioquinoline-3-carboxylic acid l-Cyclopropyl-6,7-difluoro-l,4-thioquinoline-3-carboxylic acid(2g) and 2-methyl

-piperazine(2.2g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.3g).

15 m.p.: 240-242"C(dec. )

Yield: 45%

NMR: δ(DMSO-dό) 1.20-1.45(m,4H),1.70(s,3H),2.75-3.30(a,4H),3.45-3.75(m,4H),

7.40(d,1H), 8.45(d,1H),8.80(s,1H)

Preparation 19: Preparation of l-ethyl-€^fluoro-7-piperazinyl-l,4-dihydro- - 20 thioquinoline l-Ethyl-6,7-difluoro-l,4-thioquinoline(lg) and piperazined.15g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.2g). m.p.: 106-108°C 25 Yield: 89%

NMR: δ(DMS0-d ₆ ) 1.40(t,3H),2.6 -3.45(m,8H),4.40(q,2H),7.05-7.85(m,3H),8.40(d,lH)

Preparation 20: Preparation of l-ethyl-6-fluc*x_>-7-(N-«ethylpiperazinyl)-l,4-dihyd_ro ^4-thioquinoline l-Ethyl-6,7-difluoro-l,4-thioquinolinedg) and N-methylpiperazine(1.33g) were

30 reacted in the same method as described in Preparation 9 to give the yellow above-indicated compoundd.lg). m.p.: 184-186°C(dec.) Yield: 77%

NMR: δ(DMS0-d ₆ ) 1.40(t,3H),2.28(s,3H),2.48-2.55(ra,4H).3.25-3.35(m.4H),4.42( q,2H), ^" 35 7.05(d,lH),7.15(d,lH),7.88(d,lH), ^β .40(d,lH)

Preparation 21: Preparation of l-€thyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4-dihydro -4—thioquinoline 1-Ethy1-6,7-difluoro-l,4-thioquinolinedg) and l-ethylpiperazine(1.52g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.23g). m.p. : 159-161°C Yield: 82%

NMR: δ(DMSO-dό) 1.20(t,3H),1.40(t,3H),2.40-3.50(m,8H) _f 3.80(q,2H),4.40(q,2H), 7.05-7.20(m,2H),7.85(d,1H),8.45(d,1H)

Preparation 22: Preparation of l-ethyl-6-fluoro-7-(2-βethyIpiperazinyl)-l,4- dihydr -4-thioquinoline l-Ethyl-6,7-difluoro-l,4-thioquinolinedg) and 2-methylpiperazine(1.33g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.25g). m.p.: 125-127 ^<> C(dec.) Yield: 87%

NMR: δ(DMS0-d ₆ ) 1.15(d,3H),1.40(t,3H),2.40-3.60(m,7H),4.40(q,2H),7.05-7.40(m ,3H), 8.45(d.lH)

Preparation 23: Preparation of l-allyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline l-Allyl-6,7-difluoro-l,4-thioquinoline(2g) and piperazine(2.2g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(2.3g). m.p-.: 93-95°C Yield: 86%

NMR: δ(DMSO-dύ) 2.64-3.40(m,8H),5.10(d,2H),5.15-6.20(m,3H),7.05-7.90(m,3H), 8.40(d,lH)

Preparation 24: Preparation of l-allyl-6-fluoro-7-(N-βethylpiperazinyl)-l,4-dihydτo

-4-thioquinoline l-Allyl-6,7-difluoro-l,4-thioquinoline(2g) and N-methyipiperazine(2.5g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(2.3g). m.p.: 145-147°C Yield: 82% NMR: δ ⁽ DMSO-dβ) 2.25(s,3H).2.60-3.30(m,8H),5.10 ⁽ d,2H).5.30-6.05(a,3H),

7. 1 -7.80(m, 3H) , 8.40(d, lH)

Preparation 25: Preparation of l-allyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4-dihydro- 4-thioquinoline l-Allyl-6,7-difluoro-l,4-thioquinoline(2g) and 2-ethylpiperazine(2.9g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(2.35g). m.p.: 118-1201C

Yield: 80%

NMR: δ(DMSO-dό) 1.15(t,3H),2.30-3.30(m,10H),5.05(d,2H),5.20-6.20(m,3H) , 7.05-7.80(m,3H), 8.40(d,lH)

Preparation 26: Preparation of l-allyl-6^fluoro-7-(2-_ethylpiperazinyl)-l,4-dihydro -4-thioquinoline l-Allyl-6,7-difluoro-l,4-thioquinoline(2g) and 2-methylpiperazine(2.5g) were reacted in the same method as described in Preparation 9 to give the yellow above-indicated compound(1.9g). m.p.: 162-164°C Yield: 68%

NMR: δ(DMS0-d ₆ ) 1.05(d,3H),2.40-3.50(m,7H),5.05(d,2H),5.20(d,lH),5.30(d,lH), 5.98-6.12(m,lH),7.00(d,lH),7.18(d,lH),7.85(d,lH),8.38(d,lH)

Exaβple 1 : Synthesis of 7-[(Z)-2-(2-a___ιinothiazol→4-yl)-2-(βethoxyi«ino)aceta «ido] -3-(l-βethyl-6-fluoro-7-piperazinylquinoliniuβ-4-yl)thioβ ethyl-S-oepheβ -4-carboxy1ate

To a solution of 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimi no) acetamido]-3-cephem-4-carboxylic acid(0.73g) suspended in i:i(V/V) mixture of acetonitrile/water(30ml) were added l-raethyl-6-fluoro-7-piperaziny1-1,4-dihydro -4-thioquino-line(0.5g) and sodium iodide(2.4g). The reaction mixture was heated to 60°C for 5 hours.

The organic solvent was removed under reduced pressure. The residue was added acetone. The precipitates were filtered, and dried to give the above-indicated compound(0.6g) .

IR: (KBr.cnr ¹ ) 1762( 3-lactam)

NMR: δ(DMS0-d ₆ ) 3.00-3.70(m,10H),3.85(s,3H),3.90(s,3H),4.30(s,2H),5.05(d,lH) ,

5.65(dd,lH),6.75(s,lH),6.90-7.50(m,4H),7.75(d,lH),8.30(d, lH),9.20-9.60(m,lH)

Example 2 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(βethoxyi«ino)aceta«ido] -3-[l-*ethy1-6-f1uoro-7-(N-βethylpiperaziny1)quinoliniuβ-4 -y1]thioβethyl -3-cepheβ-4-carbox 1ate

3-acetoxymethyl-7-[(Z)-2- ⁽ 2-aminothiazol-4-yl)-2-(aethoxyimino)acetamido]-3- cephem-4-carboxylic acid(0.7g) and l-aethyl-6-fluoro-7-(N-oethylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.5g) were reacted in the sane Banner as described in Example 1 to give the above-indicated compound(0.61g). IR: (KBΓ.CDΓ ¹ ) 1760( _/ S-lactam)

NMR: δ(DMSO-dώ) 2.38<s,3H),3.20-3.70(n,10H),3.80(s,3H),3.90(s,3H),4.25(s, 2H), 4.95(d,lH),5.50(dd,lH),6.60(s,lH),6.80-7.40(m,4H),7.70 (d,lH),8.70(d.lH), 9.40-9.65(B,1H)

Example 3 : Synthesis of 7-[(Z)-2-(2-a«inothiazol-4-yl)-2-(____ethoxyi«ino)aceta«i do] -3-[l-«ethyl-6-fluo_ro-7-(l-ethylpiperazinyl)quinoliniu«-4 -yl]thioβethyl -3-cephe«-4-caτboxy1ate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimi no)acetamido]-3- cephem-4-carboxylic acid(0.67g) and l-methyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.5g) were reacted in the same Banner as described in Example 1 to give the above-indicated compound(0.53g). IR: (KBΓ.CHT ¹ ) 1760(/3-lactam) NMR: δ(DMS0-d ₆ ) 1.0O(t,3H),2.40(q,2H),2.80-3.7O(n,lOH),3.80(s,3H),3.95(s,3H) , 4.30(s,2H), 4.95(d,lH),5.50(dd,lH),6.65(s,lH),6.80-7.30(B,4H),7.90(d,lH) , 8.40(d,lH), 9.30(d,lH)

Example 4 : Synthesis of 7-[(Z)-2-(2-a«inothiazol-4-yl)-2-(BethoxyiBino)aceta_Bido] -3-(l-*ethyl-6-fluor r-7-(2-βethyl)piperazinylquinoliniu»-4-^13thioβethyl-3-ce pheB -4-carbox late

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(aethoxy imino)acetamido]-3-cep hem-4-carboxylic acid(0.7g) and l-oethyl-6-fluoro-7-(2-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.57g). IR: (KBr.cuT ¹ ) 1760( 9-lactam)

NMR: δ(DMS0-d ₆ ) 1.70(s,3H),2.75-3.70(a,9H),3.70(s,3H),3.85(s,3H),4.40(s,2H), 5.0O(d.lH),5.5O(dd,lH),6.60(s,lH),6.90-7.3O(a _f 4H),7.8O(d,lH),8.7O(d,lH) ₁ 9.40(d,lH)

Example 5 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido] -3-(l-cyclopropyl-6- luoro-7-piperazinylquinolinium-4-yl)thioβethy1-3- cephem-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxy imino)acetamido]-3- cephem-4-carboxylic acid(0.68g) and l-cyclopropyl-6-fluoro-7-piperazinyl-l,4- dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.53g). IR: (KBr.cuT ¹ ) 1760( /3-lactam)

NMR: δ(DMSO-dό) 0.95-1.40(m,4H),2.95-3.60(m,lH),3.85(s,3H),4.20(s.e. ,2H), 4.95(d ₁ lH),5.50(dd,lH),6.6O-7.3O(a,5H),7.70(d,lH),8.20(d,lH), 9.3O-9.50(m,lH)

Example B : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido] -3-[1-cycloprop 1-6-fluoro-7-(N-βethylpiperaziny1)quinolinium-4-yl thioβethy1-3- cephem-4-carboxylate

3-acetoxymethy1-7-[(Z)-2-(2-aminothiazo1-4-y1)-2-(aethoxy i ino)acetarnido]-3- cephem-4-carboxylic acid(0.65g) and 1-eyelopropy1-6-fluoro-7-(N-methylpiperazinyl) -l,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.52g). IR: (KBΓ.CΠΓ ¹ ) 1760( /3-lactam)

NMR: δ(DMS0-d ₆ ) 1.00-1.45(m,4H),2.30(s,3H),3.10-3.80(m,llH),3.90(s,3H), 4.OO-4.40(s.e.,2H) _I 4.95(d,lH),5.5O(dd,lH),6.70(s,lH),6.95-7.3O(m,4H), 7.70(d,lH), 8.45(d,lH),9.42(d,lH)

Example 7 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido] -3-[l-cyclopropy1-6-fluoro-7-(1-ethylpiperazinyl)quinoliniu� �-4-yl]- thioβethy1-3-cephem-4-carboxy1ate 3-acetoxyraethyl-7-[(Z)-2-(2-aminothiazol-4-y1)-2-(methoxyim ino)acetamido]-3- cephem-4-carboxylic acid(0.63g) and l-cyclopropyl-6-fluoro-7-d-ethylpiperazinyl) -l,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.57g). IR: (KBr.cnr ¹ ) 1760( 3-lactam) NMR: δ(DMS0-d ₆ ) 1.00-1.40(m,7H),2.45(q,2H),3.00-3.80(m,llH),3.90(s.3H),4.40( s,2H), 4.95(d,lH),5.45(dd,lH),6.65(s _I lH),6.90-7.35(B,4H),7.70(d,lH),8.45(d,lH),9.40 (d.lH)

Example 8 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(methoxyimino)acetaaido] -3-[l-cyclopropy1-6-fluoro-7-(2-βethylpiperazinyl)quinolini um-4-yl] thioβethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyiι nino)acetamido]-3-cep hem-4-carboxylic acid(0.65g) and 1-eyelopropy1-6-fluoro-7-(2-methylpiperazinyl)- l,4-dihydro-4-thioquinoline(0.5g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.6lg). IR: (KBr.ciT ¹ ) 1760( 3-lactam)

NMR: δ(DMS0-d6) 1.00-1.35(a,4H),1.74(s,3H),2.70-3.75(a,10H),3.90(s,3H),4.40( s.2H), 5.00(d,1H),5.50(dd, 1H),6.65(s,1H),6.90-7.30(m,4H),7.70(d,1H),8.40(d,1H), 9.40(d,lH)

Example 9 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(βethoxyimino)acetamido] -3-(1-ethy1-6-fluoro-7-piperazinylquinolinium-4-yl)thioβeth yl-3-cephem

-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(aethoxy imino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-ethyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoine(0.21g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.24g). IR: (KBr.cπr ¹ ) 1760( _/ 3-lactam)

NMR: δ(DMSO-dό) 1.45(t,3H),2.65-3.60(m,10H),3.90(s,3H),4.10(q,2H),4.40(s,2H) , 5.00(d,lH),5.50(dd,lH),6.6O(s,lH),6.85-7.2O(B,4H),7.75(d,lH) ,8.4O(d,lH), 9.45(d.l!I)

Example 10 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(βethoxyimino)acetamido]

-3-(l-ethyl-6-fluoro-7-(N-«ethylpiperazinyl)quinoliniu» -4-yl]thioβethyl -3-cepheβ-4-caτboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(aethoxy imino)acetamido]-3- cepbem-4-carboxylic acid(0.3g) and l-ethyl-6-fluoro-7-(N-aethylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in

Example 1 to give the above-indicated compound(0.25g).

IR: (KBr.cur ¹ ) 1760(/3-lactam)

NMR: δ(DMS0-d ₆ ) 1.40(t,3H),2.45(s,3H),2.65(t,4H),3.30-3.60(a,6H),3.90(s,3H),

4.10(q,2H),4.40(s,2H),5.05(d,lH),5.50(dd,lH),6.65(s,lH),7 .05-7.40(m,4H), 7.45(d,lH),8.45(d,lH),9.40(d,lH)

Example 11 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(βethoxyimino)acetamido] -3-[1-ethy1-6-fluoro-7-(l-ethylpiperazinyl)quinoliniua-4-yl] thioβethyl -3-cepheβ-4-caτboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxy imino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-ethyl-6-fluoro-7-d-ethylpiperazinyl)-l,4-

dihydro-4-thioquinoline(0.23g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.26g). IR: (KBr.cπr ¹ ) 1760( 3-lactam)

NMR: δ(DMS0-d ₆ ) 1.20(t,3H),1.40 ⁽ t,3H),2.30-2.85(a,6H),3.30-3.85(a,6H),3.85(s,3H), 4.10(q,2H),4.40(s,2H),4.95(d,lH),5.50(dd,lH),6.65(s,lH),6.80 -7.15(m,4H), 7.25(d,lH),8.45(d,lH),9.40(d,lH)

Example 12 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(«ethoxyiminc>)acetamid o]

-3-[l-ethyl-6-fluoro-7-(2-βethylpiperazinyl)quinolinium- 4-y11thioβethyl -3-cephem-4-carboxy1ate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimi no)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-ethyl-6-fluoro-7-(2-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in

Example 1 to give the above-indicated compound(0.26g).

IR: (KBr.cπT ¹ ) 1760( 3-lactam) NMR: δ(DMS0-d ₆ ) 1.40(t,3H),1.70(s ₎ 3H),2.65-3.25(m,3H),3.45-3.75(m,6H),3.90(s,3H),

4.10(q,2H),4.45(s,2H),5.00(d,lH),5.50(dd,lH),6.65(s,lH),6 .70-7.30(m,4H),

7.4O(d,lH),8.45(d,lH),9.40(d,lH)

Example 13 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(methoxyimino)acetamido] -3-(1-ally1-6-f1uoro-7-piperazinylquinolinium-4-y1)thioβeth y1-3-cephem -4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxy iraino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-allyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline(0.2g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.23g). IR: (KBr.cπr ¹ ) 1760( /3-lactam)

NMR: δ(DMSO-dό) 2.65-3.60(m,10H),3.90(s,3H),4.40-4.50(m,4H),4.95(d,lH),

5.20(d,2H),5.45(dd,lH),6.10-6.25(m,lH),6.65(s,lH),6.9O-7. 45(m,4H),7.75(d,lH), 8.40(d,lH),9.40(d,lH)

Example 14 : Synthesis of 7-[(Z)-2-(2-aminothiazol-^4-yl)-2-(methoxyimino)acetamido] -3-[l-allyl-6-fluoro-7-(N-methylpiperazinyl)quinolinium-4-yl ]thioβethyl

-3-cephem-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(aethoxy imino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-allyl-6-fluoro-7-(N-fliethylpiperazinyl)-l,4- dihydro-4-th ^' ioquinoline(0.2g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.25g).

dihydro-4-thioquinoline(0.23g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.26g). IR: (KBr.cuT ¹ ) 1760( _/ 3-lactam)

NMR: δ(DMS0-d ₆ ) 1.20(t,3H),1.40(t,3H),2.30-2.85(a,6H),3.30-3.85(a,6H),3.85(s ,3H), 4.10(q,2H),4.40(s,2H),4.95(d, 1H),5.50(dd,1H),6.65(s,1H),6.80-7.15(m,4H), 7.25(d,1H),8.45(d,1H),9.40(d,1H)

Example 12 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(aethoxyiBino)acetaaido]

-3-[l-ethy1-6-fluoro-7-(2-aethylpiperazinyl)quinolinium-4 -yl]thioβethyl -3-cephem-^4-carboxy1ate 3-acetoxyraethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyi� �nino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-ethyl-6-fluoro-7-(2-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in

Example 1 to give the above-indicated compound(0.26g).

IR: (KBr.cπr ¹ ) 1760(/3-lactam) NMR: δ(DMS0-d ₆ ) 1.40(t,3H),1.70(s,3H),2.65-3.25(B,3H),3.45-3.75(a,6H),3.90(s ,3H),

4.1O(q,2H),4.45(s,2H),5.O0(d,lH),5.5O(dd,lH),6.65(s,lH),6 .7 -7.30(m,4H),

7.40(d.lH),8.45(d,lH),9.40(d,lH)

Example 13 : Synthesis of 7-[(Z)-2-(2-a«inothiazol-4-yl)-2-(Bethoxyimino)acetaMido] -3-(1-allyl-6-fluoro-7-piperazinylquinoliniu*-4-y1)thioβeth yl-3-cepheβ -4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxy iιιιino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-allyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline(0.2g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.23g). IR: (KBr.cuT ¹ ) 1760(/3-lactam)

NMR: δ(DMSO-dβ) 2.65-3.60(m,10H),3.90(s,3H),4.40-4.50(m,4H),4.95(d,1H) ,

5.20(d,2H),5.45(dd,lHJ,6.10-6.25(a,lH),6.65(s,lH),6.90-7. 45(B,4H ⁾ ,7.75(d,lH), 8.40(d,lH).9.40(d,lH)

Example 14 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(methoxyimino)acetamido] -3-[l-allyl-6-fluoro-7-(N-βethylpiperazinyl)quinol inium-4-yl]thioβethyl

-3-cephem-4-carboxy1ate

3-acet.oxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methox yimino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and 1-ally1-6-fluoro-7-(N-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.2g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.25g).

over silica gel. Elution with a 4:l(V/V) mixture of acetonitrile/water gave the above-indicated compound(0.65g). IR: (KBr.cur ¹ ) 1761( 3-lactam)

NMR: δ(DMS0-d ₆ ) 3.55(s,2H),3.85(s,3H),3.95(s,3H),4.40(s,2H),4.95(d,IH) , 5.50(dd,lH),6.65(s,lH) _t 6.70(d,lH).6.80-7.40(a,6H),7.85 ⁽ s,lH),8.50(d,lH), 9.40(d,lH)

Example 18 : Synthesis of 7-L(Z)-2-(2-aβinothiazol-4-yl)-2-(methoxyiιaino) ^" acetamido] -3-[l-βethy1-6-fluoro-7-(4-βethylimidazolyl)quinolinium-4- yl]thioβethyl -3-cephem-4-carboxy1ate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyira ino)aeetamido]-3- cephera-4-carboxylic acid(0.45g) and l-methyl-6-fluoro-7-(4-raethyl imidazolyl)-l,4- dihydro-4-thioquinoline(0.3g) were reacted in the same manner as described in Example 17 to give the above-indicated com ound(0.38g). IR: (KBr.cur ¹ ) 1762( /S-lactam) NMR: δ(DMS0-d ₆ ) 2.40(s,3H),3.5O(s,2H),3.8O(s,3H),3.90(s,3H),4.4O(s,2H),5.00( d,lH), 5.50(dd,lH),6.6 -6.85(ra,3H),7.05-7.6O(m,5H),8.50(d ₍ lH),9.40(d,lH)

Example 19 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetaaido] -3-(l-cycloprop 1-6-fluoro-7-imidazolylquinolinium-4-yl)thioβethyl-3- cephem-4-carboxy1ate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimi no)acetamido]-3-cephem -4-carboxylic acid(0.8g) and l-cyclopropyl-6-fluoro-7-imidazolyl-l,4-dihydro-4- thioquinoline(0.55g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.66g). IR:. (KBr.cur ¹ ) 1762( _/ 3-lactam) NMR: δ(DMS0-d ₆ ) 0.95-1.40(B,4H),3.40-3.65(B,3H),3.90(s,3H),4.40(s,2H),4.95(d ,IH), 5.50(dd,lH),6.65(s,lH),6.85-7.35(B,6H),7.40(d,lH),7.85(s,lH) ,8.50(d,lH), 9.40(d,lH)

Example 20 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(methoxyimino)acetamido] -3-ri-cyclopropy1-6-fluoro-7-(4-methylimidazolyl)quinolinium -4-yl]thio- methyl-3-cepheιι-4-carboxylate

3-acetoxyraethyl-7-[(Z)-2-(2-aιninothiazol-4-yl)-2-(meth oxyiιnino)a(;(?tamido]-3- ceplιem-4-carboxylic acid(O.δg) and l-cyclopropyl-6-fluoro-7-(4-Bethylimidazolyl) -l,4-dihydro-4-thioquinoline(0.58g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.67g). IR: (KBr.cπr ¹ ) 1761( 3-lactam)

NMR: δ ⁽ DMSO-dό) 0. 90-1.40(m, 4H) , 2.45(s, 3H) , 3.45-3.60(m, 3H) , 3.90(s, 3H) , 4.40(s, 2H) , 5.00(d, lH) , 5.50(dd, lH) , 6. 65(s _I lH) , 6. 90-7. 50(m, 6H) .7.65( :;, lH) , 8.45(d, lH) , 9.40(d. lH)

Example 21 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido] -3-(l-aethyl-6-fluoro-7-piperazinylquinolinium-4-yl)thioβet hyl-3-cephem

-4-carbox late

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yimino)acetamido]-3- cephem-4-carboxylic acid(0.4g) and l-raethyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline(0.26g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.34g). IR: (KBr.cur ¹ ) 1762( _/ 3-iactanι)

NMR: δ(DMS0-d ₆ ) 2.65-3.10(m,8H),3.58(s,2H),3.90(s,3H),4.40(s,2H),5.05-5.80(m ,4H), 5.85-6.15(m,3H),6.85(s _> lH),6.95-7.30(m,4H),7.65(d,lH),8.40(d,lll),9.40(d,lH)

Example 22 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(aIlyloxyimino) acetamido]-3-[l-βethyl-6-fluoro-7-(N-methylpiperaziny1)quin olinium-4- yl]thioβethyl-3-cephem-4-caτbox late

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yimino)acetamido]-3- cephem-4-carbox lic acid(0.4g) and l-methyl-6-fluoro-7-(N-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.33g). IR: (KBr.cπr ¹ ) 1760(/3-lactam)

NMR: δ(DMSO-dό) 2.40(s,3H),2.6 -3.65(m,10H),3.80(s,3H),4.40(s,2H),5.00-6.10(m,7H), 6.55-7.05(m,4H),8.40(d,lH),9.45(d,lH)

Example 23 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(allyloxyi ino) aceta«ido]-3-[l-βethyl-6-fluoro-7-(1-ethylpiperazinyl)quin olinium-4- yl]thioβethyl-3-cephem-4-caτboxylate _

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-y1)-2-(allylox yimino)acetaaido]-3- cephem-4-carboxylic acid(0.4g) and l-methyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.28g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.33g). IR: (KBr.cπr ¹ ) 1761(/3-lactam)

NMR: δ(DMS0-d ₆ ) 1.20(t,3H),2.35-2.80(a,6H),3.30-3.60(B,6H),3.80(S.3H),4.45(S ,2H), 5.05-5.90(m,6H),6.10-6.70(a,3H).7.05-7.25(m,2H),8.50(d,lH),9 .45(d,lH)

Example 24 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(al lyloxyiaino)acetamido]

-3-[l- ^β ethyl-6-fluoro-7-(2-βethylpiperazinyl)quinoliniua-4-y lIthioβethyl -3-cephea-4-carboxy1ate

3-acetoxymethyl-7-[(Z)~2- ⁽ 2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]-3- cephem-4-carboxylic acid(0.4g) and l-raethyl-6-fluoro-7-(2-met ylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.34g) . IR: (KBr.cm- ¹ ) 1762( /3-lactam)

NMR: δ(DMS0-d ₆ ) 1.70(s,3H),2.70-3.75(a,9H),3.85(s,3H),4.45(s,2H),5.00-5.80(m ,6H), 5.95-6.65(m,3H),7.05-7.30(m,2H),8.50(d, IH),9.40(d,IH)

Example 25 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(allyloxyimino)acetamido] -3-(l-cyclopropy1-6-fluoro-7-piperazinylquinolinium-4-yl)thi oβethy1-3- cepheB-4-carboxy1 te

3-acetoxyraethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylo xyimino)acetamido]-3- cephem-4-carboxylic acid(0.3g) and l-cyclop_ropyl-6-fluoro-7-ρiperazinyl-l,4-dihydro -4-thioquinoline(0.2g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0,25g). IR: (KBr.car ¹ ) 1760(/3-lactam)

NMR: δ(DMS0-d ₆ ) 0.85-1.40(m.4H),2.80-3.9O(m,HH),4.30-4.80(m,4H),4.90-5.30(m, 3H), 6.90-7.50(a,5H),7.70(d,lH),8.20(d,lH),9.20-9.50(m,lH)

Example 26 : Synthesis of 7-[(Z)-2-(2-aminothiazol-^-yl)-2-(allyloxyimi_πo)a*taaido] -3-[l-cyclopropyl-6-fluoro-7-(N-βethylpiperazinyl)quinolini uB-4-yl]thioβethyl-3- cepheB-4-carboxy1ate

3-auetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yiππ _o)acetaιιιido]-3- cephem-4-carboxylic acid(0.3g) and 1-eyelopropy1-6-fluoro-7-(N-methylpiperazinyl) -l,4-dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in

Example 1 to give the above-indicated compound(0.24g).

IR: (KBr.cur ¹ ) 1761( /3-lactam)

NMR'- δ(DMS0-d _ώ ) 0.95-1.40(m,4H),2.35(s,3H),3.00-3.70(m,llH),4.42-4.80(m,3H), 5.00-5.40(m,3H),5.70-6.00(ra,3H),6.00(s,lH),6.95-7.40(m,4ll) ,7.70(d,lH), 8.20(d,lH),9.40(d,lH)

Example 27 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(al lyloxyimino)acetamidol -3-[l-cyclopropyl-6-fluoro-7-(1-ethylpiperazinyl)quinoliniua -4-yl]thio- ■ethy1-3-cepheβ-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yimino)acetamido]-3- cephem-4-carboxylie acid(0.3g) and 1-eye1opropy1-6-f1uoro-7-( 1-ethy1piperaziny1 ⁾

-l,4-dihydro-4-thioquinoline(0.23g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.24g). IR: (KBr.cur ¹ ) 1761( 3-lactam)

NMR: δ(DMS0-d ₆ ) 0.90-1.40(m,7H),2.45-3.55(ra,13H),4.42-4.90(m,3H),5.05-5.50( m,3H), 5.65-6.10(m,3H),6.50(s,lH),6.90-7.30(m.4H),7.45(d,lH),8.45(d ,lH),9.45(d,lH)

Example 28 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(allyloxyimino)acetamido] -3-[l-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)quinoliniu m--4-yl]thio- ■ethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazo1-4-y1)-2-(a1lylox yimino)acetamido]-3- cephem-4-carbox lic acid(0.3g) and 1-cyclopropyl-6-fIuoro-7-(2-methylpiperazinyl) -l,4-dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.23g). IR: (KBr.cur ¹ ) 1762(/3-lactam)

NMR: δ(DMS0-d ₆ ) 1.00-1.40(m,4H),1.70(s,3H),2.90-3.75(a,10H),4.45-4.95(B,3H), 5.0O-5.45(m.3H) ₎ 5.70-6.15(m,3H),6.60(s,lH),6.80-7.25(m,4H),7.40(d ₎ lH), 8.50(d,lH),9.45(d,lH)

Example 29 : Synthesis of 7-[(Z)-2-(2-aai_nothiazol-4-yl)-2-(allyloxyiBino)acetamido] -3-(1-eth 1-6-f1uoro-7-piperaziny1quinoliniua-4-y1)thioβethy1-3-cephe B- 4-carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyim ino)acetamido]-3- cephem-4-carboxylic acid(0.15g ⁾ and l-ethyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline(O.lg) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.llg). IR:- (KBr,cm" ¹ ) 1760( β-lactam) NMR: δ(DMS0-d ₆ ) 1.45U.3H),2.65-3.55(B,10H),4.10(q,2H),4.45-5.40(m,6H),

5.75-6.20(m,3H),6.60(s,lH),6.9O-7.55(m,4H).7.7O(d,lH),8.4 0(d,lH),9.4O(d,lH)

Example 30 : Synthesis of 7-[(Z)-2-(2-aaiι»thiazol-4-yl)-2-(allyloxyimino)acetaaido] —3-[1-ethy1-6-fluoro-7-(N-βethylpiperazinyl)quinoliniua-4 -yl]thioβethy1 -3-cephe*-4-carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyim ino)acetamido]-3- cephem-4-carboxylic acid(O.lόg) and 1-ethy1-6-fluoro-7-(N-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.lg) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.llg). IR: (KBr,cm" ¹ ) 1760( 3-lactam) NMR: δ(DMS0-d ₆ ) 1.40(t,3H),2.40(s,3H),2.60-3.60(m,lOH),4.10(q,2H),4.4O-5.55( m,6H),

5.80-6.25(m,3H) , 6.65(s, lH) , 6.90-7.35(m,4H) , 7.40(d, lH) , 8.45(d, lH) , 9.45(d, lH)

Example 31 : Synthesis of 7-[(Z)-2-(2-aBinothiazol-4-yl)-2-(allyloxyimino)acetaaido] -3-[l-ethy1-6-fluoro-7-(1-ethylpiperazinyl)quinolinium-4-yl] thioβethyl- 3-cepheβ-4-caτboxy1ate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyi� �πino)acetamido]-3- cephem-4-carboxylic acid(0.15g) and 1-ethyl-6-fluoro-7-(1-ethylpiperazinyl)-1,4- dihydro-4-thioquinoline(0.11g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.12g). IR: (KBr.cm- ¹ ) 1760( /3-lactam) NMR: δ(DMS0-d ₆ ) 1.20(t,3H),1.40(t,3H),2.50-3.55(ra,12H),4.10(q,2H), 4.40-4.85(m,3H) , 4.95-5.50(m,3H),5.80-6.15(ra,3H),6.60(s,lH),6.75-7.20(m,4H), 7.30(d,lH), 8.45(d,lH),9.40(d,lH)

Example 32 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(allyloxyiBino)acetaBido] -3-[l-ethyl-6-fluoro-7-(2-aethylpiperazinyl)quinoliniua-4-yl ]thioβethyl -3-cepheB-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yimino)acetamido]-3- cephem-4-carboxylic acid(0.15g) and l-ethyl-6-fluoro-7-(2-methylpiperazinyl)-1,4- dihydro-4-thioquinoline(0.lg) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.12g). IR: (KBr,cm" ¹ ) 1761(/3-lactam)

NMR: δ(DMS0-d ₆ ) 1.40(t,3H),1.70(s,3H),2.65-3.70(m,9H),4.10(q,2H),4.45-4.90(m ,3H), 5.0 -5.65(m,3H),5.90-6.20(m,3H),6.60-6.70(m,2H),6.9O-7.25(m,3H), 7.40(d,lH),8.4 5(d.lH),9.40(d,lH)

Example 33 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido] -3-(l-allyl-6-fluoro-7-piperazinylquinoliniuB-4-yl)thioβeth yl-3-cepheB -4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yimino)acetamido]-3- cephem-4-carboxylic acid(0.15g) and 1-allyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline(O.lg) were reacted in the same manner as described in Example 1 to give the above-indicated corapound(0.12g). IR: (KBr,cm" ¹ ) 1760( /3-lactam)

NMR: δ(DMS0-d6) 2.65-3.65(m,10H),4.40-4.50(m,4H),4.95-6.20(m,10H),6.65(s,IH) , 6.90-7.50(ra,4H),7.75(d.lH),8.40(d,lH),9.45(d,lH)

Example 34 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyloxyimino)acetamido]

-3-[l-allyl-6-fluoro-7-(N-βethylpiperazinyl)quinoliniu«-4- yl]thioβethyl —-cephem-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-a inothiazol-4-yl)-2-(allyloxyimino)acetamido]-3- cephem-4-carboxylic acid(0.15g) and l-allyl-6-fluoro-7-(N-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.1g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.llg). IR: (KBr.cur ¹ ) 1758( 3-lactam) NMR: δ(DMSO-dό) 2.40(s,3H),2.70-3.55(m,10H),4.45-4.55(a,4H),4.95-5.45(m,6H),

5.50-6.15(m,4H),6.60(s,lH).6.85-7.50(m,4H),7.55(d,lH),8.4 0(d,lH),9.40(d,lH)

Example 35 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(allyloxyiBino)acetamido] -3-[l-allyl-6-fluoro-7-(l-ethylpiperazinyl)quinoliniua-4-yl] thioβethyl -3-cepheβ-4-caτboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yimino)acetamido]-3- cephem-4-carboxylic acid(0.15g) and l-allyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4- dihydrυ-4-thioquinoline(0.11g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.12g). IR: (KBr.cm- ¹ ) 1759(/S-lactam)

NMR: δ(DMS0-d6) 1.15(t,3H),2.40-3.50(m,12H),4.40(a,4H),4.95-5.60(m,6H),5.75- 6.15 (m,4H),6.60-6.70(m,2H),6.90-7.15(m,3H),7.30(d,lH),8.40(d,lH) _f 9.40(d,lH)

Example 36 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allyioxyimino)acetamido] -3-[1-allyl-6-fluoro-7-(2-βethylpiperazinyl)quinolinium-4-y l]thioβethyl -3-cepheβ-4-caτboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(allylox yimino)acetamido]-3- cephem-4-carboxylic acid(0.15g) and l-allyl-6-fluoro-7-(2-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.1g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.llg). IR: (KBr.cπr ¹ ) 1758( _/ 3-lactam) NMR: δ(DMSO-dό) 1.70(s,3H),2.70-3.75(m,9H),4.45(m,4H),4.80-5.45(m,6H) ,

5.70-6.15(m,4H),6.65(m,2H),6.85-7.30(m.3H),7.35(d.lH),8.5 0(d,lH),9.45(d,lH)

Example 37 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(propargyIoxyimino) acetamido]-3-(1-βethy1-6-fluoro-7-piperazinylquinolinium-4- y1)thioβethyl-3-cephem-4 -carboxylate

3-acetoxyaethyl-7-[(Z)-2-(2-aminothiazol-4-y1)-2-(proparg yloxyimino)acetamido]- 3-cephem-4-carboxylic acid(0.4g) and l-methyl-6-fluoro-7-piperazinyl-l,4-dihydro-4- thioquinoline(0.26g) were reacted in the same manner as described in Example 1 to

give the above-indicated compound (0.33g) . IR: (KBΓ. CBΓ ¹ ) 1759( /3 -lactam)

NMR: δ(DMS0-d ₆ ) 2.6 -3.50(m, 9H) ,3.65(s, 2H) , 3.90(s,3H) , 4.45(s, 2H) , 4.75( s, 2H) , 5.05(d, lH) , 5. 55(dd, lH) , 6.65(s, lH) , 6.80-7.50(m, 4H) , 7.65(d, lH) , 8.40(d, lH) , 9.45(d, lH)

Example 38 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(propargyloxyimino) acetaBido]-3-[l-βethyl-6-fluoro-7-(N-βethylpiperazinyl)qui noliniua-4 -y1]thioβethy1-3-cephem-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2- ⁽ 2-aminothiazol-4-yl)-2-(propargyloxyimino)acetamido]- 3-cephem-4-carboxylic acid(0.4g) and l-methyl-6-fluoro-7-(N-aethylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in

Example 1 to give the above-indicated compound(0.34g).

IR: (KBr,cm" ¹ ) 1760( _/ 3-lactam)

NMR: δ(DMSO-dό) 1.70(s,3H),2.70-3.75(m,9H),4.45(m,4H),4.8O-5.45(m,6H), 5.70-6.15(m,4H),6.65(m,2H),6.85-7.30(m,3H),7.35(d,lH),8.50(d ,lH),9.45(d,lH)

Example 39 : Synthesis of 7-[(Z)-2-(2-a«inothiazol-4-yl)-2-(propargyloxyimino) acetaaido]-3-[1-βethy1-6-fluoro-7-(1-ethylpiperazinyl)quino liniuβ-4-yl] thioβethy1-3-cephem-4-carboxy1ate

3-acetoxyaethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(proparg yloxyimino)acetamido] -3-cephem-4-carboxylic acid(0.4g) and l-methyl-6-fluoro-7-(l-ethylpiρerazinyl)-l,4- dihydro-4-thioquinoline(0.29g) were reacted in the same manner as described in

Example 1 to give the above-indicated compound(0.36g).

IR: (KBr,cm" ¹ ) 1760(/3-lactam)

NMR> δ(DMSO-dώ) 1.15(t,3H),2.40-3.50(m,llH),3.60(s,2H),3.80(s,3H),4.40(s,2H) , 4.80(s,2H),5.05(d,IH),5.50(dd,IH),6.60(m,2H),6.75-7.20(m,3H) ,7.25(d,IH), 8.50(d,lH), 9.45(d,lH)

Example 40 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propaτgyloxyimino) acetaaido]-3-[l-βethyl-6-fluoro-7-(2-βethylpiperazinyl)qui noliniua-4-yl]thioβethyl-3 -cephem-4-carboxy1ate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargylo xyimino)acetamido]-3- cephem-4-carboxylic acid(0.4g) and l-methyl-6-fluoro-7-(2-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.27g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.35g). IR: (KBr.cør ¹ ) 1759( /3-lactam) NMR: δ(DMS0-d ₆ ) 1.70(s,3H) ,2.70-3.70(m,10H),3.85(s,3H),4.45(s,2H),4.80 ⁽ s,2H) ,

5.00(d, IH) , 5.50(dd, IH) , 6.65(m, 2H) , 6.85-7.20(m,3H) , 7.30(d, IH) , 8.50(d, IH) , 9.45(d, lH)

Example 41 Synthesis of 7-[(Z)-2-(2-amiι»thiazol-4-yl)-2-(propargyloxyimino) ac«tamido]-3-(l-cyclopropyl-^-fluoro-7-piperazinylquiιιol iniua--4-yl)thioβethyl-3- cephea-4-carboxylate

3-acetoxymethy1-7-[(Z)-2-(2-aminothiazo1-4-y1)-2-(proparg y1oxyimino)acetamido]-

3-cephem-4-carboxylic acid(0.4g) and l-cyclopropyl-6-fluoro-7-piperazinyl-l,4- dihydro-4-thioquinoline(0.28g) were reacted in the same manner as described in

Example 1 to give the above-indicated compound(0.33g). IR: (KBr.cm- ¹ ) 1758(/3-lactam)

NMR: δ(DMSOd ₆ ) 0.90-1.40(m,4H),2.60-3.40(a,10H),3.60(s,2H),4.45(s,2H),

4.75(s,2H),5.05(d,lH),5,55(dd,lH),6.60(s,lH),6.80-7.40(a, 4H),7.70(d,lH),8.40(d,lH),

9.45(d,lH)

Example 42 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(propargyloxyiaino) acetamido]-3-[l-cyclopropyl-6-fluoro-7-(N-methylpiperazinyl) quinoliniuβ-4-yl]thio- Bethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(proparg yloxyimino)acetamido]- 3-cephem-4-carboxylic acid(0.4g) and 1-cyclopropy1-6-fluoro-7-(N-methylpiperazinyl) -l,4-dihydro-4-thioquinoline(0.29g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.32g). IR: (KBr,cm" ¹ ) 1760(/3-lactam)

NMR: δ(DMS0-d ₆ ) 0.95-1.40(m,4H),2.35(s,3H),2.65-3.60(m,12H),4.40(s,2H), 4.70(s,2H),4.95(d,lH),5.50(dd,lH),6.65(s,lH),6.85-7.30(m,4H) .7.40(d,lH),8.40(d _f lH), 9.4θ(d,lH)

Example 43 : Synthesis of 7-[(Z)-2-(2^aaiικ>thiazol-4-yl)-2-(propa_rgyloxyimi_no) acetamido]-3-cepheB-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(proparg yloxyimino)acetamido]-

3-ceplιem-4-carboxylic acid(0.4g) and l-cyclopropyl-6-fluoro-7-d-ethylpiperazinyl)

-l,4-dihydro-4-thioquinoline(0.3g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.32g) .

IR: (KBr,cm ^"1 ) 1759(3-lactam)

NMR: δ(DMS0-d ₆ ) 0.90-1.40(m,7H),2.30-3.60(m,14H),4.45(s,2H),4.70(s,2H),

4.95(d,lH),5.55(dd,lH).6.60(s,lH).6.90-7.35(ra,4H),7.40(d ,lH),8.45(d,lH),9.40(d,lH ⁾

Example 44 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(propargyloxyimino)

acetaaido]-3-[l-cyclopropyl-6-fluoro-7-(2-Bethylpiperazinyl) quinolinium-4-yl]thio- methy1-3-cephem-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(proparg yloxyimino)acetamido]- 3-cephem-4-carboxylic acid(0.4g) and 1-cyclopropy1-6-fluoro-7-(2-methylρiperazinyl) -l,4-dihydro-4-thioquinoline(0.29g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.33g). IR: (KBr,cm" ¹ ) 1759( _/ 3-lactam) NMR: δ(DMS0-d ₆ ) 0.95-1.40(m,4H),1.70(s,3H),2.70-3.75(m,11H),4.40(s,2H),

4.75(s,2H),5.05(d,lH),5.45(dd,lH),6.65(s,lH),6.85-7.30(m, 4H),7.40(d,lH),8.50 ⁽ d,lH ⁾ ,9.45(d,lH)

Example 45 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino) acetamido]-3-(l-ethyl-6-fluoro-7-piperazinylquinolinium-4-yl )thioβethyl -3-cephem-4-caτboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(proparg yloxyimino)acetamido]- 3-cephem-4-carboxylic acid(0.5g) and 1-ethy1-6-fluoro-7-piperaziny1-1,4-dihydro-4- thioquinoline(0.33g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.40g).

IR: (KBr,cm" ¹ ) 1760( _/ 3-lactam)

NMR: δ(DMSO-dό) 1.40(t,3H),2.60-3.50(m,llH),4.10-4.70(m,6H),5.00(d,lH), 5.50(dd,lH),6.65(s,lH),6.90-7.50(m,4H),7.70(d,lH),8.40(d,lH) ,9.40(d,lH)

Example 46 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(propargyloxyimino) acetamido]-3-[l-ethyl-6-fluoro-7-(N-βethylpiperazinyl)quino liniua-4-yl]thioβethyl-3 -cepheB-4-carboxylate

^■ 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(prop argyloxyimino)acetamido] -3-cephera-4-carboxylic acid(0.5g) and l-ethyl-6-fluoro-7-(N-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.35g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.39g). IR: (KBr,cm" ¹ ) 1760( _/ 3-lactam)

NMR: δ(DMS0-d ₆ ) 1.40U.3H),2.40(s,3H),2.65-3.55(m,1110,4.10-4.75(m,6H), 4.95(d.lH),5.50(dd,lH),6.65(s,lH),6.85-7.30(ra,4H),7.40(d,lH ),8.45(d,lH).9.45(d,lH)

Example 47 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(propargyloxyiBino) acetaaido]-3-[1-ethy1-6-fluoro-7-(l-ethylpiperazinyl)quinoli niua-4-yl]thioβethyl-3- cepheB-4-carboxylate

3-acetoxymethy1-7-[(Z)-2-(2-aminothiazo1-4-y1)-2-(proparg y1oxyi ino)acetamido]- 3-cepheπι- -carboxylic acid(0.5g) and l-ethyl-6- luoro-7-(l-ethylpiperazinyl)-l,4-

dihydro-4-thioquinoline(0.37g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.45g). IR: (KBr,cm" ¹ ) 1760(/3-lactam)

NMR: δ(DMS0-d ₆ ) 1.20(t,3H),1.40(t,3H),2.3 -3.60(a,13H),4.10-4.40(a,4H),4.80(s,2H), 5.00(d,lH),5.45(dd,lH),6.70(m,2H),6.85-7.20(m,3H),7.25(d,lH) ,8.45(d,lH), 9.45(d,lH)

Example 48 : Synthesis of 7—L(Z)-2—(2—aminothiazol—4— l)- 2—(propargyloxyimino) acetamido]-3-[1-ethy1-6-fluoro-7-(2-aethylpiperazinyl)quinol iniu«-4-yl] thioβethy1-3-cepheB-4-carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargylo xyimino)acetamido] -3-ceρhem-4-carboxylic acid(0.5g) and l-ethyl-6-fluoro-7-(2-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.35g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.40g). IR: (KBr,cm" ¹ ) 1760(/3-lactam) NMR: δ(DMS0-d ₆ ) 1.40(t,3H).1.70(s,3H),2.65-3.70(m,10H),4.10-4.80(m,6H),5.00( d,IH), 5.60(dd,IH),6.65(m,2H),6.85-7.30(m,3H),7.35(d,IH),8.45(d,IH) ,9.40(d,IH)

Example 49 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yI)-2-(propargyloxyimino) ac«tamido]-3-(l-allyl-6-fluon_)-7-piperazinylquinolinium-4- yl)thioeethyl-3-cepheB-4- carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargylo xyimino)acetamido]-3- cephem-4-carboxylic acid(0.5g) and 1-allyl-6-fluoro-7-piperaziny1-1,4-dihydro-4- thioquinoline(0.31g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.41g). IR: (KBr,cm" ¹ ) 1758( 3-lactam) NMR: δ(DMS0-d ₆ ) 2.65-3.60(m,11H),4.40-4.80(m,6H),5.00-5.25(a,3H),5.65(dd,lH) , 6.05-6.20(m,lH),6.65(s,lH),6.85-7.40(B,4H),7.80(d,lH),8.40(d ,lH),9.45(d,lH)

Example 50 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propaτgyloxyimino) acetamido]-3-[l-allyl-6-fluoro-7-(N-βethylpiperazinyl)quino liniuβ-4-yl]thioβethyl-3 -cephem-4-carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargylo xyimino)acetamido] -3-cephem-4-carboxylic acid(0.5g) and l-allyl-6-fluoro-7-(N-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.34g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.42g). IR: (KBr,en" ¹ ) 1759( _/ 3-lactam) NMR: δ(DMS0-d ₆ ) 2.40(s,3H) .2.65-3.55(m,llH),4.45-4.70(m,6H),5.00(m,3H),5.60(dd,lH) ,

5.9O-6.05 ⁽ m, lH) , 6.60 ⁽ s, lH ⁾ , 6.8O-7.40(m, lH) , 7.55(d, lH) , 8.40(d, lH) , 9.45(d, lH)

Example 51 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyloxyimino) acetamido]-3-[l-allyl-6-fluoro-7-(l-ethylpiperazinyl)quinoli nium-4-yl]thiomethyl-3- cephem-4-carboxylate 3-acetoxymethyl-7-[(Z)-2- ⁽ 2-aminothiazol-4-yl)-2-(propargyloxyimino)acetaraido] -3-cephera-4-carboxylic acid(0.5g) and l-allyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.35g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.40g). IR: (KBr,cm" ¹ ) 1760( /3-lactauι) NMR: δ(DMSO-dό) 1.20(t,3H),2.30-3.55(m,13H),4.40-4.80(ra,6H),4.95(a,3H) ,5.60(dd,IH) , 5.95-6.10(m,lH ⁾ ,6.65(m,2H),6.80-7.20(m,3H),7.30(d,lH),8.40(d,lH),9.45 (d,lH)

Example 52 : Synthesis of 7-[(Z)-2-(2-aminothiazol^4-yl)-2-(propargyloxyimino) acetaaido]-3-[l-allyl-6-fluoro-7-(2-aethylpiperazinyl)quinol iniuj__Hl-yl]thioβethyl-3

-cepheB-4-carboxy1ate 3-acetoxyraethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(propargyl oxyimino)acetamido] -3-cephem-4-carboxylic acid(0.5g) and l-allyl-6-fluoro-7-(2-methylpiperazinyl)-l,4- dihydro-4-thioquinoline(0.34g) were reacted in the same manner as described in Example 1 to give the above-indicated compound(0.38g). IR: (KBr,cm" ¹ ) 1759( _/ 3-lactam) NMR: δ(DMS0-d ₆ ) 1.70(s,3H),2.70-3.75(m,10H),4.40-4.75(m,6H),5.00(d,lH) ,5.10(d,2H) , 5.55(dd.lH),6.05(m,lH ⁾ ,6.60(m,2H),6.80-7.25(ra,3H),7.40(d,lH),8.50(d,lH),9.4 5(d,lH)

Example 53 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxy- imino)acetamido]-3-(1-βethy1-6-fluoro-7-piperazinylquinolin ium-4-y1)thio ethy1-3- cephem-4-carboxylate 3-acetoxymethyl-7-t(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyp rop-2-oxyimino)acet¬ amido]-3-cephem-4-carboxylie acid(0.4g) and l-methyl-6-fluoro-7-piperazinyl-l,4- dihydro-4-thioquinoline(0.24g) were reacted in the same Banner as described in Example 17 to give the above-indicated compound(0.29g). IR: (KBr,cm" ¹ ) 1763( /3-lactam) NMR: δ(DMS0-d ₆ ) 1.45(d,6H),2.60-3.55(m,10H),3.90(s,3H),4.40(s,2H),5.00(d,IH) , 5.65(dd,lH),6.70(s,lH),7.00-7.40(ra,4H),7.65(d,lH),8.40(d,lH ).9.25(d,lH)

Example 54 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxy -imino)aootaaido]-3-| l-βethyl-6-fluoro-7-(N-βothylpiperazinyl)quinoIinium-4-yl Ithio ■e hyl-3-cephem-4-carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyp rop-2-oxyimino)acet-

amldo]-3-cep ^} ιem-4-carboxyl ic acid(0.4g) and l-methyl-6-f luoro-7-(N-methyl- piperazinyl)-l,4-dihydro-4-thioquinoline(0.25g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.29g) . IR: (KBr, cm" ¹ ) 1763( /3-lactam) NMR: δ(DMS0-d ₆ ) 1.38(s,3H) , 1.42(s, 3H) , 2.30(s,3H) , 2.7O-3.60(m, 10H) ,3.95(s,3H) ,

4.40(s, 2H ⁾ , 5.00 ⁽ d, lH ⁾ , 5.65 ⁽ dd, lH) , 6.70(s, lH) , 7.05(d _> lH) , 7. 15(ra, 2H) , 7.35(d, lH) , 7.85 (d, IH) .8.40(d, IH) , 9.10(d, IH)

Example 55 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxy -imino)acetamido]-3-[1-βethy1-6-f1uoro-7-(1-ethylpiperaziny 1)quinolinium-4-y1]thio methyl-3-cephem-4-carboxylate

3-acetoxymethy1-7-[(Z)-2-(2-aminothiazo1-4- 1)-2-(2-carboxyprop-2-oxyimino)acet -amido]-3-cephem-4-carbox lic acid(0.4g) and 1-methy1-6-fluoro-7-(l-ethyl- piperazinyl)-l,4-dihydro-4-thioquinoline(0.26g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.3lg). IR: (KBr,cm" ¹ ) 1761( _/ 3-lactam)

NMR: δ(DMS0-d ₆ ) 1.20(t,3H),1.40(s,6H),2.30-2.85(m,6H),3.20-3.55(m,6H),3.95(s ,3H), 4.40(s.2H),5.10(d,lH).5.65(dd,lH),6.70(s,lH),6.80(d,lH),6.90 -7.30(m _f 3H),7.35(d,lH), 8.50(d,lH),9.30(d,lH)

Example 56 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(2-carboxyprop-2-oxy- iBino)acetamido]-3-[l-aethyl-6-fluoro-7-(2-aethylpiperazinyl )quinolinium-4-yl] thioβethy1-3-cephem-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carbo xyprop-2-oxyimino)acet-ami do]-3-cephem-4-carboxylic acid(0.4g) and 1-methy1-6-fIuoro-7-(2-methyl- piperazinyl)-l,4-dihydro-4-thioquinoline(0.25g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.30g). IR: (KBr.cuT ¹ ) 1762( _/ 3-lactam)

NMR: δ(DMSO-db) 1.45(s,6H) ,1.70(s,3H ⁾ ,2.70-3.70(ra.9H),3.90(s,3H),4.40(s,2H), 5.10(d,111),5.65(dd,IH),6.70(ιn,2H),6.80-7.20(m,3H),7.40(d, IH),8.50(d,IH),9.25(d,IH)

Example 57 : Synthesis of 7-[(Z)-2-(2-aminothiazol- -yl)-2-(2-carboxyprop-2-oxy- iBino)acetamido]-3-(l-cyclopropyl-6-fluoro-7-piperazinylquin oliniua- -yl)thioβethyl -3-cepheB- -carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carbo xyprop-2-oxyimino)acet -amido]-3-cephem-4-carboxylic acid(0.8g) and l-cyclopropyl-6-fluoro-7-piperazinyl -l,4-dihydro-4-thioquinoline(0.54g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.67g).

IR: (KBr, cm" ¹ ) 1763 ( _/ 3 -lactam)

NMR: δ ⁽ DMS0-d ₆ ) 0.90-1.45(m, 10H) , 2.70-3.55(ra, 11H) ,4.40( s,2H) , 5.05(d, IH) ,

5.65 ⁽ dd, lH ⁾ , 6.70 ⁽ s, lH ⁾ , 6.90-7. 50 ⁽ a, 4H ⁾ , 7.70 ⁽ d, lH) , 8.40(d _l lH) , 9.30(d, lH)

Example 58 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxy- i ^β ino)ac«tamido]-3-[l-cyclop_ropyl-^-fluorx)-7-(N-aethy lpiperazinyl )quinoliniua-4- yl ]thioα_ethyl-3-cephem-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl )-2-(2-carboxyprop-2-oxyimino)acet -amido]-3-cephem-4-carboxyl ic acid(0.8g) and l-cyclopropyl-6-fluoro-7-(N-methyl- piperazinyl )-l ,4-dihydro-4-thioquinol ine(0.56g) were reacted in the same manner as described in Example 17 to give the above- indicated compound(0.66g) . IR: (KBr.c - ¹ ) 1763( _/ 3-lactam)

NMR: δ(DMS0-d ₆ ) 0.95-1.50(m, 10H) , 2.40(s, 3H) , 2.60-3.55(a, llH) , 4.40(s, 2H) , 5. 10(d, lH) , 5.65 ⁽ dd, lH ⁾ , 6.70 ⁽ s, lH) , 6.85-7.30(ra, 4H) , 7.40(d, lH) , 8.40(d, lH) , 9.20(d, lH)

Example 59 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(2-carboxyprop-2-oxy- imino)acetamido]-3-[l-cyclopropyl-6-fluoro-7-(1-ethylpiperaz inyl)quinoliniuβ-4-yl] thioβethyl-3-cephea-4-carboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carbo xyproρ-2-oxyimino)acet- amido]-3-cephera-4-carboxylic acid(O.δg) and l-cyclopropyl-6-fluoro-7-d-ethyl

-piperazinyl)-l,4-dihydro-4-thioquinoline(0.58g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.68g).

IR: (KBr,cm" ¹ ) 1762( /3-lactam)

NMR: δ ⁽ DMS0-d ₆ ) 1.00-1.50(a,13H),2.40-2.65(a,6H ⁾ .3.30-3.60(B,7H),4.25(s.e. ,2H),

5.00(d,lH),5.65(dd,lH),6.70(s,lH),7.10(d,lH),7.50(d,lH),7 .75(d,lH),7.85(d,lH),8.10

(d,lH),8.35(d,lH),8.90(d,lH)

Example 60 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyproρ-2-oxy- iBino)acetamido]-3-[1-cyclopropy1-6-fluoπo-7-(2-βethylpipe razinyl)quinolinium-4-yl] thioβethy1-3-cepheB-4-carboxy1ate

3-acetoxyraethyl-7-[(Z)-2-(2-a»ιinothiazol-4-y1)-2-(2-c arboxyprop-2-oxyimino)acet -amido]-3-cephem-4-carboxylic acid(0.8g) and 1-cyclopropy1-6-fluoro-7-(2-methyl- piperazinyl)-l,4-dihydro-4-thioquinoline(0.56g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.64g).

IR: (KBr,cm ^"1 ) 1762( /3-lactam)

NMR: δ(DMS0-d ₆ ) 1.00-1.45(a, lOH),1.70(s,3H),2.70-3.70 ⁽ ra, 10H),4.25(s,2H),5.00 ⁽ d,IH), 5.60(dd,lH),6.70(s,lH),6.85-7.30(ra,4H),7.50(d,lH),8.50(d,lH ),9.20(d,lH)

Example 61 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxy-

imino)acetamido]-3-Ll-ethyl-6-fluoro-7-(1-ethylpiperazinyl)q uinolinium-4-yl]thio- ethyl-3-cephem-4-carboxy1ate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carbo xyprop-2-oxyimino)acet- amido]-3-cephem-4-carboxylic acid(O.δg) and l-ethyl-6-fluoro-7-(l-ethylpiperazinyl) -1,4-dihydro-4-thioquinoline(0.53g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.67g). IR: (KBr,cm" ¹ ) 1763(/3-lactam)

NMR: δ(DMSO-d ₆ ) 1.20(t,3H) , 1.40U.3H),1.45(s,6H),2.50-3.55(a,12H),4.10-4.45(ra _J 4H), 5.05(d,lH),5.65(dd,lH),6.70(s,lH),6.8O-7.20(m,4H),7.4O(d,lH) ,δ.45(d,lH),9.2O(d,lH)

Example 62 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(2-carboxyprop-2-oxy- imino)acetamido]-3-[l-ethyl-6-f luoro-7-(2-βethylpiperazinyl )quinol inium-4-yUthio ■ethy 1 -3-cepheβ-4-carboxy late

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carbo xyprop-2-oxyimino)acet- amido]-3-cephem-4-carboxylic acid(O. δg) and 1-ethy 1-6-f luoro-7-(2-methyI- piperazinyl )-l, 4-dihydro-4-thioquinoline(0.51g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.65g) .

IR: (KBr, cm" ¹ ) 1762 ( _/ 3-lactam)

NMR: δ(DMS0-d ₆ ) 1.40(t,3H) , 1.45(s, 6H) , 1.70(s,3H) _I 2.65-3.50(m, 9H) ,4.15-4.35(m, 4H) ,

5.00(d, lH) _t 5.65(dd, lH) , 6.70(m, 2H) , 6.85-7.30(m,3H) , 7.50(d, lH) , 8.45(d, lH) , 9.30(d, lH)

Example 63 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2- arboxyprop-2-oxy- imino)acetamido]-3-[l-allyl-6-fluoro-7-(l-ethylpiperazinyl)q uinolinium-4-yl]thio BethyI-3-cephem-4-caτboxylate

3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carbo xyproρ-2-oxyimino)acet- ami-do]-3-cephem-4-carboxylie acid(0.8g) and l-allyl-6-fluoro~7-(l-ethylpiperazinyl)

-l,4-dihydro-4-thioquinoline(0.51g) were reacted in the same manner as described in

Example 17 to give the above-indicated compound(0.66g).

IR: (KBΓ.CDΓ ¹ ) 1763( 3-lactam)

NMR: δ(DMS0-d ₆ ) 1.20U.3H) ,1.40(s,6H),2.50-3.50(m,12H),4.40-4.55(m,4H),4.95-5.10 (m,3H),5.7 -6.O0(m.2H),6.7O(m,2H),6.8O-7.30(m,3H),7.55(d,lH),8.4O(d,lH) ,9.25(d,lH)

Example 64 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(2-carboxyprop-2-oxy- imino)acetamido]-3-[l-allyl-6-fluoro-7-(2-methylpiperazinyl) quinolinium-4-yl]thio

■ethyl-3-cephem-4-caτboxylate

3-aoeloxyme.thyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carb oxyproi)-2-oxyimino)acet- amido]-3-cephem-4-carboxylic acid(0.8g) and 1-allyl-6-fluoro-7-(2-methylpiperazinyl)

-l,4-dihydro-4-thioquinoline(0.49g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.63g). IR: (KBr,cm ^"1 ) 1763( 3-lactam)

NMR: δ(DMS0-d ₆ ⁾ 1.40 ⁽ s,6H ⁾ , 1.70 ⁽ s,3H ⁾ ,2.70-3.75(ra,9H),4.45(m,4H) ,5.00-5.10(m,3H), , 5.65(dd,lH),6.05(m,lH ⁾ ,6.65(nι,2H ⁾ ,6.90-7.30(ιn,31l),7.45(d,lH),8.5O(d,lH),9.45(d,lH)

Example 65 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyproρ-2-oxy- imino)acetamido]-3-(l-βethyl-6-fluoro-7-imidazolylquinolini uβ-4-yl)thioβethy1-3- cephem-4-carboxy1ate

3-acetoxymetlιyl-7-t(Z)-2- ⁽ 2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyiraino)acet - amido]-3-cepheιn-4-carboxylic acid(0.4g) and l-methyl-6-fluoro-7-imidazolyl-l,4- dihydro-4-thioquinoline(0.22g) were reacted in the same manner as described in

Example 17 to give the above-indicated compound(0.31g).

IR: (KBr,cm ^"1 ) 1760( /3-lactam)

NMR: δ(DMS0-d ₆ ) 1.50(s,6H),3.65(s,2H),3.90(s,3H),4.45(s,2H),5.00(d,lH),5.65( dd,lH), 6.65(d,lH),6.70(s,lH),6.δ5-7.40(m,6H),7.δ5(s,lH),δ.50(d,l H),9.40 ^J d,lH)

Example 66 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxy- imino)acetamido]-3-[l-βethyl-6-fluoro-7-(4-βethylimidazoly l)quinoliniuβ-4-yl]thioβe thy1-3-cephem-4-carboxy1ate

3-acetoxymethy1-7-[(Z)-2-(2-aminothiazo1-4-y1)-2-(2-carbo xyproρ-2-oxyimino)acet- amido]-3-cephem-4-carboxylic acid(0.4g) and l-methyl-6-fluoro-7-(4-raethylimidazol¬ yl)-l,4-dihydro-4-thioquinoline(0.23g) were reacted in the same manner as described in Example 17 to give the above-indicated corapound(0.33g). IR: (KBr,cm" ¹ ) 1761( /3-lactam)

NMR-' δ(DMS0-d _ό ) 1.50(s,6H),2.40(s,3H),3.65(s,2H),3.95(s,3H),4.45(s,2H), 5.05(d,lH), 5.70(dd,IH),6.60-6.85(m,3H),6.90-7.40(a,4H),7.60(d,IH),8.50( d,IH),9.30(d,IH)

Example 67 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxy- iaino)acetaaido]-3-(1-cyclopropy1-6-fluoro-7-imidazolylquino liniua-4-ylHhioβethyl- 3-cepheB-4-carboxy1ate

3-acetoxyιnethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-car boxyprop-2-oxyimino)acet- a ido]-3-cephem-4-carboxylic acid(0.3g) and 1-eyelopropy1-6-fluoro-7-imidazolyl- l,4-dihydro-4-thioquinoline(0.18g) were reacted in the same manner as described in

Example 17 to give the above-indicated compound(0.24g).

IR: (KBr,cm" ¹ _. ) 1760( /3-lactam)

NMR: δ(DMS0-d ₆ ) 1.00-1.45(m, 10H) ,3.50-3.65(ra,3H),4.45(s,2H),5.10(d,IH),5.70(dd,IH) , 6.70(s,lH),6.90-7.40(m,7H),7.85(s,lH),8.50 d,lH),9.35(d,lH)

Example 68 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-caτboxyprop-2-oxy^ iBino)acetamido]-3-[1-cyclopropy1-6-fluoro-7-(4-aethyli idazolyl)quinolinium→l-yl] thioβethyl-3-cephem-4-carboxy1ate

3-acetoxyraethy1-7-[(Z)-2-(2-aminothiazo1-4-y1)-2-(2-carb oxyprop-2-oxyimino)acet- araido]-3-cephera-4-carboxylic aαid(0.3g) and 1-cyclopropy1-6- luoro-7-(4-methyl- iιπidazolyl ⁾ -l,4-dihydro-4-thioquinoline(0.19g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.23g).

IR: (KBr,cm ^"1 ) 1761( 3-lactam) NMR: δ(DMS0-d ₆ ) 0.95-1.45(a,10H) ,2.45(s,3H),3.45-3.60(m,3H),4.50(s,2H),5.10(d,lH),

5.70(dd,IH),6.70(s,IH) ,6.90(s, IH),6.95-7.60(m,6H),8.45(d,IH),9.30(d,IH)

Example 69 : Synthesis of 7-[(Z)-2-(2-aainothiazol-4-yl)-2-(βethoxyimino) ac«tamido]-3-[l-cycloprx_ιpyl-3-carboxylicacid-6-fluoro-7- (l-ethylpiperazi_nyl) quinoliniuB-4-yl]thioβethyl-3-cepheB-4-carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methox imino)acetamido]-3-cephem -4-carboxylic acid(0.7g) and l-cyclopropyl-6-fluoro-7-(l-ethylpiperazinyl)-l,4- dihydro-4-thioquinoline-3-carboxylic acid(0.63g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.59g). IR: (KBr,cm ^"1 ) 1761(/3-lactam) NMR: δ(DMS0-d ₆ ) 1.00-1.40(m,7H),2.75-3.70(a,13H),3.90(s,3H),4.40(s _I 2H),5.00(d,lH), 5.50(dd,IH),6.65(s,IH),7.40(d,IH),8.40(d, IH),8.85(s,IH),9.50(d,IH)

Example 70 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(βethoxyiBino)acet- amido]-3-[l-cyclopropyl-3-carboxylicacid-6-fluoro-7-(2-βeth yIpiperazinyl) quinolinium-4-ylIthioβethyl-3-cephe»-4-carboxylate ^' 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimi no)acetamido]-3- cephem-4-carboxylic acid(0.6g) and l-cyclopropyl-6-fluoro-7-(2-methylpiperazinyl)- l,4-dihydro-4-thioquinoline-3-carboxylic acid(0.52g) were reacted in the same manner as described in Example 17 to give the above-indicated coBpound(0.52g). IR: (KBr.cπr ¹ ) 1760( _/ 3-lactam) NMR: δ(DMS0-d ₆ ) 1.10-1.45(m,4H), 1.70(s,3H),2.75-3.70(m,10H),3.90(s,3H),4.40(s,2H), 5.05(d,lH),5.50(dd,lH),6.65(s,lH),7.40(d,lH),8.45(d,lH),δ.7 5(s,lH),9.50(d,lH)

Example 71 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2- xy- i _B ino)acetamido]-3-[l-cyclopropyl-3-carboxylicacid-6-flu <M )-7-(l-ethylpiperazinyI) quinoliniu«-4-yl]thioβethyl-3-cephem-4-carboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazo1-4-y1)-2-(2-carboxyp rop-2-oxyimino)acet¬ amido]-3-cephem-4-carboxylie acid(0.4g) and l-cyclopropyl-6-fluoro-7-d-ethyl-

piperazinyl ⁾ -l,4-dihydro-4-thioquinoline-3-carboxylic acid(0.31g) were reacted in the same manner as described in Example 17 to give the above-indicated compound(0.34g). IR: (KBr,cm' ¹⁾ 1760( /3-lactam) NMR: δ ⁽ DMS0-d ₆ ) 1.00-1.50(m, 13H),2.75-3.60(m, 1311),4.50(s,2H),5.10(d,IH). 5.70(dd,lH), 6.70 ⁽ s,lH),6.95-7.40(m,3H),8.40(d,lH).8.80 ⁽ s,lH ⁾ ,9.55(d,lH)

Example 72 : Synthesis of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyρ op-2-oxy- iBino)acetamido]-3-[l-cyclopropyl-3-c^boxylic_acid-6-fluoπ- 7-(2--methylpiperazinyl) quinoliniuβ-4-y1]thionethyl-3-cepheB-4-caτboxylate 3-acetoxymethyl-7-[(Z)-2-(2-aminothiazol-4-yl )-2-(2-carboxyprop-2-oxyimino)acet- aiDidu]-3-c.ephem-4-carboxyl ic acid(0.4g) and 1-cyc lopropy 1-6-f luoro-7-(2-methyl- piperazinyl )-l , 4-dihydro-4-t.hioquinol ine-3-carboxyl ic acid(0.3g) were reacted in the same manner as described in Example 17 to give the above-indicated compound (0.32g) . IR: (KBr, cm" ¹ ) 1760( 3-lactam)

NMR: δ(DMS0-d ₆ ) 1. 10-1 . 45( B, 10H) , 1.70(s, 3H) , 2.75-3.60(m, 10H) , 4.50(s, 2H) , 5. lO(d. lH) ,

5.70(dd, lH) , 6.70(s, lH) , 6.90-7.35(m,3H) , 8.50(d, lH) , 8.85(s, lH) , 9.50(d, lH)

In order to illustrate the usefulness of the invented compounds, the minimal inhibitory concentrations-(MIC) thereof against standard strains were determined and compared with Cefotaxime, a noun compound.

Also, the in vitro antibacterial activity was determined by a two-fold dilution method as described below:

That is, the two-fold serial dilutions of the compound were made and dispersed in Muller Hinton Broth medium. Standard test strain which had the 10 ⁶ CFU per ml was inoculated on the medium, and was incubated at 37°C for 18 to 20 hours. The results of the MIC tests are shown in Table 3.

Table 3: Antibacterial Activity(MIC,/^g/nl )

Table 3: Antibacterial Activity(MIC,μg/ml)

* CTX: Cefotaxime