NOVEL QUINOLONE COMPOUNDS AND PROCESSES FOR PREPARATION THEREOF

Abstract: This invention relates to the novel quinolone compound of formula (I) having excellent antimicrobial activity both against gram positive and negative bacteria, its pharmaceutically acceptable salt, and the process for preparation thereof; wherein R<1> is hydrogen or protective group, R<2> is hydrogen, amino, alkylamino from one to four carbon atoms, hydroxy, alkoxy from one to four carbon atoms, mercapto, alkylthio from one to four carbon atoms, or halogen, R<3> is alkyl from one to four carbon atoms, alkenyl from two to four carbon atoms, cycloalkyl from three to six carbon atoms, haloalkyl, hydroxyalkyl from two to four carbon atoms, methoxy, amino, alkylamino from one to two carbon atoms, dimethylamino, or optionally substituted phenyl with more than one of halogen atoms or alkyl from one to three carbon atoms, Z is an amine of formula (II), (wherein R<4> is hydrogen or alkyl from one to four carbon atoms, R<5> and R<7> are, same or different, hydrogen or alkyl from one to two carbon atoms), X is N or C-R<6> (wherein R<6> is hydrogen, hydroxy, methyl, cyano, nitro, methoxy, halogen, or can form a bridge of formula (a), (b), (c) or (d) with R<3>.

Description: NOVEL QUINOLONE COMPOUNDS AND PROCESSES FOR PREPARATION THEREOF BACKGROUND OF THE INVENTION Field of the Invention This invention relates to novel quinolone compounds having more improved antimicrobial activity and their pharmaceutically acceptable salts, and processes for preparation thereof. Description of the Prior Art Previously developed quinolone antimicrobial agents such as norfloxacin, pefloxacin, ofloxacin, ciprofloxacin, and sparfloxacin show excellent antimicrobial activities against gram negative bacteria, but show comparatively low activities against gram positive bacteria. Moreover, a lot of resistant bacterial strains to these agents are also found clinically, demanding more potent and improved antimicrobial agents. Recently, considerable effort for overcoming these problems and providing more improved quinolone antimicrobial agents has been made. Various kinds of diazabicyclic compounds are reported as a substituent at 7-position of quinolone antimicrobial agents, and some examples are described in the following. European Patent Application No. 215,650-A 2 discloses compounds having the following structural formula, wherein R 2 is a diazabicycloalkyl group selected from the following structural formula. (wherein n is 1, 2, or 3, m is 1 or 2, P is 0 or 1, Q is hydrogen or (C x ~ C 3 ) alkyl) European Patent Application No. 266,576-A 2 discloses compounds having the following structural formula, wherein, R 1 is substituted or unsubstituted tert-alkyl group, Z is a N-heterocyclic group selected from the following structural formula. R 2_ N (CH 2 ) n N- (wherein R 2 is hydrogen or alkyl group, n is an integer from 0 to 3). But the above mentioned diazabicycloamine derivatives didn't exhibit much improved properties in antimicrobial aspects compared to the previously developed ones. SUMMARY OF THE INVENTION The object of present invention is to provide more potent and improved quinolone antimicrobial agents than previously developed ones both against gram positive and negative bacteria by introducing novel amine substituents at C 7 - position of quinolone nucleus. This invention relates to novel quinolone compounds of Formula(I) and thier pharmaceutically acceptable salts. wherein, R 1 is hydrogen or protective group, R 2 is hydrogen, amino, alkylamino from one to four carbon atoms, hydroxy, alkoxy from one to four carbon atoms, mercapto, alkylthio from one to four carbon atome, or halogen, R 3 is alkyl from one to four carbon atoms, alkenyl from two to four carbon atoms, cycloalkyl from three to six carbon atoms, haloalkyl, hydroxyalkyl from two to four carbon atoms, methoxy, amino, alkylamino from one to two carbon atoms, dimethylamino, or optionally substituted phenyl with more than one of halogen atoms or alkyl from one to three carbon atoms, Z is an amine of the following Formula, (wherein, R 4 is hydrogen or alkyl from one to four carbon atoms, R 5 and R 7 are, same or different, hydrogen or alkyl from one to two carbon atoms) X is N or C-R 6 (wherein, R 6 is hydrogen, hydroxy, methyl, cyano, nitro, methoxy, halogen, or can form a bridge of the following Formula with R 3 ; NH - CH 2 - CH - CH 3 , 0 - CΑ l - CΑ- CΑ 3 , S - CHj - CH- CH,, or - CIL, - OE^ - CH - CH 3 ). This invention includes a process for preparing a compound of the above Formula(I) by reacting a compound of Formula(II) with a compound of Formula (III) in the presence of a solvent and a base. ( m ) ( π ) wherein, R 1 , R 2 , R 3 , X and Z are as defined above, and Y is halogen. DETAILED DESCRIPTION OF THE INVENTION The novel quinolone compound of the above Formula(I) in accordance with this invention has excellent antimicrobial activity both against gram positive and negative bacteria. The compound of Formula(I) in this invention is characterized by introducing Z group, a novel 3,6-diazabicyclo[3.1.0] hexane derivative of the following Formula. wherein R 4 , R 5 and R 7 are as defined above, at -position of quinolone nucleus. This invention also relates to the process for preparing a compound of Foιmula(ι) by reacting 3-quinolinecarboxylic acid derivative of Formula(II) with 3,6-diazabicyclo[3.1.0] hexane derivative of Formula(III) in the presence or absence of solvent at a temperature of 15 to 30012 , l o wherein R 1 , R 2 , R 3 , Z, and X are as defined above, Y is halogen, and to the phamiaceutical composition containing one or more of the compound of Formula® or its pharmaceutically acceptable salt as an active ingredient More particularly, the compound of Formula(I) is easily prepared by reacting a compound of FormulaQI) with an amine of Foιmula(πi) according to the 5 following scheme, 0 ( m ) ( H ) 5 ( I ) wherein, R 1 , R 2 , R 3 , Z, X, and Y are as defined above. A compound of Formula(II) can be prepared according to the reported methods or applying them, for example, Chem. Pharm. Bull., 34(10), 4098- 4102(1986), J. Med. Chem., 30(3), 504-509(1987), U.S .Patent No. 4,885,386, E.P. Publication No. 235,762, J.RPublication No. 7203085, G.B. Patent No. 2,057,440, and so on. A novel amine compound of Formula(III) is prepared in three ways according to the following reaction schemes. [ Scheme A ] 2R H 2 - H 2 SO 4 , heat ( m-6 ) ( πi ) wherein, R 5 and R 7 are as defined above, R is amino protective group which can be removed by acid or base hydrolysis, or catalytic hydrogenation, and R' is alkyl from one to four carbon atoms or amino protective group. In the reaction sequence of Scheme A, the maleimide compound of Forniula(ni-3) is obtained by reacting maleic anhydride compound of Formula(JII- 1) with benzylamine derivatives (R-NH 2 ) and cyclizing the mixture of maleamic acid(πi-2a + III-2b) with acetic anhydride-sodium acetate system, or by in situ reaction of maleic anhydride compound of Formula(III-l) with benzylamine devivatives(R-NH 2 ) and bisbenzylammonium sulfate. 1,3-Dipolar cycloaddition of (πi-3) with alkyl azide(R ! -N 3 ) affords a mixture of triazoline compounds(QI-4a + m-4b). Subsequent thermolysis or photolysis reaction of the above mixture affords a compound of Foιmula(HI-5) which the pyrrolidine ring and aziridine ring are fused together. Reduction of (Ht-5) using lithium aluminium hydride affords a compound of Formula(m-6) which is deprotected by hydrolysis or hydrogenolysis to give a novel amine compound of Formula(III). [ Scheme B ] (m-9) (m-io) (m-iia) (m-iib) ι o DEAD (m-6) (m) 0 wherein, X' is halogen such as chloro or bromo, R, R 4 , and R 5 are as defined above. In the reaction sequence of Scheme B, a compound of Formula(LII-8) (in the 5 case of R 5 =H, it is commercially available, but in the case of R 5 =alkyl, it is prepared from (III- 1) through reduction and halogenation) is cyclized using an amine(R 4 -NH 2 ) to afford a compound of Foιmula(HI-9). 3-Pyπroline derivative (III-9) is reacted with chlorine gas, and the resulting chlorohydrine intermmediate is cyclized with base to obtain an epoxide compound of Formula(iπ-10). Reaction of (IE- 10) with an amine (R -NH 2 ) affords a mixture of amino alcohols (Iϋ-lla+III-llb), which is subsequently cyclized to aziridiπe compound of Formula(III-6) with diethylazodicarboxylate(DEAD) and triphenylphosphine(Ph 3 P) . Deprotection of (R-6) finally affords a novel amine compound of Formula(m). [ Scheme C] (m-io) ( -12a) (m-12b) (m-13a) (HI-13b) reduction R 4 deprotection N„ _R 5 deprotection H ( ) wherein, R' is an amino protective group, X" is a leaving group such as halogen, methanesulfonyl oxy, p-toluene-sulfonyloxy, diethylphosphoryl oxy, diethylthiophosphoryloxy, acetoxy, or alkoxy, R, R\ and R 5 are as defined above. In the reaction sequence of Scheme C, a compound of Formula(III-lO) is reacted with sodium azide(NaN 3 ) to obtain a mixture of azido alcohols (III-12a-r-III- 12b), which is subsequently derivatized to a mixture of compounds (III-13a+m- 13b) having good leaving group. Reduction of the above mixture affords an aziridine compound of Formula(III-6a). A compound of Foιmula(III-6a) is directly deprotected or another protective group is introduced at aziridine ring followed by selective deprotection to afford a novel amine compound of Formula(III). Thereafter, a compound of Formula(I) is prepared by reacting a compound of Formula(II) with an amine of Formula(III). Examples of proper reaction solvents include tetrahydrofuran, dimethylsulfoxide, N,N-dimethylformamide, N,N- dimethylacetamide, N-methylpymolidone, acetonitrile, water, alcohol(for example, methanol, ethanol, n-propanol, or iso-propanol), glycol monomethyl ether, pyridine, or a mixture of them. This reaction can be carried out in the absence of solvent, but it is desirable to add some base in the reaction mixture if the solvent is not a basic solvent(ex. pyridine). The base promotes the completion of reaction by reacting with hydrohalide formed from the reaction mixture. Typical inorganic or organic base such as alkali metal hydroxide, alkali metal carbonate, organic amine and amidine, especially, triethylamine, 1,4- diazabicyclo[2.2.2] octane(DABCO), 1 ,8-diazabicyclo[5.4.0]unde-7-cene(DBU), l,5-diazabicyclo[4.3.0] non-5-ene(DBN), or excess amount of amine(III) can be desirably used. This reaction can be carried out at a temperature of 15 ~ 30012 , desirably at 60 ~ 12012 or reflux temperature of the solvent. This reaction can be carried out for several days, desirably for 1 ~ 24 hr. Typically, the higher reaction temperature reduces the reaction time. The amine compound of Formula(III) can be used in the reaction in the form of an inorganic or organic salt. Some examples of inorganic or organic salt include hydrochloride, hydrobromide, sulfate, formate, acetate and oxalate. In addition, one to six equivalent of amine compound of Formula(III) against quinoline carboxylic acid of Formula(II) is desirably used. It has been proved form the following in vitro tests that the compounds of general Formula© in this invention possess potent antibacterial activity against a wide spectrum of gram positive and gram negative bacteria. The compounds of the invention are therefore useful in the antibiotic treatment of susceptible bacterial infections in both humans and animals. In addition, the compounds may be used in scrub solutions, for surface inhibition of bacterial growth, e.g., on counter surfaces, and the like. Susceptible organisms generally include those gram positive and gram negative, aerobic and anaerobic organisms whose growth can be inhibited by the compounds of the invention, such as Staphylococcus, Lactobacillus, Streptococcus, Sarcina, Escherichia, Enterobacter, Klebsiella, Pseudomonas, Acinetobacter, Proteus, Citrobacter, Nisseria, Baccullus, Bacteroides, Peptococcus, Clostridium, Salmonella, Schigella, Serratia, Haemophilus, Brucella, and other organisms. The in vitro activity spectrum of the compounds according to this invention was measured by two fold agar-dilution method using Mueller-Hinton agar. According to the standard procedure recommended by Japanese Society of Chemotheraphy[Chemotheraphy, 29(1), 76-79(1981)], an overnight culture of test organisms which was diluted for each bacterial inoculum to be contained about 10 4 colony forming unit (10 6 cells ώ) was inoculated onto drug-containing agar, and incubated for 18hr at 37 . The MIC was defined as the lowest drug concentration which prevented visible bacterial growth. The MIC of compounds according to the invention is listed in Table 1 compared with ciprofloxacin, and the test compounds are denoted as the number of Examples. Test organisms 1. Streptococcus pyogenes 308 A 2. Streptococcus pyogenes Ilk 3. Streptococcus faecium MD 86 5 4. Staphylococcus auieus SG511 5. Staphylococcus auieus 285 6. Staphylococcus auieus 503 7. Escheπchia coli 055 8. Escheπchia coli DCO ι o 9. Escheπchia coli DC2 10. Escheπchia coli TEM 11. Escheπchia coli 1507E 12. Pseudomonas aeruginosa 9027 13. Pseudomonas aeruginosa 1592E 15 14. Pseudomonas aeruginosa 1771 15. Pseudomonas aeruginosa 1771M 16. Salmonella typhimuπum 17. Klebsieϋa oxytoca 1082E 18. Klebsiella aerogenes 1522E 0 19. Entewbacter cloacae P99 20. Entewbacter cloacae 1321E 5 Table 1. MIC Gug/røZ) values measured by agar dilution method. Table 1. continued Table 1. continued Table 1. continued Table 1. continued Table 1. continued Table 1. continued Table 1. continued Some pharmacokinetic parameters of the compound according to thi invention was measured in mouse. Test compound was administered orally and subcutaneously to ICR mous weighed about 18g as 40mg/kg of dose, collected serum after 10, 20, 30, 45, 60, 90 120, 150, 180, 240 min and urine for 24 hr after administration. The pharmacokinetic parameters were determined by bioassay using E. col 055 as a standard organism, and the results are denoted in Table 2. Table 2. Pharmacokinetic parameters in mouse PO : per os SC : Subcutaneous Cmax : maximum concentration in serum Tmax : time for maximum concentration in serum T 1/2 : serum half life AUC : area under curve UR : urinary recovery In the one hand, the compounds of Formula© according to this invention are capable of forming pharmaceutically acceptable salts, herein the term "pharmaceutically acceptable salts" means nontoxic acid addition and base salts formed by alkali metal, alkaline earth metal, or organic amines. These salts can be prepared in situ during the final isolation and purification of the compounds of Formula©, or by separately reacting the base or acid functions with a suitable organic or inorganic acid or base, respectively. Representative acid addition salts in this case include hydrochloride, hydrobromide, sulfate, bisulfate, formate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, p-toluenesulfonate, methanesulfonate, citrate, maleate, fumarate, succinate, tartarate, and ascorbate, and representative alkali metal and alkali earth metal salts include sodium, potassium, calcium, and magnesium salts. In addition, examples of suitable organic amines are N,N'-dibenzyl- ethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N- methylglucamine, and procaine. Among the term, protective group, in this invention, carboxyl protective group is intended to include all the reported protective groups such as alkyl of from one to four carbon atoms, cycloalkyl of from three to seven carbon atoms and benzyl group, and amino protective group include acyl, alkoxycarbonyl, (substituted)sulfonyl, (substituted) benzyloxycarbonyl, (substituted)benzyl, and so on. The term, alkyl, is intended to include both straight and branched carbon chains such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, t-butyl, and so on, alkenyl also include both straight and branched carbon chains such as ethenyl, propenyl, iso-propenyl, and so on. The term, haloalkyl, is intended to include alkyl group substituted with more than one halogen atom which is same or different, and the term, halogen, include fluorine, chlorine, bromine and iodine. Certain compounds of the invention exist in optically active form, especially pure D isomer, pure L isomer as well as mixtures thereof ; including racemic mixtures, meso-isomer, dl-isomer, diastereomeric mixtures, are contemplated by the invention. Asymmetric caibon atoms may be present in a substituent such as an alkyl group or fused caibon atoms, but all such isomers as well as mixtures thereof are intended to be included in the invention. The representative compounds of Formula© according to this invention are illustrated in the following. (1) l-Cyclopropyl-6-fluoro-7-(6-methyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)- 1 ,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (2) l-Cyclopropyl-6,8-difluoro-7-(6-methyl-3,6-diazabicyclo[3.1.0]hexan-3- yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salt. (3) 5-Amino-l-cyclopropyl-6,8-difIuoro-7-(6-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxyIic acid and its salts. (4) l-Cyclopropyl-6-fluoro-7-(6-methyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)- l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid and its salts. (5) 6,8-Difluoro-l-(2,4-difluorophenyl)-7-(6-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (6) l-Cyclopropyl-8-chloro-6-fluoro-7-(6-methyl-3,6-diazabicyclo[3.1.Ojhexan- 3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (7) 9-Fluoro-2,3-dihydro-3-methyl-10-(6-methyl-3,6-diazabicyclo[3.1.0]hexan- 3-yl)-7-oxo-7H-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acid and its salts. (8) l-Cyclopropyl-6-fluoro-8-methoxy-7-(6-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yI)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (9) l-Cyclopropyl-6-fluoro-7-(l,6-dimethyl-3 ,6-diazabicyclo[3.1.0]hexan-3- yl)-l,4-dihydro-4-oxo-l,8-naphthyridine-3-.carboxylic acid and its salts. (10) l-Cyclopropyl-6-fluoro-7-(l,6-dimethyl-3,6-diazabicyclo[3.1.0]hexan-3- yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (11) 5-Amino-l-cyclopropyl-6,8-difluoro-7-(l,6-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (12) 9-Fluoro-2,3-dihydro-3-methyl-10-(l ,6-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-7-oxo-7H-pyrido[l ,2,3-de]-l ,4-benzoxazine-6- carboxylic acid and its salts. (13) l-Cyclopropyl-6-fluoro-8-methoxy-7-( l,6-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (14) l-Cyclopropyl-6,8-difluoro-7-(l,6-dimethyl-3,6-diazabicyclo[3.1.0]hexan- 3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (15) l-Cyclopropyl-8-chloro-6-fluoro-7-(l ,6-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (16) l-Cyclopropyl-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6-fluoro-l,4-dihydro- 4-oxo-l,8-naphthyridine-3-carboxylic acid and its salts. (17) l-Cyclopropyl-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6-fluoro-l,4-dihydro- 4-oxo-3-quinolinecarboxylic acid and its salts. (18) l-Cyclopropyl-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6,8-difluoro-l ,4- dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (19) l-Cyclopropyl-8-chloro-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6-fluoro-l,4- dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (20) 5-Amino-l-cyclopropyl-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6,8-difluoro- l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (21) 7-(3,6-Diazabicyclo[3.1.0]hexan-3 -yl)-6 ,8-difluoro- 1 -ethyl-1 ,4-dihydro- 3- quinolinecarboxylic acid and its salts. (22) 9-Fluoro-2,3-dihydro-3-methyl-10-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-7- oxo-7H-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acid and its salts. (23) l-Cyclopropyl-6,8-difluoro-7-(l-methyl-3,6-diazabicyclo[3.1.0]hexan-3- yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. 5 (24) l-Cyclopropyl-8-chloιo-6-fluoro-7-(l-methyl-3,6-diazabicyclo[3.1.0]hexan- 3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (25) 5-Amino-l-cyclopropyl-6,8-difluoro-7-(l-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts, l o (26) l-Cyclopropyl-6-fluoro-7-(l-methyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)- l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid and its salts. (27) l-Cyclopropyl-6-f luoro-7-(l-methyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)- l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (28) 9-Fluoro-2,3-dihydro-3-methyl-10-(l-methyl-3,6-diazabicyclo[3.1.0]hexan- 5 3-yl)-7-oxo-7H-pyrido[ 1 ,2,3-de] - 1 ,4-benzoxazine-6-carboxylic acid and its salts. (29) 6,8-Difluoro-l-(2,4-difluorophenyl)-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)- l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (30) 6,8-Difluoro-l-(2,4-difluorophenyl)-7-(l-methyl-3,6-diazabicyclo 0 [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (31) 6,8-Difiuoro- l-(2,4-difluorophenyl)-7-(l ,6-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. 5 (32) l-Cyclopropyl-6,8-difluoro-7-(l,5-dimethyl-3,6-diazabicyclo[3.1.Ojhexan- 3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (33) l-Cyclopropyl-8-chloro-6-fluoro-7-(l,5-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (34) ό-Amino-1 -cyclopropyl-6,8-difluoro-7-(l ,5-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (35) l-Cyclopropyl-7-(l,5-dimethyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)-6- fluoro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid and its salts. (36) l-Cyclopropyl-7-( l,5-dimethyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)-6- fluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (37) l-Ethyl-7-(l,5-dimethyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)-6,8-difluoro- l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (38) 9-Fluoro-2,3-dihydro-3-methyl-10-(l ,5-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-7-oxo-7H-pyrido[l ,2,3-dej-l ,4-benzoxazine-6- carboxylic acid and its salts. (39) 6,8-Difluoro-l-(2,4-difluorophenyl)-7-(l,5-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)- 1 ,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (40) l-Cyclopropyl-6,8-difluoro-7-(l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (41) 8-Chloro-l-cyclopropyl-6-fluoro-7-( l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (42) 5-Amino-l-cyclopropyl-6,8-difluoro-7-(l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (43) l-Cyclopropyl-6-flouro-7-(l,5,6-trimethyl-3,6-diazabicyclo[3.1.0]hexan-3- yl)-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid and its salts. (44) l-Cyclopropyl-6-fluoro-7-(l,5,6-trimethyl-3,6-diazabicyclor3.1.0]hexan-3- yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. (45) l-Enthyl-6,8-difluoro-7-(l ,5,6-trimethyl-3,6-diazabicyclo[3.1.0]hexan-3- yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its salts. The compounds of this invention may also be formulated into compositions together with pharmaceutically acceptable carriers for parental injection, for oral administration in solid or liquid form, for rectal administration, for ointment, and the like. Compositions according to the invention for parental injection may comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, suspensions or emulsions. Examples of suitable nonaqueous carriers, diluents, solvents or vehicles include propylene glycol, polyethylene glycol, vegetable oils, such as olive oil or sesame oil, and injectable organic esters such as ethyl oleate. Such compositions may be sterilized, for example, by filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is admixed with at least one inert carrier such as sucrose, lactose, dicalcium phosphate, cellulose, pectin, dextrin, gelatin or starch. Such dosage forms can also comprise, as in normal practice, additional substances other than inert solid carriers, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, and syrups containing inert diluents commonly used in the art, such as water. Besides such inert diluents, compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and perfuming agents. Compositions for rectal administration are preferably suppositories which may contain, in addition to active substance, excipients such as cocoa butter or a suppositiony wax. Ointment preparations contain metal salts of a compound of Formula© with a pharmaceutically acceptable carrier. The carrier is desirably a conventional water-dispersible hydrophilic or oil-in-water carrier, particularly a conventional semi-soft or cream-like water-dispersible or water-soluble, oil-in- water emulsion which may be applied to an affected burn surface or infected surface with a minimum of discomfort. Suitable compositions may be prepared by merely incorporating or homogeneously admixing finely divided compounds with the hydrophilic carrier or base or ointment. Actual dosage levels of active ingredient in the compositions of the invention may be varied so as to obtain an amount of active ingredient effective to achieve antibacterial activity in accordance with the desired method of administration. The selected dosage level therfore depends upon the nature of the active compound administered, the route of administration, the desired duration of , treatment and other factors. Generally, daily dosage levels of the compounds of Foimula© of about 0.5 to about 500mg of active ingredient per kg of body weight are effective when administered orally to a mammalian patient suffering from an infection caused by a susceptable organism. If desired, the daily dose may be divided into multiple doses for administration, e.g., two or four times per day. The following examples illustrate this invention in more detail, but are not to be construed as limiting its scope. Preparation 1 N-Benzylmaleamic Acid To a stirred solution of 9.8g(0.10 M) of maleic anhydride in 150?πZ of methylene chloride was added 10.7g(0.10 mole) of benzylamine as dropwise for 30 min at room temperature. The reaction mixture was stirred for 3hr at room temperature, filtered, washed with methylene chloride, and dried to afford 17.8g(yield : 87%) of titled compound as a white crystalline solid, m. p. : 135 ~ 13612 1 H-NMR(CDC1 3 ) : S 4.2(s, 2H), 6.0 ~ 7.9,(m, 7H), 9.7(s, 1H), 13.0 ~ 16.0(broad s, 1H). Preparation 2 N-Benzylmaleimide 5 A mixture of 5g(24 mM) of N-benzylmaleamic acid and 1.2g of sodium acetate in 12ml of acetic anhydride was stirred for 1.5 hr at 95 ~ 10012. The reaction mixutre was poured into 50g of crushed ice and stirred mechanically for 2hr. Aqueous layer was decanted, 500a_Z of ether was added to the dark- l o brownish residue, and stirred for 20 min. The insoluble dark-brownish solid was removed by filtration, and the filtrate was washed with saturated sodium bicarbonate solution, dried over magnesium sulfate, and evaporated in vacuo. The residue was recrystallized from methanol, and afforded 2g(yield : 44%) of titled compound as a light yellow crystalline solid. 5 m. p. : 67 - 6812 Η-NIVEKCDO,) : δ 4.6(s, 2H), 6.6(s, 2H), 7.3(s, 5H). Preparation 3 2-Methyl-2,3,4,7-tetraazabicyclo[3.3.0]-oct-3-en-6,8-dione To a 1 1 3-neck flask equipped with thermometer, dropping funnel and 0 condenser were added 8.46g(0.13M) of sodium azide and 21g of NaHC0 3 - NA2C0 3 (1 : 1 mole ratio) in 480 ml of H 2 0, and heated in an oil bath. In another vessel was dissolved 4g(21.4mM) of maleimide in 100ml of toluene and cooled to - 50 ~ -7812 in a dry ice-acetone bath. The two vessels were connected by glass tube in order for the methyl azide gas evolved to be transferred into the N- 5 benzylmaleimide solution, and NaOH trap was connected between them. To the basic solution was dropped 37.2JBZ(0.4M) of dimethyl sulfate for 40min at 75 ~ 8512 and removed the dry ice-acetone bath from the reaction solution. The reaction mixture was stood overnight at room temperature, and evaporated in vacuo. The residue was filtered, washed with ether, and dried in vacuo to afford 4.8g (yield : 93%) of titled compound as a white crystalline solid. m. p. : 13912 Η-NMR CDC^) : δ 3.4(s, 3H), 4.1(d, 1H, J=12.0Hz), 4.6(s, 2H), 5.4(d, 1H, J=12.0Hz), 7.2(s, 5H). Preparation 4 3-Benzyl-6-methyl-3,6-diazabicyclo[3.1.0]hexan-2,4-dione [ Method 1 : Photolysis reaction ] To a 500ml of quartz reactor was added 4.0g(12.3mM) of 2-methyl-2,3,4,7- tetraazabicyclo[3.3.0]-oct-3-en-6,8-dione in 300ml of 1,4-dioxane and N 2 gas was bubbled for 15 min. The reaction solution was irradiated with 254nm UV lamp for 4hr. The solvent was evaporated in vacuo, and the residue was rccrystallized from isopropyl ether to afford 2.2g(yield : 62%) of titled compound as a light yellow solid. m. p. : 78 - 8012 l H-NMR(CDC_ 3 ) : δ 2.4(s, 3H), 2.8(s, 2H), 4.5(s, 2H), 7.3(s, 5H). [ Method 2 : Thermolysis reaction ] A mixture of 13.7g (56.1 mM) of 2-methyl-2,3,4,7-tetraazabicyclo[3.3.0] oct-3-en-6,8-dione in 300ml xylene(mixture of ortho-, meta- and para-isomer) was heated to reflux for 7hr. Xylene was evaporated in vacuo, the residue was partly purified by column chromatography (Eluent ; ethyl acetate : n-hexane = 1 : 3), and further purified by 3 to 4 times of reciystallization from isopropyl ether to afford 3.6g (yield : 30%) of titled compound as a light yellow solid. m.p. and Η-NMR data are same as in method 1. Preparation 5 3-Benzyl-6-methyl-3,6-diazabicyclo[3.1.OJhexane To a stirred solution of 1.76g (46.3mM) of lithium aluminium hydride in 50 ml of dry tetrahydrofuran was added as dropwise 5g(23.1mM) of 3-benzyl-6- methyl-3,6-diazabicyclo[3.1.0] hexane-2,4-dione in 15mZ of dry tetrahydrofuran at room temperature. The reaction mixture was heated to reflux for 3hr, cooled in an ice bath, and added 0.85τπZ of water, 0.85 ml of 15%-KOH solution, and 2.5τπZ of water, 5 successively. Tetrahydrofuran was evaporated in vacuo, and the residue was extracted with 100ml of chloroform. The chloroform extract was washed with saturated sodium chloride solution, dried, filtered, and evaporated in vacuo to afford 4.0g of brownish residue. The residue was purified by column chromatopraphy(Eluent ; ethanol : ethyl o acetate = 1 : 4), and afforded 1.44g(yield : 33%) of titled compound as a yellow oil. Η-NMR(CDCl 3 ) : δ 2.0(s, 2H), 2.2(s, 3H), 2.3(dd, 2H), 3.1(d, 2H, J=12.0Hz), 3.6(s, 2H), 7.3(s, 5H). Preparation 6 6-Methyl-3,6-diazabicyclo[3.1.0]hexane • acetate A mixture of l.Og (5.3 mM) of 3-benzyl-6-methyl-3,6-diazabicyclo[3.1.0] hexane, 0.32g (5.3mM) of acetic acid and l.Og of 10% Pd-C catalyst in 100mZ of methanol was hydrogenated for Ihr at room temperature under 60 psi of H 2 pressure. The reaction mixutre was filtered through celite pad, and evaporated in vacuo to afford 0.78g(yield : 93%) of titled compound as a pale brown semi-solid. Η-NMR^DCL,) : δ 2.0(s, 3H), 2.1(s, 2H), 2.3(s, 3H), 2.8(d, 2H, J=12.0Hz), 3.2(d, 2H, J=12.0Hz), 7.4(s, 1H), 8.2(broad s, 2H). Preparation 7 Mixture of 2-methyl-5-benzylmaleamic acid and 3-methyl- 5-benzylmaleamic acid (1 : 1 mixture) To a stirred solution of 11.2g (0.1M) of citraconic anhydride in 150ml of methylene chloride was added 10.7g(0.10M) of benzylamine as dropwise for 30min at room temperature. The reaction mixture was stirred for 3hr at room temperature, filtered, washed with 50ml of methylene chloride, and dried to afford 17.6g (yield : 80%) of titled compound as a white crystalline solid. m. p. : 103 - 10512 Η-NMR(DMSO-d 6 ) : δ 1.9(s, 3H), 4.3(d, 2H), 5.7(s, 1/2H), 6.1(s, 1/2H), 7.3(s, 5H), 8.5(broad s, 1/2H), 8.9(broad s, 1/2H). 5 Preparation 8 l-Benzyl-3-methylmaleimide A mixture of 8g(36.5 mM) of 2- and 3-methyl-5-benzylmaleamic acid(l : 1 mixture, compound of preparation 7) and 1.6g of sodium acetate in 16ml of acetic anhydride was stirred for lhr at 100 - 11012. The reaction mixture was poured o into 60g of crushed ice, and stirred mechanically for lhr. Aqueous layer was decanted, 500ml of ether was added to the dark- brownish residue, and stirred for 10 min. The insoluble dark-brownish solid was removed by filtration, and the filtrate was washed with saturated sodium bicarbonate solution, dried over magnesium sulfate, and evaporated in vacuo. 5 The residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 2.9g (yield : 40%) of titled compound as a yellow oil. Η-NMR(CDC1 3 ) : £ 2.0(s, 3H), 4.6(s, 2H), 6.3(s, 1H), 7.3(s, 5H). 0 Preparation 9 Mixture of l,2-dimethyl-2,3,4,7-tetraazabicyclo[3.3.0] oct- 3-en-6,8-dione and l,4-dimethyl-2,3,4,7-tetraazabicyclo [3.3.0] oct-3-en-6,8-dione To a 3 I 3-neck flask equipped with thermometer, dropping funnel and condenser were added 56.2g(0.86M) of sodium azide and 86.4g of NaHCO 3 - Na^O^l : 1 mole ratio) in 1.8 I of H 2 O, and heated in an oil bath. In another vessel was dissolved 18g(89.6mM) of 1 -benzyl-3-methyl maleimide in 360ml of toluene and cooled to -50 - -7812 in a dry ice- acetone bath. The two vessels were connected by glass tube in order for the methyl azide gas evolved to be transferred into the maleimide solution, and NaOH trap was connected between them. To the basic solution was dropped 203g(1.6M) of dimethyl sulfate for lhr 20 min at 75 — 85O and removed the dry ice-acetone bath from the reaction solution. The reaction mixture was stood overnight at 80 - 85 2 and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 21g (yield : 91 %) of titled compound as a pale yellow solid. m. p. : 86 - 8812 Η-NMR(CDCl 3 ) : δ 1.5(s, 3/5 x 3H), 1.6(s, 2/5 x 3H), 3.3(s, 3/5 x 2H), 3.4(s, 2/5 x 2H), 3.8(s, 2/5 x 1H), 4.6(s, 2H), 5.1(s, 3/5 x 1H), 7.3(s, 5H). Preparation 10 3-Benzyl-l,6-dimethyl-3,6-diazabicyclo[3.1.0]hexan-2,4- dione [ Method 1. Photolysis reaction ] To a 500zπ of Quartz reactor was added 4.0g(ϊl.6mM) of triazoline compound(preparation 9) in 300n-Z of 1,4-dioxane and N 2 gas was bubbled for 15 min. The reaction solution was irradiated with 254nm UV lamp for 6hr. The solvent was evaporated in vacuo, and the residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3) to afford 2.3g(yield : 65%) of titled compound as a pale yellow crystalline solid, m. p. : 79 - 8112 Η-NMR(CDCl 3 ) : δ 1.5(s, 1/4 x 3H), 1.6(s, 3/4 x 3H), 2.3(s, 1H), 2.4(s, 3/4 x 3H), 2.5(s, 1/4 x 3H), 4.6(s, 2H), 7.3(s, 5H). [ Method 2. Thermolysis reaction ] A mixture of lO.Og (29mM) of triazoline compound (preparation 9) in 300 ml of diphenyl ether was stirred for 6hr at 170 - 180 , and evaporated in vacuo to remove diphenyl ether. The residue was purified by column chromatogrphy(Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 6.7g(yield : 75%) of titled compound as a light yellow solid. m. p. and 'H-NMR date are same as in method 1. Preparation 11 3-Benzyl-l ,6-dimethyl-3,6-diazabicyclo[3.1.0]hexane To a stirred solution of 2.0g (52.6mM) of lithium aluminium hydride in 100 ml dry tetrahydrofuran was added as dropwise 5.0g (21.7mM) of 3-benzyl-l,6- dimethyl-3,6-diazabicyclo[3.1.0]hexan-2,4-dione in 25ml of dry tetrahydrofuran at room temperature. The reaction mixture was heated to reflux for 3hr, cooled in an ice bath, and added 0.85τπZ of water, 0. \5ml of 15%-KOH solution, and 2.5ml of water, successively, at about 1012. Tetrahydrofuran was evaporated in vacuo, and the residue was extracted with 100 l of chloroform. The chloroform extract was washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated in vacuo. The yellow residue was purified by column chromatography(Eluent ; ethanol : ethyl acetate = 1 : 4), and afforded 2.2g (yield : 50%) of titled compound as a light yellow oil. Η-NMR(CDCl 3 ) : δ 1.3(s, 3H), 1.7(s, 1H), 2.1 ~ 2.6(m, 2H), 2.3(s, 3H), 2.8 - 3.2(m, 2H), 3.6(s, 2H), 7.3(s, 5H). Preparation 12 l,6-Dimethyl-3,6-diazabicyclo[3.1.0]hexane • acetate A mixture of 1.0g(5.0mM) of 3-benzyl- l,6-dimethyl-3,6-diazabicyclo [3.1.0]hexane, 0.30g(5.0mM) of acetic acid and l.Og of 10% Pd-C catalyst in 100 ml of methanol was hydrogenated for 1.5hr at room temperature under 60 psi of H 2 pressure. The reaction mixture was filtered through celite pad, and evaporated in vacuo to afford 0.80g(yield : 95%) of titled compound as a light yellow semi-solid. Η-NMR(CDα,) : δ I.3(s, 3H), 1.9(s, 4H), 2.3(s, 3H), 2.9(dd, 4H, J=12Hz), 8.5(s, 1H). Preparation 13 l-Benzyl-3-pyrroline To a stirred solution of 12.5g(0.10M) of cis-l,4-dichloro-2-butene in ΛOOml of benzene was added 33.2g(0.31M) of benzyl amine as dropwise at room temperature. The reaction mixture was stirred for 1 hr and stood overnight. The solid was removed by filtration, and filtrate was washed with water, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography (Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 13.5g(yield : 85%) of titled compound as a light yellow oil. Η-NMR^DCL,) : δ 3.4(s, 4H), 3.7(s, 2H), 5.8(s, 2H), 7.2(s, 5H). Preparation 14 l-Benzyl-3,4-epoxypyrrolidine To a stirred solution of 16g(0.1M) of l-benzyl-3-pyrroline in 100ml of water and 10ml of cone, hydrochloric acid was bubbled chlorine gas for 30min at room temperature. The pH of the solution was adjusted to 9 - 10 with 20%- NaOH solution, extracted with 500M * of methylene chloride, and evaporated in vacuo. To the residue was added 100ml of 20%-NaOH solution, and the resulting solution was stirred for overnight. It was extracted with 500mZ of methylene chloride, dried, and evaporated in vacuo. The residue was purified by column chromatography (Eluent ; ethyl acetate : n-hexane = 2 : 1), and afforded 11.5g(yield : 66%) of titled compound as a light brownish oil. •Η-NMR CDO,) : δ 2.5(d, 2H, J=12Hz), 3.2(d, 2H, J=12Hz), 3.5(s, 2H), 3.7(s, 2H), 7.3(s, 5H). Preparation 15 l-Benzyl-trans-4-azido-3-hydroxypyrrolidine 5 To a stirred solution of 6.0g (34 mM) of l-benzyl-3,4-epoxypyrrolidine in 100ml of acetone and 100ml of distilled water was added 13.4g(0.21M) of sodium azide at room temperature. The reaction mixture was refluxed overnight, extracted with 2 x 200ml of chloroform, and dried over magnesium sulfate. It was filtered, evaporated in vacuo, and purified by column ι o chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 1) to afford 6.8g (yield : 92%) of titled compound as a dark brownish oil. Η-NMR CDCt,) : δ 2.1 - 3.3(m, 5H), 3.6(s, 2H), 3.5 - 3.9(m, 1H), ' 4.1 ~ 4.3(m, 1H), 7.3(s, 5H). 15 Preparation 16 l-Benzyl-trans-4-azido-3-mesyloxy-pyrrolidine To a stirred solution of 5.0g (23mM) of l-benzyl-trans-4-azido-3- hydro xypyrrolidine in 150ml of dry benzene was added 3.0g(30mM) of triethylamine in an ice-bath, and added 3.2g(28mM) of methanesulfonyl chloride in 20ml of dry benzene as dropwise for lOmin. 0 The reaction mixture was stirred for 2hr, and added 1 ml of water to it, transferred to separatoiy funnel, and washed with water. The benzene layer was collected, dried, and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 6.4g(yield : 95%) of titled compound as a dark brownish oil. 5 Η-NMRζCDClg) : δ 2.4 - 3.2(m, 4H), 3.0(s, 3H), 3.6(s, 2H), 3.9 - 4.2(m, 1H), 4.8 ~ 5.1(m, 1H), 7.3(s, 5H). Preparation 17 3-Benzyl-3,6-diazabicyclo[3.1.0]hexane To a stirred solution of l.Og (3.4mM) of l-benzyl-trans-4-azido-3- mesyloxypyirolidine in 30ml of dry ether was added 0.25g(6.8mM) of lithium aluminium hydride as portionwise at room temperature. 5 The reaction mixture was stirred for 2hr at room temperature, and added 0.15ml of water, 0.5ml of 15%-KOH solution, 0.5ml of water, and 20ml of ether- acetone^ : 1, v/v), successively. The resulting solution was filtered, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethanol : ethyl l o acetate = 1 : 3), and afforded 0.5g (yield : 85%) of titled compound as a yellow oil. Η-NMR(CDCl 3 ) : δ 1.8(broad s, 1H), 2.3(d, 2H, J=10Hz), 2.4(s, 2H), 3.1(d, 2H, J=10Hz), 3.6(s, 2H), 7.2(s, 5H). Preparation 18 3,6-Diazabicyclo[3.1.0]hexane 5 A mixture of 0.5g (2.9mM) of 3-benzyl-3,6-diazabicyclo[3.1.0]hexane, 170 /4(2.9mM) of acetic acid and 0.5g of 10% Pd-C catalyst in 60ml of methanol was hydrogenated for lhr at room temperature under 50 psi of H 2 pressure. ' - The reaction mixture was filtered through celite pad, evaporated in vacuo and afforded 0.39g of titled compound as a crude acetic acid salt. It was purified 0 by column chromatography(Eluent ; methanol : 40%-methylamine = 24 : 1), and afforded 0.12g(yield : 45%) of titled compound as a colorless oil. Η-NMR(CDC1 3 ) : δ 1.4(s, 2H), 2.5(s, 2H), 2.9(q, 4H, J=12Hz). Preparation 19 3-Benzyl-6-methoxycarbonyl-3,6-diazabicyclo[3.1.0]hexane 5 To a stirred solution of 3.5g(20mM) of 3-benzyl-3,6-diazabicyclo [3.1.0]hexane in 100ml of dry benzene were added 2.4g(24mM) of triethylamine and 2.1g(22mM) of methyl chloroformate in 20mZ of dry benzene as dropwise for 15min at room temperature. The reaction mixture was stirred for 2.5hr at room temperature and filtered. The filtrate was washed with water, dried over magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 4.3g(yield : 92%) of titled compound as a dark brownish oil. 5 Η-NMR^DO,) : δ 2.3(d, 2H, J=10Hz), 2.9(s, 2H), 3.3(d, 2H, J=10Hz), 3.6(s, 2H), 3.7(s, 3H), 7.3(s, 5H). Preparation 20 6-Methoxycarbonyl-3,6-diazabicyclo[3.1.0]hexane A mixture of 1.5g(6.5mM) of 3-benzyl-6-methoxycarbonyl-3,6-diaza- ι o bicyclo[3.1.0]hexane and 0.75g of 10% Pd-C catalyst in lOOnzZ of methanol was hydrogenated for 4.5hr at room temperature under 50 psi of H 2 pressure. The reaction mixture was filtered through celite pad, evaporated in vacuo, and purified by column chromatography (Eluent ; ethanol : ethyl acetate = 1 : 3) to afford 0.60g(yield ; 65%) of titled compound as a white solid. 15 m. p. : 8012 Η-NMR(CDCl 3 ) : £ 1.3(broad s, 1H), 2.7(s, 2H), 3.3(d, 2H, J=12Hz), 3.6(s, 2H), 5.6(d, 2H, J=12Hz). Preparation 21 3,6-Diazabicyclo[3.1.0]hexane • acetate 0 To a stirred solution of 1.5 g (llmM) of 6-methoxycarbonyl-3,6- diazabicyclo[3.1.0]hexane in 35M * of methanol was added 3g of sodium hydroxide, and stirred overnight at 70 - 8012. The reaction mixture was cooled in an ice bath, added 4.5g of acetic acid as dropwise and evaporated in vacuo. The residue was extracted with 100ml of chloroform, and evaporated in vacuo to afford 5 1.34g(yield : 88%) of titled compound as a semi-solid. Η-NMR CDO,) : δ 1.9(s, 3H), 2.7(s, 2H), 3.0(q, 4H, J=12Hz), 3.4(s, 2H), 5.6(broad s, 1H). Preparation 22 cis-l,4-Dihydroxy-2-methyl-2-butene To a stiired solution of 6.7g (0.18M) of lithium aluminium hydride in 300M " of dry tetrahydrofuran was added 10.0g(0.089M) of citraconic anhydride as dropwise at -20 - -1012. The reaction mixture was stiired for lhr at -20 - -1012 , adjusted pH of the solution as 7 - 8 with 30%-H 2 SO 4 solution, filtered, and washed with 300ml of ether-acetone(l : 1, v/v) mixture. The combined filtrate was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethyl acetate), and afforded l.lg(yield : 12%) of titled compound as a yellow oil. Η-NMRtCDCy : δ 1.7(s, 3H), 3.2 - 3.8(m, 2H), 3.9 - 4.2(m, 4H), 5.5(t, 1H, J=8Hz). Preparation 23 cis-l,4-dibromo-2-methyl-2-butene To a stiired solution of l.Og (9.8mM) of cis-l,4-dihydroxy-2-methyl-2- butene and 2.3g(23mM) of triethylamine in 30M * of dry methylene chloride was added 5.9g(22mM) of phosphorous tribromide as dropwise in an ice bath. The reaction mixture was stirred for 1.5hr, added 1M * of water, and transferred it to separatoiy funnel. Organic layer was washed with 10M * of water, separated, and dried. The solution was filtered, evaporated in vacuo, and the residue was purified by column chromatographyCEluent : ethyl acetate : n-hexane = 1 : 4) to afford 1.5g(yield : 67%) of titled compound as a pale yellow oil. Η-NMRζCDCy : δ 1.9(s, 3H), 4.0 ~ 4.2(m, 4H), 5.6(t, 1H). Preparation 24 l-Benzyl-3-methyl-3-pyrroline To a stiired solution of 3.0g(13mM) of cis-l,4-dibromo-2-methyl-2-butene in 120πzZ of benzene was dropped 4.4g(41mM) of benzylamine at room temperature, and stiired for 30min. The resulting solution was stood overnight and the precipitate was removed by filtration. The filtrate was washed with water, dried, and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 1.6g(yield : 70%) of titled compound as a yellow oil. Η-NMR CDCl,) : δ 1.7(s, 3H), 3.4(s, 4H), 3.7(s, 2H), 5.4(s, 1H), 7.3(s, 5H). Preparation 25 l-Benzyl-3,4-epoxy-3-methylpyrrolidine To a stirred solution of 1.0g(5.7mM) of l-benzyl-3-methyl-3-pyrroline in 10 M * f water and 1 ml of cone, hydrochloric acid was bubbled chlorine gas for 20min at room temperature. The pH of the solution was adjusted to 9 - 10 by adding 20%-NaOH solution, extracted with 50ml of methylene chloride, and evaporated in vacuo. To the residue was added 5ml of 20%-NaOH solution and stiired overnight at room temperature. The resulting solution was extracted with 2 x 50 ml of methylene chloride and the extract was dried and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 2 : 1), and afforded 0.68g(yield : 62%) of titled compound as a yellow-brownish oil. Η-NMR CDCla) : <* 1.5(s, 3H), 2.2 - 2.7(m, 2H), 3.9 - 3.3(m, 2H), 3.4(s, 1H), 3.7(s, 2H), 7.3(s, 5H). Preparation 26 Mixture of l-benzyl-trans-4-azido-3-hydroxy-3 methylpyrro- lidine and l-benzyl-trans-4-azido-3-hydroxy-4-methylpyrro- lidine To a stiired solution of 1.0g(5.3mM) of l-benzyl-3,4-epoxy-3-methylpyrro- lidine in 30M * of N,N-dimethylformamide were added 1.0g(15mM) of sodium azide and 0.03g(0.56mM) of ammonium chloride, and stiired overnight at 75 - 8012 . To the reaction mixture was added 30M" of chloroform, filtered, and the filtrate was evaporated in vacuo. To the residue was added 50ml of chloroform again, and filtered. The filtrate was evaporated in vacuo, and the residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 1) to afford 0.92g(yield : 75%) of titled compound as a red-brownish oil. Η-NMR^DO,) : δ 1.3(s, 3H), 2.1 ~ 3.4(m, 5H), 3.6(s, 2H), 3.8 ~ 4.1(m, 1H), 7.3(s, 5H). Preparation 27 Mixture of l-benzyl-trans-4-azido-3-mesyloxy-3-methyl- pyrrolidine and l-benzyl-trans-4-azido-3-mesyloxy-4- methyl pyrrolidine To a stiired solution of 2.0g(8.6mM) of azido alcohol(compound from preparation 26) in 60M * of dry benzene were added l.lg(llmM) of triethylamine and 1.2g(10mM) of metiianesulfonyl chloride in 10ml of dry benzene for 5 min at 0 - 512. The reaction mixture was stiired for 8hr at room temperature, added 0.5 ml of water as dropwise, transferred the solution to separatoiy funnel, and washed with water. Benzene layer was separated, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 5), and afforded 1.7g(yield : 65%) of titled compound as a red- brownish oil. Η-NMR(CD .) : δ 1.4(s, 3H), 2.5 - 3.5(m, 4H), 3.0(s, 3H), 3.6(s, 2H), 4.6 ~ 4.9(m, lH), 7.3(s, 5H). Preparation 28 3-Benzyl-l-methyl-3,6-diazabicyclo[3.1.0]hexane To a stirred solution of 1.0g(3.2mM) of azido mesylate(compound from preparation 27) in 30ml of dry ether was added 0.24g(6.5mM) of lithium aluminium hydride as portionwise at room temperature. The reaction mixture was stiired for 4hr at room temperature, and added 0.15mZ of water, 0.5M * of 15%-KOH solution, 0.5 ml of water, zm&30ml of ether-acetone(l : 1, v/v), successively. The resulting solution was filtered, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography(Eluent ; ethanol : ethyl acetate = 1 : 5), and afforded 0.46g(yield : 76%) of titled compound as a yellow oil. Η-NMR^DO,) : δ 1.2(s, 3H), 1.8(broad s, 1H), 2.2(t, 2H, J=10Hz), 2.9(t, 2H, J=10Hz), 3.6(s, 2H), 7.3(s, 5H). Preparation 29 l-Methyl-3,6-diazabicyclo[3.1.0]hexane • acetate A mixture of 0.5g(2.7mM) of 3-benzyl-l-methyl-3,6-diazabicyclo[3.1.0] hexane, 157/4(2.7mM) of acetic acid and 0.5g of 10% Pd-C catalyst in 60M * of methanol was hydrogenated for 1.5hr at room temperature under 50 psi of H 2 pressure. The reaction mixture was filtered through celite pad, and evaporated in vacuo to afford 0.38g (yield : 91%) of titled compound as an oil. Η-NMR(D 2 0) : δ l.3(s, 3H), 1.8(s, 3H), 2.7(s, 1H), 3.2 - 3.4(m, 4H). Preparation 30 l-Benzyl-trans-3-hydroxy-4-methylaminopyrrolidine To a stiπed solution of 1.0g(5.7mM) of l-benzyl-3,4-epoxypyιrolidine in 5 ml of 1,4-dioxane was added 25 ml of 40%-methylamine solution, and stirred overnight at 40 - 4512. The reaction mixture was evaporated in vacuo, added 30 ml of chloroform to it, dried over magnesium sulfate, and filtered. The filtrate was evaporated in vacuo, and afforded l.lg(yield : 94%) of titled compound as a yellow-brownish oil. Η-NMR(CDCl 3 ) : δ 2.2 - 3.2(m, 7H), 2.3(s, 3H), 3.6(s, 2H), 3.8 ~ 4.1(m, lH), 7.3(s, 5H). Preparation 31 3-Benzyl-6-methyl-3,6-diazabicyclo[3.1.0] hexane To a stirred solution of 2.0g(9.7mM) of l-benzyl-trans-3- hydroxy- 4- methylaminopyirolidine in 25 M * of dry tetrahydrofuran was added 3.1g(12mM) of triphenylphosphine at 0 - 512. To the above solution was added 1.85M" (12mM) of diethylazodicarboxylate(DEAD) and stiired for lhr at 0 - 512 and 7hr at room temperature. The resulting solution was evaporated in vacuo, added 30ml of ethyl acetate-pet. ether(l : 1, v/v) to it, and the precipitate was removed by filtration. The filtrate was evaporated in vacuo, and the residue was purified by column chromatography(Eluent ; ethanol : ethyl acetate = 1 : 3) to afford 1.25g(yield : 69%) of titled compound as a red-brownish oil. Η-NMR^DO,) : δ 2.0(s, 2H), 2.2(s, 3H), 2.3(dd, 2H), 3.1(d, 2H, J=12Hz), 3.6(s, 2H), 7.3(s, 5H). Preparation 32 Mixture of l-Benzyl-trans-4-methylamino-3-hydroxy-3- methylpyrrolidine and l-benzyl-trans-4-methylamino-3- hydroxy-4-methylpyrrolidine To a stiired solution of 1.0g(5.3mM) of l-benzyl-3,4-epoxy-3-methylpyrro- lidine in 5ml of 1,4-dioxane was added 30ml of 40%-methylamine solution and stiired overnight at 50 - 6012. The reaction solution was evaporated in vacuo, added 30ml of chloroform to it, and dried over magensium sulfate. It was filtered and the filtrate was evaporated in vacuo to afford l.lg(yield : 92%) of titled compound as a yellow-brownish oil. Η-NMR^DO,) : δ 1.3(s, 3H), 2.0 - 3.8(m, 7H), 2.4(s, 3H), 3.6(s, 2H), 7.3(s, 5H). Preparation 33 3-Benzyl- 1 ,6-dimethyl-3,6-diazabicyclo[3.1.0]hexane To a stiired solution of 1.0g(4.5mM) of aminoalcohol(compound of preparation 33) in 15ml of dry tetrahydrofuran were added 1.4g(5.5mM) of triphenylphosphine and 0.9mZ(5.7mM) of diethylazodicarboxylate successively at 0 - 512. The reaction solution was stiired for lhr at 0 - 512 and overnight at room temperature. The resulting solution was evaporated in vacuo, added 20ml of ethyl acetate-pet. ether(l : 1, v/y) to it, and the precipitate was removed by filtration. The filtrate was evaporated in vacuo, and the residue was purified by column chromatography(Eluent ; ethanol : ethyl acetate = 1 : 3) to afford 0.61g(yield : 66%) of titled compound as a red-brownish oil. 'H-NMR data is same as in preparation 11. Preparation 34 l-Benzyl-3,4-dimethylmaleimide A suspension of 13.4g(0.14M) of sulfuric acid in 500τnZ of toluene was cooled in an ice-bath, added 14.6g(0.14M) of benzylamine as dropwise to it, and afforded bisbenzylammonium sulfate slurry. In another vessel, 34g(0.32M) of benzylamine was added as dropwise to a solution of 30g(0.23M) of 2,3-dimethylmaleic anhydride in 500-HZ of toluene, stirred for 2hr at room temperature, and afforded N-benzylmaleamic acid as slurry. To the N-benzylmaleamic acid slurry was added bisbenzylammonium sulfate sluπy, equipped with Dean-Stark apparatus, and heated to reflux. The extent of reaction was monitored by measuring the amount of water collected in Dean-Stark apparatus. After the reaction was finished, it was cooled and removed bisbenzylammonium sulfate by filtration. The filtrate was washed with 3 x 500ml of water, dried and evaporated in vacuo. The crude product was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3), and afforded 48.7g(yield : 95%) of titled compound as a white crystalline solid, m. p. : 39 - 4012 Η-NMR(CDC1 3 ) : δ 1.9(s, 6H), 4.6(s, 2H), 7.3(s, 5H). Preparation 35 2.7-Dibenzyl- l,5-dimethyl-2,3,4,7-tetraazabicyclo [3.3.0]oct-3-en-6,8-dione To a stirred solution of 32g(0.15M) of l-benzyl-3,4-dimethylmaleimide in in 300ml of toluene was added 20g(0.15M) of benzyl azide as dropwise at room temperature, and heated to reflux for 4 days. The resulting solution was evaporated in vacuo, and purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3) to afford 14.2g(yield : 27%) of titled compound as a pale yellow solid. m. p. : 108 - 10912 Η-NMR(CDCl 3 ) : δ 1.2(s, 3H), 1.5(s, 3H), 4.6(s, 2H), 4.9(d, 2H, J=4Hz), 7.3(s, 10H). Preparation 36 3,6-Dibenzyl-l,5-dimethyl-3,6-diazabicyclo[3.1.Ojhexan- 2,4-dione Method 1 A mixture of 6.9 g (20mM) of triazoline compound(compound of preparation 35) in 20ml of diphenyl ether was stirred for 2hr at 200 - 21012. The reaction mixture was cooled to room temperature, and purified by column chromatogτaphyQ31uent ; 1st ; n-hexane, 2nd ethyl acetate : n-hexane = 1 : 3) to afford 5.8g(yield : 93%) of titled compound as a pale yellow syrup. 1 H-NMR(CDC1 3 ) : δ 1.4(s, 6H), 3.4(s, 2H), 4.6(s, 2H), 7.3(broads s, 10H). Method 2 To a stiired solution of 19.5g (0.09M) of l-benzyl-3,4-dimethylmaleimide in 300ml of toluene was added 24g(0.18M) of benzyl azide as dropwise at room temperature, and the reaction mixture was heated to reflux for a week. Toluene was evaporated in vacuo, and the residue was purified by column chromatography (Eluent ; ethyl acetate : n-hexane = 1 : 6) to afford 17.9g (yield : 62%) of titled compound as a pale yellow syrup. *H-NMR data is same as in Method 1. Preparation 37 3,6-Dibenzyl-l,5-dimethyl-3,6-diazabicyclo[3.1.0] hexane To a stirred mixture of 1.37g (36mM) of lithium aluminium hydride in 100 ∞"of dry tetrahydrofuran was added 5.8g (18mM) of 3,6-dibenzyl-l,5-dimethyl-3,6- diazabicyclo[3.1.0]hexane-2,4-dione in 25M" of dry tetrahydrofuran as dropwise at room temperature, and the reaction mixture was heated to reflux for 2 days. The resulting solution was cooled in an ice-bath and added successively 0.8 ml of water, 0.8M" of 15%-KOH solution, and 2.5M" of water. It was filtered, and filter cake was washed with tetrahydrofuran. The combined filtrate was dried 5 over sodium sulfate, filtered and evaporated in vacuo to afford 4.8g(yield : 90%) of titled compound as a pale yellow syrup. 1 H-NMR(CDC1 3 ) : δ 1.2(s, 6H), 2.6(d, 2H, J=10Hz), 3.1(d, 2H, J=10Hz), 3.6(s, 3H), 4.2(s, 2H), 7.3(s, 10H). ι o Preparation 38 l,5-Dimethyl-3,6-diazabicyclo[3.1.0]hexane To a stirred solution of 2.7g(9.2mM) of 3,6-dibenzyl-l ,5-dimethyl-3,6- diazabicyclo[3.1.0] hexane and 4.3g(84mM) of ammonium foimate in \0ml of methanol was added 2.7g of 10% Pd-C catalyst slowly, and stirred for 4.5hr at room temperature. 1-5 The reaction mixture was filtered through celite, and the filtrate was evaporated in vacuo. The residue was dissolved in 70M " of chloroform, stiired for 30min, filtered, and the filtrate was evaporated in vacuo to afford 1.5g of titled compound as formate. It was dissolved in AOml of methanol, added 0.4g(10mM) of sodium 0 hydroxide, and stiired for lhr at room temperature. Methanol was evaporated in vacuo, and added 70M" of chloroform for extraction. The chloroform extract was evaporated in vacuo, and afforded 0.96g(yield : 93%) of titled compound as a pale brown oil. Η-NMR CDCy : δ 1.2(s, 6H), 1.6(broad s, 2H), 2.8(q, 4H, J=12Hz). 5 Preparation 39 7-Benzyl-l,2,5-trimethyl-2,3,4,7-tetraazabicyclo[3.1.0]oct- 3-en-6,8-dione A mixture of 31g(0.144M) of l-benzyl-2,3-dimethylmaleimide and 51g (0.89M) of methyl azide in 300ml of toluene was stirred for 5 days at 100 - 105 . 30g(0.52M) of methyl azide was added again, and reacted for 5 days at the same temperature. The reaction mixture was evaporated in vacuo, and the residue was used in the next step without further purification. Small amount of analytical sample was purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 3). Η-NIVHUCDCI,) : δ 1.4(s, 3H), 1.5(s, 3H), 3.4(s, 3H), 4.6(s, 2H), 7.3(s, 5H). Preparation 40 3-Benzyl-l ,5, 6-trimethyl-3 ,6-diazabicyclo[3.1.0]hexane- 2,4-dione A mixture of 0.144M of triazoline compound(compound of preparation 39) in 40JHZ of diphenyl ether was stirred for 2hr at 180 - 19012. The reaction mixture was cooled to room temperature, and purified by column chromatography(Eluent ; ethyl acetate : n-hexane = 1 : 10) to afford 34.7g(yield : 99%) of titled compound as a pale yellow oil. • 1 H-NMR(CDC1 3 ) : δ 1.4(s, 6H), 2.3(s, 3H), 4.6(s, 2H), 7.3(s, 5H). Preparation 41 3-Benzyl-l,5,6-trimethyl-3,6-diazabicyclo[3.1.0]hexane To a stiired mixture of 1.51g(40mM) of lithium aluminium hydride in 200 ml of dry tetrahydrofuran was added 4.42g(18.1mM) of 3-benzyl-l,5,6-trimethyl- 3,6-diazabicyclo[3.1.0]hexan-2,4-dione in 20ml of dry tetrahydrofuran as dropwise at room temperature, and the reaction mixture was heated to reflux for 20hr. The resulting solution was cooled in an ice-bath, and added 30ml of water- tetrahydrofuran mixture(l : 2, v/v) slowly. The solid was filtered, washed with 50 ml of tetrahydrofuran, and the combined filtrate was dried over magnesium sulfate. It was filtered, and the filtrate was evaporated in vacuo. The residue was purified by column chromatography (Eluent ; ethyl acetate : ethanol = 3 : 1), and afforded 3.34g(yield : 85%) of titled compound as a pale yellow oil. Η-NMR CDCl,) : δ 1.2(s, 6H), 2.5(s, 3H), 2.6(2d, 4H), 3.6(s, 2H), 7.3(s, 5H). Preparation 42 1 ,5,6-Trimethyl-3,6-diazabicyclo[3.1.0]hexane A mixture of 4.67g(21.6mM) of 3-benzyl-l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexane and 5g of 10% Pd-C catalyst in 230M" of methanol was hydrogenated for 5hr at room temperature under 62 psi of H 2 pressure. The reaction mixture was filtered through celite pad, and the filtrate was evaporated in vacuo. The residue was purified by column chromatography (Eluent ; methanol : 40%-methylamine solution = 24 : 1), and afforded a pale yellow oil. It was further purified by vacuum distillation, and afforded 1.3g(yield : 48%) of titled compound as a white solid. m. p. : 39 - 4012 Η-NMR CDCy : δ l.l(s, 6H), 2.1(s, 1H), 2.2(s, 3H), 2.6(2d, 4H). Example 1 l-Cyclopropyl-6-fluoro-7-(6-methy 1-3 ,6-diazabicyclo [3.1.0]hexan-3-yl)- l ,4-dihydro-4-oxo-3-quinoline carboxylic acid A mixture of 100mg(0.377mM) of l-cyclopropyl-6,7-difluoro-l,4-dihydro- 4-oxo-3-quinolinecarboxylic acid, 129mg(1.34mM) of 6-methyl-3,6-diazabicyclo [3.1.0]hexane and 59mg(0.377mM) of l,8-diazabicyclo[5.4.0]unde-7-cene in 2ml of acetonitrile and lml of N,N-dimethylformamide was heated to reflux for 4hr. The resulting solution was refrigerated overnight, precipitate was filtered and washed with acetonitrile, water and acetonitrile, successively. The crude product was reciystallized from ethanol, and afforded 60mg (yield : 46%) of titled compound, m. p. : 237 - 23912 Η-NMR CDO,) : δ 1.1 ~ 1.4(m, 4H), 2.4(s, 5H), 3.4 - 3.8(m, 3H), 4.0(dd, 2H, J=4Hz, 12Hz), 6.8(d, 1H, J=8Hz), 7.7(d, 1H, J=16Hz), 8.5(s, 1H). IR(KBr) : 1723, 1630, 1544, 1507 cm 1 Example 2 1 -Cy clopropyl-6, 8-difluoro-7- (6-methy 1-3,6- diazabicyclo [3.1.0)hexan-3-yl)-l,4-dihydro-4-oxo-3-quinoline carboxylic acid A mixture of 100mg(0.697mM) of l-cyclopropyl-6,7,8-trifluoro-l,4- dihydro-4-oxo-3-quinolinecaιboxylic acid, 112mg(0.707mM) of 6-methyl-3,6- diazabicyclo [3.1.0]hexane • acetate and 106mg(0.389mM) of 1,8-diazabicyclo [5.4.0]unde-7-cene in 2ml of acetonitrile and 1M * of N,N-dimethylformamide was heated to reflux for 4hr. The resulting solution was refrigerated overnight, the crystals were filtered and washed witi acetonitrile, water, acetonitrile, successively. The crude product was recrystallized from ethanol, and afforded 60mg(yield : 48%) of titled compound. m. ρ. : 208 - 21012 I H-NMR(CT>α 3 ) : <* 1.1 - 1.4(m, 4H), 2.3(s, 2H), 2.4(s, 3H), 3.5 - 4.2(m, 5H), 7.8(d, 1H, J=16Hz), 8.7(s, 1H). IR(KBr) : 1725, 1624, 1541, 1514 cm 1 Example3 5- Amino- l-cyclopropyl-6, 8-difluoro-7- (6-methy 1-3, 6- diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3- quinolinecarboxylic acid In the same manner as described in Example 2, 100mg(0.336mM) of 5- amino-l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid was allowed to react with 106mg(0.671 mM) of 6-methyl-3,6-diazabicyclo [3.1.0]hexane • acetate for 8hr, and afforded 38mg(yield : 30%) of titled compound. m. p. : 236 - 23812 Η-NMR(CDCl 3 + DMSO-d 6 ) : δ 1.1 ~ 1.4(m, 4H), 2.3(s, 2H), 2.4(s, 3H), 3.5 - 4.2(m, 5H), 7.5(bs, 2H), 8.6(s, 1H). IR(KBr) : 1725, 1626, 1513, 1425 cm "1 Example4 l-Cyclopropyl-6-fluoro-7-(6-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-l ,8-naphthyridine-3- carboxylic acid In the same manner as described in Example 2, 100mg(0.354mM) of 1- cyclopropyl-7~chloro-6-fluoro-l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid was allowed to react with 112mg(0.708 mM) of 6-methyl-3,6-diazabicyclo [3.1.0]hexane • acetate for 30min, and recrystallized from n-butanol to afford 81mg(yield : 66%) of titled compound. m. p. : 209 - 21212 Η-NMR(CDC1 3 + DMSO-d 6 ) : δ 1.1 ~ 1.4(m, 4H), 2.4(s, 5H), 3.5 - 4.0(m, 3H), 4.2(dd, 2H, J=4Hz, 12Hz), 7.9(d, 1H, J=12Hz), 8.7(s, 1H). IR(KBr) : 1723, 1631, 1604, 1454 cm "1 Example 5 6,8-Difluoro-l-(2,4-difluorophenyl)-7-(6-methyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid A mixture of 100mg(0.28mM) of l-(2,4-difluorophenyl)-6,7,8-trifluoro-l,4- dihydro-4-oxo-3-quinolinecarboxylic acid, 65mg(0.41mM) of 6-methyl-3,6- diazabicyclo[3.1.0]hexane • acetate and 79mg(0.56mM) of triehylamine in 5ml of acetonitrile was heated to reflux for 8hr. The reaction mixture was refrigerated overnight, the crystals were filtered and washed with acetonitrile. The filtrate was evaporated in vacuo and the residue was crystallized from ethanol to afford 25mg(yield : 20%) of titled compound. m. p. : 150 - 15212 Η-NMR(CDC1 3 ) : δ 2.3(s, 2H), 2.4(s, 3H), 3.8(dd, 4H, J=12Hz, 20Hz), 6.8 -8.0(m,4H), 8.4(s, 1H). IR(KBr) : 1728,1627,1538,1510cm "1 Example 6 l-Cyclopropyl-8-chloro-6-fluoro-7-(6-methyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3- quinolinecarboxylic acid A mixture of 100mg(0.334mM) of l-cyclopropyl-8-chloro-6,7-difluoro-l,4- dihydro-4-oxo-3-quinolinecarboxylic acid, 158mg(1.0mM) of 6-methyl-3,6-diaza- 1 bicyclo [3.1.0]hexane • acetate in 3ml of pyridine was stirred overnight at 40 - 50 12. Pyridine was evaporated in vacuo, 2ml of acetonitrile and lml of N,N- dimethylformamide were added to the residue, and filtered the crystals formed. The filtrate was refrigerated overnight and filtered again. The two crops of crystals were washed with small amount of acetonitrile, water, and ethanol, successively, and dried to afford 44mg(yield : 35%) of titled compound as a light- yellow solid, m. p. : 190 - 19112 1 H-NMR(CDC1 3 ) : δ 0.8 - 1.4(m, 4H), 2.2(s, 2H), 2.3(s, 3H), 3.7(q, 4H, J=12Hz), 4.0 - 4.5(m, 1H), 7.9(d, 1H, J=14Hz), 8.8(s, 1H). IR(KBr) : 1726, 1617, 1500, 1446 cm 1 Example 7 9-Fluoro-2,3-dihydro-3-methyl-10 -(6-methy 1-3,6- diazabicyclo[3.1.0]hexan-3-yl)-7-oxo-7H-pyrido[l,2,3-de]- l,4-benzoxazine-6-carboxylic acid A mixture of 100mg(0.356mM) of 9,10-difluoro-2,3-dihydro-3-methyl-7- oxo-7H^)yrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acid and 169mg(1.07mM) of 6-methyl-3,6-diazabicyclo[3.1.0]hexane • acetate in 3ml of pyridine was stiired for 2 days at 55 - 6012. Pyridine was evaporated in vacuo, and the crude product was purified by column chromatography(Eluent ; chloroform : methanol : water = 10 : 3 : 1) to afford 31mg(yield : 24%) of titled compound. m. p. : 206 - 21012 1 H-NMR(CDC1 3 ) : δ 1.5(d, 3H, J=7Hz), 2.2(s, 2H), 2.3(s, 3H), 3.4 ~ 3.8(m, 2H), 3.9 - 4.7tøι, 5H), 7.6(d, 1H, J=15Hz), 8.5(s, 1H). IR(KBr) : 1721, 1621, 1524, 1452cm "1 Example8 l-Cyclopropyl-6-fluoro-8-methoxy-7-(6-methyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid In the same manner as described in Example 7, 100mg(0.339mM) of 1- cyclopropyl-6,7-difluoro-8-methoxy-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid was allowed to react with 175mg of 6-methyl-3,6-diazabicyclo [3.1.0]hexane • acetate, and afforded 27mg(yield : 21%) of titled compound. m. p. : 193 - 19512 Η-NMR(CDCl 3 ) : δ 0.8 - 1.2(m, 4H), 2.2(s, 2H), 2.3(s, 3H), 3.3 - 4.2(m, 5H), 3.6(s, 3H), 7.7(d, 1H, J=15Hz), 8.7(s, 1H). IR(KBr) : 1728, 1622, 1513, 1440 cm "1 Example 9 l-Cyclopropyl-6-fluoro-7-( l,6-dimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-l ,8-naphthyridine-3- carboxylic acid A mixture of 100mg(0.354mM) of l-cyclopropyl-7-chloro-6-fluoro-l,4- dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid, 92mg(0.533mM) of 1,6- dimethyl-3,6-diazabicyclo[3.1.0]hexane • acetate and 49mg(0.320mM) of 1 ,8- diazabicyclo[5.4.0]unde-7-cene in 2ml of acetonitrile was stirred overnight at room temperature. The solid was filtered, washed successively with acetonitrile, water, and acetonitrile, and dried to afford 42mg(yield : 40%) of titled compound. m. p. : 186 - 18812 Η-NMR(CD ,) : δ 0.9 - 1.4(m, 4H), 1.5(s, 3H), 2.1(s, 1H), 2.4(s, 3H), 3.4 ~4.4(m, 5H), 7.9(d, 1H, J=14Hz), 8.6(s, 1H). IR(KBr) : 1725, 1629, 1541, 1452 cm "1 Example 10 l-Cyclopropyl-6-fluoro-7-( l,6-dimethyl-3,6-diazabicyclo 5 [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinoline carboxylic acid A mixture of 100mg(0.337mM) of l-cyclopropyl-6,7-difluoro-l,4-dihydro- 4-oxo-3-quinolinecarboxylic acid and 195mg(1.13mM) of l,6-dimethyl-3,6-diaza- bicyclo[3.1.0]hexane • acetate in 3ml of pyridine was stirred overnight at 40 - 50 0 12. Pyridine was evaporated in vacuo, added 3ml of methanol to the residue, and stirred overnight at room temperature. Precipitate was filtered, washed successively with small amount of methanol, water, methanol, and recrystallized from acetonitrile to afford 42mg(yield : 31%) of titled compound. 5 m. p. : 214 - 21512 Η-NMR^DCl,) δ 1.0 - 1.4(m, 4H), 1.5(s, 3H), 2.1(s, 1H), 2.5(s, 3H), 3.2 - 4.2(m, 5H), 6.7(d, 1H, J=8Hz), 7.8(d, 1H, J=16Hz), 8.5(s, 1H). IR(KBr) : 1725, 1630, 1511, 1466 cm "1 C Example 11 5-Amino- l-cyclopropyl-6,8 -difluoro-7-(l, 6-dimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid A mixture of 100mg(0.336mM) of 5-amino-l-cyclopropyl-6,7,8-trifluoro- l,4-dihydro-4-oxo-3-quinolinecarboxylic acid, and 173mg(1.01mM) of 1,6- dimethyl-3,6-diazabicyclo[3.1.0]hexane • acetate in 3M * of pyridine was stirred overnight at 50 - 6012. Pyridine was evaporated in vacuo, added 2ml of acetonitrile and 1M" of N,N-dimethylformamide to the residue, and the resulting solution was refrigerated overnight. , The solid was filtered, washed successively with small amount of acetonitrile, water, and acetonitrile, and dried to afford 36mg(yield : 28%) of titled compound. m. p. : 204 - 20612 Η-NMRtCDO,) : δ 0.8 - 1.4(m, 4H), 1.5(s, 3H), 2.1(s, 1H), 2.5(s, 3H), 3.4 ~ 4.3(m, 5H), 6.3(broad s, 2H), 8.5(s, 1H). IR(KBr) : 1725, 1633, 1516, 1436 cm "1 Example 12 9-Fluoro-2,3-dihydro-3-methyl- 10-( l,6-dimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-7-oxo-7H-pyrido[l,2,3,-de]- l,4-benzoxazine-6-carboxylic acid A mixture of 100mg(0.356mM) of 9,10-difluoro-2,3-dihydro-3-methyl-7- oxo-7H-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acid and 184mg(1.07mM) of l,6-dimethyl-3,6-diazabicyclo[3.1.0]hexane • acetate in 3ml of pyridine was stirred for 2 days at 50 - 6012. Pyridine was evaporated in vacuo, and the residue was purified by column chromatography (Eluent ; chloroform : methanol : water = 10 : 3 : 1) to afford 28mg(yield : 22%) of titled compound, m. p. : 162 - 16412 Η-NMR CDCy : δ 1.5(d, 3H, J=7Hz), 1.9(s, 1H), 2.4(s, 3H), 3.2 ~4.5(m, 7H), 7.5(d, 1H, J=15Hz), 8.5(s, 1H). IR(KBr) : 1722, 1621, 1525, 1466 cm "1 Example 13 l-Cyclopropyl-6-fluoro-8-methoxy-7-(l,6-dimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid In the same manner as described in Example 12, 100mg(0.339mM) of 1- cyclopropyl-6,7-difluoro-8-methoxy-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid was allowed to react with 175mg(1.02mM) of l,6-dimethyl-3,6-diazabicyclo [3.1.0]hexane • acetate, and afforded 28mg(yield : 21%) of titled compound. m. p. : 166 - 16812 Η-NMR(CDCl 3 ) : δ 0.8 - 1.4(m, 4H), 1.5(s, 3H), 1.9(s, 1H), 2.5(s, 3H), 3.2 - 4.2(m, 5H), 3.6(s, 3H), 7.7(d, 1H, J=14Hz), 8.7(s, 1H). IR(KBr) : 1728, 1621, 1512, 1456cm "1 Example 14 l-Cyclopropyl-6,8-difluoro-7-(l,6-dimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid In the same manner as described in Example 12, 100mg(0.353mM) of 1- cyclopropyl-6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinolinecaii)oxylic acid was allowed to react with 182mg(1.06mM) of l,6-dimethyl-3,6-diazabicyclo [3.1.0] hexane • acetate, and afforded 36mg(yield : 27%) of titled compound. m. p. : 144 - 14612 1 H-NMR(CDC1 3 ) : δ 1.0 - 1.4(m, 4H), 1.5(s, 3H), 2.1(s, 1H), 2.5(s, 3H), 3.4 - 4.2(m, 5H), 7.7(d, 1H, J=14Hz), 8.7(s, 1H). IR(KBr) : 1730, 1626, 1517, 1459 cm 1 Example 15 l-Cyclopropyl-8-chloro-6-fluoro-7-(l,6-dimethy 1-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3- quinolinecarboxylic acid In die same manner as described in Example 12, lQ0mg(0.334mM) of 1- cyclopropyl-8-chloro-6,7 -difluoro- 1 ,4-dihydro-4-oxo-3-quinolinecaιboxylic acid was allowed to react with 172mg(1.0mM) of l,6-dimethyl-3,6-diazabicyclo [3.1.0] hexane • acetate, and afforded 33mg(yield : 24%) of tided compound, m. p. : 198 -20212 Η-NMR(CDCl 3 ) : δ 0.7 - 1.4(m, 4H), 1.5(s, 3H), 1.9(broad s, 1H), 2.5(s, 5H), 3.4 - 4.0(m, 4H), 4.0 - 4.4(m, 1H), 7.9(d, 1H, J=14Hz), 8.8(s, 1H). IR(KBr) : 1735, 1621, 1577, 1451 cm "1 Example 16 l-Cyclopropyl-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6- fluoro- l,4-dihydro-4-oxo-l,8-naphthyridine-3-carboxyli acid A mixture of 70mg(0.25mM) of l-cyclopropyl-7-chloro-6-fluoro-l,4- dihydro-4-oxo- l,8-naphthyridine-3-carboxylic acid, 27mg(0.33mM) of 3,6 diazabicyclo[3.1.0]hexane and 34mg(0.25mM) of l,8-diazabicyclo[5.4.0]unde-7 cene in 2ml of acetonitrile was stirred for 6hr at room temperature. The solid was filtered, washed successively with small amount o acetonitrile, water, and acetonitrile, and dried to afford 55mg(yield : 67%) of title compound. m. p. : 248 - 25212 Η-NMR CDO,) : δ 0.9 - 1.4(m, 4H), 2.8(broad s, 2H), 3.4 - 4.3(m, 5H), 7.9(d, 1H, J=14Hz), 8.5(s, 1H). IR(KBr) : 1717, 1635, 1563, 1469 cm "1 Example 17 l-Cyclopropyl-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6- fluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid A mixture of 100mg(0.38mM) of l-cyclopropyl-6,7-difluoro-l,4-dihydro-4- oxo-3-quinolinecarboxylic acid, and 164mg(l.lmM) of 3,6-diazabicyclo [3.1.0] hexane • acetate in 3M " of pyridine was stirred overnight at 45 - 5512 Pyridine was evaporated in vacuo, added 4ml of methanol to the residue, and stirred for 6hr at room temperature. The solid was filtered, washed successively with methanol, water, and methanol, and dried to afford 70mg(yield : 56%) of titled compound. m. p. : 244 - 24812 Η-NMR(DMSO-d 6 ) : δ 1.0 - 1.4(m, 4H), 2.8(broad s, 2H), 3.4 - 4.0(m, 5H), 7.0(d, 1H, J=8Hz), 7.8(d,; iH, J=16Hz), 8.5(s, 1H). IR(KBr) : 1719, 1632, 1508, 1473 cm -ι Example 18 l-Cyclopropyl-7-(3,6-diazabicyclo[3.1.0]hexan-3-yl)-6,8- difluoro- l,4-dihydro-4-oxo-3-quinoIinecarboxylic acid A mixture of 100mg(0.35mM) of l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro- 4-oxo-3-quinolinecarboxylic acid, 87mg(0.42mM) of 3,6-diazabicyclo [3.1.0] hexane • acetate and 118mg(0.77mM) of l,8-diazabicyclo[5.4.0]unde-7-cene in 1.5 ml of acetonitrile and 1.5ml of N,N-dimethylformamide was stirred overnight at 40 -5012 The reaction mixture was cooled to room temperature, filtered the crystals formed, and washed successively with small amount of acetonitrile, water, and acetonitrile. It was recrystallized from N,N-dimetf ylformamide, and afforded 44mg(yield : 36%) of titled compound as a white solid. m. p. : 230 - 23212 Η-NMR^DO,) : δ 0.9 - 1.4(m, 4H), 2.8(s, 2H), 3.5 - 4.3(m, 1H), 3.8(q, 4H, J=12Hz), 7.8(d, 1H, J=14Hz), 8.6(s, 1H). IR(KBr) : 1727, 1628, 1517, 1464 cm "1 Example 19 l-Cyclopropyl-8-chloro-7-(3,6-diazabicyclo[3.1.0]hexan-3- yl)-6-fluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid In the same manner as described in Example 17, 100mg(0.33mM) of 1- cyclopropyl-8-chloro-6,7 -difluoro- 1 ,4-dihydro-4-oxo-3-quinolinecaιboxylic acid was allowed to react with 144mg(1.0mM) of 3,6-diazabicyclo[3.1.0] hexane • acetate, and afforded 50mg(yield : 41%) of titled compound. m. p. : 214 - 21612 Η-NMR^DO j ) : δ 0.8 - 1.6(m, 4H), 2.7(s, 2H), 3.7(s, 4H), 4.2 - 4.5(m, 1H), 8.0(d, 1H,J=14Hz), 8.8(s, 1H). IR(KBr) : 1726, 1614, 1502, 1448cm "1 Example 20 5-Amino- 1 - cyclopropyl -7-(3,6-di azabicyclo[3.1.0]hexan-3 yl)-6,8 -difluoro-1 ,4-dihydro-4-oxo- 3-quinolinecarboxyli acid A mixture of 117mg(0.39mM) of 5-amino-l-cyclopropyl-6,7,8-trifluoro 5 l,4-dihydro-4-oxo-3-quinolinecaιboxylic acid, 68mg(0.47mM) of 3,6-diazabicycl [3.1.0]hexane • acetate and 131mg(0.87mM) of l,8-diazabicyclo[5.4.0]unde-7-cen in lml acetonitrile and 2M" of N,N-dimethylformamide was stirred overnight at 5 - 6012 The reaction mixture was cooled to room temperature, solid was filtered an o washed successively with small amount of acetonitrile, water, and acetonitrile, an dried to afford 55mg(yield : 39%) of titled compound as a yellow solid. m. p. : 218 - 22012 Η-NMR(DMSO-d 6 ) : δ 0.9 - 1.2(m, 4H), 2.6(s, 2H), 3.4 - 4.2(m with dd at 3.7, 5H, J=8Hz, 12Hz), 5 7.0(broad s, 2H), 8.4(s, 1H). IR(KBr) : 1726, 1638, 1542, 1517cm "1 Example 21 7-(3,6-Diazabicyclo[3.1.0]hexan-3-yl)-6,8-difluoro-l- ethyl- 1 ,4-dihydro-4-oxo- 3-quinolinecarboxylic acid 0 A mixture of 100mg(0.37mM) of l-ethyl-6,7,8-trifluoro- 1 ,4-dihydro-4-oxo- 3-quinolinecatboxylic acid and 158mg(l.lmM) of 3,6-diazabicyclo [3.1.0]hexane • acetate in 3M" of pyridine was stirred overnight at 55 - 6512. The reaction mixture was cooled and the solid was filtered. It was dispersed in 10ml of methanol, filtered, and reciystallized from chloroform to afford 5 76mg(yield : 61 %) of titled compound, m. p. : 222 - 22412 Η-NMR(DMSO-d 6 ) : δ 1.4(t, 3H, J=6Hz), 2.6(s, 2H), 3.7(dd, 4H, J=8Hz, 12Hz), 4.3 ~ 4.7(m, 3H), 7.7(d, 1H, J=14Hz), 8.8(s, 1H). IR(KBr) : 1712,1628,1521,1468,1445cm "1 Example 22 9-Fluro-2, 3-dihydro-3 -methy 1-10- (3 ,6-diazabicycl [3.1.0]hexan-3-yl)-7-oxo-7H-pyrido[ 1,2,3-de]- 1 ,4 benzoxazine-6-carboxylic acid A mixture of 100mg(0.36mM) of 9,10-dffluoro-2,3-dihydro-3-methyl-7- oxo-7H-pyrido[l,2,3-de)-l,4-benzoxazine-6-caιboxylic acid and 154mg(l.lmM) o 3,6-diazabicyclo[3.L0]hexane • acetate in 3ml of pyridine was stiired ovemight a 60 - 7012. After cooling the reaction solution, the solid was removed by filtration, the filtrate was evaporated in vacuo, added 5JΠZ of methanol to the residue, and stiired for 3hr at room temperature. The solid was filtered, washed successively with small amount of methanol, water, and methanol, and dried to afford 38mg(yield : 31 %) of titled compound. m. p. : 242 -24412 Η-NMR^DCL,) : δ 1.5(d, 3H, J=6Hz), 2.6(s, 2H), 3.4 - 4.0(m, 5H), 4.3 - 4.8(m, 3H), 7.7(d, 1H, J=14Hz), 8.6(s, 1H). IR(KBr) : 1712, 1621, 1531, 1474 cm 1 Example 23 l-Cyclopropyl-6,8-difluoro-7-(l-methyl-3 ,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinoline- carboxylic acid A mixture of 100mg(0.35mM) of l-cyclopropyl-6,7,8-trifluoro- 1 ,4-dihydro- 4-oxo-3-quinolinecarboxylic acid and 166mg(l.lmM) of l-methyl-3,6-diazabicyclo [3.1.0]hexane • acetate in 3M " of pyridine was stirred overnight at 45 - 5012. The reaction mixture was cooled and the solid was filtered. It was dispersed in 10ml of methanol, filtered, and reciystallized from chloroform to afford 97mg(yield : 76%) of titled compound. m. p. : 228 - 23012 Η-NMR(CDα,) : δ 0.9 - 1.4(m, 4H), 1.5(s, 3H), 2.4(s, 1H), 3.4 - 4.2(m, 5H), 7.6(d, 1H, J=14Hz), 8.7(m, 1H). 5 IR(KBr) : 1721, 1627, 1547, 1518, 1449 cm "1 Example 24 l-Cyclopropyl-8-chloro-6-fluoro-7-(l-methyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3- quinolinecarboxylic acid o A mixture of 100mg(0.33mM) of l-cyclopropyl-8-chloro-6,7-difluoro-l,4- dihydro-4-oxo-3-quinolinecarboxylic acid and 161mg(1.0mM) of l-methyl-3,6- diazabicyclo[3.1.0]hexane • acetate in 3ml of pyridine was stirred overnight at 60 - 6512. The reaction mixture was evaporated in vacuo, added 3ml of acetonitrile to 5 the residue, and stiired for 4hr at room temperature. The solid was filtered and dried to afford 41mg(yield : 32%) of titled compound, m. p. : 216 -21812 Η-NMR^DCl,) : δ 0.7 - 1.5(m, 4H), 1.4(s, 3H), 2.4(s, 1H), 3.6(q, 4H, J=10Hz), 4.0 - 4.4(m, 1H), 0 7.9(d, 1H, J=14Hz), 8.8(s, 1H). IR(KBr) : 1726, 1617, 1500, 1452 cm 1 Example 25 5-Amino-l-cyclopropyl-6,8-difluoro-7-( l-methyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid A mixture of 100mg(0.34mM) of 5-amino-l-cyclopropyl-6,7,8-trifluoro- l,4-dihydro-4-oxo-3-quinolinecarboxylic acid and 159mg(1.0mM) of l-methyl-3,6- diazabicyclo[3.1.0]hexane • acetate in 3ml of pyridine was stirred overnight at 65 - 7012. Pyridine was removed in vacuo, added 3ml of methanol to the residue, and stiired for 5hr at room temperature. The solid was filtered, washed successively with small amount of methanol, water, and methanol, and dried to afford 29mg(yield : 23%) of titled compound. m. p. : 224 -22612 1 H-NMR(CDC1 3 ) : δ 0.7 - 1.5(m, 4H), 1.4(s, 3H), 2.4(s, 1H), 3.4 - 4.1(m, 5H), 6.4(broad s , 2H), 8.7(s, 1H). IR(KBr) : 1718, 1632, 1516, 1430 cm "1 Example 26 l-Cyclopropyl-6-fluoro-7-(l-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yl l,4-dihydn>4-oxo-l,8-naphthyridine-3- carboxylic acid A mixture of 74mg(0.26mM) of l-cyclopropyl-7-chloro-6-fluoro-l,4- dihydro-4-oxo-l,8-naphthyιidine-3-carboxylic acid, 50mg(0.32mM) of 1-methyl- 3,6-diazabicyclo[3.1.0]hexane • acetate, and 86.«f(0.57mM) of 1,8-diazabicyclo [5.4.0]unde-7-cene in 3ml of acetonitrile was stirred for 6hr at room temperature. The solid was filtered, washed successively with small amount of acetonitrile, water, and acetonitrile, and dried to afford 74mg(yiel : 79%) of titled compound. m. p. : 249 - 25112 Η-NMR(DMSO-d 6 ) : δ 0.9 - 1.4(m, 4H), 1.4(broad s, 3H), 2.4(s, 1H), 3.4 - 4.3(m, 5H), 7.9(d, 1H, J=14Hz), 8.5(s, 1H). IR(KBr) : 1718, 1635, 1502, 1467 cm "1 Example 27 l-Cyclopropyl-6-fluoro-7-(l-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid A mixture of 100mg(0.38mM) of l-cyclopropyl-6,7-difluoro-l,4-dihydro-4- oxo-3-quinolinecarboxylic acid, 72mg(0.45mM) of l-methyl-3,6-diazabicyclo [3.1.0]hexane • acetate, and 125 4(0.83mM) of l,8-diazabicyclo[5.4.0]unde-7-cene in 5 M" of acetonitrile was stirred for 8hr at 50 - 6012. The solid was filtered, washed successively with small amount of acetonitrile, water, and acetonitrile, and dried to afford 100mg(yield : 78%) of tided compound. m. p. : 267 - 269 2 Η-NMR(DMSO-d 6 ) : δ 1.0 - 1.4(m, 4H), 1.4(broad s, 3H), 2.4(s, 1H), 3.4 - 4.0(m, 5H), 7.0(d, 1H, J=8Hz), 7.8(d, 1H, J=16Hz), 8.5(s, 1H). IR(KBr) : 1712, 1632, 1512, 1469 cm "1 Example 28 l-Cyclopropyl-6-fluoro-7-(l-methyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)- l,4-dihydro-4-oxo-3-qui nolinecarboxylic acid • lactate To a stirred solution of 0.15g(0.44mM) of l-cyclopropyl-6-fluoro-7-(l- methyl- 3, 6- diazabicyclo [3. 1.0] hexan- 3- yl) -1 ,4 -dihydr 0-4- oxo-3 - quinolinecarboxylic acid in 20ml of chloroform and 5ml of methanol was added 36mg(90%, 30 4) of lactic acid, and the resulting solution was stiired for 30 min at room temperature. The solvent was evaporated in vacuo, and crystallized by adding 10M" of ether. The solid was filtered, and dried in vacuo to afford 154mg(yield : 82%) of titled compound as a white solid. m. p. : 160 - 16212 Η-NMR CDO,) : δ 1.0 - 1.5(m, 4H), 1.4(s, 3H), 2.7(s, 1H), 3.0 - 4.2(m, 11H), 6.8(d, 1H, J=8Hz), 7.7(d, 1H, J=16Hz), 8.4(s, 1H). Example 29 9-Fluoro-2,3-dihydro-3-methyl-10-(l-methyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-7-oxo-7H-pyrido[l,2,3-de)- l,4-benzoxazine-6-carboxylic acid A mixture of 100mg(0.36mM) of 9,10-difluoro-2,3-dihydro-3-methyl-7- 5 oxo-7H-pyrido[l,2,3-de]-l,4-benzoxazine-6-caιboxylic acid and 169mg(l.lmM) of l-methyl-3,6-diazabicyclo[3.1.0]hexane • acetate in 3M * of pyridine was stirred overnight at 60 - 7012. The reaction solution was evaporated in vacuo, and the residue was purified by column chromatography (Eluent ; chloroform : methanol : water = 10 : 3 : 1) to o afford 30mg(yield : 23%) of tided compound as a yellow solid. m. p. : 220 - 22212 Η-NMR(CDCl 3 ) : δ 1.4(d, 3H, J=6Hz), 1.5(s, 3H), 2.3(s, 1H), 3.2 - 4.0(m, 5H), 4.1 - 4.8(m, 3H), 7.6(d, 1H, J=14Hz), 8.6(s, 1H). IR(KBr) : 1719, 1623, 1531, 1476 cm "1 Example 30 6,8-Difluoro-l-(2,4-difluorophenyl)-7-(3,6-diazabicyclo [3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3-quinoline- carboxylic acid A mixture of 100mg(0.28mM) of l-(2,4-difluorophenyl)-6,7,8-trifluoro-l ,4- dihydro-4-oxo-3-quinolinecarboxylic acid and 121mg(0.84mM) of 3,6-diazabicyclo [3.1.0]hexane • acetate in Ami of pyridine was stirred overnight at 55 - 6012. The solid was removed by filtration, and the filtrate was evaporated in vacuo. The residue was crystallized by adding etiier, filtered, washed witi water, and dried to afford 45mg(yield : 38%) of titled compound as a pale yellow solid. m. p. : 245 - 24712 1 H-NMR(CDC1 3 ) : δ 2.1(s, 1H), 2.7(s, 2H), 3.7(q, 4H, J=12Hz), 4.8(broad s, 1H), 6.9 - 7.7(m, 3H), 7.8(d, 1H, J=16Hz), 8.4(s, 1H). IR(KBr) : 1732, 1622, 1511, 1467 cm "1 Example 31 l-Cyclopropyl-6,8-difluoro-7-( l,5-dimethyl-3,6-diaza- bicyclo[3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3-quinoline- carboxylic acid A mixture of 100mg(0.35mM) of l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro- 4-oxo-3-quinolinecarboxylic acid and 93mg(0.83mM) of l,5-dimehyl-3,6- diazabicyclo[3.1.0]hexane in 3ml of pyridine was stirred overnight at 40 - 6512. The reaction mixture was cooled, and obtained the crystal by filtration. The crystal was dispersed in 10ml of methanol, filtered, and dried to afford 53mg(yield : 40%) of titled compound as a white solid. m. p. : 240 - 24212 Η-NMR^DC^) : δ 0.9 - 1.5(m, 4H), 1.4(s, 6H), 3.4 - 4.2(m, 5H), 7.8(d, 1H, J=14Hz), 8.7(s, 1H). IR(KBr) : 1722, 1625, 1517, 1450 cm "1 Example 32 l-Cyclopropyl-8-chloro-6-fluoro-7-( l,5-dimeth.yl-3,6- diazabicyclo[3.1.0]hexan-3-yl)- l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid A mixture of 100mg(0.33mM) of l-cyclopropyl-8-chloro-6,7-difiuoro-l,4- dihydro-4-oxo-3-quinolinecarboxylic acid and 113mg(1.0mM) of l,5-dimetiιyl-3,6- diazabicyclo[3.1.0]hexane in 3ml of pyridine was stirred overnight at 50 - 6012. Pyridine was evaporated in vacuo, and added 5ml of methanol to the residue. The precipitate was filtered, washed successively with methanol and acetonitrile, and dried to afford 78mg(yield : 59%) of tided compound as a white solid. m. p. : 220 - 22212 Η-NMR(CDCl 3 ) : 0.8 - 1.2(m, 2H), 1.2 - 1.5(m, 2H), 1.4(s, 6H), 3.6(s, 4H), 4.1 ~ 4.5(m, 1H), 8.0(d, 1H, J=14Hz), 8.8(s, 1H). IR(KBr) : 1722, 1617, 1444 cm "1 Example 33 5-Amino-l-cyclopropyl-6,8-difluoro-7-(l,5-dimethyl-3,6- 5 diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3- quinolinecarboxylic acid In the same manner as described in Example 32, 100mg(0.34mM) of 5- amino-l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid was allowed to react with 113mg(1.0mM) of l,5-dimethyl-3,6-diazabicyclo[3.1.0] ι o hexane, and afforded 68mg(yield : 52%) of tided compound as a yellow solid. m. p. : 219 - 22112 Η-NMR^DO,) : δ 0.8 - 1.4(m, 4H), 1.3(s, 6H), 3.4 - 4.1(m, 5H), 6.4(broads,2H), 8.6(s, 1H). IR(KBr) : 1723,1632,1516,1429cm "1 5 Example 34 l-Cyclopropyl-7-( l,5-dimethyl-3 ,6-diazabicyclo [3.1.0]hexan-3-yl)-6-fluoro- 1 ,4-dihydro-4-oxo-l ,8- naphthyridine-3-carboxylic acid A mixture of 50mg(0.18mM) of l-cyclopropyl-7-chloro-6-fluoro-l,4- 0 dihydro-4-oxo-l,8-naphthyridine-3-carboxylic acid, 41mg(0.26mM) of l,5-dimemyl-3,6-diazabicyclo[3.1.0]hexane • formate-3-carboxylic acid, and 27mg (0.18mM) of 1,8-diazabicyclo [5.4.0]unde-7-cene in 3ml of acetonitrile was stirred for 4hr at room temperature. The precipitate was filtered, washed successively with acetonitrile, water, 5 and acetonitrile, and dried to afford 46mg(yield : 73%) of titled compound as a white solid. m. p. : 256 - 25712 Η-NMR(DMSO-d 6 ) : δ 0.9 - 1.5(m, 4H), 1.4(s, 6H), 3.4 - 4.4(m, 5H), 7.9(d, 1H, J=14Hz), 8.6(s, 1H). Example 35 l-Cyclopropyl-7-( l,5-dim,ethyl-3,6-diazabicyclo[3.1.0] hexan-3-yl)-6-fluoro- l ,4-dihydro-4-oxo-3-quinoline carboxylic acid A mixture of 60mg(0.23mM) of l-cyclopropyl-6,7-difluoro-l ,4-dihydro-4- 5 oxo-3-quinolinecarboxylic acid and 107mg(0.68mM) of l,5-dimethyl-3,6- diazabicyclo[3.1.0]hexan • foimate in 3ml of pyridine was stirred overnight at 60 - 8012. The reaction mixture was cooled to room temperature, and the precipitate was filtered. It was washed successively with methanol, water, and methanol, and o dried to afford 43mg(yield : 53%) of tided compound as a white solid. m. p. : 258 - 26012 1 H-NMR(CF 3 C0 2 H) : δ 1.2 - 1.8(m, 4H), 1.9(s, 6H), 3.8 - 4.2(m, 1H), 4.1(d, 2H, J=14Hz), 4.8(d, 2H, J=14Hz), 7.5(d, 1H, J=8Hz), 5 8.2(d, 1H, J=14Hz), 9.2(s, 1H). IR(KBr) : 1711, 1631, 1512, 1471 cm "1 Example36 l-Ethyl-7-(l,5-dimethyl-3,6-diazabicyclo[3.1.0]hexan-3-yl)- 6,8-difluoro- 1 ,4-dihydro-4-oxo-3-quinolinecarboxylic acid A mixture of 60mg(0.22mM) of l-ethyl-6,7,8-trifluoro-l,4-dihydro-4-oxo- 3-quinolinecarboxylic acid and 74mg(0.66mM) of l,5-dimethyl-3,6-diazabicyclo [3.1.0]hexane in 3ml of pyridine was stirred overnight at 40 - 5012. The reaction mixture was cooled, evaporated in vacuo, and added methanol to the residue. The precipitate was filtered, washed successively with methanol, water, and methanol, and dried to afford 54mg(yield : 68%) of titled compound as a white solid, m. p. : 240 - 24112 Η-NMR CDClg) : δ 1.4(s, 6H), 1.5(t, 3H, J=6Hz), 3.7(q, 4H, J=14Hz), 4.2 - 4.7(m, 2H), 7.9(d, 1H, J=14Hz), 8.5(s, 1H). IR(KBr) : 1722, 1627, 1521, 1447cm "1 Example37 9-Fluoro-2,3-dihydro-3-methyl-10-(1,5-dimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-7-oxo-7H-pyrido[l,2,3-de]- l,4-benzoxazine-6-carboxylic acid A mixture of 100mg(0.36mM) of 9,10-difluoro-2,3-dihydro-3-methyl-7- oxo-7H-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acid and 120mg(l.lmM) of l,5-dimethyl-3,6-diazabicycIo[3.1.0]hexane in 3ml of pyridine was stirred for 3 days at 60 - 7512. The precipitate was obtained by filtration, the filtrate evaporated in vacuo, and added 3M * of methanol to the residue for crystallization. The two crops of precipitate were combined, dispersed in 5ml of metiianol, filtered, and dried to afford 79mg(yield : 59%) of titled compound as a pale green solid. m. p. : 286 - 28812 Η-NMR(CDCl 3 ) : δ 1.3(s, 6H), 1.6(d, 3H, J=7Hz), 3.3 - 4.8(m, 7H), 7.6(d, 1H,J=14Hz), 8.6(s, 1H). IR(KBr) : 1718, 1622, 1525, 1448cm "1 Example38 6,8-Difluoro-l-(2,4-difluorophenyl)-7-(l,5-dimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3- quinolinecarboxylic acid A mixture of 100mg(0.28mM) of l-(2,4-difluorophenyl 6,7,8-trifluoro-l,4- dihydro-4-oxo-3-quinolinecarboxylic acid and 95mg(0.85mM) of l,5-dimetfιyl-3,6- diazabicyclo[3. l.Ojhexane in Ami of pyridine was stirred overnight at 45 - 5512. The reaction mixture was evaporated in vacuo, and added methanol to the residue. The precipitate was filtered, washed with methanol, and dried to afford 85mg(yield : 68%) of tided compound as a pale yellow solid. m. p. : 230 - 23212 Η-NMR^DO,) : δ 1.3(s, 6H), 3.6(q, 4H, J=12Hz), 6.8 - 7.6(m, 3H), 7.9(d, 1H, J=14Hz), 8.4(s, 1H). IR(KBr) : 1725, 1622, 1508, 1441 cm "1 5 Example39 l-Cyclopropyl-6,8-difluoro-7-(l,5,6-trimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)- l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid A mixture of 0.22g(0.78mM) of l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro- 4-oxo-3-quinolinecarboxylic acid and 0.2g(1.58mM) of l ,5,6-trimethyl-3,6- ι o diazabicyclo[3.1.0]hexane in 2ml of pyridine was stirred for 2hr at 50 - 6012. To the reaction mixture was added 3M " of methanol and cooled gradually to room temperature. The precipitate was filtered, washed with methanol, and recrystallized several times from chloroform-methanol(l : 3, v/v) to afford 0.2g(yield : 66%) of titled compound as a white solid. 15 m. p. : 212 - 21312 Η-NMR(CDCL,) : δ 1.1 - 1.5(m, 4H), 1.3(s, 6H), 2.4(s, 3H), 3.4 - 4.2(m, 5H), 7.7(d, 1H, J=14Hz), 8.7(s, 1H). IR(KBr) : 1730, 1627, 1541, 1452 cm "1 0 Example 40 8-Chloro-l-cyclopropyl-6-fluoro-7-(l,5,6-trimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)- l ,4-dihydro-4-oxo-3- quinolinecarboxylic acid In the same manner as described in Example 39, 0.22g(0.74mM) of 8- chloro- 1 -cyclopropyl-6,7 -difluoro- 1 ,4-dihydro-4 -oxo-3-quinolinecarboxyl ic acid 5 was allowed to react with 0.19g(1.48mM) of l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexane, and afforded 0.21g(yield : 70%) of titled compound, m. p. : 202 - 20312 Η-NMR CDCl,) : δ l.l(m, 4H), 1.3(s, 6H), 2.4(s, 3H), 3.8(m, 4H), 4.3(m, 1H), 7.8(d, 1H, J=14Hz), 8.8(s, 1H). IR(KBr) : 1731, 1616, 1550, 1497, 1438cm -1 Example41 5-Amino-l-cyclopropyl-6,8-difluoro-7-(1 ,6-trimehyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo-3- quinolinecarboxylic acid In the same manner as described in Example 39, 0.22g(0.74mM) of 5- ammo-l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid was allowed to react with 0.91g(1.48mM) of l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexane, and afforded 0.2g(67%) of tided compound as a yellow solid. m. p. : 203 -20412 Η-NMR(CDCl 3 ) : δ l.l(m, 4H), 1.3(s, 6H), 2.4(s, 3H), 3.9(m, 5H), 6.4(broad s, 2H), 8.6(s, 1H). IR(KBr) : 1726, 1633, 1515, 1434 cm "1 Example 42 l-Cyclopropyl-6-fluoro-7- (l ,5,6-trimethyl-3,6- diazabicyclo[3.1.0]hexan-3-yl)-l,4-dihydro-4-oxo- 1,8- naphthyridine-3-carboxylic acid In the same manner as described in Example 39, 0.2g(0.71mM) of 1- cyclopropyl-7-chloro-6-fluoro - 1 ,4-dihy dro-4-oxo- 1 , 8-nap hthyridine-3-caιboxylic acid was allowed to react with 0.18g(1.42mM) of l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexane, and afforded 0.1g(yield : 38%) of tided compound. m. p. : 230 - 23112 Η-NMR^DO,) : δ 1.0 - 1.3(m, 4H), 1.3(s, 6H), 2.3(s, 3H), 3.4~ 4.3(m, 5H), 8.0(d, 1H, J=14Hz), 8.7(s, 1H). IR(KBr) : 1725, 1631, 1561, 1505, 1452 cm "1 Example 43 l-Cyclopropyl-6-fluoro-7-(l,5,7-trimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3-quinoline- carboxylic acid In the same manner as described in Example 39, 0.18g(0.68mM) of 1- cyclopropyl-6,7 -difluoro- 1 ,4-dihy dro-4-oxo-3-quinolinecarbox ylic acid was allowed to react with 0.17g(1.36mM) of l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexane, and afforded 0.2g(yield : 79%) of titled compound. m. p. : 238 - 23912 Η-NMR(CDα,) δ 1.1 ~ 1.7(m, 4H), 1.4(s, 6H), 2.3(s, 3H), 3.2 - 4. l(m, 5H), 6.8(d, 1H, J=6Hz), 7.9(d, 1H,J=16Hz), 8.7(s, 1H). IR(KBr) : 1729, 1631, 1511, 1469, 1404 cm "1 Example44 l-Ethyl-6,8-difluoro-7-(l,5,6-trimethyl-3,6-diazabicyclo [3.1.0]hexan-3-yl)-l ,4-dihydro-4-oxo-3-quinoline- carboxylic acid In the same manner as described in Example 39, 0.17g(0.63mM) of 1-ethyl- 6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinolinecarboxylic acid was allowed to react with 0.16g(1.26mM) of l,5,6-trimethyl-3,6-diazabicyclo[3.1.0]hexane, and afforded 0.14g(yield : 62%) of tided compound. m. p. : 204 - 20512 Η-NMR CDO,) : δ 1.3(s, 6H), 1.5(t, 3H, J=6Hz), 2.4(s, 3H), 3.4 ~ 4.6(m, 6H), 7.8(d, 1H, J=14Hz), 8.5(s, 1H). Following Example 45 to 47 illustrate pharmaceutical compositions containing the compounds of the invention as active ingredients. Example 45 Compound of Example 11 or 18 25g Starch 5g Lactose 3.5g Talc 1.5g The above components were blended with ethanol, granulated and filled into 100 capsules in accordance with conventional methods. Example 46 Compound of Example 11 or 18 25g Starch 5.4g Calcium carboxymethyl cellulose 4.0g Microcrystalline cellulose 5.0g Magnesium stearate 0.6g The above components were blended with ethanol, granulated and made into 100 tablets in a known manner. Example 47 Compound of Example 22 0.5g Lactic acid 1.2g The above components were dissolved in 100M" of distilled water, adjusted to pH 4 with an aqueous sodium hydroxide solution, and tiien filled in ampules(10 ml) to make an injectable solution.

Claims: CLAIMS What is claimed is : 1. A novel quinolone compound of the following Formula© and its pharma- ceutically acceptable salts thereof wherein, R 1 is hydrogen or protective group, R 2 is hydrogen, amino, alkylamino from one to four carbon atoms, hydroxy, alkoxy from one to four carbon atoms, mercapto, alkylthio from one to four carbon atoms, or halogen, R 3 is alkyl from one to four carbon atoms, alkenyl from two to four carbon atoms, cycloalkyl from three to six carbon atoms, haloalkyl, hydroxy alkyl from two to four carbon atoms, methoxy, amino, alkylamino from one to two carbon atoms, dimethylamino, or optionally substituted phenyl with more than one of halogen atoms or alkyl from one to three carbon atoms, Z is an amine of the following Formula, (wherein, R 4 is hydrogen or alkyl from one to four carbon atoms, R 5 and R 7 are, same or different, hydrogen or alkyl from one to two carbon atoms) X is N or C-R 6 (wherein, R 6 is hydrogen, hydroxy, methyl, cyano, nitro, methoxy, halogen, or can form a bridge of the following Foimula with R 3 ; -NH-CH,-CH-CH 3 , -O-CI CH-σ^ -S-C^-CH-CH,, or - CH 2 - CH, - CH - CH 3 ). A process for preparing a compound of Formula© which comprises reacting a compound of Formula(II) with an amine of Formula(III) or its acid addition salts in the presence of solvent and base. ZH (HI) wherein R 1 , R 2 , R 3 , X and Z are as defined in claim 1, and Y is halogen. 3. The process as defined in claim 2, wherein the solvent is more than one selected from die group of acetonitrile, N,N-dimedιylformamide, dimethyl- sulfoxide, alcohol, water, pyridine and picoline. 4. The process as defined in claim 2, wherein the base is more than one selected from the group of sodium hydroxide, potassium hydroxide, triethylamine, pyridine, picoline, lutidine, 1,4-diazabicyclo [2.2.2] octane [DABCO], 1,8- diazabicyclo [5.4.0] unde-7-cene(DBU), and 1,5-diazabicy- clo[4.3.0]non-5-ene(DBN). An antibacterial composition which comprises more than one of the compound of Formula© or its pharmaceutically acceptable salts as active ingredients. wherein R 1 , R 2 , R 3 , Z, and X are as defined in claim 1.

Inventors: CHANG YOUNG KIL, CHUN JONG PIL, GIL YOUNG HWAN, KIM SANG TAE, KOH JOON HYUNG, LEE GWAN SUN, MOON SOON KU, MOON YOUNG HO, RYOO EUI SANG, CHANG, YOUNG, KIL, CHUN, JONG, PIL, GIL, YOUNG, HWAN, KIM, SANG, TAE, KOH, JOON, HYUNG, LEE, GWAN, SUN, MOON, SOON, KU, MOON, YOUNG, HO, RYOO, EUI, SANG
Applicants: HANMI PHARMACEUTICAL CO LTD, HANMI PHARMACEUTICAL CO., LTD.
Application year: 1992
Main classification: C07D487
IPC codes: C07D487, C07D519