Title of Invention	"NOVEL COMPOUNDS OF IMIDAZO FUSED 4-HYDROXY QUINOLINE CARBOXAMIDES"
Abstract	The invention relates to the synthesis of new tricyclic hydroxyl quinoline carboxamides derivatives fused at 7,8 positions by imidazole ring as in Formula 1. The novel molecules such as 7,8-imidazofused quinoline-3-carboxamide compounds obtained as intermediates for heterofused quinolones.

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NOVEL COMPOUNDS OF IMIDAZO FUSED 4-HYDROXY QUINOLINE CARBOXAMIDES. Field of the invention The present invention relates to novel imidazo fused quinoline carboxamides of the general formula I R, R2 represent C1 and C2 alkyls, R1 is hydrogen and R3 represents Ci-C5 alkyl or aryl which is optionally substituted by alkyl, alkoxy, halogens, N,N-dialkylamino and furyl groups or polymethylene moiety containing 4-7 carbon atoms. (FORMULA REMOVED) The invention particularly relates to the synthesis of new tricyclic hydroxy quinoline carboxamide derivatives fused at 7,8 positions by imidazole ring as in I and II. The novel molecules such as 7,8-imidazofused quinoline-3-carboxamide compounds obtained as intermediates for heterofused quinolones. (FORMULA REMOVED) Background of the invention: Fluoroquinolone carboxylic acids are considered as potent antibacterials in vitro / in vivo and have good pharmacological applications for the last two decades with several molecules being commercially available as drugs. However, recent investigations have shown the occurrence of multidrug resistance to bacterial infections.(Chem.Ind.l7-2-1997, page 131). In order to overcome this problem, extensive research is in progress to synthesise polycyclic fluoroquinolones by novel and innovative methods. U.S patent 4,623,650 (1986) discloses the synthesis and antibacterial activity of certain 6-fluoro-7-aryl-l,4-dihydroquinoline-3-carboxylic acids having the formula (FORMULA REMOVED) in which R1 is H, alkyl (C1-C4), benzyl or a cation; R2 is H or F; Y is 1-3 carbon alkyl, H or polyhaloalkyl, hydroxyethyl, cyclopropyl, vinyl, alkylphenyl, etc; R4 is H, 3-hydroxy or 3-chloro provided both R3 and R4 are not hydrogens. U.S patent 3,472,859 (1969) discloses certain compounds having the formula (FORMULA REMOVED) where in R is lower alkyl and their fungicidal activity is disclosed. U.S patent 3,907.808 (1975) described certain 1,4-dihydro-l-(lower alkyl)-4-oxo-7-(4-pyridyl)-3-quinoline carboxylic acid and esters with the formula (FORMULA REMOVED) where in R is H, lower alkyl or CH2OAC; R1 is lower alkyl, etc; R2 is H, halogen etc; n is 0 or 1; R3, R4, R5, R6 are each selected from H, lower alkyl, halogen, etc; as antibacterial agents U.S patents 5,605,910 (1997) and 5,457,104 (1995) disclose new quinolones and Naphthyridone carboxylic acid derivatives which are substituted in the 7-position by a tricyclic amine radical, their salts and hydrogen in the 6 position respectively and their antibacterial activity. Quinolone and Naphthyridone carboxylic acid derivatives with H in 6th position have antibacterial activity. Examples can be found in U.S patent 4,416,884 (1983), EP 393,400 (1990). 8-methyl-7-piperazinylquinolone carboxylic acids were described in DE 3,007,006 (1985) and 7-(3-aminopyrrolidinyl)-8-fluoroquinolone carboxylic acids in J.Med.Chem.35,198 (1992). Objects of the Invention The main object of the present invention is to provide a novel compounds of imidazo fused 4-hydroxy quinoline carboxamides. Another object of the present invention is to provide the quinoline compounds useful as antibacterial agents. Accordingly the present invention provide novel imidazo fused quinoline carboxamides of the general formula I R, R2 represent C1 and C2 alkyls, R1 is hydrogen and R3 represents C1-C5 alkyl or aryl which is optionally substituted by alkyl, alkoxy, halogens, N,N-dialkylamino and furyl groups or polymethylene moiety containing 4-7 carbon atoms. (FORMULA REMOVED) In an embodiment of the present invention wherein the imidazo fused quinoline carboxamides is 7-8 imidazo fused quinoline carboxamides having structural formula la wherein R, R2 represent C1 and C2 alkyls, R1 is hydrogen, R3 represents C1-C5 alkyl, aryl which is optionally substituted by alkyl, alkoxy, halogens, N,N-dialkylamino and furyl groups. (FORMULA REMOVED) In another embodiment of the present invention wherein the spiro fused dihydroimidazo quinoline carboxamides is having structural formula lb given below wherein R, R2 are alkyl, R1 is hydrogen and n represents 4-7 methylenes. (FORMULA REMOVED) In another embodiment of the present invention wherein the representative compound of formula la are following Formula la I. 2-Phenyl-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N-methyl carboxamide. II. 2-[4'-Chlorophenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N-methyl carboxamide. 2-[4'-Fluorophenyl]-3 -methyl imidazo[4,5-h]-4-fluoro-6-hydroxyquinoline-7-N-methyl carboxamide. 2-[4'-Methyl phenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N-methyl carboxamide. V. 2-[4'-Methoxy phenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline- 7-N-methyl carboxamide. VI. 2[4'-N,N dimethyl amino phenyl]-3-methyl imidazo-[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N-methyl carboxamide. VII. 2-[4'-Nitrophenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N methyl carboxamide. VIII. 2[4'Hydroxy phenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N- methyl carboxamide. IX. 2-Furyl-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N methyl carboxamide. X. 2-Ethyl-3- methyl imidazo [4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. XI. 2-Propyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxyl quinoline-7-N-methyl carboxamide. XII. 2-Isopropyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxy quinoline -7-N-methyl carboxamide 2-n-Butyl-3-methyl imidazo[4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. 2-Isobutyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxyl quinoline-7-N-methyl carboxamide. XV. 2-n-Pentyl-3-methyl imidazo[4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. XVI. 2-n-Hexyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. XVII. 2,3- Dimethyl imidazo [ 4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. XVIII. 2-Trifluoromethyl -3- methyl imidazo[4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. In another embodiment of the present invention wherein the representative compound of formula lb are following Formula lb I. 3-Methyl-4-fluoro-6-hydroxy-lH-Spiro[imidazo(4,5-h)quinoline-2,rcyclopentane] -7-N-methyl carboxamide II. 3-Methyl-4-fluoro-6-hydroxy-lH-Spiro[imidazo(4,5-h)quinoline-,l 'cyclohexane] -7-N-methyl carboxamide 3-Methyl-4-fluoro-6-hydroxy-lH-Spiro[imidazo(4,5-h)quinoline-,l'cycloheptane] -7-N-methyl carboxamide 3-Methyl-4-fluoro-6-hydroxy-lH-Spiro[imidazo(4,5-h)quinoline-2,l'cyclooctane] -7-N-methyl carboxamide The present invention provides novel 7,8-fused imidazoquinoline carboxamides of the formula I in which R,R2 represent C1 and C2 alkyls, R1 is H, R3 represents aryl which is optionally substituted by alkyl, alkoxy, halogens, N,N-dialkylamino and furyl groups. The formula II in which spirofused dihydroimidazoquinoline carboxamides where R, R2 are alkyl, R1 is H and n represents 4-7 methylenes. In another embodiment, the synthesis of intermediate tricyclic quinolines of formula I represents R, R2 are alkyls, R1 is H, R3 represents phenyl and p-substituted phenyl includes methyl, chloro, fluoro, methoxy, nitro, dimethylamino, hydroxy and heteroaryl like furyl. In another embodiment, novel compounds of formula II represents spiro fused dihydro imidazo quinolines where R and R2 are methyls, R1is hydrogen and n indicates for number of methylenes 4-7. The novelty of the present invention includes the synthesis of new class of 7,8 imidazofused quinoline carboxamide tricyclic fluoroquinolines. Details of invention Various substituents on quinolone ring system are prepared and fusion of third ring between 1,2; 2,3; 6,7; 8,1 positions is the current interest worldwide as some of them showed promising antibacterial activity. The present invention relates to the synthesis of new class of 7,8-hetero ring fused tricyclic 4-hydroxy quinolines which are intermediates for quinolone carboxamides. The present invention confines to the synthesis of 7,8 fused quinolines starting from 6-fluoro-7-methylamino-8-amino-4-hydroxy quinoline-3-N-methylcarboxamide III and the products are 2-aryl/alkyl-3-methyl imidazo [4,5-h]-4-fluoro-6-hydroxyquinoline-7-N -methyl carboxamide I 3-methyl-4-fluoro-6-hydroxy-1 H-spiro[imidazo(4,5-h)quinoline-2,1 'cycloalkyl]-7-N-methyl carboxamide II and The alkyl groups contemplated by the invention are both straight and branched carbon chains of one to about five carbon atoms unless otherwise stated. Representatives of such groups are methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, n-pentyl and the like. The aryl groups intended to include substituted or unsubstituted phenyl. The substituents include halogen, nitro, alkyl, alkoxy. The term heteroaryl intended to include furan. The term halogen is intended to include fluorine and chlorine. The cyclo alkyl groups contemplated by the invention are those having from five to eight carbon atoms unless otherwise stated. Representatives of such groups are cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, and the like. The compounds of formula I and II are prepared by the following method, which comprises the condensation of diaminoquinoline III with aromatic aldehydes resulted 7,8-fused imidazo quinolines I (as major) and 1,8-fused quinolones (minor) where as with aliphatic aldehydes afforded exclusively I ( scheme-1 and Table-1). (FORMULA REMOVED) The spirofused -4-hydroxy dihydroimidazoquinolines II prepared from diamine III with cyclic ketones (scheme - II and Table-2) (SCHEME REMOVED) EXPERIMENTAL The following examples are given by way of illustration and therefore, should not be construed to limit the scope of the present invention. Example -1 Imidazo [4,5-h]quinoline (I). A mixture of 6-fluoro -7-methyl amino -8-amino-4-hydroxy quinoline 3-N-methyl carboxamide III (10 mmole) and benzaldehyde (10 mmole) was taken in acetic acid (10ml) and refluxed for 4hrs.The reaction mixture was cooled and poured on to crushed ice. The resulted solid was filtered, washed with water and dried. The separated solid was purified through column of silicagel using chloroform to get the 7,8 fused compound la as major product. 2-Phenyl-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N methyl carboxamide la M.p : >300°c, Yield : 60.4% I R(KBr)v : 3350-3250,1680cm'1. H'-NM^DMSO-De): 53.0 (d,3H,-CH3), 4.1(s,3H,- CH3), 7.4 (m,3H,phenyl), 7.7 (m, 2H, phenyl), 7.9 (d,lH,Ar-H), 8.8(s,lH,Ar-H), 10.0 (m,lH, -NH-), 13.0(b,lH,-OH).Mass(FAB): 351(M++1) Example - 2 Imidazo [4,5-h] alkyl substituted Quinolines I. A mixture of diamine III (10 mmole) and propanaldehyde (10 mmole) was taken in acetic acid (10ml) and refluxed for 4h.The reaction mixture was cooled and poured on to crushed ice. The resulted solid was filtered, washed with water and dried. The separated solid was purified through column on silicagel using methanol as eluent to give the 7,8 fused compound Ij. 2-Ethyl-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N methyl carboxamide Ij M.p :>300°c, Yield : 65.5% IR(KBr)v :3175,1654cm-1.'H-NMR(DMSO-D6) 5: 1.5 (m,3H,-CH3); 2.9 (t,2H,- CH2); 3.0 (d,3H,-CH3); 4.0 (s,3H,-CH3); 8.0 (d,lH,Ar-H); 8.7 (s,lH,Ar-H); 10.0 (b,lH, -NH-); 13.0(b,lH,-OH). Mass(FAB) : 303 (M++l). Example - 3 3-Methyl-4-fluoro-6-hydroxy-lH-Spiro[imidazo(4,5-h) quinoline-2,1 'cyclopentane] -7- N-methyl carboxamide Ha A mixture of diamine III (10 mmole) and cyclopentanone (10 mmole) was taken in acetic acid (10 ml) and refluxed for 4hrs. The reaction mixture was cooled and poured on to crushed ice, the resulted solid was filtered, washed with water and dried. The dried solid was purified through column chromatography on silicagel using chloroform and methanol as eluent to give the title compound Ha. M.p:>300°c, Yield: 71% I R(KBr) v : 3190,1655,1610cm-1. Mass(FAB) : 331 (M++l), 300, 272. Analysis Calcd. for C17H19FN4O2: C,61.80; H,5.79; N,16.95. Found : C,61.70; H,5.72, N,16.82%. Biological activity details Example -4 Antibacterial Activity studies : The minimum inhibitory concentration was done by broth dilution method (NCCLS1982). A set of sterilized test tubes with nutrient broth medium capped with cotton plugs (1-9). The test compound is dissolved in suitable solvent and concentration of 100µg/ml of the test compound is added in the first test tube, which is serially diluted from 1-9. A fixed volume of 0.5ml overnight culture is added in all the test tubes and are incubated at 37°C for 24h. After 24h, these tubes were measured for turbidity The final products of the present invention are tested for their activity. Some of the compounds showed promising antibacterial activity .The compounds are particularly effective against bacterial micro-organisms such as staphylococcus aureus. Other organisms like bacillus subtilis and bascillus sphaerius also used in the experimentation. The data is tabulated in table 3. Table -3 Antibacterial assay:Minimum Inhibitory Concentration of Compounds II (TABLE REMOVED) We Claim: 1. The novel imidazo fused quinoline carboxamides of general formula I wherein R, R2 represents C1 and C2 alkyls, R1 is hydrogen and R3 represents C1-C5 alkyl or aryl which is optionally substitutes by alkyl, alkoxy, halogens, N,N-dialkylamino and furyl groups or polymethylene moiety containing 4-7 carbon atoms where dotted line indicates presence of single or double bond. (Formula Removed) X. A novel imidazo fused quinoline carboxamides of the general formula I as claimed in claim 1 wherein the representative compound of formula Ia are following Formula Ia I. 2-Phenyl-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N methyl carboxamide. II. 2-[4'-Chlorophenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline -7-N-methyl carboxamide. III. 2-[4'-Fluorophenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxyquinoline-7-N-methyl carboxamide. IV. 2-[4'-Methyl phenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N-methyl carboxamide. V. 2-[4'-Methoxy phenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N-methyl carboxamide. VI. 2[4'-N,N dimethyl amino phenyl]-3-methyl imidazo-[4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. VII. 2-[4'-Nitrophenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline- 7-N methyl carboxamide. VIII. 2[4'Hydroxy phenyl]-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoline-7-N methyl carboxamide. IX. 2-Furyl-3-methyl imidazo[4,5-h]-4-fluoro-6-hydroxy quinoime-7-N methyl carboxamide. X. 2-Ethyl-3- methyl imidazo [4,5-h]-4-fluoro-6- hydroxy quinoline-7-N- methyl carboxamide. XI. 2-Propyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxyl quinoline-7-N- methyl carboxamide. XII. 2-Isopropyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxy quinoline -7-N-methyl carboxamide XIII. 2-n-Buty 1-3-methyl imidazo[4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. XIV. 2-Isobutyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxyl quinoline-7-N-methyl carboxamide. XV. 2-n-Pentyl-3-methyl imidazo[4,5-h]-4-fluoro-6- hydroxy quinoline-7-N- methyl carboxamide. XVI. 2-n-Hexyl-3-methyl imidazo [4,5-h]-4-fluoro-6- hydroxy quinoline-7-N- methyl carboxamide. XVII. 2,3- Dimethyl imidazo [ 4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide. XVIII. 2-Trifluoromethyl -3- methyl imidazo[4,5-h]-4-fluoro-6- hydroxy quinoline-7-N-methyl carboxamide.

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