Title of Invention	A NOVEL PYRROLO[2,1-C) [1,4]BENZODIAZEPINE HYBRIDS AND A PROCESS FOR PREPARATION THEREOF
Abstract	Pyrrolo[2,1 -c] [ 1,4]benzodiazepine Pyrrolo[2,1 -c][l ,4]benzodiazepine of formula wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5.

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FIELD OF THE INVENTION The present invention relates to novel pyrrolo[2,l-c][l,4]benzodiazepme hybrid This invention also relates to a process for the preparation of novel pyrrolo[2,l-c][l,4] benzodiazepine hybrid These novel pyrrolo [2, l-c][l,4]benzodiazepine hybrid are useful as antitumour agents More particularly, it relates to a process for the preparation of 7-methoxy-8-{n-[4-(2-oxo-2H-4-chromenyl)piperazino]alkyl}-oxy-(11aS)-l,2,3,11a-5H-pyrrolo[2,1 -c] [ 1,4]benzodiazepin-5-one and 7-methoxy-8-{n-[4-(7-alkoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]alkyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo [2,1 -c] [ 1,4] benzodiazepine-5-one with aliphatic chain length variations for these compounds The structural formula of these novel pyrrolo[2,l-c][l,4]benzodiazepines is given below (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5 BACKGROUND OF THE INVENTION Pyrrolo[2,l-c][l,4]benzodiazepine antitumour antibiotics are commonly known as anthramycin class of compounds In the last few years, a growing interest has been shown in the development of new pyrrolo [2, l-c][l,4]benzodiazepines (PBDs) These antibiotics react covalently with DNA to form an N2-guamne adduct that lies within the minor groove of duplex DNA via an acid-labile aminal bond to the electrophihc lmine at the N10-C11 position (Kunimoto, S , Masuda, T , Kanbayashi, N , Hamada, M , Naganawa, H , Miyamoto, M , Takeuchi, T , Unezawa, H J Antibiot, 1980, 33, 665 , Kohn, K W and Speous, C L J Mol Biol, 1970, 57, 551 , Hurley, L H, Gairpla, C and Zmyewski, M Biochem Bwphys Acta, 1977, 475, 521 , Kaplan, D J and Hurley, L H Biochemistry, 1981, 20, 7572) The molecules have a right-handed twist, which allows them to follow the curvature of the minor groove of B-form double-stranded DNA spanning three base pairs A recent development has been the linking of two PBD units through their C-8 positions to give bisfunctional-alkylating agents capable of cross-linking DNA (Thurston, D E , Bose, D S , Thomson, A S , Howard, P W , Leom, A, Croker, S J , Jenkms, T C , Neidle, S and Hurley, L H J Org Chem 1996, 61, 8141) (Formula Removed) Recently, PBD dimers have been developed that comprises two C2-exo-methylene substituted DC-81 subunits tethered through their C-8 position via an inert propanedioxy linker (Gregson, S J, Howard, P W, Hartely, J A, Brooks, N A, Adams, L J , Jenkins, T C , Kelland, L R and Thurston, DEJ Med Chem 2001, 44, 737) Recently, a noncross-hnking mixed lmine-amide PBD dimers have been synthesized that have significant DNA binding ability and potent antitumour activity (Kamal, A , Ramesh, G Laxman, N , Ramulu, P , Snnivas, O , Neehma, K, Kondapi, A K, Snnu, V B , Nagarajaram, H M J Med Chem 2002, 45,4679) Naturally occurring pyrrolo[2,l-c][l,4]benzodiazepmes belong to a group of antitumour antibiotics derived from Streptomyces species Recently, there is much impetus for the PBD systems as they can recognize and bind to specific sequence of DNA Examples of naturally occurring PBD's include anthramycin, DC-81, tomaymycin, sibiromycin and neothramycm However, the clinical efficacy for these antibiotics is hindered by several limitations, such as poor water solubility, cardiotoxicity, development of drug resistance and metabolic mactivation OBJECTIVES OF THE INVENTION The main objective of the present invention is to provide novel pyrrolo[2,l-c][l,4]benzodiazepine hybrids Yet another object is to provide a process for the preparation of novel pyrrolo[2,l-c][l,4]benzodiazepine hybrids SUMMARY OF THE INVENTION Accordingly the present invention provides a novel pyrrolo[2,l-c][l,4]benzodiazepine of formula 5 (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5 In an embodiment of the present invention the compound obtained is selected from the group consisting of 7-Methoxy-8- {3 - [4-(2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)- 1,2,3,11a- 5H-pyrrolo[2,1 -c] [1,4]benzodiazepin-5-one(5a),7-Methoxy-8- {4-[4-(2-oxo-2H-4- chromenyl)piperazino]butyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4]benzodiazepin -5-one(5b),7-Methoxy-8- {5-[4-(2-oxo-2H-4-chromenyl)prperazino]pentyl} -oxy-( 11 aS)- 1,2,3,1 la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one (5c), 7-Methoxy-8-{3-[4-(7-metho xy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]propyl}-oxy-(llaS)-l,2,3,lla-5H- pyrrolo[2,1 -c] [ 1,4]benzodiazepin-5-one(5d),7-Methoxy-8- {4-[4-(7-methoxy-8-methyl-2- oxo-2i/-4-chromenyl)piperazino]butyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4]ben zodiazepin-5-one(5e),7-Methoxy-8-{5-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chrom enyl)piperazino]pentyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4]benzodiazepin-5- one(5f),7-Methoxy-8-{3-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazmo] propyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4]benzodiazepm-5-one(5g),7- Methoxy-8-{4-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino] butyl}-oxy}- (1 laS)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one(5h),7-Meth oxy-8-{5-[4-(7- ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]pentyl}-oxy-(l 1 a 5)-l,2,3,11a.-5H- pyrrolo[2,1 -c][1,4]benzodiazepin-5-one(5i), 7-Methoxy-8-{3-[4-(7-isopropoxy-8-methyl- 2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-(l 1 aS)-1,2,3,11 a-5H-pyrrolo[2,1 - c][l,4]benzodiazepin-5-one (5j), 7-Methoxy-8-{4-[4-(7-isopropoxy-8-methyl-2-oxo-2H- 4-chromenyl)piperazino]butyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4] benzodiazepin-5-one(5k), 7-Methoxy-8- {5-[4-(7-isopropoxy-8-methyl-2-oxo-2H-4- chromenyl)piperazino]pentyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrol2,1 -c] [ 1,4] benzodiazepin-5-one (51) In yet another embodiment the compound pyrrolo[2,l-c][l,4]benzodiazepine is active against human tumour cell lines derived from cancer type selected from the group consisting of leukemia, non-small-cell-lung, colon, CNS, melanoma, ovarian, renal, prostate, breast cancer In yet another embodiment the compound novel pyrrolo[2,l-c][l,4]benzodiazepine exhibits in vitro anti tumouric activity when a dose of -5 to -8 Logio (mol/L), -4 to -7 Logio(mol/L) and -3 to -5 Logio(mol/L) of the said compound is exposed for at least 48 hrs to about sixty human tumour cells derived from nine cancer types such as leukemia, non-small-cell-lung, colon, CNS, melanoma, ovarian, renal, prostate, breast cancer, for GI50, TGI and LC50, respectively The present invention further provides a pharmaceutical composition comprising novel pyrrolo[2,l-c][l,4]benzodiazepine, its derivatives, analogues, salts or mixture thereof optionally with pharmaceutically acceptable carriers In yet another embodiment the novel pyrrolo[2,l-c][l,4]benzodiazepine hybnde used is composing the compound of general formula 5 (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5 The present invention further provides a process for the preparation of novel pyrrolo[2,l-c][l,4]benzodiazepme of formula 5 (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5, the said process comprising the steps of a) reacting 4-piperazino-2H-2-chromenone or 7-alkoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 1 (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5 with (2S)-N-[4-(n-bromoalkyl)-oxy-5-methoxy-2-nitrobenzoyl]pyrrohdine -2-carboxaldehydediethylthioacetal of formula 2 (Formula Removed) in presence of a base, in a dry organic solvent, for a penod of about 48 h under reflux, followed by extraction in water and isolating the compound of (2S)-N-{4-[4-[n-[4-(2-oxo-2H-2-chromenyl)piperazino]alkyl]oxy]-5-methoxy-2-nitrobenzoyl} pyrrohdine-2-carboxaldehydediethylthioacetal or (2S)-N-{4-[4-[n-[4-(7-alkyloxy-8-methyl-2-oxo-2H-2-chromenyl)piperazi no]alkyl]oxy]-5 -methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehyde di ethylthioacetal of formula 3 by known methods, (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5, b) reducing the above said nitro compound of formula 3 with SnCl2 2H2O or an acid catalyst in presence of an organic solvent, under reflux, for a penod of 1-2 hrs, followed by neutralizing the resultant reaction mixture at a pH of about 8 and isolating the amino compound (2S)-N-{4-[4-[n-[4-(2-oxo-2H-2-chromenyl) piperazino]alkyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxald ehyde diethylthioacetal or (2S)-N-{4-[4-[n-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]alkyl]oxy]-5-methoxy-2-amino benzoyl} pyrroh dine-2-carboxaldehyde diethylthioacetal of formula 4 by known methods, (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5, c) reacting the above said amino compound of formula 4 with de-protectmg agent in the presence of a aqueous organic solvent, at a temperature in the range of 20-25°C, for a period of about 12 hrs, separating the organic layer from the resultant reaction mixture followed by evaporation under vacuum to obtain the residue and diluting the above said residue with ethyl acetate followed by slowly mixing with saturated sodium bicarbonate, filtering, washing and evaporating the resultant filtrate, followed by purification by known methods to obtain the desired pyrrolo[2,l-c][l,4]benzodiazepine hybrid of formula 5 In yet another embodiment the compound the base used in step (a) is selected from K2CO3 and Na2C03 In yet another embodiment the compound the organic solvent used in step (a) is selected from acetomtnle, acetone and N, iV-demethyl formamide In yet another embodiment the compound the acid catalyst used in step (b) is selected from the group consisting of Sn/HCl, Zn/CH3COOH and Pd/C-H2 In yet another embodiment the organic solvent used in step (b) is selected from methanol, ethanol and ethylacetate In yet another embodiment the compound the de-protectmg agent used in step (c) is selected from the group consisting of HgCl2/CaCO3, HgO/HgCl2 and Bi(OTf)3 xH20 In yet another embodiment the organic solvent used in step (c) is selected from acetomtnle, dichloromethane and chloroform In yet another embodiment the compound obtained from the above said process is represented by a group of the following compounds 7-Methoxy-8- {3- [4-(2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3,1 la- 5H-pyrrolo[2,1 -c] [ 1,4] benzodiazepin-5-one(5a),7-Methoxy-8- {4-[4-(2-oxo-2H-4- chromenyl)piperazino]butyl}-oxy-(l laS)-1,2,3,1 la-5H- pyrrolo[2,l- c][l,4]benzodiazepin-5-one(5b),7-Methoxy-8-{5-[4-(2-oxo-2H-4-chromenyl)piperazino]pentyl}-oxy-(l laS)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4]benzodiazepm-5-one (5c),7-Methoxy-8-{3-[4-(7-methoxy-8-methyl-2-oxo-2i/-4-chromenyl)piperazino]propyl}-oxy-(l laS)-l,2,3, 11a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one(5d),7-Me thoxy-8-{4-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]butyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [1,4] benzodiazepin-5-one(5e),7-Methoxy-8-{5-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]pentyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4] benzodiazepm-5-one(5f),7-Methoxy-8-{3-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chrom e nyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4]benzodiazepin-5-one(5g),7-Methoxy-8-{4-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino] butyl}-oxy}-(11aS)-l,2,3,11a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one(5h),7-Meth oxy-8- {5-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]pentyl} -oxy-( 11 aS)-1,2,3,1 la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one(5i),7-Methoxy-8-{3-[4-(7-isopropoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,l-c][l,4]benzodia zepine-5-one (5j), 7-Methoxy-8-{4-[4-(7-isopropoxy-8-methyl-2-oxo-2if-4-chromeny l)piperazino] butyl}-oxy-(l laS)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4] benzodiazepin-5-one(5k), 7-Methoxy-8-{5-[4-(7-isopropoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazmo]pentyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrol2,1 -c] [ 1,4] benzodiazepin-5-one (51) DETAIL DESCRIPTION OF THE INVENTION These new analogues of pyrrolo[2,l-c][l,4]benzodiazepine hybrids linked at C-8 position have shown promising DNA binding activity and efficient anticancer activity in various cell lines The molecules synthesized are of immense biological significance with potential sequence selective DNA-binding property This resulted in design and synthesis of new congeners as illustrated in Scheme-1, which comprise 1 The ether linkage at C-8 position of DC-81 intermediates with 4-piperazino-2H-2-chromenone/7-alkoxy-8-methyl-4-piperazino-2i/-2-chromenone moiety 2 Refluxing the reaction mixtures for 48 h 3 Synthesis of C-8 linked PBD antitumour antibiotic hybrid lmines 4 Purification by column chromatography using different solvents like ethyl acetate, hexane, dichloromethane and methanol The following examples are given by way of illustration and therefore should not be construed to the present limit of the scope of invention Example 1 To a solution of (2S)-N-[4-(3-bromopropyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (521 mg, 1 0 mmol), 4-piperazino-2H-2-chromenone of formula 2 (230 mg, 1 0 mmol) and K2C03(414 mg, 3 0 mmol), in dry acetomtrile (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (11), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[3-[4-(2-oxo-2H-2-chromenyl)piperazino]propyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal 3 H1 NMR (CDC13, 200 MHz) δ 1 20-1 40 (m, 8H), 1 70-2 40 (m, 4H), 2 50-2 85 (m, 6H), 3 15-3 30 (m, 6H), 3 40-3 80 (m, 4H), 3 95 (s, 3H), 4 0-4 15 (t, 2H, J = 6 04 Hz), 4 60- 4 70 (m, 1H), 4 80-4 85 (m, 1H), 5 70 (s, 1H), 6 80 (s, 1H), 7 15-7 25 (t, 1H, J = 7 55 Hz), 7 28-7 45 (d, 1H, J= 7 55 Hz), 7 40-7 50 (t, 1H, J= 7 55 Hz), 7 52-7 56 (d, 1H, J = 7 55 Hz), 7 65 (s, 1H) MS (FAB) 671 [M+H]+ (2S)-N-{4-[4-[3-[4-(2-Oxo-2H-2-chromenyl)piperazino]propyl]oxy]-5-methoxy-2-mtrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 3 (670 mg, 1 0 mmol) was dissolved in methanol (10mL) and to this was added SnCI2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCO3 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N- {4- [4- [3 - [4-(2-oxo-2H-2-chromenyl)piperazino]propyl] oxy] -5 -methoxy-2-aminobenzoyl} pyrrolidine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[3-[4-(2-oxo-2H-2-chromenyl)piperazino]propyl] oxy]-5-methoxy-2-aminobenzoyl}pyrrolidine-2-carboxaldehydediethylthioacetal of formula 4 (640 mg, 1 mmol), HgCl2 (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H2O (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCO3 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{3-[4-(2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3,11 a- 5H-pyrrolo [2,1 -c] [ 1,4] benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDC13, 200 MHz) δ 1 80-1 90 (m, 2H), 2 20-2 60 (m, 4H), 2 80-2 90 (m, 4H), 3 25-3 40 (m, 4H), 3 45-3 85 (m, 4H), 3 90 (s, 3H), 4 15-4 30 (m, 3H), 5 70 (s, 1H), 6 85 (s, 1H), 7 15-7 20 (t, 1H, J= 6 69 Hz), 7 30-7 38 (d, 1H, J = 8 18 Hz), 7 44-7 50 (d, 1H, J= 8 18 Hz), 7 55-7 59 (t, 1H, J= 7 43 Hz), 7 62 (s, 1H), 7 64-7 68 (d, 1H, J= 3 72 Hz),MS (FAB) 517 [M+H]+ Example 2 To a solution of (2iS)-N-[4-(4-bromobutyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrolidine-2-carboxaldehydediethylthioacetal of formula 1 (535 mg, 1 0 mmol), 4-piperazino-2H-2-chromenone of formula 2 (230 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (11), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[4-[4-(2-oxo-2H-2-chromenyl)piperazino]butyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal 3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 6H), 1 65-2 35 (m, 8H), 2 60-2 85 (m, 6H), 3 15-3 30 (m, 6H), 3 40-3 80 (m, 4H), 3 95 (s, 3H), 4 0-4 15 (t, 2H, J = 6 04 Hz), 4 60- 4 70 (m, 1H), 4 80-4 85 (m, 1H), 5 65 (s, 1H), 6 80 (s, 1H), 7 18-7 20 (t, 1H, J = 7 55 Hz), 7 25-7 35 (d, 1H, J= 8 68 Hz), 7 40-7 50 (t, 1H, J= 6 93 Hz), 7 55-7 60 (d, 1H, J= 7 93 Hz), 7 61 (s, 1H) MS (FAB) 685 [M+H]+ (2S)-N-{4-[4-[4-[4-(2-Oxo-2H-2-chromenyl)piperazino]butyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 3 (684 mg, 1 0 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCO3 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[4-[4-(2-oxo-2i/-2-chromenyl)piperazino]butyl]oxy]-5-methoxy-2-amino benzoyl} pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[4-[4-(2-oxo-2H-2-chromenyl)piperazino]butyl] oxy] -5 -methoxy-2-aminobenzoyl} pyrrolidine-2-carboxaldehydediethylthioacetal of formula 4 (654 mg, 1 mmol), HgCl2 (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H2O (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCO3 was added slowly at room temperature and the mixture was filtered through a celite bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{4-[4-(2-oxo-2H-4-chromenyl)piperazino]butyl} -oxy-( 11 aS> 1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4] benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 80-2 00 (m, 4H), 2 20-2 60 (m, 4H), 2 70-2 90 (m, 4H), 3 25-3 40 (m, 4H), 3 60-3 85 (m, 4H), 3 90 (s, 3H), 4 15-4 30 (m, 3H), 5 70 (s, 1H), 6 82 (s, 1H), 7 15-7 20 (t, 1H, J= 6 69 Hz), 7 30-7 38 (d, 1H, J= 8 18 Hz), 7 44-7 50 (d, 1H, J= 8 18 Hz), 7 55-7 59 (t, 1H, J= 7 43 Hz), 7 62 (s, 1H), 7 64-7 68 (d, 1H, J= 3 72 Hz),MS (FAB) 531 [M+H]+ Example 3 To a solution of (2S)-N-[4-(5-bromopentyl)-oxy-5-methoxy-2-nitrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (549 mg, 1 0 mmol), 4-piperazino-2H-2-chromenone of formula 2 (230 mg, 1 0 mmol) and K.2C03(414 mg, 3 0 mmol), in dry acetomtrile (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (11), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel elutmg with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[5-[4-(2-oxo-2H-2-chromenyl)piperazino]pentyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal 3 H1 NMR (CDC13, 200 MHz) δ 1 20-1 40 (m, 8H), 1 70-2 40 (m, 6H), 2 60-2 85 (m, 8H), 3 15-3 35 (m, 6H), 3 40-3 80 (m, 4H), 3 95 (s, 3H), 4 10-4 25 (t, 2H, J= 6 04 Hz), 4 60- 4 70 (m, 1H), 4 80-4 85 (m, 1H), 5 70 (s, 1H), 6 80 (s, 1H), 7 18-7 20 (t, 1H, J = 7 55 Hz), 7 25-7 35 (d, 1H, J= 8 68 Hz), 7 40-7 50 (t, 1H, J= 6 93 Hz), 7 55-7 60 (d, 1H, J = 7 93 Hz), 7 61 (s, 1H) MS (FAB) 699 [M+H]+ (2iS)-N-{4-[4-[5-[4-(2-Oxo-2H-2-chromenyl)piperazino]pentyl]oxy]-5-methoxy-2-mtrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 3 (698 mg, 1 0 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHC03 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[5-[4-(2-oxo-2H-2-chromenyl)piperazino]pentyl]oxy]-5-methoxy-2-aminobenzoyl }pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[5-[4-(2-oxo-2H-2-chromenyl)piperazino]pentyl] oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 4 (668 mg, 1 mmol), HgCl2 (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H2O (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHC03 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{5-[4-(2-oxo-2H-4-chromenyl)piperazino]pentyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo [2,1 -c] [ 1,4]benzo diazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHC13 methanol (9 1) H1 NMR (CDCI3,200 MHz) δ 2 08-2 20 (m, 6H), 2 22-2 60 (m, 4H), 2 63-2 82 (m, 4H), 3 25-3 40 (m, 4H), 3 45-3 85 (m, 4H), 3 90 (s, 3H), 4 15-4 25 (m, 3H), 5 68 (s, 1H), 6 82 (s, 1H), 7 15-7 20 (t, 1H, J= 6 69 Hz), 7 30-7 38 (d, 1H, J= 8 18 Hz), 7 44-7 50 (d, 1H, J = 8 18 Hz), 7 55-7 59 (t, 1H, J= 7 43 Hz), 7 62 (s, 1H), 7 64-7 68 (d, 1H, J= 3 72 Hz) MS (FAB) 545 [M+H]+ Example 4 To a solution of (2S)-N-[4-(3-bromopropyl)-oxy-5-methoxy-2-nitrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (521 mg, 1 0 mmol), 7-methoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 2 (274 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtrile (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (11), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure(2S)-N-{4-[4-[3-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]propyl] oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 8H), 1 90-2 19 (m, 4H), 2 21 (s , 3H), 2 31-2 40 (t, 2H, J= 7 85 Hz), 2 60-2 82 (m, 8H), 3 18-3 30 (m, 4H), 3 35-3 40 (t, 2H, J = 7 07 Hz), 3 90 (s, 3H), 3 95 (s, 3H), 4 15-4 20 (m, 2H), 4 60-4 80 (m, 1H), 4 80-4 90 (m, 1H), 5 51 (s, 1H), 6 68-6 72 (d, 1H, J= 8 64 Hz), 6 79 (s, 1H), 7 31-7 38 (d, 1H, J = 9 43 Hz), 7 64 (s, 1H), MS (FAB) 715 [M+H]+ (2S)-N-{4-[4-[3-[4-(7-Methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] propyl] oxy] -5 -methoxy-2-nitrobenzoyl} pyrrohdine-2-carboxaldehydediethylthioacetal of formula 3 (714 mg, 1 0 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H20 (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCO3 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[3-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]propyl] oxy] -5 -methoxy-2-aminobenzoyl} pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[3-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]propyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 4 (714 mg, 1 mmol), HgCl2 (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H20 (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCO3 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{3-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chromenyl) piperazino]propyl}-oxy-(l laS)-1,2,3,1 la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 2 00-2 20 (m, 2H), 2 22-2 40 (m, 7H), 2 60-2 80 (m, 4H), 3 20-3 35 (m, 4H), 3 45-3 80 (m, 4H), 3 90 (s, 3H), 3 92 (s, 3H), 4 15-4 25 (m, 3H), 5 60 (s, 1H), 6 74-6 78 (d, 1H, J= 8 91 Hz)), 6 84 (s, 1H), 7 38-7 42 (d, 1H, J= 8 91 Hz), 7 50 (s, 1H), 7 64-7 68 (d, 1H, J= 3 72 Hz), MS (FAB) 561 [M+H]+ Example 5 To a solution of (2iS)-N-[4-(4-bromobutyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (535 mg, 1 0 mmol), 7-methoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 2 (274 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (1 1), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[4-[4-(7-methoxy-8-methyl-2-oxo-2if-2-chromenyl)piperazino]butyl] oxy]-5-methoxy-2-nitrobenzoyl}pyrrolidine-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 10H), 1 60-2 18 (m, 8H), 2 21 (s, 3H), 2 60-2 80 (m, 8H), 3 18-3 30 (m, 4H), 3 84 (s, 3H), 3 90 (s, 3H), 4 14-4 20 (m, 2H), 4 60-4 71 (m, 1H), 4 78-4 84 (m, 1H), 5 55 (s, 1H), 6 71-6 75 (d, 1H, J= 8 92 Hz), 6 78 (s, 1H), 7 34-7 38 (d, 1H, J= 8 18 Hz), 7 62 (s, 1H) MS (FAB) 729 [M+H]+ (2S)-N-{4-[4-[4-[4-(7-Methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] butyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 3 (728 mg, 1 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCCh solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[4-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazmo]butyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrolidine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[4-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]butyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 4 (698 mg, 1 mmol), HgCb (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H2O (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCO3 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{4-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chromenyl) piperazino]butyl}-oxy-(l laS)-l,2,3,l la-57/-pyrrolo[2,l-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel elutmg first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 90-2 10 (m, 4H), 2 20-2 40 (m, 7H), 2 60-2 80 (m, 4H), 3 20-3 35 (m, 4H), 3 45-3 80 (m, 4H), 3 90 (s, 3H), 3 92 (s, 3H), 4 15-4 25 (m, 3H), 5 60 (s, 1H), 6 74-6 78 (d, 1H, J= 8 91 Hz)), 6 84 (s, 1H), 7 38-7 42 (d, 1H, J= 8 91 Hz), 7 50 (s, 1H), 7 64-7 68 (d, 1H, J= 3 72 Hz), MS (FAB) 575 [M+H]+ Example 6 To a solution of (2S)-N-[4-(5-bromopentyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (549 mg, 1 0 mmol), 7-methoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 2 (274 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (11), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[5-[4-(7-methoxy-8-methyl-2-oxo-27/-2-chromenyl)piperzino]pentyl] oxy]-5-methoxy-2-mtrobenzoyl}pyrrohdme-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 8H), 1 40-1 70 (m, 4H),1 82-2 18 (m, 4H), 2 21 (s , 3H), 2 47-2 55 (t, 2H, J= 7 55 Hz), 2 62-2 82 (m, 8H), 3 20-3 30 (m, 4H), 3 32- 3 42 (m, 2H), 3 90 (s, 3H), 3 95 (s, 3H), 4 05-4 13 (t, 2H, J = 6 04 Hz), 4 62-4 70 (m, 1H), 4 80-4 84 (m, 1H), 5 50 (s, 1H), 6 68-6 78 (d, 1H, J= 9 07 Hz), 6 80 (s, 1H), 7 32-7 40 (d, 1H, J= 9 07 Hz), 7 65 (s, 1H) MS (FAB) 743 [M+H]+ (2S)-N-{4-[4-[5-[4-(7-Methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] pentyl]oxy]-5-methoxy-2-mtrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 4 (742 mg, 1 mmol) was dissolved m methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCO3 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[5-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]pentyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrolidme-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[5-[4-(7-methoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazmo]pentyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrolidine-2- carboxaldehydediethylthioacetal of formula 4 (712 mg, 1 mmol), HgCk (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol), HgCb (mmol) and CaCO3 (mmol) in CH3CN/H2O (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHC03 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{5-[4-(7-methoxy-8-methyl-2-oxo-2i/-4-chromenyl)piperazino]pentyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHC13 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 82-2 15 (m, 6H), 2 20-2 60 (m, 7H), 2 62-2 80 (m, 4H), 3 20-3 40 (m, 4H), 3 45-3 80 (m, 4H), 3 90 (s, 3H), 3 92 (s, 3H), 4 10-4 20 (m, 3H), 5 60 (s, 1H), 6 75-6 78 (d, 1H, J= 9 43 Hz)), 6 80 (s, 1H), 7 38-7 42 (d, 1H, J= 8 64 Hz), 7 50 (s, 1H), 7 64-7 68 (d, 1H, J= 4 71 Hz), MS (FAB) 589 [M+H]+ Example 7 To a solution of (2iS)-N-[4-(3-bromopropyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (521 mg, 1 0 mmol), 7-ethoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 2 (288 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (1 1), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[3-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]propyl] oxy]-5-methoxy-2-mtrobenzoyl}pyrrolidine-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 8H), 1 44-1 50 ( t, 3H, J = 6 80 Hz), 1 50-2-00 (m, 4H), 2 30-2 40 (m , 5H), 2 60-3 00 (m, 8H), 3 18-3 40 (m, 6H), 3 90 (s, 3H), 4 02-4 20 (m, 4H), 4 60-4 70 (m, 1H), 4 80-4 82 (m, 1H), 5 60 (s, 1H), 6 68-6 75 (d, 1H, J = 9 07 Hz), 6 80 (s, 1H), 7 28-7 38 (d, 1H, J = 9 07 Hz), 7 62 (s, 1H), MS (FAB) 729 [M+H]+ (2S)-N-{4-[4-[3-[4-(7-Ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] propyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 3 (728 mg, 1 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHC03 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[3-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]propyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[3-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl) piperazmo]propyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrolidine-2-carboxaldehyde diethylthioacetal of formula 4 (698 mg, 1 mmol), HgCb (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol), HgCl2 (mmol) and CaCO3 (mmol) in CH3CN/H20 (4 I) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCO3 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{3-[4-(7-ethoxy-8-methyl-2-oxo-2/7-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo [2,1 -c] [ 1,4] benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHC13 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 40-1 50 (t, 3H, / =6 65 Hz), 1 80-2 00 (m, 2H), 2 15 (s, 3H), 2 50-2 80 (m , 4H), 2 80-3 00 (m, 4H), 3 15-3 50 (m, 4H), 3 60-3 80 (m, 4H), 3 95 (s, 3H), 4 15-4 20 (m, 5H), 5 60 (s, 1H), 6 70-6 78 (d, 1H, J= 8 34 Hz), 6 80 (s, 1H), 7 28-7 38 (d, 1H, J = 8 34 Hz), 7 45 (s, 1H), 7 64-7 68 (d, 1H, J = 3 74 Hz), MS (FAB) 575 [M+H]+ Example 8 To a solution of (2S)-N-[4-(4-bromobutyl)-oxy-5-methoxy-2-nitrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (535 mg, 1 0 mmol), 7-ethoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 2 (288 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (1 1), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[4-[4-(7-ethoxy-8-methyl-2-oxo-27/-2-chromenyl)piperazino]butyl] oxy]-5-methoxy-2-mtrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 10H), 1 44-1 50 (t, 3H, J = 6 80 Hz), 1 50-2-00 (m, 4H), 2 30-2 40 (m , 5H), 2 60-3 00 (m, 8H), 3 18-3 40 (m, 6H), 3 90 (s, 3H), 4 02-4 20 (m, 4H), 4 60-4 70 (m, 1H), 4 80-4 82 (m, 1H), 5 60 (s, 1H), 6 68-6 75 (d, 1H, J= 9 07 Hz), 6 80 (s, 1H), 7 28-7 38 (d, 1H, /= 9 07 Hz), 7 62 (s, 1H) MS (FAB) 743 [M+H]+ (2S)-N-{4-[4-[4-[4-(7-Ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]butyl] oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdme-2-carboxaldehydediethylthioacetal of formula 3 (742 mg, 1 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCO3 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[4-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]butyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdme-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[4-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl) piperazino]butyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehyde diethylthioacetal of formula 4 (712 mg, 1 mmol), HgCl2 (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H2O (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHC03 was added slowly at room temperature and mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8- {4-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazmo]butyl} -oxy} -(11a5)-l,2,3,11a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 50-1 52 (t, 3H, J = 7 04 Hz), 1 60-2 00 (m, 4H), 2 15 (s, 3H), 2 20-2 40 (m , 4H), 2 60-2 80 (m, 4H), 3 20-3 35 (m, 4H), 3 60-3 89 (m, 4H), 3 95 (s, 3H), 4 10-4 20 (m, 5H), 5 60 (s, 1H), 6 70-6 78 (d, 1H, J= 8 64 Hz), 6 80 (s, 1H), 7 35-7 38 (d, 1H, J = 8 64 Hz), 7 50 (s, 1H), 7 64-7 68 (d, 1H, J = 3 93 Hz), MS (FAB) 589 [M+H]+ Example 9 To a solution of (2S)-N-[4-(5-bromopentyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (549 mg, 1 0 mmol), 7-ethoxy-8-methyl-4-piperazmo-2H-2-chromenone of formula 2 (288 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (1 1), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[5-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]pentyl] oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 12H), 1 40-1 50 (t, 3H, J = 6 80 Hz), 1 62-2 18 (m, 8H), 2 21 (s , 3H), 2 45-2 82 (m, 8H), 3 18-3 30 (m, 4H), 3 90 (s, 3H), 4 02-4 20 (m, 4H), 4 60-4 70 (m, 1H), 4 78-4 82 (m, 1H), 5 59 (s, 1H), 6 68-6 72 (d, 1H, J= 9 07 Hz), 6 80 (s, 1H), 7 28-7 38 (d, 1H, J= 9 07 Hz), 7 62 (s, 1H) MS (FAB) 757 [M+H]+ (2S)-N-{4-[4-[5-[4-(7-Ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] pentyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula III (756 mg, 1 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHC03 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[5-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]pentyl] oxy] -5 -methoxy-2-aminobenzoyl} pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[5-[4-(7-ethoxy-8-methyl-2-oxo-2H-2-chromenyl) piperazino]pentyl] oxy] -5 -methoxy-2-aminobenzoyl} pyrrolidine-2-carboxaldehyde diethylthioacetal of formula 4 (726 mg, 1 mmol), HgCl2 (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H2O (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCC«3 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{5-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]pentyl}-oxy-(11aS)-l,2,3,11a-5i/-pyrrolo[2,l,-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 40-1 50 (t, 3H, J = 6 75 Hz), 1 70-2 00 (m, 6H), 2 10 (s, 3H), 2 60-2 90 (m, 4H), 3 00-3 15 (m, 4H), 3 40-3 52 (m, 4H), 3 70-3 90 (m, 4H), 3 95 (s, 3H), 4 15-4 20 (m, 5H), 5 60 (s, 1H), 6 78 (s, 1H), 6 80-6 82 (d, 1H, J = 9 03 Hz), 7 32-7 45 (d, 1H, J = 9 03 Hz), 7 52 (s, 1H), 7 65-7 85 (d, 1H, J = 4 50 Hz), MS (FAB) 603 [M+H]+ Example 10 To a solution of (2S)-N-[4-(3-bromopropyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (521 mg, 1 0 mmol), 7-isopropoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 2 (302 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetonitnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (11), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[3-[4-(7-isopropoxy-8-methyl-2-oxo-2f/-2-chromenyl)piperazino] propyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCl3, 200 MHz) δ 1 20-1 40 (m, 12H), 1 50-2 00 (m, 6H), 2 10-2 40 (m, 5H), 2 60-3 10 (m, 8H), 3 25-3 40 (m, 6H), 3 95 (s, 3H), 4 0-4 2 (m, 2H), 4 25-4 30 (m, 1H), 4 60-4 68 (m, 1H), 4 78-4 80 (m, 1H), 5 65 (s, 1H), 6 68-6 70 (d, 1H, J= 9 15 Hz), 6 78 (s, 1H), 7 25-7 35 (d, 1H, J= 8 31 Hz), 7 62 (s, 1H) MS (FAB) 743 [M+H]+ (2iS)-N-{4-[4-[3-[4-(7-Isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] propyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrolidine-2-carboxaldehydediethylthioacetal of formula 3 (742 mg, 1 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCO3 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[3-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]propyl] oxy] -5 -methoxy-2-aminobenzoyl} pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2,S)-N-{4-[4-[3-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]propyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 4 (712 mg, 1 mmol), HgCl2 (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H20 (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCO3 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-memoxy-8-{3-[4-(7-isopropoxy-8-methyl-2-oxo-2H-4-chromenyl) piperazmo]propyl}-oxy-(l laS)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 40-1 50 (d, 6H, J= 7 61 Hz), 1 65-2 10 (m, 4H), 2 15 (s, 3H), 2 61-2 80 (m, 4H), 3 0-3 15 (m, 4H), 3 40-3 55 (m, 4H), 3 95 (s, 3H), 4 0-4 2 (m, 6H), 5 65 (s, 1H), 6 68-6 70 (d, 1H, J= 9 15 Hz), 6 78 (s, 1H), 7 25-7 35 (d, 1H, J= 8 31 Hz), 7 62 (s, 1H), 7 64-7 74 (d, 1H, J= 3 70 Hz) MS (FAB) 589 [M+H]+ Example 11 To a solution of (2S)-N-[4-(4-bromobutyl)-oxy-5-methoxy-2-nitrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (535 mg, 1 0 mmol), 7-isopropoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 2 (302 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtnle (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (1 1), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2iS)-N-{4-[4-[4-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] butyl] oxy] -5 -methoxy-2-mtrobenzoyl} pyrrohdine-2-carboxaldehydediethy lthioacetal 3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 12H), 1 50-2 00 (m, 8H), 2 10-2 40 (m, 5H), 2 60-3 10 (m, 8H), 3 25-3 40 (m, 6H), 3 95 (s, 3H), 4 0-4 2 (m, 2H), 4 25-4 30 (m, 1H), 4 60-4 68 (m, 1H), 4 78-4 80 (m, 1H), 5 65 (s, 1H), 6 68-6 70 (d, 1H, J= 9 15 Hz), 6 78 (s, 1H), 7 25-7 35 (d, 1H, J= 8 31 Hz), 7 62 (s, 1H) MS (FAB) 757 [M+H]+ (2iS)-N-{4-[4-[4-[4-(7-Isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazmo] butyl] oxy] -5 -methoxy-2-mtrobenzoyl} pyrrolidme-2-carboxaldehydediethy lthioacetal of formula 3 (756 mg, 1 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHCO3 solution and then extracted with ethyl acetate (3x20 ml) The combined orgamc phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[4-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]butyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[4-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]butyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrolidine-2-carboxaldehydediethylthioacetal of formula 4 (726 mg, 1 mmol), HgCk (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H20 (4 1) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHC03 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{4-[4-(7-isopropoxy-8-methyl-2-oxo-2H-4-chromenyl) piperazino]butyl}-oxy-(l laS)-l,2,3,l la-5if-pyrrolo[2,l-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 40-1 50 (d, 6H, J= 6 10 Hz), 1 65-2 10 (m, 6H), 2 15 (s, 3H), 2 61-2 80 (m, 4H), 3 0-3 15 (m, 4H), 3 40-3 55 (m, 4H), 3 95 (s, 3H), 4 0-4 2 (m, 6H), 5 65 (s, 1H), 6 68-6 70 (d, 1H, J= 9 15 Hz), 6 78 (s, 1H), 7 25-7 35 (d, 1H, J= 8 31 Hz), 7 62 (s, 1H), 7 64-7 74 (d, 1H, J= 3 70 Hz),MS (FAB) 603 [M+H]+ Example 12 To a solution of (2S)-N-[4-(5-bromopentyl)-oxy-5-methoxy-2-mtrobenzoyl] pyrrohdine-2-carboxaldehydediethylthioacetal of formula 1 (549 mg, 1 0 mmol), 7-isopropoxy-8-methyl-4-piperazmo-2H-2-chromenone of formula 2 (302 mg, 1 0 mmol) and K2CO3 (414 mg, 3 0 mmol), in dry acetomtrile (40ml) was refluxed for 48 hrs After the completion of the reaction as indicated by TLC, EtOAc hexane (1 1), the reaction mixture was poured on to the water and then extracted with ethyl acetate This was concentrated under reduced pressure gave the crude product which was further purified by column chromatography on silica gel eluting with EtOAc hexane (3 7) to give the pure (2S)-N-{4-[4-[5-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] pentyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal3 H1 NMR (CDCI3, 200 MHz) δ 1 20-1 40 (m, 14H), 1 50-2 00 (m, 8H), 2 10-2 40 (m, 5H), 2 61-3 10 (m, 8H), 3 20-3 40 (m, 6H), 3 95 (s, 3H), 4 0-4 2 (m, 2H), 4 25-4 30 (m, 1H), 4 60-4 70 (m, 1H), 4 80-4 83 (m, 1H), 5 65 (s, 1H), 6 68-6 70 (d, 1H, J= 9 15 Hz), 6 78 (s, 1H), 7 25-7 35 (d, 1H, J= 8 31 Hz), 7 62 (s, 1H) MS (FAB) 771 [M+H]+ (2S)-N-{4-[4-[5-[4-(7-Iisopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino] pentyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal of formula 3 (770 mg, 1 mmol) was dissolved in methanol (10mL) and to this was added SnCl2 2H2O (1 125 g, 5 mmol) and was refluxed for 1 5 h The reaction mixture was neutralized to pH 8 with NaHC03 solution and then extracted with ethyl acetate (3x20 ml) The combined organic phase was dried over Na2SO4 and evaporated under reduced pressure to afford the crude (2S)-N-{4-[4-[5-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]pentyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrohdine-2-carboxaldehydediethylthioacetal 4 To a solution of (2S)-N-{4-[4-[5-[4-(7-isopropoxy-8-methyl-2-oxo-2H-2-chromenyl)piperazino]pentyl]oxy] -5 -methoxy-2-aminobenzoyl} pyrrohdine-2-carboxaldehydediethylthioacetal of formula 4 (740 mg, 1 mmol), HgCk (613 mg, 2 26 mmol) and CaCO3 (246 mg, 2 46 mmol) in CH3CN/H20 (4 I) was stirred at room temperature for 12 h until the completion of the reaction as shown by TLC (EtOAc) The organic layer is evaporated in vacuum and the residue is diluted with EtOAc To this, saturated NaHCO3 was added slowly at room temperature and the mixture was filtered through a cehte bed and washed with ethyl acetate The filtrate was evaporated in vacuum to get crude 7-methoxy-8-{5-[4-(7-isopropoxy-8-methyl-2-oxo-2i/-4-chromenyl) piperazino]pentyl}-oxy-(l laS)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one 5, which was further purified by column chromatography on silica gel eluting first with ethyl acetate to remove traces of mercuric salts and then with CHCI3 methanol (9 1) H1 NMR (CDCI3, 200 MHz) δ 1 40-1 50 (d, 6H, J= 6 53 Hz), 1 65-2 10 (m, 8H), 2 15 (s, 3H), 2 61-2 80 (m, 4H), 3 0-3 15 (m, 4H), 3 40-3 55 (m, 4H), 3 95 (s, 3H), 4 0-4 2 (m, 6H), 5 65 (s, 1H), 6 68-6 70 (d, 1H, J= 9 15 Hz), 6 78 (s, 1H), 7 25-7 35 (d, 1H, 7=8 31 Hz), 7 62 (s, 1H), 7 64-7 74 (d, 1H, J= 3 70 Hz) MS(FAB)617[M+H]+ Biological Activity: In vitro biological activity studies were earned out at the National Cancer Institute (USA) Cytotoxicity. The compounds 7-methoxy-8-{5-[4-(2-oxo-2i/-4-chromenyl)piperazino] pentyl}-oxy-(l laS)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one, 7-methoxy-8-{3 - [4-(7-methoxy- 8-methyl-2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3,1 la-5i/-pyrrolo[2,l-c][l,4]benzodiazepin-5-one and 7-methoxy-8-{5-[4-(7-methoxy -8-methyl-2-oxo-2H-4-chromenyl)piperazino]pentyl}-oxy-(11aS)-l,2,3,l\a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one were evaluated for in vitro anticancer activity against sixty human tumour cells derived from nine cancer types (leukemia, non-small-cell lung, colon, CNS, melanoma, ovarian, prostate, and breast cancer) as shown in (Table 2) For each compound, dose response curves for each cell line were measured at a minimum of five concentrations at 10 fold dilutions A protocol of 48 h continuous drug exposure was used and a sulforhodamine B (SRB) protein assay was used to estimate cell viability or growth The concentration causing 50% cell growth inhibition (GI50), total cell growth inhibition (TGI 0%growth) and 50% cell death (LC50, -50% growth) compared with the control was calculated The mean graph midpoint values of logio TGI and logio LC50 as well as logio GI50 for 5c, 5d and 5f are listed in Table 1 As demonstrated by mean graph pattern, compound 5c exhibits an interesting profile of activity and selectivity for various cell lines The mean graph mid point of logio TGI and logio LC50 showed similar pattern to the logio GI50 mean graph mid points Table 1 Logi0GI50 logioTGI and logi0LC50 mean graphs midpoints (MGMID) of in vitro cytotoxicity data for the representative compounds against human tumour cell lines (Table Removed) Table 2 LogioLC50 concentration in mol/L causing 50% lethality values for the representative compounds (Table Removed) Each cancer type represents the average of six to nine different cancer cell lines We claim 1. Pyrrolo[2,l-c][l,4]benzodiazepine of formula 5 (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5. 2. A compound as claimed in claim 1 is represented by a group of the following compounds: 7-Methoxy-8-{3-[4-(2-oxo-2H-4-chromenyl)piperazino]propyl}-oxy-(11aS)-l,2,3,11 a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one (5a), 7-Methoxy-8-{4-[4-(2-oxo-2H-4-chromenyl)piperazino]butyl}-oxy-(11aS)-1,2,3, 11a-5H-pyrrolo[2,l-c][l,4]benzodiaze pin-5-one(5b),7-Methoxy-8-{5-[4-(2-oxo-2H-4-chromenyl)piperazino]pentyl}-oxy-(1 laS)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one (5c), 7-Methoxy-8-{3-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3 ,11a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one(5d),7-Methoxy-8-{4-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]butyl }-oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo [2, l-c][ 1,4]benzodiazepin-5-one (5e), 7-Methoxy-8-{5-[4-(7-methoxy-8-methyl-2-oxo-2H-4-chromeny l)piperazino]penty 1} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4] benzodiazepin-5-one(5f),7-Methoxy-8-{3-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chrom e nyl)piperazino]propyl}-oxy-( 1 la5)-1,2,3,11 a-5H-pyrrolo[2,1 -c][ 1,4]benzodiazepin-5-one(5g),7-Methoxy-8-{4-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino] butyl} -oxy} -(11 aS)-1,2,3,11 a-5H-pyrrolo[2,1 -c] [ 1,4]benzodiazepin-5-one(5h),7-Meth oxy-8-{5-[4-(7-ethoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]pentyl}-oxy-( 11 a S)-l,2,3,l la-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one (5i), 7-Methoxy-8-{3-[4-(7-isopropoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]propyl} -oxy-( 11 aS)-1,2,3,11 a-5H-pyrrolo[2,l-c][l,4]benzodiazepin-5-one (5j), 7-Methoxy-8-{4-[4-(7-isopropoxy-8-methyl-2-oxo-2H-4-chromenyl)piperazino]butyl }-oxy-(l 1 a5)-1,2,3,11 a-5H-pyrrolo [2,l-c][l,4]benzodiazepin-5-one(5k), 7-Methoxy-8-{5-[4-(7-isopropoxy-8-methyl-2- 3. A process for the preparation of novel pyrrolo[2,l-c][l,4]benzodiazepine of formula 5 (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R.2 is H or CH3 and n is an integer varying from 3-5, the said process comprising the steps of: a) reacting 4-piperazino-2H-2-chromenone or 7-alkoxy-8-methyl-4-piperazino-2H-2-chromenone of formula 1 (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5 with(2S)-N-[4-(n-bromoalkyl)-oxy-5-methoxy-2-nitrobenzoyl]pyrrolidine -2-carboxaldehydediethylthioacetal of formula 2 (Formula Removed) in presence of a base, in a dry organic solvent, for a period of about 48 h under reflux, followed by extraction in water and isolating the compound of (2S)-N-{4-[4-[n-[4-(2-oxo-2H-2-chromenyl)piperazino]alkyl]oxy]-5-methoxy-2-nitrobenzoyl} pyrrolidine-2-carboxaldehydediethylthioacetal or (2S)-N-{4-[4-[n-[4-(7-alkyloxy-8-methyl-2-oxo-2H-2-chromenyl)piperazi no]alkyl]oxy]-5-methoxy-2-nitrobenzoyl}pyrrolidine-2-carboxaldehyde di ethylthioacetal of formula 3 by known methods, (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5, b) reducing the above said nitro compound of formula 3 with SnCl2.2H20 or acid catalyst in presence of an organic solvent, under reflux, for a period of 1-2 hrs, followed by neutralizing the resultant reaction mixture at a pH of about 8 and isolating the amino compound (2S)-N-{4-[4-[n-[4-(2-oxo-2H-2- chromenyl) piperazino]alkyl]oxy]-5-methoxy-2-aminobenzoyl}pyrrolidine- 2-carboxald ehyde diethylthioacetal or (2S)-N-{4-[4-[n-[4-(7-methoxy-8- methyl-2-oxo-2H-2-chromenyl)piperazino]alkyl]oxy]-5-methoxy-2-amino benzoyl} pyrroli dine-2-carboxaldehyde diethylthioacetal of formula 4 by known methods, (Formula Removed) wherein R1 is H or alkoxy group selected from methoxy, ethoxy and propoxy groups, R2 is H or CH3 and n is an integer varying from 3-5, c) reacting the above said amino compound of formula 4 with a de-protecting agent in the presence of an aqueous organic solvent, at a temperature in the range of 20-25°C, for a period of about 12 hrs, separating the organic layer from the resultant reaction mixture followed by evaporation under vacuum to obtain the residue and diluting the above said residue with ethyl acetate followed by slowly mixing with saturated sodium bicarbonate, filtering, washing and evaporating the resultant filtrate, followed by purification by known methods to obtain the desired pyrrolo[2,l-c][l,4]benzodiazepine hybrid of formula 5. 4. A process as claimed in claim 7, wherein the base used in step (a) is selected from K2CO3 and Na2CO3. 5. A process as claimed in claim 7, wherein the organic solvent used in step (a) is selected from acetonitrile, acetone and N, N-demethyl formamide. 6. A process as claimed in claim 7, wherein the acid catalyst used in step (b) is selected from the group consisting of Sn/HCl, Zn/CH3COOH and Pd/C-H2. 7. A process as claimed in claim 7, wherein the organic solvent used in step (b) is an alcohol selected from the group consisting of methanol, ethanol and ethylacetate. 8.. A process as claimed in claim 7, wherein the de-protecting agent used in step (c) is selected from the group consisting of HgCl2/CaCO3, HgO/HgC12 and Bi(OTf)3.xH2O. 9. A process as claimed in claim 7, wherein the organic solvent used in step (c) is selected from the group consisting of acetonitrile, dichloromethane and chloroform.

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3013-DEL-2005-Abstract-(02-07-2012).pdf

3013-del-2005-abstract.pdf

3013-DEL-2005-Claims-(02-07-2012).pdf

3013-del-2005-claims.pdf

3013-DEL-2005-Correspondence Others-(02-07-2012).pdf

3013-DEL-2005-Correspondence-Others-(07-08-2009).pdf

3013-del-2005-correspondence-others.pdf

3013-del-2005-description (complete).pdf

3013-del-2005-drawings.pdf

3013-del-2005-form-1.pdf

3013-del-2005-form-18.pdf

3013-del-2005-form-2.pdf

3013-DEL-2005-Form-3-(02-07-2012).pdf

3013-DEL-2005-Form-3-(07-08-2009).pdf

3013-del-2005-form-3.pdf

3013-del-2005-form-5.pdf

3013-DEL-2005-Petition-137-(02-07-2012).pdf