| Title of Invention | NOVEL ARYLALKYL INDOLES HAVING SEROTONIN RECEPTOR AFFINITY AND PROCESS FOR THEIR PREPARATION |
|---|---|
| Abstract | The present invention relates to novel tetracyclic arylalkyl indoles, their derivatives, their analogues, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, novel intermediates described herein and pharmaceutically acceptable compositions containing them. This invention particularly relates to novel tetracyclic arylalkyl of the general formula (I), their derivatives, their analogues, their tautomeric forms, their "stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, novel intermediates described herein and .pharmaceutically acceptable compositions containing them, This invention also relates to process/es for preparing such compound/s of general formula (I), composition/s containing effective amount/s of such a compound and the use of such a compound/composition in therapy. |
| Full Text | Novel arylalky( indoles having serotonin receptor affinity useful as therapeutic agents, process for their preparation and pharmaceutical compositions containing them. Field of Invention: The present invention relates to novel tetracyclic arylalkyi indoles, their derivatives, their analogues, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, novel intermediates described herein and pharmaceuticaliy acceptable compositions containing them. The present invention also relates to the process for preparing the compounds of general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their geometric fomis, Iheir N-oxIdes, their polymorphs, their pharmaceutically acceptable salts, their phannaceutically acceptable solvates, novel intermediates described herein and pharmaceutically acceptable compositions containing them. The compounds of the general fonnula (I) of this invention are 5-HT (Serotonin) ligands e.g. agonists or antagonists. The compounds of the general formula {!) of this invention, by the virtue of there chemical characteristic, could either independently or simulteneously modulate the melatonin receptor i.e. either they are melatonergic ligands e.g. agonists or antagonists, or they interact v^ith both 5-HT as vi/ell as melatonin receptor. Thus, compounds of general fomiula (1) of this invention are useful for treating diseases \Mnerein activity of either 5-HT (Serotonin) and/or melatonin is modulated to obtain the desired effect. Specifically, the compounds of this invention are useful in the treatment and / or prophylaxis of psychosis, paraphrenia, psydiotic depression, mania, schizophrenia, schizophreniform disorders, anxiety, migraine headache, depression, drug addiction, convulsive disorders, personality disorders, hypertension, autism, post-traumatic stress syndrome, alcoholism, panic attacks, obsessive-compulsive disorders, chronobiological abnormalities, circadian rhythms, anxiolytic, osteoporosis, ischemic stroke, lower the risk of SIDS in young infants with low endogenous melatonin levels, reproduction, glaucoma and sleep disorders. The compounds of general formula (I) of this invention are also useful to treat psychotic, affective, vegetative and psychomotor symptoms of schizophrenia and the extrapyramidal motor side effects of other antipsychotic dnjgs. The compounds of general formula (I) of this invention are also useful to treat neurodegenerative disorders like Alzheimer"s disease, Parkinsonism and Huntington"s chorea and chemotherapy-induced vomiting. The compounds of general formula (I) of this invention are also useful in modulation of eating behavior and thus are useful in reducing the morbidity and mortality associated with excess weight. Background of the Invention Many diseases of the central nervous system are influenced by the adrenergic, the dopaminergic and the serotenergic neurotransmitter systems. Serotonin has been implicated in a number of diseases and conditions, which originate in the central nervous system, tiese include diseases and conditions related to sleeping, eating, perceiving pain, controlling body temperature, controlling blood pressure depression, anxiety, schizophrenia and other bodily states. (References; Fuller, R. W., Drugs Acting on Serotonergic Neuronal Systems, Biology of Serotonergic Transmission, John Wiley & Sons Ltd, (1982), 221-247; Boullin D. J., Serotonin in Mental abnormalities (1978), 1. 316; Barchas J. et, al., Serotonin and Behavior (1973)). Serotonin also plays an important role in tfie peripheral systems, such as the gastrointestinal system, wt\ere it has been found to mediate a variety of contractile, secretory and electrophysiologic effects. Due to the broad distribution of serotonin within the body, there is lot of interest and use, in the drugs that affect serotonergic systems. Particularly, preferred are the compounds which have receptor specific agonism and/or antagonism for the treatment of a wide range of disorders, including anxiety, depression, hypertension, migraine, obesity, compulsive disorders, schizophrenia, autism, neurodegenerative disorders like Al^eimer"s disease, Parkinsonism and Huntington"s chorea and chemotherapy-induced vomiting (References. Gershon M. D. et. al.. The peripheral actions of 5-Hydroxytryptamine (1989), 246; Saxena P. R, et. al.. Journal of Cardiovascular Pharmacology (1990). supplement 7, 15). The major classes of serotonin receptors (5-HT,.7) contain fourteen to eighteen separate receptors that have been fonnally classified (References; Glennon et al, Neuroscience and Behavioral Reviews (1990), 14, 35 and Hoyer D. et al, Phanmacol. Rev. (1994), 46, 157-203). Recently discovered information regarding sub-t^e identity, distribution, structure and funcyon suggests that it is possible to identify novel, sub-type specific agents having improved therapeutic profiles with lesser side effects. The S-HTe receptor was identified in 1993 (References: Monsma et al, Mol. Pharmacol. (1993), 43, 320- 327 and Ruat M. et al, Biochem. Biophys. Res. Com. (1993), 193, 269-276), Several antidepressants and atypical antipsychotics bind to the S-HTe receptor with high affinity and this binding may be a factor in their profile of activities (References: Rofri et al, J. Pharm. Exp. Therapeut, (1994). 268, 1403-1410; Sleight et al, Exp. Opin. Ther Patents (1998), 8, 1217-1224; Bourson et al, Brit J. Pharmacol. (1998), 125, 1562-1566; Boess et al, Mol. Pharmacol., 1998, 54, 577-583; Sleight et al, Brit. J. Pharmacol. (1998), 124, 556-562). In addition, 5-HT6 receptor has been linked to generalized stress and anxiety states (Reference: Yoshioka et al, Life Sciences (1998), 17;i8,1473-1477). Together these studies and observations suggest that compounds that antagonize the S-HTe receptor will be useful in treating various disorders of the central nervous system. There is very strong evidence that Melatonin is important for the regulation of a variety of neural and endocrine functions, espedally those that exhibit circadian and circannual rtiythmicity. Great interest therefore lies in the possibility of making available to the clinician melatonin analogues that are metabolically more stable and have an agonist or antagonist character and of which the tiierapeutic effect may be expected to be superior to that of the homione itself. PCT patent application gives extensive literature c^ studies \Mth Melatonin and potential therapeutic application of various ligands reported till date. Those various effects are exerted via the intermediary of specific Melatonin receptors. Molecular biology studies have demonstrated the existence of a numtjer of receptor sub-types that are capable of binding that hormone (Trends Pharniacol. Sci., 1995, 16, p. 50; WO 97 04094), Melatonin acts on the CNS to affect neural mechanisms through receptors located in the brain. Additionally, a number of studies indicate the existence of direct effects of Melatonin in peripheral organs via peripheral melatonin receptors. Melatonin receptors are present in the heart, lungs, prostate gland, gonads, vjhUe blood cells, retina, pituitary, thyroid, kidney, gut and blood vessels (Withyachumnamkul et al.. Life Sci, 12 65, 1986). Three Melatonin receptor subtypes have been identified so far MT-I, MT-2 and Mel 1 c (Barrett et al., Biol. Signals Recept., 1999, 8: 6-14). There is evidence suggesting both Melatonin agonists and antagonists would be of potential therapeutic use for a variety of maladies and conditions. PCT application WO 00/72815, discuss in depth applications and use of such compounds and details of which are incorporated herein by reference. Also U. S. patent 6465660 and U. S. patent application publication number US 2003/0105087 discuss some tricyclic indole and tricyclic azaindole derivatives having very valuable pharmacological characteristics in respect of melatoninergic receptors. U. S. patent 4,839,377 and U. S. patent 4,855,314 refer to 5-substituted 3-aminoalkyl indoles. The compounds are said to be useful for the treatment of migraine. British Patent 2,035,310 refers to 3-aminoaIkyl-1H-indole-5-thioamides and cartoxamides. The compounds are said to be useful in treating hypertension, Raymond"s disease and migraine, European Patent Publication 303,506 refers to 3-polyhydropyridyl-5-substituted-1H-indoles. The compounds are said to have 5-HTi receptor agonists and vasoconstrictor activity and to be useful in treating migraine. European Patent Publication 354,777 refers to N-piperidinylindolylethyl-alkane sulfonamide derivatives. The compounds are said to be 5-HTi receptor agonists and have vasoconstrictor activity and are useful in treating cephalic pain. European Patent Publication 438,230, refers to rndole-substituted five-membered heteroaromatic compounds. The compounds are said to have "5-HTi-like" receptor agonist activity and to be useful in the treatment of migraine and other disorders for which a selective agonist of these receptors is indicated. European Patent Publication 313,397 refers to 5-heterocyclic indole derivatives. The compounds are said to have exceptional proper^s for the treatment and prophylaxis of migraine, cluster headache and twadache associated with vascular disorders. These compounds are also said to have exceptional "5-HTi-like" receptor agonism. International Patent Publication WO 91/16897, refers to 5-heterocydic indole derivatives. The compounds are said to have exceptional properties for the treatment and prophylaxis of migraine, cluster headache, and headache associated with vascular disorders. These compounds are also said to have exceptional ""5-HTrlike" receptor agonism. European Patent Publication 457,701 refers to aryloxy amine derivatives as having high affinity for 5-HTio serotonin receptors. These compounds are said to be useful for treating diseases related to serotonin receptor dysfunction, for example, migraine. European Patent Publication 497,512 A2, refers to a class of imidazole, triazole and tetrazole derivatives which are selective agonists for "5-HTrlike" receptors. These compounds are said to be useful for treating migraine and associated disorders. International Patent Publication WO 93/00086, describes a series of tetrahydcX)caft)azole derivatives, as 5-HTi receptor agonists, useful for the treatment of migraine and related conditions. International Patent Putilication WO 93/23396, refers to fused imidazole and triazole derivatives as 5-HTi receptor agonists, for tfie treatment of migraine and other disorders. Schoeffter P. et al. refer to methyl 4-{4-[4-(1,1,3-trioxo-2H-1,2-benzoisothiazol-2-yl)butyll-1-pipera2inyl}1H-indole-3-carboxylate as a selective antagonist for the 5-HTIA receptor in their paper "SDZ216-525, a selective and potent 5-HTIA receptor antagonist" European Journal of Pharmacology, 244, 251-257 (1993). International Patent Publication WO 94/06769, refers to 2-substituted-4-piperazine-benzothiophene derivatives that are serotonin 5-HTIA and 5-HT,o receptor agents useful in the treatment of anxiety, depression, migraine, stroke, angina and hypertension. Summary of tt^e Invention: The present invention relates to novel tetracyclic arylalkyl, their derivatives, their analogues, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, novel Intermediates described herein and pharmaceutically acceptable compositions containing them. More particularly, the present invention relates to novel tetracyclic arylalkyl of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their phamiaceuticalty acceptable solvates, novel intemiediates described herein and pharmaceutically acceptable compositions containing them and use of these compounds in medicine. I wherein Ro is either hydrogen or linear or branched (Ci-C2)alkyli Ri, R:, R3, R4. R5, Re, R7, Rs, R9. Rio, R11 and R,2 may be same or different and each independently represent hydrogen, halogen, 0x0, thio, pertialoalkyi, hydroxy, amino, nitro, cyano, formyl, amidino, guanidino, substituted or unsubstituted groups such as linear or branched (Ci-C,2)alkyl, (Cj-C.zjalkenyl, (CrCi2)alkynyl, (C3-C7)cycloalkyl, (C3-CTJcydoalkenyl, bicycloalkyl, bicycloaikenyl, (C,-Cii)alkoxy, cyclo(C3-CT)alkoxy, aryl, aryloxy, aralkyi, aralkoxy, heterocyclyl, heteroaryl, heterccyclylalkyi, heteroaralkyl, heteroaryloxy, heleroaralkoxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino, monoalkylamino, dialkylamino, arylamino, diarylamino, aralkylamino, alkoxycarbonyl, aryloxycarbonyl. aralkoxycarbonyl, heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl. aminoalkyi, monoalkylaminoalkyl, dialkylaminoatkyi, alkoxyalkyl, aryfoxyalkyf. aralkoxyalkyi, alkylthio, thioatkyi, alkoxycarbwiylamino, arytoxycartxinylamino, aralkyloxycartMnylamino, aminocartranylamino, alkylaminocartwnylamino, dialkylaminocarbonylamtno, alkylamidino, The compounds of general formula (I) of this invention are useful in the treatment and/ or prophylaxis of a condition wherein modulation of melatonin activity is desired. The compounds of general formula (I) of this invention are useful in the treatment and/ or prophylaxis of a condition wherein modulation of 5-HT and melatonin activities gives desired effect. The present invention provides for use of the compounds of general formula (I) according to above, for the manufacture of the medicaments for the potential use in the treatment and/ or prophylaxis of certain CNS disorders such as, anxiety, depression, convulsive disorders, obsessive-compulsive disorders, migraine headache, cognitive memory disorders e.g. Alzheimer"s disease and age-related cognitive decline, ADHD {Attention Deficient Disorder/ Hyperactivity Syndrome), personality disorders, psychosis, paraphrenia, psychotic depression, mania, schizophrenia, schizophreniform disorders, withdrawal from dnjg abuse such as cocaine, ethanol, nicotine and benzodiazepines, panic attacks, chronobiological abnormalities, circadian rhythms, anxiolytic, osteoporosis, ischemic stTXJke. lower the risk of SIOS in young infants with low endogenous melatonin levels, reproduction, glaucoma, sleep disorders (including disturbances of Circadian rhythm) and also disorders assodated witii spina! trauma and / or head injury such as hydrocephalus. Compounds of tine invention are further expected to be of use in the treatment of mild cognitive impairment and other neurodegenerative disorders like Alzheimer"s disease. Parkinsonism arwl Huntington"s chorea. The compounds of the invention are also expected to be of use in the treatment of certain Gl (Gastrointestinal) disorders such as IBS (Irritable bowel syndrome) or chemotherapy induced emesis. The compounds of the invention are also expected to be of use in the modulation of eating behavior and these compounds can also be used to reduce morbidity and mortality associated with the excess weight. The present invention provides a method for the treatment of a human or a animal subject suffering from certain CNS disorders such as, anxiety, depression, convulsive disorders, obsessive-compulsive disorders, migraine headache, cognitive memory disorders e.g. Alzheimer"s disease and age-related cognitive decline, ADHD (Attention Deficient Hyperactivity Disorder), personality disorders, psychosis, paraphrenia, psychotic depression, mania, schizophrenia, schizophreniform disorders, withdrawal from dnjg abuse such as cocaine, ethanol, nicotine ar^d benzodiazepines, panic attacks, chronobiological abnonnalities, circadian rhythms, anxiolytic, osteoporosis, ischemic stroke, lower the risk of SIDS in young infants with low endogenous melatonin levels, reproduction, glaucoma, sleep disorders (including disturbances of Circadian rtiythm) and also disorders associated with spinal trauma and /or head injury such as hydrocephalus. Compounds of the invention are further expected to be of use in the treatment of mild cognitive impaimient and other neurodegenerative disorders like Alzheimer"s disease, Parkinsonism and Huntington"s chorea. The present invention also provides a method for modulating 5-HT and/ or melatonin receptor function desired in certain cases. The present invention also includes a isotopically-latselled compounds, which are identical to those defined in the general fomiula (1), but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number found usually in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphoais, fluorine, chlorine, iodine, bromine and mTecnitium, exemplified by ^H, ^H. "C, "C, ^^C, ^^N, "^N. "=0, ""F, """Tc, ""P, S, ^^=1 and "^1. Compounds of present invention and pharmaceuticaify acceptable salts and prodrugs of said compounds that contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Isotopically labelled compounds of the present invention are useful in drug and/or substrate tissue distribution and target occupancy assays. For example, isotopically latielled compounds are particularly useful in SPECT (single photon emission computed tomography) and in PET (positron emission tomography). An effective amount of a compound of general fonnula (1) or its salt is used for producing medicaments of the present invention, along with conventional pharmaceutical auxiliaries, carriers and additives. The present invention also relates to a pharmaceutical composition for treating and/or prophylaxis of disorders, a condition wherein modulation of 5-HT and/or melatonin is desired in a mammal, comprising: a. a pharmaceutically acceptable carrier b. a compound of general formula (I) as defined above, and c. a 5-HT re-uptake inhibitor, or its pharmaceutically acceptable salt; wherein the amounts of each active compound (a compound of general fonnula (1) and a 5-HT re-uptake inhibitor), is such that the combination is effective in treating such a condition. The present invention also relates to a method of treatment and/or prophylaxis of disorders, a condition wherein modulation of 5-HT and/or melatonin is desired in a mammal, comprising: a. a pharmaceutically acceptable carrier b. a compound of general formula (I) as defined above, and c. a 5-HT re-uptake inhibitor, or its pharmaceutically acceptable salt; wherein the amounts of each active compound (a compound of general fomiula (I) and a 5-HT re-uptake inhibitor), is such that the combination is effective in treating such a condition. The present invention also relates to a pharmaceutical composition for treating and/or prophylaxis of disorders, a condition wherein modulation of 5-HT and/or melatonin is desired in a mammal, comprising: a. a pharmaceutically acceptable carrier b. a compound of general formula (!) as defined above, and c. either of serotonergic or melatonergic ligand, or its pharmaceutically acceptable salt; wherein the amounts of each active compound (a compound of general formula (1) and a serotonergic or melatonergic ligand), is such that the combination is effective in treating such a condition. The present invention also relates to a method of treatment and/or prophylaxis of disorders, a condition vi^erein modulation of 5-HT and/or melatonin is desired in a mammal, comprising. a. a pharmaceutically acceptable carrier b. a compound of general formula (I) as defined above, and c. either of a serotonergic or melatonergic ligand, or its pharmaceutically acceptable salt; wherein the amounts of each active compound (a compound of general formula (1) and a serotonergic or melatonergic ligand), is such that the combination is effective in treating such a condition. The present invention also relates to a process for the preparation of the above said novel compounds, their derivatives, their analogues, their tautomeric forms, their stereoisomers, their geometric forms, their N-oxides, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, novel intermediates described herein and pharmaceutical compositions containing them. Detailed description of the invention: The present invention relates to novel tetracyclic arylalkyi, their derivatives, their analogues, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates, novel intermediates described herein and pharmaceutically acceptable compositions containing them. More particularty, the present invention relates to novel tetracyclic arylalkyi of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their phannaceuticaily acceptable salts, ttieir pharmaceutical ly acceptable solvates, novel intermediates described herein and phamiaceutically acceptable compositions containing them and use of these compounds in medicine. wherein Ro is either hydrogen or linear or branched ind^iendenUy represent tiydrogen, halogen, 0x0, thio, perhaloalkyi, hydroxy, amino, nitro, cyano, fomiyl, amidino, guanidino, substituted or unsubstituted groups such as linear or branched {Ci-Ci2)aikyl, (CrC,2)alkenyl, (C2-Ci2)alkynyl, (C3-C7)cyc|oalkyl, (C3- C7)cycloalkenyl, bicycloalkyi, bicyctoalkenyl, (Ci-Ci2)alkoxy, cyclo(C3-Cv)alkoxy, aryl, aryloxy, aralkyi, aralkoxy, heterocydyl, heteroaryl, heterocyclylalkyl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino, monoatkylamino, dialkylamino, arylamino, diarylamino, aralkylamino, alkoxycartjonyl, aryloxycarbonyl, aralkoxycarbonyl, heterocyclyialkoxycarbonyl, heteroaryloxy carbon yl, hydroxyalkyi, aminoalkyi, monoalkylaminoalkyi, dialkylaminoalkyl, atkoxyaikyi, aryloxyalkyi, arajkoxyalkyl, alkylthio, thioalkyi, alkoxycarbonylamino, aryloxycartsonylamino, aralkyloxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino. dialkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino, hydrazine, hydroxylamino, carboxylic acid and its derivatives, sulfonic acids and its derivatives, phosphoric acid and its derivatives; or the adjacent groups like Ri and R; or R^ and Rs or R3 and R4 or Rs and Rs or Re and R7 or R? and Rs together with carbon atoms to which they are attached may fomi a 5, 6, or 7 membered ring, vt/hich may further optionally contain one or more double bonds and/or one or more hejeroatoms such as the group "Oxygen", "Nitrogen", "Sulfur" or "Selenium" and combinations of double bond and heteroatoms; or Rg and R10 or Rn and R12 together represent double bond attached to "Oxygen" or "Sulfur"; or Rg and Rm or Rn and R,2 togefrier with the carbon atoms to which tfiey are attached may form a 3, 4, 5, or 6 membered ring, which may further optionally contain one or more double bonds, and/or one or more heteroatoms such as the group "Oxygen", "Nitrogen", "Sulfur or "Selenium" and also includes combination of one or more double bonds with "heteroatoms", as above defined. Ri3 and Ri^ may be same or different and each independently represents hydrogen, substituted or unsubstituted groups such as linear or branched (Ci-C,2)alkyl, (C2-Ci2)alkenyl, (C2-Ci2)alkynyi, (C2-Ci2)alkanoyi {C3-C7)cycloalkyl, {C3-C7)cycloalkenyl, bicydoalkyi, bicycloalkenyl, aryt, aralkyi, heteroaryl, heterocyclylalkyi; optionally R13 and Ri^ along wiWi the nitrogen atom, may form a 3, 4, 5, 6 or 7-membered heterocyclic ring, wherein the ring may be further substituted, and it may have either one, two or three double bonds or "additional heteroatoms", as defined above, "n" is an integer ranging from 1 to 8. It is preferred that n be 1 to 4. The carbon chains which "n" represents may be either linear or branched. Suitable groups represented by Ri, R2, R3. R-i, Rs, Re. R?, Ra, R9. Rio, Rn and Ri; may be a halogen atom such as fluorine, chlorine, bromine or iodine; perhaloalkyi particularly perhalo(CrC6)alkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, fluoroefriyl, difluoroethyl and the like; substituted or unsubstituted (CrCi2)alkyl group, linear or branched (Ci-Ca)alkyl group, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyi, hexyl, iso-hexyl, heptyl, octyl and the like; substituted or unsubstituted {C2-Ci2)alkenyl group such as ethylene, n-propylene pentenyl, hexenyl, heptynyl, heptadienyl and the like; {C2-Ci2)alkynyi substituted or unsubstituted (C2-Ci2)alkynyl group such as acetylene and the like; cyclo(C3-C7)alkyl group such as cyclopropyl, cydobutyl, cydopentyl, cyclohexyl, cycloheptyl, the cycloalkyi group may be substituted; cydo(C3-C7)alkenyl group such as cyclopentenyl, cyclohexenyl, cydoheptynyl, cycloheptadienyl, cydoheptatrienyl and the like, the cycloalkenyl group may be substituted; (Ci-Ci2)alkoxy, especially, (Ci-Cejalkoxy group such as methoxy, ethoxy, propyloxy, butyloxy. iso-propyloxy and the like, which may be substituted; cyclo(C3-C7} alkoxy group such as cyclopropyloxy, cyclobutyloxy, cydopentyloxy, cyclohexyloxy, cydoheptyloxy and the like, the cyctoalkoxy group may be substituted; aryl group such as phenyl or naphthyl, the aryl group may be substituted; aralkyi group such as benzyl, phenethyl, C6HsCH2CH2CH2, naphthylmethyl and the like, the aralkyi group may be substituted and the substituted aralkyi is a group such as CH3C6H4CH2, Hal-C6H4CH;, CHaOCeH^CHj, CH30C6H4CH2CH2 and the like; aralkoxy group such as benzyloxy, phenethyloxy, naphthylmethyloxy, phenyl propyloxy and the like, the aralkoxy group may be substituted; heterocyclyl groups such as azihdinyl, pyrrolidinyl, morpholinyl, piperidinyf, piperazinyl and the like, the heterocyclyl group may be substituted; heteroaryl group such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, imidazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, benzofuranyl and the like, the heteroaryl group may be substituted; heterocyclo(Ci-C6)alkyl, such as pyrrolidinylalkyi, piperidinylalkyi, morpholinylalkyl, thiomorpholinylalkyi, oxazolinylalkyi and the like, the heterocydo(Ci-C6)alkyl group may be substituted; heteroaratkyi group such as furanylmethyl, pyridinylmethyl, oxazolyl methyl, oxazolylethyl and the like, the heteroaralkyi group may be substituted; heteroaryloxy, heteroaralkoxy, heteracycloalkoxy, wherein heteroaryl, heteroaralkyl, heterocydoalkyi and heterocyclyialkyi moieties are as defined earlier and may be substituted; acyl groups such as acetyl, propionyl or benzoyl, the acyl group may be substituted; acyloxy group such as CH3COO, CHaCHjCOO, CeHsCOO and the like which may optionally be substituted, acylamino group such as CH3CONH, CH3CH3CONH, C3H7CONH, CeHgCONH which may be substituted, (CrCelmonoalkylamtno group such as CHaNH, C2HSNH, C3H7NH, CeHnNH and the like, which may be substituted, (Ci-C6)dialkytamino group such as N(CH3)2, CH3(C;H5)N and the like, which may be substituted; arylamino group such as CeHgNH, CH3{C6Hs)N, C6H„(CH3)NH, NH-CeHrHal and the like, which may be substituted; arylalkylamino group such as CeHsCHjNH, CeHsCHjCHzNH, CsHsCHjNCHa and the like, which may be substituted; hydroxy(Ci-C6)alkyl which may be substituted, amino{CrC6)alkyl which may be substituted; mono{Ci-C6)alkylamino(CrC6)a!kyl, di(Ci-C6)a!kylamino(Ci-C6)alkyl group wtiich may be substituted, alkoxyalkyl grciup such as methoxymethyl, ethoxymethyl, methoxyefriyl, ethoxyethyi and the like, which may be substituted; aryloxyalkyi group such as CeHgOCHj, C6H50CH2CH2, naphthyloxymethyl and the like, which may be substituted; araikoxyalkyi group such as CsHsCHjOCH;, C6H5CH2OCH2CH2 and the like, which may be substituted; (CrC6)alkytthio, thio(C,-C6)alkyl which may be substituted, alkoxycarbonylamino group such as CjHsOCONH, CHaOCONH and the like which may be substituted; aryloxycartjonylamino group as CeHgOCONH, C6HsOCONCH3, CeHsOCONCjHs, C6H4CH3OCONH, C6H4(OCH3)OCONH and the like which may be substituted; aralkoxycarbonylamino group such C6H5CH2OCONH, CgHsCHjCHzOCONH, CgHsCHsOCONCCHa). C6HsCH20CON(C2H5), C6H4CH3CH2OCONH, C6H40CH3CH20CONH and the like, which may be substituted; aminocarbonylaniino group; (Ci-C6)alkylaminocarbonylamino group, di(Cr Cejalkylaminocarbonylamino group; (CrCeJalkylamidino group, (Ci-C6)alky[guanidino, di(Ci-C6)alkyiguanidino groups, hydrazine and hydroxyiamino groups; carboxylic acid or its derivatives such as amides, like CONHj, alkylaminocarbonyl like CH3NHCO, (CH3)2NCO, C2HENHC0, (C2H5)2NC0, arylaminocarbonyl like PhNHCO, NapthylNHCO and the like, aralkylaminocarbonyl such as PhCH2NHC0, PhCH2CH2NHCO and the like, heteroarylaminocarbonyl and heteroaralkylamino carbonyl groups where the heteroaryl groups are as defined earlier, heterocyclylaminocarbonyi where the heterocyclyl group is as defined earlier, carboxylic acid derivatives such as esters, w+ierein the ester moieties are alkoxy carbonyl groups such as unsubstituted or substituted phenoxycarbonyl, naphthyloxycarbonyl and the like; aralkoxycarbonyl group such as benzyloxycarbonyl, phenethyloxycarbonyl, naphthylmethoxycarbonyl and the like, heteroaryloxycarbonyl, heteroaralkoxycarbonyl, wherein the heteroaryl group is as defined earlier, heterocycloxycarbonyl where heterocycle is as defined earlier and these carboxylic acid derivatives may be substituted; sulfonic acid or its derivatives such as SOjNHz, S0zNHCH3, S02N{CH3)2, SOzNHCFa, S02NHCO(Ci-C6)alkyl, S02NHC0aryl where the aryl group is as defined earlier and the sulfonic acid derivatives may be substituted; phosphoric acid and its derivatives such as P(0)(0H)2, P{0)(OCi-C6-alkyl)2, P(0)(0-aryl)2 and the like. Suitable cyclic staictures formed by the two adjacent groups like R, and R2 or R? and Rs or R3 and R4 or R5 and R5 or Re and R7 or R7 and Rs together with carbon atoms to w^ich they are attached may form a five or a six membered ring, which may further optionally contain one or more double bonds and/or one or more heteroatoms such as the group "Oxygen", "Nitrogen", "Sulfur or "Selenium" or a combination of one or more double bonds and hetero atoms, the cyclic structures may be optionally substituted phenyl, naphthyl, pyridyl, furanyl, thienyl, pyrrolyl, imidazolyl, pyrimidinyl, pyrazinyl and the like. Suitable substituents on the cyclic structure formed by R, and R2 or Rz and Rs or Rs and R^ or Rs and Re or Re and R? or R7 and Rs together with the adjacent cartton atoms to which they are attached include 0x0, hydroxy, halogen atom such as chlorine, bromine and iodine; nitro, cyano, amino, formyl, (d-CaJalkyl, (d-CaJalkoxy, throalkyi, alkylthio phenyl or benzyl groups. Ri3 and R14 represents hydrogen, substiUjted or unsubstituted linear or branched (C-Ci2)alkyl such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, pentyl, hexyl, octyl and the like; (C2-C,2}alkanoyl such as acetyl, propanoyi and the like; aryl group such as phenyl or naphthyl, the aryl group may be substituted; cycIo(C3-C7)alkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, ttie cycloalky! group may be substituted; the aralkyi group may be substituted and the substituted aralkyi is a group such as CH3C6H4CH2, Hal-C6H4CH2, CH3OC6H4CH2, CH3OC6H4CH2CH2 and the like; (C3-C7)cycloheteroaikyl with heteratoms like "Oxygen", "Nitrogen", "Sulfur" or "Selenium" optionally containing one or two, multiple bonds such as double or triple bonds. Suitable hetero cyclic rings fonned between Ri3 and R,4 along with "Nitrogen atom" be such as pyrrolyl, pyrrolidinyl, piperidinyl, pyridine, 1,2,3,4-Tetrahydro-pyridine, imidazolyl, pyrimidinyl, pyrazinyl, piperazinyl, diazolinyl and the like; the heterocyclyl group may be substituted: heteroaryl group such as pyridyl, imidazolyl, tetrazolyl and the like, the heteroaryl group may be substituted; heterocyclo(Ci-C6)alkyl, such as pyrrolidinealkyi, piperidinealkyi, morpholinealkyi, thiomorpholinealkyl, oxazolinealkyi and the like, the heterocyclo(CrC6)alkyl group may be substituted; heteroaralkyi group such as furanmethyl, pyridinemethyl, oxazolemethyl. oxazolethyl and the like, ttie heteroaralkyi group may be substituted; heteroaryloxy, heteroaralkoxy, heferocycloaikoxy, wherein heteroaryl, heteroaralkyi, heterocycloalkyi and heterocyclylalkyi moieties are as defined eariier and may be ftjrther substituted. In the case of the compounds of general formula (1) having an asymmetric carbon atom the present invention relates to the D-form, the L-form and D,L- mixtures and in the case of a number of asymmetric cartoon atoms, the diastereomeric forms and the invention extends to each of these stereoisomeric forms and to mixtures thereof including racemates. Those compounds of general formula (I) which have an asymmetric carbon and as a rule are obtained as racemates can be separated one from the other by the usual methods, or any given isomer may be obtained by stereospecific or asymmetric synthesis- Hovi"ever, it is also possible to employ an optically active compound from the start, a con"espondingly optically active or diastereomeric compound then being obtained as the final compound. In the case of the compounds of general formula (I), where tautomerism may exist, the present invention relates to all of the possible tautomeric forms and the possible mixture thereof. In the case of the compounds of general formula (I) containing geometric isomerism the present invention relates to all of these geometric isomers. Suitable pharmaceutically acceptable acid addition salts of compounds of the general formula (I) can be prepared of the aforementioned base compounds of this invention are those which form non-toxic acid addition salts, includes, salts containing pharmacoiogicaliy acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisuffate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benezenesulfonate, p-tolunesulfonate, palmoate and oxalate. Suitable phannaceutically acceptable base addition salts of compounds of the general formula (I) can be prepared of the aforementioned acid compounds of this invention are those which fomi non-toxic base addition salts, includes, salts containing pharmaceutically acceptable cations, such as lithium, sodium, potassium, calcium and magnesium, salts of organic bases such as lysine, arginine, guanidine, diethanolamine, choline, tromethamine and the like; ammonium or substituted ammonium salts. Pharmaceutically acceptable salts forming part of this invention are intended to define but not limited to the above list. In addition, pharmaceutically acceptable salts of the compound of formula {I) can be obtained by converting derivatives which have tertiary amino groups into the corresponding quartemary ammonium salts in the methods known in the literature by using quarternizing agents. Possible quarternizing agents are, for example, alkyl halides such as methyl iodide, ethyl bromide and n-propyl chloride, including arylalkyi halides such as benzyl chloride or 2-phenylethyl bromide. In the addition to pharmaceutically acceptable salts, other salts are included in the invention. They may serve as intermediates in the purification of the compounds, in the preparation of other salts, or in the identification and characterization of the compounds or intemiediales. The pharmaceutical ly acceptable salts of compounds of formula (1) may exists as solvates, such as with water, methanol, ethanol, dimethylformamide, ethyl acetate, and the liKe. Mixtures of such solvates can also be prepared. The source of such solvate can be from the solvent of crystallization, inherent in the solvent preparation or crystallization, or adventitious to such solvent. Such solvates are within the scope of this invention. The invention also encompasses the pharmaceutically acceptable prodrugs of the compounds of the formula (1). A prodrug is a drug which has been chemically modified and may be biologically in-active at the site of action, but vi+iich may be degraded or modified by one or more enzymatic or other in-vivo processes to the parent form. This prodrug should have a different pharmacokinetic profile than the parent, enabling easier absorption across the mucosal epithelium, better salt formation, or solubility, and/or improved systemic stability {an increase in the plasma half-life, for example). Typically, such chemical modifications include the following: 1. ester or amide derivatives which may be cleaved by esterases or lipases; 2. peptides which may be recognized by specific or non-specific proteases; or 3. derivatives ttiat accumulate at a site of action frirough membrane selection of a prodrug from or a modified prodmg fomi; or any combination of 1 to 3, above. Conventional procedures for the selection and preparation of suitable prodnjg derivatives are described, for example, in H. Bundgard, Design of prodrugs, (1985). Compounds of general formula (I) can be prepared by any of the methods descritwd below. The present invention also provides processes for preparing compounds of general fonnula (I) as defined above, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their geometric forms, their polymorphs, their pharmaceutically acceptable salts and their pharmaceutically acceptable solvates, novel intermediates described herein, vi"here R,, R;, R3, R4, Rs, Re, R?, Re, R9, RIQ, Rn, Ri:. Ri3, Ri4 and "n" are as defined previously can be prepared by any of the methods described below: Scheme -1 : Compounds of general formula (I), may be prepared by cyclizing a novel intenmediate of formula (II) given below. vWierein X is halogen such diloro, bromo or iodo, Ro, Ri, R2, R3, R4, Rs, Re, R7, Ra, Rg, Rio, Rn, Riz, Ri3, Ri i) converting a compound of the formula (I) into another compound of the fomiula (I); and/or ii) removing any protecting groups; and/or iii) forming a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof. This cycljzation reaction can be achieved using variety of palladium catalysts. The reaction may be affected in the presence of a base such as CH3COOK. This reaction may be carried out in the presence of solvents such as THF, DMF, DMSO, DMA, DME, acetone and the like and preferably using Dimethylacetamide. The inert atmosphere may be maintained by using inert gases such as N2, Ar or He. The reaction temperature may range from 50 "C to 200 °C based on the choice of solvent and preferably at a temperature of 160 °C. The duration of the reaction may range from 1 to 24 hours, preferably from 10 to 20 hours. Scheme - 2 : Compounds of general formula (I), may be prepared by reacting a compound of formula (III) given below, wherein Ro, Ri, R2, R3, R*. Rs, Re, R?, Rs, R9, Rio, Rn, R13 and "n" are as defined previously, with a suitable alkylating agent such as R,3 X or R14 X or XR13R14X in successive steps or in one step, wherein X is good leaving group such as halogen, hydroxyl and the like; and thereafter if desired or necessary canying out steps (i), (ii) and/or (iii) as described above. The reaction is preferably carried in an organic solvent inert to the conditions of the reaction, such as acetone, THF or DMF and the like or mixtures thereof. The inert atmosphere may be maintained by using inert gases such as N2, Ar or He. The reaction may be affected in ttie presence of a base such as K3C03, Na2C03, TEA or mixtures thereof. The reaction temperature may range from 20 °C to 200 -^C based on the solvent employed and preferably at a temperature in the range from 30 °C to 150 "C. The duration of the reaction may range from 1 to 24 hours, preferably from 2 to 6 hours. Scheme - 3 : Compounds of general formula {I}, may be prepared by reacting a compound of formula (IV) given below, wherein Ro, Ri, R2, R3, R4, Rs, Re, R7, Ra and "n" are as defined previously, with formaldehyde and a compound of formula (V) given below, NHR,3Ri^ (V) wherein R13 and R14 are as defined earlier; and thereafter if desired or necessary carrying out steps (i), (ii) and/or (iii) as described above. The above reaction is preferably carried out at a temperature of 50 °C to 150 °C. The formaldehyde can be in the form of as aqueous solution i.e. 40 % formalin solution, or a polymeric form of formaldehyde such as paraformaldehyde or trioxymethylene. \Mien such polymeric forms are used, a molar excess of mineral acid, for example hydrochloric acid, is added to regenerate the free aldehyde from the polymer. The reaction is preferably carried in an organic solvent inert to the conditions of the reaction, such as methanol, ethanol or 3-methylbutanol and the like or a mixture thereof, and preferably using either acetone or DMF. The inert atmosphere may be maintained by using inert gases such as N^, Ar or He. The reaction temperature may range from 20 °C to 150 °C based on the choice of solvent and preferably at a temperature in the range from 30 °C to 100 "C. The duration of the reaction may range from 1 to 24 hours, preferably from 2 to 6 hours. Scheme - 4 : Compounds of general formula {!), may be prepared from another compound of formula (1) containing -C(=0) group/s in the side chain, by known methods of reduction to the corresponding -C(OH,H) or-C(H,H) compound; and thereafter if desired or necessary carrying out steps (i), (ii) and/or (iii) as described above. Novel intermediates of general formula (II), their stereoisomers and their salts. represented as given below, Vi"herein X is halogen such c^loro, bromo or iodo. Ro is either hydrogen or linear or branched (C,-C2)alkyl. Ri, R;, Ra, R4, Rs, Re. R7, RB. R9, Rio, Rn and R,; may be same or different and each independently represent hydrogen, halogen. 0x0, thio, perhaloalkyi, hydroxy, amino, nitro, cyano, formyl, amidino, guanidino, substituted or unsubstituted groups such as linear or branched (C,-Ci2)alkyl, (C2-Ci:)alkenyl, (C2-Ciz)alkynyl, (Cs-Cyjcycloalkyl, (C3-C7)cydoalkenyl, bicycloalkyi, bicycloalkenyl, (CrCi2)alkoxy, cyclo(C3-C7)alkoxy, aryl, aryloxy. aralkyi, aralkoxy, heterocyclyl, heteroaryl, heterocyclylalkyi, heteroaralkyl, heteroaryloxy. heteroaralkoxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino, morioalkylamino. dialkylamino, arylamino, diarylamino, aralkylamino, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl. aminoalkyl, monoalkylaminoalkyi, dialkylaminoalkyi, alkoxyalkyl, aryloxyalkyi, aralkoxyalkyl. alkylthio, thioalkyi, alkoxycarbonylamino, aryloxycarbonylamino, aralkyioxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkyteqiidino, alkylguanidino, dialkylguanidino, hydrazine, hydroxylamino, carboxylic acid and Its derivatives, sulfonic acids and its derivatives, phosphoric acid and its derivatives; or the adjacent groups like Ri and R2 or R2 and R3 or R3 and R:, or Rs and Re or Re and R7 or R7 and RB together with carbon atoms to which they are attached may form a 5, 6, or 7 membered ring, which may further optionally contain one or more double bonds and/or one or more heteroatoms such as the group "Oxygen", Nitrogen", "Sulfur" or "Selenium" and combinations of double bond and heteroatoms; or Rg and R,o or R,i and Ri2 together represent double bond attached to "Oxygen" or "Sulfur"; or Rg and R,o or Rn and Ri2 together with tfie carbon atoms to which they are attached may form a 3, 4, 5, or 6 membered ring, w/hich may further optionally contain one or more double bonds, and/or one or more heteroatoms such as the group "Oxygen", "Nitrogen", "Sulfur" or "Selenium" and also includes combination of one or more double bonds with "heteroatoms", as above defined. Ri3 and Ri4 may be ^me or different and each independently represents hydrogen, substituted or unsubstituted groups such as linear or branched (Ci-Ci2}alkyl, {Cz-Ci2)alkenyl, (C2-Ci2)alkynyl, {C2-Ci2}alkanoyl (C3-C7)cycloalkyl, (C3-C7)cycloalkenyl. bicycloalkyi, bicycloalkenyl, aryl, aralkyi, heteroaryl, heterocyclylalkyi; optionally R13 and Ri "n" is an integer ranging from 1 to 8. It is preferred that n be 1 to 4. The carbon chains which "n" represents may be either linear or branched. The present invention also provides processes for preparing the novel intermediate represented by the general formula (11), Route -1 : Compounds of general formula {II), may be prepared by reacting a compound of formula (VI) given below. where R,, R2, R3, R^, Rg, Rio, Rii,Ri2, Ri3 and R14 are as defined in relation to formula (1); with a compound of formula (VII) where Ro, R5, Re, R7 and RB are as defined in relation to formula (I) and X is a halogeno, preferably chloro, bromo or iodo. This reaction may be carried out in the presence of solvents such as THF, DMF, DMSO, DME, acetone and the like and preferably using either acetone or DMF. The inert atmosphere may be maintained by using inert gases such as Nj, Ar or He. The reaction may be affected in the presence of a base such as K2C03, Na2C03, NaH, KH or mixtures thereof. The reaction temperature may range from 20 °C to 150 X based on the choice of solvent and preferably at a temperature in the range from 30 °C to 100 "C. The duration of the reaction may range from 1 to 24 hours, preferably from 2 to 6 hours. (Reference: Bio Org. Med Chem. 2000, 10, 2295-2299). Preferably the substituents selected for the compounds of formula (VI) and (VII) are either not affected by the reaction conditions or else the sensitive groups are protected using suitable groups. Compounds of formula (V!) are commercially available, or they may be prepared by conventional methods or by modification, using known processes, of commercially available compounds of formula (VI), PCT patent application WO 02/078693 also provides methods to prepare variously substituted indoles as well as tryptamines and is incorporated herein by reference. Route - 2 : Compounds of general formula (II) may be prepared by the following route wherein X is halogen such as chloro, bromo or iodo; R5, Rg, R/ and Re are as defined earlier; in presence of amine hydrochloride and formaldehyde The above reaction is preferably carried out at a temperature of 50 °C to 150 °C. The formaldehyde can be in the form of as aqueous solution i.e. 40 % formalin solution, or a polymeric form of formaldehyde such as paraformaldehyde or trioxymethylene. When such polymeric forms are used, a molar excess of mineral acid, for example hydrochloric acid, is added to regenerate the free aldehyde from the polymer. The reaction is preferably carried in an organic solvent inert to the conditions of the reaction, such as mefrianol, ethanol or 3-methylbutanol and the like or a mixture thereof. The inert atmosphere may be maintained by using inert gases such as N:, Ar or He, The reaction temperature may range from 20 °C to 150 °C based on the choice of solvent and preferably at a temperature in the range from 30 °C to 100 °C. The duration of the reaction may range from 1 to 24 hours, preferably from 2 to 6 hours. Route-3: Compounds of general formula (II) may be prepared reducing another compound of formula (11) as follows, wherein R,, R;, Ra, R4, Rn, Ri2, R13, Ri4 and n (=2) are as defined in relation to formula (I); R represents either of hydrogen or a group such as. wherein X is halogen such as chloro, bromo or iodo; Ro, R5. Re, R? and Ra are as defined earlier. The first step is weli-known strecker reaction, which is followed by conversion of cyano to acid and lastly acid to amide. The first step involves addition of aqueous solution of sodium bisulfite in the presence of sodium cyanide in a suitable aqueous solvent. The latter two conversions are very-well documented in tt\e literature. wherein Ro is either hydrogen or linear or branched (Ci-C2)aikyl; Ri. Rz, R3. R4, Rs, Re, R7, Re, R9, Rio, R11 and Ri2 may be same or different and each independently represent hydrogen, halogen, 0x0, thio, perhaloall "n" is an integer ranging from 1 to 8. It is preferred that n be 1 to 4. The carbon chains which "n" represents may be either linear or branched. The present invention also provides a process for preparing the novel intermediate represented by the general formula {III). Compound of formula (III) -* Compound of formula (II) Substituted indole compounds can be alkylated with 1-dimethylamino-2-nitroethylene in the presence of trifluoroacetic acid, which can reduced with lithium aluminium hydride to give substituted tryptamines. All steps are described in J- Med. Chem., 1993, 36, 4069 and J. Med Chem., 2000, 43, 1011-1018. The compounds of formula (li) can be methylated through reductive alkylation using formaldehyde, sodium cyanoborohydride in acetonitrile stirring at room temperature to produce compounds of formula (I). Novel intermediates of general formula (IV) are represented as given below, wherein Ro is either hydrogen or linear or branched (Ci-Cz)alkyl; Ri, Rj, R3. R4, R5, Re, R? and Ra are as may be same or different and each independently represent hydrogen, halogen. 0x0, thio, perhaloalkyi, hydroxy, amino, nitro, cyano, formyl, amidino, guanidino, substituted or unsubstituted groups such as linear or branched (Ci-C,2}alkyl, (Cz-C,;)alkenyl, (CrCi2)alkynyl, (Ca-Cyjcycloalkyl, (Ca-Cjjcycloalkenyl, bicycloalkyi, bicycloalkenyl, (Ci-Ci2)alkoxy, cyclo(C3-Cr)alkoxy, aryl, aryloxy, aralkyi, araikoxy. heterocydyl, heteroarjft, heterocyclylalkyl, heteroaralkyi, heteroaryloxy, heteroaralkoxy, heterocydylalkyloxy, acyl, acyloxy, acylamino, monoalkylamino, dialkylamino, arylamino, diarylamino, aralkylamino, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, heterocyclylalkoxycarbonyl, hetero aryloxycarbonyl, hydroxyalkyl, aminoalkyi, monoalkylaminoalkyl, dialkylaminoalkyi, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyi, alkylthio, thioalkyi, alkoxycarbonylamino, aryloxycarbonylamino, aralkyloxycarbonylamrno, aminocarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino, hydrazino, hydraxylamino, carboxylic add and its derivatives, sulfonic acids and its derivatives, phosphoric acid and its derivatives; or the adjacent groups like Ri and R2 or R? and R3 or Rj and R^ or R5 and Rg or Re and R? or R7 and Ra together wWU carbon atoms to which they are attached may form a 5, 6, or 7 membered ring, which may further optionally contain one or more double bonds and/or one or more heteroatoms such as the group "Oxygen", "Nitrogen", "Sulfur" or "Selenium" and combinations of double bond and heteroatoms; and Rg and Rio here represent double bond attached to "Oxygen". The present invention also provides method to prepare intermediate by general fonnula (IV), which comprises of cyclizing compounds of formula (VIII), wherein R,, R?, R3, R4, Rs, Re, R7 and Re are as defined above; using a Pd(0) or Pd (II) derivative as a catalyst, for example tetrakis triphenylphosphine palladium, (Bis-tri-o-tolylphosphine) palladium and the like in a suitable solvent. During any of the above synthetic sequences it may be necessary and/or desirable to protect sensitive or reactive groups on any of the molecules concerned. This may be achieved by means of conventional protecting groups, such as those described in Protective Groups in Organic Chemistry, Ed J, F. W. McOmie, Plenum Press, 1973; and T. W. Greene & P. G, M. Wuts, Protective Groups in Organic Synthesis, John \Mley & Sons, 1991. For example, suitable proteding groups for the piperazine group include BOC, COCCI3, COCF3. The protecting groups may be removed according to the standard procedures. The protecting groups may be removed at a convenient subsequent stage using methods known from the art. The compounds of the present invention may contain one or more asymmetric centers and therefore they also exist as stereoisomers. The stereoisomers of the compounds of the present invention may be prepared by one or more ways presented below: i) One or more of the reagents may be used in their optically active form. ii) Optically pure catalyst or chirai ligands along with metal catalyst may be employed in the reduction process. The metal catalyst may be Rhodium, Ruthenium, Indium and the like. The chirai ligands may preferably be chirai phosphines {Principles of Asymmetric synthesis, J. E. Baldwin Ed,, Tetrahedron series, 14, 311-316). iii) The mixture of stereoisomers may be resolved by conventional methods such as forming a diastereomeric salts with chira! acids or chirai amines, or chirai amino alcohols, chirai amino acids. The resulting mixture of diastereomers may tiien be separated by methods such as fractional crystallization, chromatography and the like, which is followed by an additional step of isolating the t^tically active product by hydrolyzing the derivative (Jacques et. al., "Enantiomers, Racemates and Resolution", Wiley Interscience, 1981). iv) The mixture of stereoisomers may be resolved by conventional mefriods such as microbial resolution, resolving the diastereomeric salts fonned w\\h chirai acids or chirai bases. Chirai acids that can be employed may be tartaric acid, mandelic acid, lactic acid, camphorsu\fon]c acid, amino adds and the like. Chirai bases that can be employed may be cinchona alkaloids, brucine or a basic amino acid such as lysine, arginine and Uie like. The pharmaceutically acceptable salts forming a part of this invention may be prepared by treating the compound of formula (I) with 1-6 equivalents of a base such as Lithium, ammonia, substituted ammonia, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium t-butoxide, calcium hydroxide, calcium acetate, calcium chloride, magnesium hydroxide, magnesium chloride and the like. Solvents such as water, acetone, ether, THF, methanol, ethanol, t-butanol, dioxane, isopropanol, isopropyl ether or mixtures thereof may be used. Organic bases such lysine, arginine, methyl benzylamine, ethanolamine, diethanolamine, tromethamine, choline, guanidine and their derivatives may be used. Acid addition salts, wherever applicable may be prepared by ■ treatment with acids such as tartaric acid, mandelic acid, fumaric acid, maleic acid, lactic acid, salicyclic acid, citric acid, ascorbic acid, benzene sulfonic acid, p-toluene sulfonic acid, hydroxynaphthoic acid, metfiane sulfonic acid, malic acid, acetic acid, benzoic acid, succinic acid, palmitic acid, oxalic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and the like in solvents such as water, alcohols, ethers, ethyl acetate, dioxane, DMF or a lower alkyl Ketone such as acetone, or the mixtures thereof. Different polymorphs may be prepared by crystallization of compounds of general formula (I) under different conditions such as different solvents or solvent mixtures in varying proportions for recrystallization, various ways of crystallization such as slow cooling, fast cooling or a very fast cooling or a gradual cooling during crystallization. Different polymorphs may also be obtained by heating the compound, melting the compound and solidification by gradual or fast cooling, heating or melting under vacuum or under inert atmosphere and cooling under either vacuum or inert atmosphere. The various polymorphs may be identified by either one or more of the following techniques such as differential scanning calorimeter, powder X-ray diffraction, IR spectroscopy, solid probe NMR spectroscopy and thermal microscopy. Another aspect of the present invention comprises of a pharmaceutical composition, containing at least one of the compounds of ttie general formula (1), their derivatives, their analogs, their derivatives, their tautomeric fomis, their stereoisomers, their geometric forms, their polymorphs, their pharmaceuticatly acceptable salts, their pharmaceutically acceptable solvates friereof as an active ingredient, together with pharmaceutically employed carriers, auxiliaries and the like. The pharmaceutical compositions of the present invention may be formulated in a conventional manner using one or more pharmaceutically acceptable earners. Thus, the active compounds of the invention may be formulated for oral, buccal, intranasal, parental (e.g., intravenous, intramuscular or subcutaneous) or rectal administration or a form suitable for administration by inhatation or insufflation. The dose of the active compounds can vary depending on factors such as the route of administration, age and weight of patient, nature and severity of the disease to be treated and similar factors. Therefore, any reference herein to a pharmacologically effective amount of the compounds of general formula (I) refers to the aforementioned factors. For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with phamiaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulphate). The tablets may be coated by methods weW known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared tiy conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (e.g., methyl or propyl p-hydroxybenzoates or sorbic acid). For buccal administration, the composition may take the form of tablets or lozenges formulated in conventional manner. The active compounds of the invention may be formulated for parenteral administration by injection, including using conventional catheterization techniques or infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulating agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form for reconstitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. The active compounds of the invention may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides. For intranasal administration or administration by inhalation, the active compounds of the invention are conveniently delivered in the form of an aerosol spray from a pressurized container or a nebulizer, or from a capsule using a inhaler or insufflator. In the case of a pressurized aerosol, a suitable propellant, e.g., dichlorodlfluoromethane, trichlorofluoromettiane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas and the dosage unit may be determined by pnDviding a valve to deliver a metered amount. The medicament for pressurized container or nebulizer may contain a solution or suspension of the active compound while for a capsule it preferably should be in the form of powder. Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator may be formulated containing a powder mix of a compound of the invention and a suitable powder base such as lactose or starch. A proposed dose of the active compounds of this invention, for either oral, parenteral, nasai or buccal administration, to an average adult human, for the treatment of the conditions referred to above, is 0.1 to 200 mg of the active ingredient per unit dose which could be administered, for example, 1 to 4 times per day. Aerosol formulations for treatment of the conditions referred to above (e.g., migraine) in the average adult human are preferably arranged so that each metered dose or "pufT" of aerosol contains 20 ng to 1000 ^ig of the compound of the invention. The overall daily dose with an aerosol will be within the range 100 ng to 10 mg. Administration may be several times daily, for example 2, 3, 4 or 8 times, giving for example, 1, 2 or 3 doses each time. The affinities of the compound of this invention for the vahous serotonin receptors are evaluated using standard radioligand binding assays and are described here. Radioligand binding assays for various 5-ht receptor sub-tvpes : i) Assayfor5HTiA Materials and Methods: Receptor source : Human recombinant expressed in HEK-293 cells Radioligand ; [3H]-8-OH-DPAT (221 Ci/mmol) Final ligand concentration - [0.5 nM] Reference compound : 8-OH-DPAT Positive control: 8-OH-DPAT Incubation conditions: Reactions are carried out in 50 mM TRIS-HCI (pH 7,4) containing 10 mM MgSO^, 0.5 mM EDTA and 0.1% Ascorbic acid at room temperature for 1 hour. The reaction is temiinated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound vwth the 5HTi/\ binding site. Literature Reference: • Hoyer D., Engel G., et al. Molecular Pharmacology of SHTi and 5-HT2 Recognition Sites in Rat and Pig Brain Membranes: Radioligand Binding Studies with pH]-5HT, [^H]-8-0H- DPAT, [^"l]-lodocyanopindolol, [^H]-Mesuiergine and flHJ-Ketanserin. Eur. Jml. Pharmacol. 118: 13-23 (1985) with modificafions. * Schoeffter P: and Hoyer D. How Selective is GR 43175? Interactions with Functional 5-HTIA, 5HTIB, 5-HTIC, and 5-HTID Receptors. Naunyn-Schmiedeberg"s Arch. Pharmac. 340: 135-138 (1989) with modifications. ii) Assay for 5HTiB Materials and Methods: Receptor source : Rat striatal membranes Radioligand : [^"!]lodocyanopindolol (2200 Ci/mmol) Final ligand concentration - [0.15 nM]-Non-specific determinant: Serotonin - [10 ^M] Reference compound : Serotonin Positive control: Serotonin Incubation conditions: Reactions are carried out in 50 mM TRIS-HCI (pH 7.4) containing 60 ^M (-) isoproterenol at 37^C for 60 minutes. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound with the 5HTIB binding site. Literature Reference: • Hoyer D., Engel G., et al. Molecular Pharmacology of 5HTi and S-HT; Recognition Sites in Rat and Pig Brain Membranes; Radioligand Binding Studies with [^H]-5HT, [^H]-8-0H-DPAT, ["^^(J-Jodocya no pindolol, [^H]-Mesulergine and [^HJ-Ketanserin, Eur. Jml. Pharmacol. 118:13-23 (1985} with modifications. • Schoeffter P. and Hoyer D. How selective is GR 43175? Interactions with Functional 5-HTIA, 5HTIB, 5-HT,C, and 5-HT, Receptors, Naunyn-Schmiedeberg"s Arch. Pharmac- 340: 135-138 (1989) with modifications. iij) Assay for 5HTID Materials and Methods: Receptor source : Human cortex Radioligand : [^H] 5-Carboxamidotryptamine (20-70 Ci/mmol] Final ligand concentration - [2,0 nM] Non-specific determinant: 5-Carboxamidotryptamine (5-CT} - [1,0 nM] Reference compound ; 5-Carboxamidotryptamine (5-CT) Positive control: 5-Carboxamidotryptamine (5-CT) Incubation conditions: Reactions are earned out in 50 mM TRIS-HCI (pH 7.7) containing 4 mM CaCh, 100 nM 8-OH-DPAT, 100 nM Mesulergine, 10 uM Pargyline and 0.1% ascorbic acid at 25 "C for 60 minutes. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound with the cloned 5HTID binding site. Literature Reference: • Waeber C, Schoeffter, Pglacios J.M. and Hoyer D. Molecular Pharmacology of the 5- HT,D Recognition Sites: Radioligand Binding Studies in Human, Pig, and Calf Brain Membranes. Naunyn-Schmiedeberg"s Arch. Pharmacol, 337: 595-601 (1988) with modifications. iv) Assay for 5HT2A Materials and Methods: Receptor source : Human Cortex Radioligand : [^H] Ketanserin (60-90 Ci/mmol) Final ligand concentration - [2.0 nM] Non-specific determinant: Ketanserin - [3,0 |iM] Reference compound; Ketanserin Positive contro}: Ketanserin incubation conditions: Reactions are carried out in 50 mM TRiS-HCi (pH 7,5) at room temperature for 90 minutes. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound with the SHT;^ binding site. Literature Reference: • Leysen J. E., Niemegeers C. J,, Van Nueten J, M. and Laduron P. M. pH]Ketanserin: A Selective Tritiated Ligand for Serotontn2 Receptor Binding Sites. Mol. Pharmacol. 21; 301-314 (1982) with modifications. • Martin, G, R. and Humphrey, P. P, A. Classification Review: Receptors for 5-HT: Current Perspectives on Classification and Nomenclature. Neuropharmacol, 33(3/4): 261-273 (1994), v) Assay for 5HT2C Materials and Methods: Receptor source : Pig choroid plexus membranes Radioligand : [^H] Mesulergine (50-60 Ci/mmol) Final ligand concentration - [1,0 nM] Non-specific determinant: Serotonin - [100 nM] Reference compound : Mianserin Positive control: Mianserin Incubation conditions; Reactions are carried out in 50 mM TRIS-HCI (pH 7,7) containing 4 mM CaCI; and 0.1% ascorbic acid at 37 °C for 60 minutes. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound with the 5HT2C binding site. Literature Reference: • A- Pazos, D. Hoyer, and J. Palacios. The Binding of Serotonergic Ligands to the Porcine Choroid Plexus: Characterization of a New Type of Serotonin Recognition Site, Eur, Jrnl. Pharmacol. 106: 539-546 (1985) with modifications, • Hoyer, D-, Engel, G,, et al. Molecular Pharmacology of 5HTi and S-HT? Recognition Sites in Rat and Pig Brain Membranes: Radioligand Binding Studies with [3H]-5HT, [3HI-8-OH-DPAT, [■""l]-lodocyanopindolol, [3H]-Mesulergine and [3H]-Ketanserin. Eur. Jrnl, Pharmacol. 118:13-23 (1985) with modifications, vj) Assay for 5HT3 Materials and Methods: Receptor source : N1E-115 cells Radioligand : [^H]-GR 65630 (30-70 Ci/mmol) Final ligand concentration - [0.35 nM] Non-specific detenninant: MDL-72222 - [10 nM] Reference compound : MDL-72222 Positive control: MDL-72222 Incubation conditions: Reactions are carried out in 20 mM HEPES (pH 7.4) containing 150 mM NaCI at 25 -C for 60 minutes. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound with the SHTa binding site. Literature Reference: • Lummis S. C, R,, Kilpatrick G, J. Characterization of 5HT3 Receptors in Intact N1E-115 Neuroblastoma Cells, Eur. Jrnl, Phamiacot. 189: 223-227 (1990) with modifications, • Hoyer D. and Neijt H. C. Identification of Serotonin 5-HT3 Recognition Sites in Membranes of N1E-115 Neuroblastoma Cells by Radioligand Binding, Mol, Pharmacol, 33: 303 (1988), • Tyers M. B. 5-HT3 Receptors and the Therapeutic Potential of 5HT3 Receptor Antagonists, Therapie. 46:431-435(1991), vii) Assay for 5HT4 Materials and Methods: Receptor source : Guinea pig striatal membranes Radioligand : [""H] GR-113808 (30-70 Ci/mmol) Final ligand concentration - [0.2 nM] Non-specific determinant: Serotonin (5-HT) - [30 [iM] Reference compound ; Serotonin (5-HT) Positive control: Serotonin (5-HT) Incubation conditions ; Reactions are carried out in 50 mM HEPES (pH 7.4) at 370C for 60 minutes. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound vifith the SHT^ binding site. Literature Reference: • Grossman Kilpatrick, C, et al. Development of a Radioligand Binding Assay for 5HT4 Receptors in Guinea Pig and Rat Brain. Brit. J Pharmco. 109: 618-624 (1993)- vjii) Assay for 5HT5A Materials and Methods: Receptor source : Human recombinant expressed in HEK 293 cells Radioligand : [^H] LSD (60-67 Ci/mmol) Final ligand concentration - [1.0 nM] Non-specific determinant: Methiothepin mesylate - [1,0 [iM] Reference compound : Methiothepin mesylate Positive control: Methiothepin mesylate Incubation conditions: Reactions are carried out in 50 mM TRIS-HCI (pH 7.4) containing 10 mM MgSO^ and 0-5 mM EDTA at 37 °C for 60 minutes. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound with the cloned SHTBA binding site. Literature Reference: • Rees S.. et al. FEBS Letters, 355: 242-246 (1994) with modifications ix) Assay for 5HT6 Materials and Methods; Receptor source : Human recombinant expressed in HEK293 cells Radioligand : [3H]LSD (60-80 Ci/mmol) Final ligand concentration - [1-5 nM] Non-specific determinant; Metfiiothepin mesylate- [0.1μM] Reference compound : Methiothepin mesylate Positive control: Methiothepin mesylate Incubation conditions: Reactions are carried out in 50 mM TRIS-HCl (pH 7.4) containing 10 mM MgCb, 0.5 mM EDTA for 60 minutes at 37 °C, The reaction is terminated fay rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound(s) with the cloned serotonin - SHTe binding site. Literature Reference: * Monsma F, J, Jr., et a!., Molecular Cloning and Expression of Novel Serotonin Receptor with High Affinity for Tricyclic Psychotropic Drugs. Mol. Pharmacol. (43): 320-327 (1993). x) Assay for S-HTy Materials and Methods: Receptor source : Human recombinant expressed in CHO cells Radioligand ; [^H]LSD (60-80 Ci/mmol) Final tigand concentration - [2.5 nM] Non-specific determinant: 5-Carboxamidotryptamine (5-CT) - [0.1 μM] Reference compound : 5-Carboxamidotryptamine Positive control: 5-Carboxamidotfyptam)ne Incubation conditions : Reactions are carried out in 50 mM TRIS-HCl (pH 7.4) containing 10 mM MgCb, 0.5 mM EDTA for 60 minutes at 37 °C. The reaction is terminated by rapid vacuum filtration onto glass fiber filters. Radioactivity trapped onto the filters is determined and compared to control values in order to ascertain any interactions of test compound(s) with the cloned serotonin -5HT7 binding site. Literature Reference: " Y. Shen, E. Monsma, M, Metcalf, P. Jose, M Hamblin, D. Sibley, Molecular Cloning and Expression of a 5-hydroxytryptamine7 Serotonin Receptor Subtype. J. Bioi. Chem. 268: 18200-16204. The following description illustrates the method of preparation of variously substituted compounds of general formula (I), according to the methods described herein. These are provided by the way of illustration only and therefore should not be construed to limit the scope of the invention. Commercial reagents were utilized without further purification. Room temperature refers to 25 - 30 °C. Melting points are uncorrected. IR spectra were taken using KBr and in solid state. Unless otherwise stated, all mass spectra were earned out using ESI conditions. 1H NMR spectra were recorded at 300 MHz on a Bruker instrument. Deuterated chloroform (99.8 % D) was used as solvent. TMS was used as Intemal reference standard. Chemical shift values are expressed in are reported in parts per million {5)-values. The following abbreviations are used for the multiplicity for the NMR signals: s=singlet, bs=broad singlet, d=doublef, t=triplet, q=quartet, qui=quintet, h=heptet, dd=double doublet, dt=double triplet, tt=trip!et of triplets, m=multiplet, NMR, mass were corrected for background peaks. Specific rotations were measured at room temperature using the sodium D (589 nm). Chromatography refers to column chromatography performed using 60 - 120 mesh silica gel and executed under nitrogen pressure (flash chromatography) conditions. Description 1 : N,N-Dimethyl-1-(2"-bromobenzyl)tryptamlne (D1) A suspension of sodium hydride (9-0 mmoles, 0.36 g (60 % suspension in mineral oil), washed with THF before use), in THF was stin-ed and cooled at 0 - 5 "C. To this cooled solution was added a solution of N,N-dimethyltryptamine (6.0 mmoles), in THF, slowly, over 15 min., maintaining the temperature below 10 °C. After completion of addtition, the mixture was warmed to 25 - 30 "C. and maintained for 60 min. The reaction hiixture was then cooled to 0 - 5 °C and solution of 2"-bromobenzyl bromide in THF (6.0 mmoies, 1,5 g in 7 mL of THF) was then added to the above well stirred mixture, maintaining the reaction temperature below 10 "C (Exothermic reaction). The reaction mixture was maintained at 20 -25 °C for further 2 - 4 hrs. After completion of reaction (TLC), the excess of THF was distilled off and the concentrate was diluted with ice-water and extracted with ethyl acetate. Combined ethyl acetate layer was washed with water, dried over sodium sulfate and evaporated under reduced pressure, below 50 °C. The coide residue was purified by silica gel column chromatography using 30 % methanol in ethyl acetate as a mobile phase, to obtain the intermediate. N,N-Dimethyl-1-{2"-bromobenzyl)tryptamine, which was identified by IR, NMR and mass spectral analyses. Description 2-26 (D2 - D26): Example -1 , 11-(2-N,N-Dimethylaminoethyl)-6H-isoindolo[2,1-a]indol6 1-(2"-bromobenzyl)-N,N-dimethyltfyptamine (0.286 mmoles, 0.102 g) was taken in a 100 mL 3 necked round bottomed flask, along with N,N-dimethyl acetamide (40 mL), potassium acetate (0.286 mmoles, 0.281 g} and dichlora bis(th-o-tolylphosphine)palladium (0.0143 mmoles, 0,01123 g). The reaction mixture was maintained under nitrogen atmosphere and was heated to 140-160 X with stirring for 3-4 hrs. After the completion of reaction (TLC), excess of dimethyl acetamide was distilled off under reduced pressure. The residue obtained was purified by silica gel column chromatography using 20 % methanol in ethyl acetate as an eluent, to afford the title compound, which was identified by IR, NMR and mass spectral analyses. The final desired compound of general formula (I) can be further purified by preparation of their acid addition salts. Melting range (°C) : 94-96; IR spectra (cm"^) : 2942, 2762, 1458, 1443; Mass (m/z) : 277 (M+H)*; "H-NMR (6 ppm) : 2.4 (6H, S), 2.60 - 2.68 (2H, m), 3.17 - 3.26 (2H, m), 5,0 {2H, s), 7.10 - 7.77 (8H, m). Example - 2 : 2-Chloro-11-(2-N,N-drmethylaniinoethyl)-6H-isoindolo[2,1-a]indote Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Melting range (°C): 76-78; IR spectra (cm-") : 2938, 277B, 1469, 1445; Mass (m/z) : 311 (M-"-H)^; "H-NMR (6 ppm) : 2,37 {6H, s), 2.59 - 2.63 (2H,m), 3.12 - 3.18 {2H, m), 5,01 (2H, s). 7.07 - 7.75 (8H, m). Example - 3 : 2-Chforo-11-(2-N,N-dimethy!amtnoethyl)-6W-isotndolot2,1-a]indole hydrochloride salt Example no. 2 (236 mg) was dissolved in 30 mL ether. To this clear solution a mixture of isopropylalcohol-hydrochloric acid (10 mL) was added. Immediately a white precipitate separates out, which was filtered, washed with ether and dried. Melting range CO : >250 (dec). Example - 4 : 2-Chloro-11-(2-N,N-dimethylaminoethyl)-6H-isoindolo[2,1-a]indole maleic acrd salt Example no. 2 (228 mg) was dissolved in 30 mL ether. To this clear solution a solution of maleic acid (90 mg, dissolved in 30 mL ether + 5 mL methanol) was added. Immediately a white precipitate separates out, which was filtered, wa^ed with ether and dried. Melting range (X): 202 - 204 (dec). Example - 5 : 2-Chloro-11-{2-N,N-dimethylaminoethyl)-6H-isoindoloI2,1-a]indole D,L-maljc acid salt Example no. 2 (190 mg) was dissolved in 30 mL ether. To this clear solution a solution of D,L- malic acid (86 mg, dissolved in 30 mL ether + 5 mL methanol) was added. Immediately a white precipitate separates out, which was filtered, washed with ether and dried. Melting range (X): 173 -176 (dec). Example-6 : 2-Chloro-11-{2-N,N-dimethylaminoethyl)-6H-isoindolo[2,1-a]indole oxalate salt Example no. 2 (198 mg) was dissolved in 30 mL ether. To this clear solution a solution of oxalic acid (86 mg, dissolved in 30 mL ether + 5 mL methanol) was added. Immediately a white precipitate separates out, which was filtered, washed with ether and dried. Melting range (°C): 222 - 224 (dec). Example- 7 : 2-Chloro-11-(2-N,N-dimethylaminoethyl)-6H-isoindolo[2,1-a]indole citrate salt Example no, 2 (213 mg) was dissolved in 30 mL ether. To this clear solution a solution of citric acid (133 mg, dissolved in 30 mL ether + 5 mL methanol) was added. Immediately a white precipitate separates out, which was filtered, washed with ether and dried. Melting range (°C): 150 -152 (dec). Example - 8 : 2-Fluoro-11-(2-N,N-dimethylaminoethyl)-6H-isoindolo[2,1-a]mdole Using essentially the general procedure described in example 1 and some non-critica! variations, ttie above derivative was prepared. Melting range ("C) . 96-100; IR spectra (cm"") : 2941. 2784, 1458, 798; Mass (m/z) : 295 (M+H)*; "H-NMR (5 ppm) ; 2,38 (6H, s), 2.560-2.65 (2H,m), 3.11-3.19 (2H, m), 5.02 (2H. s), 6.91 - 7.77 (8H, m). Example-9 : 11-(2-N,N-Dimethylamincethyl)-2-methyl-6W-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Melting range (°C) : 102-106; IR spectra (cm-1): 2934, 2761, 1439, 765; Mass (m/z) : 291 (M+H) *; "H-NMR (6 Dppm): 2.38 {6H, s), 2,46 (3H, s), 2,56 - 2.65 (2H. m), 3,12 - 3,20 (2H, m), 4,99 (2H, s), 6,98 - 7,73 (7H, m). Example-10 : 11-(2-N,N-Dimethylaminoethyl)-2-methoxy-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Melting range (°C) : 140-143; IR spectra (cm-1): 2903, 2781, 1621, 1459, 769; Mass (m/z): 307 (M+H)*; "H-NMR (5 Dppm) : 2,40 (6H, s), 2,57 - 2,66 (2H, m), 3,13 - 3,21 (2H, m), 3.88 (3H, s), 5,00 (2H, s), 6,82 - 7,73 (7H, m). Example-11 : 2-Bromo-11-(2-N,N-diethylaminoethyl)-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative vi/as prepared. IR spectra (cm-1) : 2964, 1613, 1444, 1261, 795; Mass (m/z): 383 {M+H)^ Example-12 : 2-Bromo-11-(2-N-methyl-N-cyclopropyfaminoethyt)-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. IR spectra (cm-1); 2926, 1469, 1358, 1169, 793; Mass (m/z) ; 381 (M+H)"; M-NMR (6 Gppm) : 0,44-0.61 (4H,m), 1,82-1,87 (1H, m), 2.48 (3H, S), 2.72 - 2.80 (2H, m), 2.95 - 3.07 (2H, m), 5.25 (2H, s), 7,06 - 7.32 (7H, m). Example -13 : 4-Chloro-11-(2-N,N-dimethylaminoethyl)-6>y-isoJndolo[2,1-a]Jndole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. IR spectra (cm"") : 2938, 2778, 1469, 1445; Mass (m/z): 311 (Wl+H)*. Example-14 : 3,4-Dichloro-11-(2-N,N-dime^ylaniJnoethyl)-6>y-isoindoto[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, frie above derivative was prepared. Mass (m/z): 345 (M+H)*, Example- 15 : 1-Chloro-11-(2-N,N-dimethylaminoethyl)-4-methyl-6W-isoindoto[2,1-a] indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z): 325 (M+H)", Example-16 : 3-Chloro-11-(2-N,N-dimethylaminoethyl)-4-methyl-6W-(Soindolo[2,1-ajjndole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z): 325 (M+H)*, Example -17 : 11-(2-N,N-Dimethylaminoethyl)-4-trifluoromethyl-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z) : 345 (M+H)"". Example-18 : 2,4-Difluoro-11-(2-N,N-dimethylaminoethyl)-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Melting range (°C) : 84 - 86; IR spectra (cm"") : 2941, 2784, 1458, 798; Mass (m/z) ; 313 (M+H)^; "H-NMR (5 Dppm) : 2.38 (6H, m), 2.55 - 2,63 (2H, m), 3.09 - 3.17 (2H, m), 5,22 (2H, s), 6.63 - 7.78 (6H, m). Example-19 : 11-(2-Pyrrolidin-1-yiethyl)-6W-isoindoloC2,1-alindole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative Vi/as prepared. Melting range {°C) ; 86 ■ 90; IR spectra (cm"^): 2832, 2807, 1361, 1334; Mass (m/z): 303 (M+H)"; "H-NMR (5 Dppm): 1.79-1.85 (4H, m), 2.55 - 2.68 {6H, m), 2,75 - 2.82 (2H. m), 5.28 (2H, s), 7.10 - 7.34 (8H, m). Example-20 : 2-Bromo-11-(2-pyrrolJdin-1-ylethyl)-6W-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z) : 381 (M+H)"^. Example-21 : 11-(2-(Piperidin-1-yl)ethyl)-6W-tsoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Melting range (X) : 102 - 104; IR spectra (cm"") : 2929, 2840, 1455, 1162; Mass (m/z) : 317 (M+H)+ "H-NMR (6 Dppm) : 1,44-1.52 (2H. m), 1.60-1.66 (4H. m). 2.38 - 2.43 (2H, m), 2.64 - 2.76 (6H, m), 5.28 (2H, s). 7.08 - 7.73 (8H, m). Example - 22 : 11-{2-{4-Methylpiperazin-1-yl)ethyl)-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. !R spectra (cm"") : 2937, 2803, 1634, 1455; Mass (m/z): 332 (M+H)*. Example - 23 : 11 -(3-(Pyrrolidin-1 -yl)-1 -hydroxyprop-1 -yl)-6H-isoindolo[2,1 -a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z); 333 (M+H)*. Example - 24 ; 2-Bromo-11-(3-(piperidin-1-yl)-1-hydroxyprop-1-yl)-6H-isoindolo[2,1-a] indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z): 425 (M+H)*. Example - 25 : 11-{2-N,N-Dimethylaminoethyl)-4-ethyI-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z) : 305 (M+H)*. Example - 26 : 11 -(2-N,N-Dimethylamino-1 -hydroxyethyl)-6H-isoindolo[2,1 -a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z) : 293 (M+H)*. Example - 27 : 11-(2-N,N-Dimethylaminoethyl)-4-methoxy-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z) : 307 (M+H)*. Example - 28 : 2-Bromo-11-(2-N,N-dimethylaminoethyl)-6H-isoJndolo[2,1"a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was pr^ared. Mass (m/z); 355 (M+H)*. Example-29 : 4-Bromo-11-(2-N,N-dimethylaminoethyl)-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z): 355 (M+H)*. Example- 30 : 4-Fluoro-11-(2-N,N-dimethylaminoethyl)-6W-isoindolG[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z) : 295 (M+H)*. Example- 31 : 2-Bromo-11-{2-{4-methylpiperazin-1-yl)ethyl)-6H-isoindolo[2,1-a]indole Using essentially the general procedure described in example 1 and some non-critical variations, the above derivative was prepared. Mass (m/z): 410 (M+H)*. We Claim, 1, A compound of the general formula (I), 1. A compound of the general formula (1), General Formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts and solvates, wherein Ro is either hydrogen or linear or branched {Ci-Cz)alkyl; Ri, R2, Rs, R4, Rfi, Re, R7, Rfl, RB, RIO, R11 and R12 may be same or different and each independently represent hydrogen, halogen, 0x0, thio, perhaloalkyi, hydroxy, amino, nitro, cyano, formyl, amidino, guanidino, substituted or unsubstituted gn^ups such as linear or branched (Ci-C,2)alkyl. {C2-Ci2)alkenyl, (C2-Ci2)a!kynyl, (Ca-CzjcycloalkyI, (C3- C7)cycloalkenyl, bicycloalkyi, bicycloalkenyl, (Ci-Ci2)alkoxy, cyclo(C3-C7)alkoxy, ary), aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heterocyclylatkyi, heteroaralkyi, heteroaryloxy, heteroaralkoxy, heterocyclylaikyloxy, acyl, acyloxy, acylamino, monoalkylamino, dialkylamino, arylamino, diarylamino, aralkylamino, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, heterocyclyfalkoxycartranyl, heteroaryloxycarbonyf, hydroxyalkyi, aminoalkyi, monoalkylaminoalkyi, dialkylaminoalkyi, alkoxyalkyl, aryloxyalkyi, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkyloxycarbonylamino, amlnocarbonylamlno, alkylaminocarbonylamino, dialkylamlnocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino, hydrazino, hydroxylamino, cartxixylk: acid and its derivatives, sulfonic acids and its derivatives, phosphoric add and its derivatives; or the adjacent groups like Ri and R2 or R2 and Rs or R3 and R* or R5 and Re or Re and R7 or R7 and Re together with carbon atoms to which they are attached may fomn a 5, 6, or 7 membered ring, which may further optionally contain one or more double bonds and/or one or more heteroatoms such as the group "Oxygen", "Nitrogen", "Sulfur" or "Selenium" and combinations of double bond and heteroatoms; or RB and Rio or Rn and R12 together represent double bond attached to "Oxygen" or "Suffur"; or Rg and Rio or R,, and R,2 together with the carbon atoms to which they are attached may fomn a 3, 4, 5, or 6 membered ring, which may further optionally contain one or more double bonds, and/or wherein X, R0 , R1,. R2;, R3. R4, R5. Re, R7. R6, R7, Rio, Rn, Ris. R13, Ri4 and "n", wherein all the symbols are as defined above, using a Pd(0) or Pd (II) derivative as a catalyst. 4. A process as claimed in Claim 3 comprising of carrying out one or more of the following optional steps: i) removing any protecting group; ii) resolving the racemic mixture into pure enantiomers by the known methods and iii) preparing a pharmaceutically acceptable salt of a compound of formula (I) and/or iv preparing a phamaceutically acceptable prodrug thereof. |
|---|
476-mas-2002 abstract duplicate.pdf
476-mas-2002 claims duplicate.pdf
476-mas-2002 correspondence others.pdf
476-mas-2002 correspondence po.pdf
476-mas-2002 description (complete) duplicate.pdf
476-mas-2002 description (complete).pdf
476-mas-2002 description provisional.pdf
| Patent Number | 217067 | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Indian Patent Application Number | 476/MAS/2002 | ||||||||||||||||||
| PG Journal Number | 21/2008 | ||||||||||||||||||
| Publication Date | 23-May-2008 | ||||||||||||||||||
| Grant Date | 24-Mar-2008 | ||||||||||||||||||
| Date of Filing | 21-Jun-2002 | ||||||||||||||||||
| Name of Patentee | SUVEN LIFE SCIENCES LIMITED | ||||||||||||||||||
| Applicant Address | SERENE CHAMBERS, ROAD NO.7, BANJARA HILLS, HYDERABAD - 500 034, | ||||||||||||||||||
Inventors:
|
|||||||||||||||||||
| PCT International Classification Number | C07D 487/04 | ||||||||||||||||||
| PCT International Application Number | N/A | ||||||||||||||||||
| PCT International Filing date | |||||||||||||||||||
PCT Conventions:
|
|||||||||||||||||||