This application claims the benefit of Indian provisional application number 228/CHE/2011 filed on filed on 24 Jan. 2011, which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present relates to novel indole compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their bioisosters, their diastereomers, their polymorphs, their enantiomers, their pharmaceutically acceptable salts, their pharmaceutically acceptable hydrates, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them and their use in the treatment of cancer.

BACKGROUND OF THE INVENTION

Cancer is a class of diseases characterized by out-of-control cell growth. Cancer harms the body when damaged cells divide uncontrollably to form lumps or masses of tissue called tumors (except in the case of leukemia where cancer prohibits normal blood function by abnormal cell division in the blood stream). Tumors can grow and interfere with the digestive, nervous, and circulatory systems, and they can release hormones that alter body function. Tumors that stay in one spot and demonstrate limited growth are generally considered to be benign. Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis, and when this process breaks down, cancer begins to form. Unlike regular cells, cancer cells do not experience programmatic death and instead continue to grow and divide. This leads to a mass of abnormal cells that grows out of control.

There are over 100 different types of cancer, and each is classified by the type of cell that is initially affected. Frequently types of cancer include breast cancer, bladder cancer, colon and rectal cancer, lung cancer, kidney cancer, leukemia and many more.

The available anticancer drugs have distinct mechanisms of action which may vary in their effects on different types of normal and cancer cells. A single "cure" for cancer has proved elusive since there is not a single type of cancer but as many as 100 different types of cancer. In addition, there are very few demonstrable biochemical differences between cancerous cells and normal cells. For this reason the effectiveness of many anticancer drugs is limited by their toxicity to normal rapidly growing cells in the intestinal and bone marrow areas. A final problem is that cancerous cells which are initially suppressed by a specific drug may develop a resistance to that drug. For this reason cancer chemotherapy may consist of using several drugs in combination for varying lengths of time.

Cancer Chemotherapy:

Chemotherapy drugs, are sometimes feared because of a patient's concern about toxic effects. Their role is to slow and hopefully halt the growth and spread of a cancer. There are three goals associated with the use of the most commonly-used anticancer agents.

1. Damage the DNA of the affected cancer cells.

2. Inhibit the synthesis of new DNA strands to stop the cell from replicating, because the replication of the cell is what allows the tumor to grow.

3. Stop mitosis or the actual splitting of the original cell into two new cells. Stopping mitosis stops cell division (replication) of the cancer and may ultimately halt the progression of the cancer.
Unfortunately, the majority of drugs currently on the market are not specific, which leads to the many common side effects associated with cancer chemotherapy. Because the common approach of all chemotherapy is to decrease the growth rate (cell division) of the cancer cells, the side effects are seen in bodily systems that naturally have a rapid turnover of cells including skin, hair, gastrointestinal, and bone marrow. These healthy, normal cells, also end up damaged by the chemotherapy program.

In general, chemotherapy agents can be divided into three main categories based on their mechanism of action.

Stop the synthesis of pre DNA molecule building blocks: These agents work in a number of different ways. DNA building blocks are folic acid, heterocyclic bases, and nucleotides, which are made naturally within cells. All of these agents work to block some step in the formation of nucleotides or deoxyribonucleotides (necessary for making DNA). When these steps are blocked, the nucleotides, which are the building blocks of DNA and RNA, can not be synthesized. Thus the cells can not replicate because they cannot make DNA without the nucleotides. Examples of drugs in this class include l) methotrexate (Abitrexate), 2) fluorouracil (Adrucil), 3) hydroxyurea (Hydrea), and 4) mercaptopurine (Purinethol).

Directly damage the DNA in the nucleus of the cell: These agents chemically damage DNA and RNA. They disrupt replication of the DNA and either totally halt replication or cause the manufacture of nonsense DNA or RNA (i.e. the new DNA or RNA does not code for anything useful). Examples of drugs in this class include cisplatin (Platinol) and antibiotics - daunorubicin (Cerubidine), doxorubicin (Adriamycin), and etoposide (VePesid).

Effect the synthesis or breakdown of the mitotic spindles: Mitotic spindles serve as molecular railroads with "North and South Poles" in the cell when a cell starts to divide itself into two new cells. These spindles are very important because they help to split the newly copied DNA such that a copy goes to each of the two new cells during cell division. These drugs disrupt the formation of these spindles and therefore interrupt cell division. Examples of drugs in this class of miotic disrupters include: Vinblastine (Velban), Vincristine (Oncovin) and Pacitaxel (Taxol).

There are many compounds under screeing for the treatment of cancer.Still there is substantial gap in the available mechanism of action. The present invention includes novel indole compounds useful in the treatment of cancer. These compounds are more suitable for the treatment of Human metastatic breast cancer cells, human chronic myeloid leukemia human colon cancer, kidney cancer etc.

SUMMARY OF THE INVENTION
The novel compounds of the present invention are represented by the general formula (I) their analogues, derivatives, tautomers, stereoisomers, enantiomers, diastereomers, polymorphs, pharmaceutically acceptable salts, pharmaceutically acceptable hydrates, pharmaceutically acceptable solvates and bioisosteres Wherein Q is selected from O, S, NR wherein R is hydrogen, hydroxyl, lower alkyl, lower alkoxy, acyl or aryl;

or

Q is substituted or unsubstituted lower alkyl chain optionally interrupted by an hetero atom selected from O, S or NR wherein R is selected from hydrogen, hydroxyl, lower alkyl, lower alkoxy, acyl or aryl;

T is selected from hydrogen, halogen, acyl, mesyl, COR1, COOR1;

A is optionally substituted cycloalkyl, aryl, heterocyclyl, heteroaryl;

or

A is lower alkyl chain substituted by one, two or three cyclic rings selected from cycloalkyl ,aryl ,

heterocycyl, heteroaryl , heterocycyl, heteroaryl ;

or more groups;

Rl is selected from hydrogen, halogen, hydroxyl, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl;

DETAIL DESCRIPTION OF THE INVENTION

Definitions:

"Halogen" refers to Fluorine, Chlorine, Bromine or Iodine.

The term "lower alkyl" refers to a straight or branched chain saturated aliphatic hydrocarbon that may be substituted or unsubstituted. Examples of "alkyl" include but are not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, n-pentyl, isobutyl and the like.

The term "acyl" refers to the group-C(0)Rd where Ra is Alkyl, aryl, heteroaryl, cycloalkyl or heterocyclyl each as herein defined and examples of which include acetoyl, propanoyl, butanoyl, iso-butanoyl, pentanoyl, benzoyl and the like, which may be substituted or unsubstituted.

The term "lower Alkoxy" refers to a group -ORb wherein Rb is hydrogen or alkyl as herein defined. Representative examples include but are not limited to methoxy, ethoxy and like.

The term "Alkylamino" refers to the group — N(Rb)2 wherein Rb is hydrogen or alkyl as herein defined.
The term "Aryl" refers to optionally substituted unsaturated or partially saturated aromatic ring system having five to ten carbon atoms and they may be monocyclic, bicyclic or polycyclic and may optionally be replaced by one or more heteroatoms selected from N, O and S. Exemplary aryl groups include phenyl, naphthyl, indanyl, biphenyl and like.

The term "cycloalkyl" used herein, either alone or in combination with other radicals, denotes mono, bicyclic or polycyclic saturated, partially saturated hydrocarbon ring system of about 3 to 12 carbon atoms which may be substituted or unsubstituted. Exemplary "cycloalkyl" groups include but are not limited to cyclopopyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, perhydronapthyl, adamantyl, noradamantyl or spirobicyclic groups such as spiro (4,4)non-2-yl.

The term "Heteroaryl" refers to monocyclic aromatic ring systems or fused bicyclic aromatic ring systems comprising two or more aromatic rings preferably two to three ring systems. These heteroaryl rings contain one or more nitrogen, sulfur and or oxygen atoms where N-oxides sulfur oxides and dioxides are permissible heteroatom substitutions. The term includes ring(s) optionally substituted with halogens, nitro, amino, alkoxy, alkyl sulfonyl amino, alkylcarbonylamino, carboxy, alkyl carbonoyl, hydroxy, and alkyl. Examples of heteroaryl groups include furan, thiophene, pyrrole, imidazole, pyrazole, triazole, tetrazole, thiazole, oxazole, isoxazole, oxadiazole, thiadiazole, isothiazole, pyridine, pyridazine, pyrazine, pyrimidine, quinoline, isoquinoline, benzofuran, benzothiophene, indole, indazole, chromanyl, iso chromanyl and the like.

The term "Heterocyclyl" refers to a stable 3 to 15 membered ring that is either saturated or has one or more degrees of unsaturation or unsaturated. These heterocyclic rings contain one or more heteroatoms selected from the group consisting of nitrogen sulfur and/or oxygen atoms where N-oxides, sulfur oxides and dioxides are permissible heteroatom substitutions. Such a ring may be optionally fused to one or more of another heterocyclic ring(s), aryl ring(s) or cycloalkyl ring(s). Examples of such groups may be selected from the group comprising azetidinyl, acridinyl, pyrazolyl, imidazolyl, triazolyl, pyrrolyl, thiophenyl, thiazolyl , oxazolyl, isoxazolyl, furanyl, pyrazinyl , tetrahydroisoquinolinyl, piperidinyl, piperazinyl, morpholinyl, thiomorphonilyl, pyridazinyl, indolyl, isoindolyl, quinolinyl, chromanyl and the like. "Heterocyclylalkyl" refers to a heterocyclic ring radical defined above directly bonded to an alkyl group. The heterocyclylalkyl radical may be attached to the main structure at carbon atom in the alkyl group that results in the creation of a stable structure.

Unless otherwise specified, the term "substituted" as used herein refers to mono, bi, tri or tetra substitution with any one or combination of the following substituents: hydroxy, halogen, carboxyl, cyano, nitro, oxo (=0), thio (=S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, or substituted or unsubstituted heterocyclic ring. Alternately R3 and R4 together along he nitrogen with the nitrogen they are attached with, form a 4to 8 membered ring which can be substituted or unsubstituted. According to one embodiment, the substituted or unsubstituted. According To one embodiment ,the substituents in the substituted or unsubstituted. According to one embodiment, the substituents in the aforementioned "substituted" groups cannot be further substituted. For example, when the substituent on "substituted alkyl" is "substituted aryl" the substituent on "substituted aryl" cannot be "substituted alkenyl"
"Stereoisomers" refer to certain compounds described herein containing one or more chiral centres or may otherwise be capable of existing as multiple stereoisomers. Scope of the present invention includes pure stereoisomers as well as mixtures of stereoisomers such as purified enantiomers/diastereomers or enantiomerically/diastereomerically enriched mixtures.

"Bioisosteres" refers to compounds or groups that possess near molecular shapes and volumes, approximately the same distribution of electrons and which exhibit similar physical properties such as hydrophobicity. Bioisostereic compounds affect the same biochemically associated systems as agonist or antagonists and thereby produce biological properties that are related to each other.

"Pharmaceutically acceptable salts" forming part of this invention include salts derived from inorganic bases such as Li, Na, K, Ca, Mg, Fe, Cu, Zn, Al, Mn; salts of organic bases such as N,N'-diacetylethylenediamine, 2- dimethylaminoethanol, isopropylamine, morpholine, piperazine, piperidine, procaine, diethylamine, triethylamine, trimethylamine, tripropylamine, tromethamine, choline hydroxide, dicyclohexylamine, metformin, benzylamine, phenylethylamine, dialkylamine, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, pyrimidine, spermidine, and the like; chiralbases like alkylphenylamine, glycinol, phenyl glycinol and the like, salts of natural amino acids such as glycine, alanine, valine, leucine, isoleucine, lysine, arginine, serine, threonine, phenylalanine; unnatural amino acids such as D-isomers or substituted amino acids; salts of acidic amino acids such as aspartic acid, glutamic acid; guanidine,

substituted guanidine wherein the substituents are selected from nitro, amino, alkyl, alkenyl, alkynyl, ammonium or substituted ammonium salts. Salts may include acid addition salts where appropriate which are sulphates, nitrates, phosphates, perchlorates, borates, hydrohalides, acetates, tartrates, maleates, citrates, succinates, methanesulfonates, benzoates, salicylates, hydroxynaphthoates, benzenesulfonates, ascorbates and the like.

"Pharmaceutically acceptable solvates" may be hydrates or comprising other solvents of crystallization such as alcohols.

"Compounds of the invention" or "present invention" refers to the compounds of the present invention represented by general formula (I) as here in defined, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their bioisosters, their diastereomers, their polymorphs, their enantiomers, their appropriate N-oxides, their pharmaceutically acceptable salts, their pharmaceutically acceptable hydrates, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. The compounds of the present invention are particularly useful for the treatment of

CANCER.
The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomer form or by resolving the mixture of stereoisomers by conventional methods. Some of the preferred methods include use of microbial resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic

acid, and the like wherever applicable or chiral bases such as brucine, cinchona alkaloids and their derivatives and the like. Different polymorphs of a compound of general formula (I) of present invention may be prepared by crystallization of the compound of formula (I) under different conditions .For example making use of commonly used solvents or their mixtures for recrystallization, crystallization at different temperature ranges, different cooling techniques like very fast to very slow cooling during crystallization procedure, by exposing to room temp, by heating or melting the compound followed by gradual cooling and the like. The presence of polymorphs may be determined by one or more methods like solid probe NMR spectroscopy, DSC, TGA, Powder X- Ray diffraction and IR.

The present invention also provides pharmaceutical compositions containing the compounds of invention as defined above, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their bioisosters, their polymorphs, their enantiomers, their diastereomers, their pharmaceutically acceptable salts or their pharmaceutically acceptable solvates in combination with the suitable pharmaceutically acceptable carriers, diluents. The pharmaceutical compositions according to the present invention are useful for the treatment of CANCER and its related diseases. The pharmaceutical composition may be tablets, capsules, powders, syrups, solutions, suspensions, sprays and like and may contain flavorants, sweeteners etc., in a suitable solid or liquid carriers or diluents or in a suitable sterile media to form injectable solutions or suspensions. It is understood that in any of the above schemes any reactive group in the substrate molecule may be protected according to any conventional procedure known in the prior art. Suitable protecting groups comprise N-Boc, N-Cbz, N-Fmoc, alkyl, benzophenoneimine for protection of amino group, acetal protection for aldehyde, ketal protection for ketone. The invention also encompasses prodrugs of compounds of the invention, which on administration undergo chemical conversion by metabolic processes before becoming active pharmacological substances, In general, such prodrugs will be functional derivatives of compounds of invention, which are readily convertible in vivo into compounds of the invention. The invention also encompasses the active metabolites of the compounds of the present invention of general formula (I).

The present invention relates to novel indole compounds of formula (I), their analogues, derivatives, tautomers, stereoisomers, enantiomers, diastereomers, polymorphs, pharmaceutically acceptable salts, pharmaceutically acceptable hydrates, pharmaceutically acceptable solvates and bioisosteres

Wherein

Q is selected from O, S, NR wherein R is hydrogen, hydroxyl, lower alkyl, lower alkoxy,acyl or aryl;
or

Q is substituted or unsubstituted lower alkyl chain optionally interrupted by an hetero atom selected from O, S or NR wherein R is selected from hydrogen, hydroxyl, lower alkyl, lower alkoxy, acyl or aryl;
T is selected from hydrogen, halogen, acyl, mesyl, COR1, COOR1;
A is optionally substituted cycloalkyl, aryl, heterocyclyl, heteroaryl;
or

A is lower alkyl chain substituted by one, two or three cyclic rings selected from cycloalkyl, aryl, heterocyclyl, heteroaryl which again can be optionally substituted by one or more groups;

Rl is selected from hydrogen, halogen, hydroxyl, optionally substituted lower alkyl, , optionally substituted lower alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl;

In one embodiment, the present invention relates to compound of formula(I) wherein

is selected from 0, S or NR wherein R is as defined above or substituted lower alkyl optionally interrupted by an hetero atom selected from 0, S or NR and A is selected from Wherein D is independently selected from N or CH;

Ra is selected from hydrogen, halogen, alkyl, alkoxy, acyl, COOR1, NR1R1;

In yet another embodiment, the representative compounds of the present invention are listed below without limiting the scope the invention Ethyl 2-((6-fluoro-5-iodo-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3-dihydro-lh-indene-2-carboxylate Ethyl 5,6- dimethoxy-2- ((5- methyl-1- (methylsulfonyl )-1h-indol -2-yl )methyl)-1- oxo-2,3-dihydro-1h-indene-2-carboxylate Ethyl 2-((5-iodo-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3- dihydro-1h-indene-2-carboxylate
Ethyl 5,6-dimethoxy-2-((l-(methylsulfonyl)-lh-indol-2-yl)methyl)-l-oxo-2,3-dihydro-lh-indene-2-carboxylate
Ethyl 2-((5-chloro-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3-dihydro-1 h -indene-2-carboxylate Ethyl 2-((5-fluoro-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3-dihydro-lh-indene-2-carboxylate 2-((5-fluoro-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one 2-((5-chloro-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one 5,6-dimethoxy-2-((5-methyl-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-2,3-dihydro-lh-inden-1-one
5,6-dimethoxy-2-((l-(methylsulfonyl)-lh-indol-2-yl)methyl)-2,3-dihydro-lh-inden-l -one 2-((5-iodo-6-methoxy-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one2-((5-iodo-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one . 2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-l-(methylsulfonyl)-lh-indole 2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-5-fluoro-l-(methylsulfonyl)-lh-indole 5-chloro-2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-l-(methylsulfonyl)-lh-indole

In yet another embodiment, the present invention relates to process for the preparation of the compounds of formula (I) as summarized in scheme I below wherein R1,Qand T are as defined above and A is substituted l-oxo-2,3-dihydro-lH-indene or pyridine and thiophene substituted methylene group.

According to the present invention, the compounds of formula (I) are prepared by reacting the Iodo compound of formula 5 (J. Org. Chem. 1999, 64, 9646 and Beilstein J. Org. Chem. 2009, 5, No. 46. doi:10.3762/bjoc.5.46) with a suitable alkyne of formula 3 or 9 to afford compound of formula (I) in presence of a suitable catalyst such as bis-triphenylphosphine palladium chloride, palladium acetate, palladium chloride, tetrakis triphenylphosphine palladium, palladium on charcoal etc, a suitable co-catalyst such as copper chloride, copper bromide, copper iodide, copper acetate etc, in the presence or absence of a suitable ligand such as triphenyl phosphine, tri(p-tolyl)phosphine etc, a base such as triethylamine, diisopropyl ethyl amine, piperidine, 2-aminoethanol, (S)-prolinol, sodium acetate, sodium bicarbonate, sodium carbonate, potassium carbonate etc in a solvent such as acetonitrile, dimethylformamide, dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, methanol, ethanol, i-propanol, n-butanol, water etc at temperature in between -70 to 300 °C preferable 25 to 150 °C for 30 min to 5 days preferable lh to 72h under an inert atmosphere such as argon, nitrogen etc,

In yet another embodiment, the present invention relates to process for the preparation of the compounds of formula 3 as depicted in scheme II below

Scheme II

Compound of formula A is esterified to afford compound of formula B using diethyl carbonate in presence of a base such as sodium hydride, sodium methoxide, sodium ethoxide, potassium tertiary butoxide, n-butyl lithium, s-butyl lithium, LDA etc and a suitable solvent such as benzene, toluene, xylene, tetrahydrofuran, dimethyl formamide, 1,4-dioxane and the like. The compound of formula B is alkylated using propargyl bromide in presence of suitable base such as potassium carbonate, sodium carbonate, sodium methoxide, sodium ethoxide, potassium tertiary butoxide, sodium hydride, n-butyl lithium, s-butyl lithium and suitable solvent such as dry acetone, ditheyl ether, tetrahydrofuran, toluene, dimethyl formamide to give compound of formula C which is then deesterified using sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate in presence of suitable solvent such as tetrahydrofuran, benzene, toluene, acetone, methanol, ethanol, isopropanol, n-butanol, water and the like.

In yet another embodiment, the present invention relates to process for the preparation of the compounds of formula 9 as depicted in scheme III below

According to the present invention compound of formula 7 is reacted with a suitable thiophene derivative in the presence of magnesium or s-butyl lithium and suitable solvent such as diethylether, tetrahydrofuran or 1,4-dioxane to afford the compound of formula 8 which is then treated with suitable acetylene compound in presence of a base such as potassium carbonate, sodium carbonate, sodium methoxide, sodium ethoxide, potassium tertiary butoxide, sodium hydride, n-butyl lithium, s-butyl lithium and suitable solvent such as dry acetone, ditheyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, dimethyl formamide to afford the compound of formula 9.

Biological assay
Cell lines and culture conditions
Human metastatic breast cancer cells, MDA-MB 231, human chronic myeloid leukemia cells, K562, human colon carcinoma cells, Colo-205, human neuroblastoma cells ,IMR-32 , and human embroynoic kidney cells, HEK293 , were procured from National Center for Cell Sciences, Pune, India. All cells were grown in RPMI-1640 supplemented with 10% heat inactivated fetal bovine serum (FBS), 100 IU/ml penicillin, 100 mg/ml streptomycin and 2 mM-glutamine. Cultures were maintained in a humidified atmosphere with 5% CO2 at 37 °C. The cells were subcultured twice each week, seeding at a density of about 2 x 103 cells/ml.

MTT Assay
Cell viability was determined by -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cells (5X103 cells/well) were seeded to 96-well culture plate and cultured with or without compounds at 10 μM concentration for 24 h in a final volume of 200μ1 .After treatment, the medium was removed and 20μl of MTT (5mg/ml in PBS) was added to the fresh medium. After 2 h incubation at 37 °C, 100 μl of DMSO was added to each well and plates were agitated for 1 min. Absorbance was read at 570 nm on a multi-well plate reader (Victor3, Perkin Emler). Percent inhibition of proliferation was calculated as a fraction of control (without compound).

Table showing the % inhibition in growth of various cancer cell lines by the compounds at 10 μM concentration. HEK293 cell line is taken as non cancerous cell line.


EXAMPLES
Preparation of Intermediates:
Synthesis of ethyl 5,6-dimethoxy-l-oxo-2,3-dihydro-l H-indene-2-carboxylate (2):

To a stirred suspension of NaH (5.0 g, 60% in mineral oil, 125 mmol) in diethyl carbonate (20 mL) was added drop wise a solution of 5,6-dimethoxy-l-indanone 1 (10 g, 52 mmol) in diethyl carbonate (70 mL). The mixture was refluxed at 80 °C for 2 h. After cooling to it, H2O (200 mL) was added. The aqueous phase was separated and extracted with CH2Cl2 (3 x 50 mL). The combined organic extracts were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The oily residue was purified by column chromatography to give the title compound 2 (11.68 g, 85%) as white crystalline solid (Reference: Tetrahedron 58 (2002) 4225-4236).

Synthesis of ethyl 5,6-dimethoxy-l-oxo-2-(prop-2-ynyl)-2,3-dihydro-lH- indene-2-carboxylate (3):

The ester 2 (10 g, 37.84 mmol) was dissolved in dry acetone (50 mL). To this solution was added anhydrous K2CO3 (6.2 g, 45.40 mmol) and the mixture was stirred at room temperature for 30 min. To this was added propagyl bromide (5.4 g, 45.40 mmol) drop wise over a period of 30 min. Stirring was continued at room temperature for 12 h. K2CO3 was removed by filtration and the residue was washed with acetone. The filtrate was concentrated under reduced pressure. The oily residue was purified by column chromatography to give the title compound 3 (10.30 g, 90%) as a white crystalline solid. 1 H NMR (400 MHz, CDCl3): 7.2 (s, ArH, 1H), 6.9 (s, ArH, 1H), 4.3-4.2 (q, OCH2, 2H), 3.9 (s, OCH3, 6H), 3.6 (d, ArCH2, 1H), 3.3 (d, ArCH2, 1H), 3.0 (d, CH2, 1H), 2.8 (d, CH2, 1H), 1.8 (s, CH, 1H), 1.3 (t, CH3, 3H); mass (ES mass, m\z) 303 (M+1, 100%).

Synthesis of 5,6-dimethoxy-2-(prop-2-ynyl)-2,3-dihydro-l H -inden-l-one (4):

The alkyne 3 (5 g, 16.53 mmol) was dissolved in 150 mL of 30% NaOH and THF (1:1). This solution was refluxed for 12 h. THF was removed under reduced pressure, and the aqueous mixture was adjusted to pH 7 by using concentrated HC1. The aqueous phase was extracted with EtOAc (3 x 100 mL). The organic layers were collected, combined, dried over anhydrous Na2S04 and concentrated under reduced pressure. The crude product was purified by column chromatography to afford the title compound 4 (3 g, 80%) as a white crystalline solid. 1H NMR (400 MHz, CDC13): 7.2 (s, ArH, 1H), 6.9 (s, ArH, 1H), 3.9 (s, OCH3, 6H), 3.6 (d, ArCH2, 1H), 3.3 (d, ArCH2, 1H), 3.0 (d, CH2, 1H), 2.8 (d, CH2, 1H), 1.8 (s, CH, 1H). 13C NMR (50 MHz, CDC13); mass (ES mass, m/z) 231 (M+1, 100%).

Synthesis of 2-chloropyridin-3-yl-thiophen-2-yl-methanol (8):

In a dry two necked round bottom flask, Mg metal (346 mg, 0.0142 mol) was taken in dry THF (30 mL) to which was added 2-bromothiophene (2.36 g, 0.0142 mol). The mixture was refluxed until all the Mg metal reacted. The freshly prepared Grignard reagent was cooled to 0-5 °C and 2-chloro pyridine-3-carboxylate (1 g, 0.007lmol) and LiCl (150 mg, 0.00355 mol) was added. The reaction mass was stirred at 0 °C for 30 min and stirred at room temperature for 30 min. The reaction was completed within 1 h (monitored by TLC). The mixture was quenched with NH4Cl and extracted with EtOAc (3 x 30 mL). The organic layers were collected, combined, dried over anhydrous Na2SO4 and concentrated under low vacuum to give the title compound (1.2 g, 75%). H NMR (400 MHz, CDCI3): 6.38 (s, 1H), 6.95 (m, 2H), 7.30 (m, 2H), 8.10 (dd, Jx = 7.6 Hz, J2 = 1.6 Hz, 1H), 8.32 (dd, Jx = 4.4 Hz, J2 = 1.6 Hz, 1H); 13C NMR (50 MHz, CDC13): 68.3, 122.9, 125.7, 125.9, 126.8, 136.5, 137.4, 145.3, 148.8, 149.2; mass (ES mass, m\z) 226 (M+1, 100%).

Synthesis of 2-chloro-3-prop-2-ynyIoxy thiophen-2-y!- methyl pyridine (9):

To a solution of alcohol 8 (37.84 mmol) in dry acetone (50 mL) was added anhydrous K2CO3 (45.40 mmol) and the mixture was stirred at room temperature for 30 min. To this was added propagyl bromide (45.40 mmol) drop wise over a period of 30 min. The mixture was stirred at room temperature for 12 h and filtered. The residue was washed with acetone and the filtrate was concentrated under reduced pressure. The oily residue was purified by column chromatography to give the title compound (9) (90%) as a light brown semi solid. 1 H NMR (400 MHz, CDCI3): 2.5 (s, 1H), 4.22 (m, 2H), 6.23 (s, 1H), 6.96 (dd, /, = 4.6 Hz, J2 = 3.6 Hz, 1H), 7.04 (d, J = 3.6 Hz, 1H), 7.31 (m, 2H), 8.05 (dd, J, = 8.0 Hz, J2 = 1.6 Hz, 1H), 8.35 (dd, Jx = 4.8 Hz, J2 = 2.0 Hz, 1H); 13C NMR (50 MHz, CDCI3): 29.7, 63.8, 112.3, 120.8, 121.5, 126.5, 129.6, 131.0, 131.2, 131.4, 133.2, 134.9, 148.9; mass (ES mass, m\z) 264.2 (M+1, 100%); HRMS: calcd, for C13HnNOSCl: 264.02, found: 264.02.

General procedure for the synthesis of compound of formula 1 via Sonogashira coupling reaction:
A mixture of iodo compound (0.33 mmol), 10% palladium carbon (0.0022 mmol), triphenylphosphine (0.0086 mmol), cuprous iodide (0.022 mmol) and triethylamine (0.54 mmol) in ethanol (5 mL) was stirred for 30 min under a nitrogen atmosphere. To this mixture was added alkyne of formula 3 or 9 (0.33 mmol) slowly and the mixture was refluxed and reaction was monitored by TLC. The mixture was then cooled to room temperature and filtered through celite, ethanol was removed under reduced pressure. The residue was diluted with water (50 mL) and extracted with ethyl acetate (3X25 ml). The organic layers were collected, combined, washed with water (2X25 ml), dried over anhydrous sodium sulphate and concentrated. The residue thus obtained was purified by olumn chromatography to afford compound of formula 1 as white coloured solids to semisolids.

The following compounds are prepared as per the procedure given above:
Example 1: Ethyl 2-((6-fluoro-5-iodo-l-(methylsulfonyl)-lH-indol-2-yl)methyl)-5,6-dimethoxy-1 -oxo-2,3 -dihydro-1 H-indene-2 -carboxylate
White solid, mp: 163-170 °C; Rf (40% ethylacetate:n-hexane) 0.44; IR (cm"1, neat): 3034, 2973, 2940, 1717, 1705; 1H NMR (400 MHz, CDC13): 1.17 (t, J= 7.2 Hz, 3H), 3.05 (s, 3H), 3.33 (d, J=17.2Hz, 1H), 3.50 (d, J=16.4 Hz, 1H), 3.80 (d, J=17.2 Hz, 1H), 3.90 (s, 3H), 3.95 (s, 3H), 4.03 (d, J=16.4 Hz, 1H), 4.16 (q, J= 7.0 Hz, 2H), 6.343 (s, 1H), 6.86 (s, 1H), 7.16 (s, 1H), 7.89 (m, 2H); 13C NMR (400MHz, CDC13): 14.0, 32.3, 36.2, 40.9, 56.1, 56.3, 61.1, 62.0, 78.0, 105.0, 107.1, 109.5, 115.4, 120.1, 124.6, 126.9, 129.6, 130.7, 134.9, 138.9, 149.2, 149.8, 150.2, 156.3, 170.2, 199.2; mass (ES mass, m\z) 616.03 (M+1, 60%); HRMS: calcd, for C24H24NO7SFI: 616.0302, found: 616.0307.

Example 2: Ethyl 5,6-dimethoxy-2-((5-methyl-l-(methylsulfonyl)-lH-indol-2-yl)methyl)-1 -oxo-2,3 -dihydro-1 H-indene-2-carboxylate

Semi solid; Rf(40% ethylacetate:n-hexane) 0.44; IR (cm1, neat); 3034, 2973, 2940, 1717, 1705; !H NMR (400 MHz, CDCI3): 1.17 (t, J=7.0 Hz, 3H), 2.40 (s, 3H), 2.98 (s, 3H), 3.25 (d, J=17.2 Hz, 1H), 3.52 (d, J=16.4 Hz, 1H), 3.78 (d, J=17.2 Hz, 1H), 3.89 (s, 3H), 3.94 (s, 3H), 4.03 (d, J=16.4 Hz, 1H), 4.16 (q, J= 7.0 Hz, 2H), 6.37 (s, 1H), 6.85 (s, 1H), 7.09 (d, J=78.0Hz, 1H), 7.16 (s, 1.H), 7.22 (s,lH), 7.86 (d, J=8.0Hz, 1H); 13C NMR (400 MHz, CDCI3): 14.0, 21.1, 30.6, 32.5, 40.1, 56.0, 56.2, 61.0, 63.8, 104.4, 107.3, 109.7, 113.9, 120.3, 125.6, 128.9, 129.8, 133.4, 135.2, 139.7, 148.7, 149.5, 155.6, 175.6, 201.0; mass (ES mass, m\z): 486.5 (M+1, 50%); HRMS:

Example 3: Ethyl 2-((5-chloro-l-(methylsulfonyl)-lH-indol-2-yl)methyl)-5,6-dimethoxy-1 -oxo-2,3-dihydro-1 H-indene-2-carboxylate

White solid, mp: 255-257 UC; Rf (40% ethylacetatem-hexane) 0.4; IR (cm"1, neat): 3034, 2973, 2940, 1717, 1705; 1H NMR (400 MHz, CDC13): 1.17 (t, J= 7.2 Hz, 3H), 3.05 (s, 3H), 3.33 (d, J=17.2Hz, 1H), 3.50 (d, J=16.4 Hz, 1H), 3.80 (d, J=17.2 Hz, 1H), 3.90 (s, 3H), 3.95 (s, 3H), 4.03 (d, J=16.4 Hz, 1H), 4.16 (q, J= 7.0 Hz, 2H), 6.38 (s, 1H), 6.86 (s, 1H), 7.16 (s, 1H), 7.23 (dd, J i=8.2 Hz, J2=1.8 Hz 1 H), 7.41 (d, J=1.8Hz, 1H), 7.92 (d, J-8.2Hz, 1H); 13C NMR (400MHz, CDC13): 14.0, 32.3, 36.2, 40.9, 56.1, 56.3, 61.1, 62.0, 105.0, 107.1, 109.5, 115.4, 120.1, 124.6, 126.9, 129.6, 130.7, 134.9, 138.9, 149.2, 149.8, 156.3, 170.2, 199.2; mass (ES mass, m\z) 506.3 (M+1, 40%); HRMS: calcd, for C24H25NO7SCI: 506.104, found: 506.1037.

Example 4: Ethyl 5,6-dimethoxy-2-(( 1 -(methylsulfonyl)-1 H-indol-2-yl)methyl)-1 -oxo-2,3-dihydro-lH-indene-2-carboxylate

Semi-solid; Rf (40% ethylacetate:n-hexane) 0.38; IR (cm"1, neat): 3034, 2973, 2940, 1717, 1705; 1H NMR (400 MHz, CDC13): 1.17 (t, J= 7.2 Hz, 3H), 3.02 (s, 3H), 3.25 (d, J=17.2Hz, 1H), 3.51 (d, J=16.8 Hz, 1H), 3.79 (d, J=17.2 Hz, 1H), 3.89 (s, 3H), 3.93 (s, 3H), 4.04 (d, J=16.8 Hz, 1H), 4.16 (q, J= 7.0 Hz, 2H), 6.43 (s, 1H), 6.85 (s, 1H), 7.15-7.29 (m, 2H), 7.43 (d, J ,=7.6 Hz, 1H), 7.99 (d, J=7.6Hz, 1H); 13C NMR (400 MHz, CDCI3): 14.0, 21.7, 30.6, 32.6, 40.4, 46.8,56.1, 56.3, 61.0, 63.8, 104.47, 107.4, 109.8, 114.2, 120.4, 123.8, 124.3, 129.0, 129.5, 136.9, 139.7, 148.7, 149.5, 155.7, 170.2, 199.5; mass (ES mass, m\z): 472.3 (M+1 , 28%); HRMS: calcd, for C^^NOyS: 472.143, found: 472.1416.

Example 5: Ethyl 2-((5-fluoro-l-(methylsulfonyl)-lH-indol-2-yl)methyl)-5,6-dimethoxy-1 - oxo-2,3-dihydro-1 H-indene-2-carboxylate

White solid, mp: 264-267 °C; Rf C40% ethylacetate:«-hexane) 0.4; IR (cm"1, neat): 3034, 2973, 2940, 1717, 1705; 1 H NMR (400 MHz, CDC13): 1.17 (t, J= 7.2 Hz, 3H), 3.05 (s, 3H), 3.33 (d, J=17.2Hz, 1H), 3.50 (d, J=16.4 Hz, 1H), 3.80 (d, J=17.2 Hz, 1H), 3.90 (s, 3H), 3.95 (s, 3H), 4.03 (d, J=16.4 Hz, 1H), 4.16 (q, J= 7.0 Hz, 2H), 6.38 (s, 1H), 6.86 (s, 1H), 7.16 (s, 1H), 7.23 (dd, J i=8.2 Hz, J2=1.8 Hz 1 H), 7.41 (d, J=1.8Hz, 1H), 7.92 (d, J=8.2Hz, 1H); 13CNMR (400MHz, CDC13): 14.0, 32.3, 36.2, 40.9, 56.1, 56.3, 61.1, 62.0, 105.0, 107.1, 109.5, 115.4, 120.1, 124.6, 126.9, 129.6, 130.7, 134.9, 138.9, 149.2, 149.8, 150.0, 154.3, 170.2, 199.2; mass (ES mass, m\z) 490.13 (M+1, 95%); HRMS: calcd, for C24H25NO7SR 490.1336, found: 490.1318.

Example 6: Ethyl 2-((5-iodo-l-(methylsulfonyl)-lH-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3-dihydro-lH-indene-2-carboxylate

Semi-solid; Semi-solid; Rf (40% ethylacetate:n-hexane) 0.42; IR (cm"1, neat): 3034, 2973, 2940, 1717, 1705; 1H NMR (400 MHz, CDC13): 1.17 (t, J= 7.2 Hz, 3H), 3.05 (s, 3H), 3.33 (d, J=17.2Hz, 1H), 3.50 (d, J=16.4 Hz, 1H), 3.80 (d, J=17.2 Hz, 1H), 3.90 (s, 3H), 3.95 (s, 3H), 4.03 (d, J=16.4 Hz, 1H), 4.16 (q, J= 7.0 Hz, 2H), 6.38 (s, 1H), 6.86 (s, 1H), 7.16 (s, 1H), 7.23 (dd, J i=8.2 Hz, J2=1.8 Hz 1 H), 7.41 (d, J=1.8Hz, 1H), 7.92 (d, J=8.2Hz, 1H); 13C NMR (400MHz, CDC13): 14.0, 32.3, 36.2, 40.9, 56.1, 56.3, 61.1, 62.0, 105.0, 107.1, 109.5, 115.4, 120.1, 124.6, 126.9, 129.6, 130.7, 134.9, 138.9, 149.2, 149.8, 156.3, 170.2, 199.2; mass (ES mass, m\z) 506.3 (M+1, 40%); HRMS: calcd, for C24H25NO7SI: 598.0397, found: 598.0411.

Example 7: 5,6-dimethoxy-2-((5-methyl-1 -(methylsulfonyl)-1 H-indol-2-yl)methyl)-2,3 -dihydro-1 H-inden-1 -one
White solid, mp: 180-184 °C; Rf(50% ethylacetate:«-hexane) 0.75; IR (cm1, neat): 3015, 2944, 1698, 1181; 1H NMR (400 MHz, CDC13): 2.43 (s, 3H), 2.83 (d, J=10Hz, 6H), 3.0-3.1 (m, 4H), 3.19-3.28 (m, 2H), 3.65 (m, 4H), 3.91 (s, 3H), 3.95 (s, 3H), 6.44 (s, 1H), 6.84 (s, 1H), 7.12 (d, J=7.6Hz, 1H), 7.20 (s, 1H), 7.27 (d, J=9.2Hz, 1H), 7.89 (d, J=9.2Hz, 1H); 13C NMR (100MHz, CDC13): 21.2, 30.6, 32. 6, 40.1, 46.8, 56.1, 56.2, 104.4, 107.4, 109.7, 113.9, 120.4, 125.7, 128.9, 129.8, 133.5, 135.2, 139.8, 148.7, 149.5, 155.7, 205.4; mass (ES mass, m\z): 414.3 (M+1 , 98%), HRMS: calcd, for C22H24N05S:
414.1375, found: 414.1372.

Example 8: 2-((5-chloro-1 -(rnethylsulfonyl)-1 H-indol-2-yl)rnethyl)-5,6-dimethoxy-2,3-dihydro-1 H-inden-1 -one

White solid, mp: 188-190 UC; Rf (30% ethylacetate:«-hexane) 0.4; IR (cm"1, neat): 2963, 2952, 1683, 1198; *H NMR (400 MHz, CDC13): 2.84 (dd, Jp=16.4 Hz, J2=3.6 Hz, 1 H), 3.07-3.12 (m, 4H), 3.20-3.33 (m, 2H), 3.65 (m, 4H), 3.63 (dd, J,=16.4 Hz, J2=3.6 Hz, 1H), 3.92 (s, 3H), 3.96(s, 3H), 6.45 (s, 1H), 6.85 (s, 1H), 7.20 (m, 1H), 7.47 (d, J=2Hz, 1H), 7.95 (d, J=8.8Hz, 1H); 13C NMR (100 MHz, CDC13): 30.6, 32.6, 40.7, 46.6, 56.1, 104. 5, 107.4, 108.9, 114.0, 115.3, 120.0, 124.5, 130.8, 135.3, 139.2, 141.2, 148.6, 149.6, 155.8, 205.2; mass (ES mass, m\z) 434.3 (M+1, 98%); HRMS: calcd, for C21H21NO5SCI:
434.0829, found: 434.0819.

Example 9: 5,6-dimethoxy-2-((l-(methylsulfonyl)-lH-indol-2-yl)methyl)-2,3-dihydro-1 H-inden-1-one

Light brown solid, mp: 160-162 UC; Rf(30% ethylacetate:«-hexane) 0.62; IR (cm1, neat): 3009, 2968, 1684, 1198; 1H NMR (400 MHz, CDC13): 2.85 (d, J=14Hz, 1H), 3.05-3.32 (m, 6H), 3.66 (dd, Ji=16.0 Hz, J2=3.2 Hz, 1 H), 3.92 (s, 3H), 3.95 (s, 3H), 6.51 (s, 1H),6.85 (s, 1H), 7.20 (s, 1H), 7.26-7.32 (m, 2H), 7.50 (d, J=8.0Hz, 1H), 8.02 (d, J=8.0Hz, 1H); 13C NMR (100MHz, CDC13): 30.7, 32.7, 40. 5, 46.8, 56.1, 56.2, 104.5, 107.5, 109.8,114.3, 120.5, 123.8, 124.4, 129.0, 129.6, 136.9, 139.7, 148.7, 149.6, 155.7, 205.4; mass (ES mass, m\z) 400.2 (M+1, 98%); HRMS: calcd, for C2iH22N05S: 400.1219, found:
400.1211.

Example 10: 2-((5-iodo-6-methoxy-l-(methylsulfonyl)-lH-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-1 H-inden-1 -one

Semi-solid; Rf (30% ethylacetate:n-hexane) 0.78; IR (cm"', neat): 2963, 2952, 1684, 1198; !H NMR (400 MHz, CDCi3): 2.
82 (dd, Ji=l6.4 Hz, j2=2.8 Hz, 1H), 3.0-3.07 (m, 2H), 3.60 (dd, Ji=16.0 Hz, J2=4.2 Hz, 1H), 3.92 (s, 3H), 3.94 (s, 3H), 3.96 (s, 3H), 6.37 (s, 1H), 6.85 (s, 1H), 7.20 (s, 1H), 7.58 (s, 1H), 7.89(s, 1H); 13C NMR (100MHz, CDC13): 22.7, 29.7, 32.6, 40.4, 46.7, 56.2, 56.8, 97.6, 104.5, 107.4, 108.6, 120.2, 129.0, 130.5, 139.1, 148.7, 155.8, 205.4; mass (ES mass, m\z) 556.1 (M+1, 98%); HRMS: calcd, for C22H23N06SI: 556.0291, found: 556.0277.

Example 11: 2-((5-fluoro-l-(methylsulfonyl)-lH-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-1 H-inden-1 -one
Yellow solid; 218-220 °C; Rf (20% ethylacetate:n-hexane) 0.52; IR ( cm"1, neat): 2970, 2946, 1683, 1198; 'H NMR (400 MHz, CDC13): 2.84 (dd, Ji=16.0 Hz, J2=2.6 Hz, 1H), 3.02-3.33 (m, 6H), 3.64 (dd, Ji=16.0 Hz, J2=4.7 Hz, 1 H), 3.92 (s, 3H), 3.95 (s, 3H), 6.47 (s, 1H), 6.85 (s, 1H), 7.14-7.28 (m, 3H), 7.90 (m, 1H); 13C NMR (100MHz, CDCI3): 30.7, 32.6, 40.5, 46.7, 56.1, 56.2, 104.4, 107.4, 109.5, 109.6, 115.2, 115.4, 128.9, 133.2, 141.5, 148.6, 149.6, 155.8, 157.5, 162.2, 205.3; mass (ES mass, m\z) 418.3 (M+1, 100%); HRMS: calcd, for C2iH2iN05SF: 418.1124, found: 418.1111.

Example 12: 2-((5-iodo-1 -(methylsulfonyl)-1 H-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-1 H-inden-1 -one
Semi-solid; Rf (20% ethylacetate:«-hexane) 0.43; IR (cm"1, neat): 2963, 2952, 1693, 1198; !H NMR (400 MHz, CDC13): 2.82 (d, J=16.4Hz, 1H), 3.06-3.12 (m, 3H), 3.19-3.32 (m, 2H), 3.63 (dd, Ji=18.0 Hz, J2=3.2 Hz, 1H), 3.92 (s, 3H), 3.96 (s, 3H), 6.43 (s, 1H), 6.85 (s, 1H), 7.19 (s, 1H), 7.57 (d, J=8.0Hz, 1H), 7.79 (d, J=8.0Hz, 1H), 7.84 (s, 1H); 13C NMR (100MHz, CDCI3): 30.5, 32.6, 40.8, 46.6, 56.1, 56.3, 87.9, 104.5, 107.4, 108.6, 116.1, 128.9, 129.3, 131.8, 132.8, 136.2, 140.7, 148.6, 149.6, 155.8, 205.1; mass (ES
mass, m\z) 526 (M+1, 30%); HRMS: calcd, for C21H21N05SI: 526.0185, found: 526.0184.

Example 13: 2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-1 -(methylsulfonyl)-1 H-indole
Semi-solid; Rf (30% ethylacetate: n-hexane) 0.54; 1H NMR (400 MHz, CDC13): 3.06 (s, 3H), 4.82 (s, 2H), 6.21 (s, 1H), 6.92 (m, 4H), 7.4 (m, 1H), 7.58 (d, J = 72 Hz, 1H), 7.65 (dd, J, = 8 Hz, J2 = 1.6 Hz, 1H), 7.82 (dd, Ji = 8 Hz, J2 = 1.2 Hz, 1H), 8.01 (d, J- 8.4 Hz, 1H), 8.11 (dd, Jx = 7.6 Hz, J2 = 2.0 Hz, 1H), 8.37 (dd, Jx = 4.8 Hz, J2 = 1.6 Hz, 1H); 13C NMR (50 MHz, CDC13): 40.2, 64.3, 75.3, 114.0, 121.3, 122.4, 123.7, 126.7, 127.2, 128.5, 129.9, 135.5, 135.9, 136.6, 137.2. 137.8, 139.5, 142.6, 149.1, 149.8; mass (ES mass, m\z) 433 (M+1, 100%); HRMS: calcd, for C20H17N203S2Cl: 433.04, found: 433.04.

Example 14: 5-chloro-2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-l-(methylsulfonyl)-1 H-indole

Semi-solid; Rf (30% ethylacetate: n-hexane) 0.56; 1H NMR (400 MHz, CDC13): 3.06 (s, 3H), 4.82 (s, 2H), 6.19 (s, 1H), 6.64 (s, 1H), 6.95 (dd, Jx = 4.8 Hz, J2 = 3.6 Hz, 1H), 7.04 (d, J= 2.4 Hz, 1H), 7.28 - 7.37 (m, 4H), 7.57 (m, 1H), 7.95 (d, J= 8.8Hz, 1H), 8.09 (dd, /, = 8.0 Hz, J2 = 2.0 Hz, 1H), 8.37 (dd, /, = 4.4 Hz, J2 = 1.6 Hz, 1H); 13C NMR (50 MHz, CDCI3): 41.2, 64.1, 75.4, 115.0, 120.7, 123.2, 125.4, 126.3, 126.7, 126.8, 129.6, 129.9, 131.8, 135.3, 136.5, 137.1. 138.5, 142.2, 149.1, 149.7; mass (ES mass, m\z) 467 (M+1, 100%); HRMS: calcd, for C20Hi6N2O3S2Cl2: 467.00, found: 467.00.

Example 15: 2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-5-fluoro-l -(methylsulfonyl)-1 H-indole

Semi-solid; Rf (30% ethylacetate: n-hexane) 0.58; 'H NMR (400 MHz, CDC13): 3.05 (s, 3H), 4.80 (s, 2H), 6.20 (s, 1H), 6.67 (s, 1H), 7.22 (dd, Jx = 8.4 Hz, J2 = 2.8 Hz, 1H), 7.35 (dd, Jx = 8.0 Hz, J2 = 4.8 Hz, 1H), 7.55 (dd, Jx = 8.0 Hz, J2 = 3.2 Hz, 1H), 7.62 (dd, Jx = 9.2 Hz, J2 = 3.6 Hz, 1H), 7.97 (dd, Jx = 9.2 Hz, J2 = 3.6 Hz, 1H), 8.11 (dd, Jx = 7.6 Hz, J2 = 2.0 Hz, 1H), 8.37 (dd, Jx = 4.8 Hz, J2 = 2.0 Hz, 1H); 13C NMR (50 MHz, CDCI3): 41.0, 64.2, 75.3, 114. 9, 116.9, 123.0, 125.7, 126.3, 126.7, 129.2, 129.4, 133.2, 134.0, 135.3, 136.4, 137.3,142.2, 148.6, 149.0, 149.6; mass (ES mass, m\z) 451 (M+1, 100%); HRMS: calcd, for C20H16N203S2ClF: 451.03, found: 451.03.

We claim

1. A compound of formula (I)

its analogues, derivatives, tautomers, stereoisomers, enantiomers, diastereomers, polymorphs, pharmaceutically acceptable salts, pharmaceutically acceptable hydrates, pharmaceutically acceptable solvates and bioisosteres

Wherein

Q is selected from O, S, NR wherein R is hydrogen, hydroxyl, lower alkyl, lower alkoxy, acyl or aryl;
or

Q is substituted or unsubstituted lower alkyl chain optionally interrupted by an hetero atom selected from O, S or NR wherein R is selected from hydrogen, hydroxyl, lower alkyl, lower alkoxy, acyl or aryl;

T is selected from hydrogen, halogen, acyl, mesyl, COR1, COOR1;

A is optionally substituted cycloalkyl, aryl, heterocyclyl, heteroaryl; or

A is lower alkyl chain substituted by one, two or three cyclic rings selected from cycloalkyl, aryl, heterocyclyl, heteroaryl which again can be optionally substituted by one or more groups;

R1 is selected from hydrogen, halogen, hydroxyl, optionally substituted lower alkyl, , optionally substituted lower alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl;

2. The compound according to claim 1, wherein Q is substituted or unsubstituted lower alkyl chain optionally interrupted by an hetero atom selected from o ,s or NR wherein R is selected from hydrogen, hydroxyl, lower alkyl, lower alkoxy, acyl or aryl;

3. The compound according to claim 1, wherein T is hydrogen or mesyl and R1 is independently hydrogen, hydroxyl, fluoro, chloro, iodo, methyl, ethyl, methoxy or ethoxy group.

4. The compound according to claim 1, wherein A is selected from

Wherein D is independently selected from N or CH; and Ra is selected from hydrogen, halogen, alkyl, alkoxy, acyl, COOR1, NR1 R1;

5. A compound selected from

• Ethyl 2-((6-fluoro-5-iodo-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-l -oxo-2,3-dihydro-lh-indene-2-carboxylate

• Ethyl 5,6-dimethoxy-2-((5-methyl-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-l-oxo- 2,3 -dihydro -1h- indene -2- carboylate.

• Ethyl 2-((5-iodo-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3-dihydro-1 h-indene-2-carboxylate

• Ethyl 5,6-dimethoxy-2-((l-(methylsulfonyl)-lh-indol-2-yl)methyl)-l-oxo-2,3-dihydro-1 h-indene-2-carboxylate

• Ethyl 2-((5-chloro-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3-dihydro-1h-indene-2-carboxylate

• Ethyl 2-((5-fluoro-l-(methylsulfonyl)-l h-indol-2-yl)methyl)-5,6-dimethoxy-l-oxo-2,3-dihydro-lh-indene-2-carboxylate

• 2-((5-fluoro-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one

• 2-((5-chloro-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one

• 5,6-dimethoxy-2-((5-methyl-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-2,3-dihydro-lh-inden-1-one

• 5,6-dimethoxy-2-((l-(methylsulfonyl)-lh-indol-2-yl)methyl)-2,3-dihydro-lh-inden-l-one

• 2-((5-iodo-6-methoxy-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one

• 2-((5-iodo-l-(methylsulfonyl)-lh-indol-2-yl)methyl)-5,6-dimethoxy-2,3-dihydro-lh-inden-1-one

• 2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-l-(methylsulfonyl)-lh-indole

• 2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-5-fluoro-l-(methylsulfonyl)-l h-indole

• 5-chloro-2-(((2-chloropyridin-3-yl)(thiophen-2-yl)methoxy)methyl)-l-(methylsulfonyl)-l h-indole

6. A process for the preparation of compound of formula (1) comprising the steps of reacting the Iodo compound of formula 5 with a suitable alkyne of formula 3 or 9 to afford compound of formula (I) in presence of a suitable catalyst selected from bis-triphenylphosphine palladium chloride, palladium acetate, palladium chloride, tetrakis triphenylphosphine palladium, palladium;

a suitable co-catalyst selected from copper chloride, copper bromide, copper iodide, copper acetate;

a base such as triethylamine, diisopropyl ethyl amine, piperidine, 2-aminoethanol, (S)-prolinol, sodium acetate, sodium bicarbonate, sodium carbonate, potassium carbonate;

a solvent selected from acetonitrile, dimethylformamide, dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, methanol, ethanol, i-propanol, n-butanol, water etc at temperature in between -70 to 300 °C preferable 25 to 150 °C, in the presence or absence of a suitable ligand such as triphenyl phosphine, tri(p- tolyl)phosphine;

7. A pharmaceutical composition comprising compound of formula (1) or its pharmaceutically acceptable salts or solvates and a pharmaceutically acceptable carrier

8. A pharmaceutical composition according to claim 7, wherein the composition is in the form of a tablet, capsule, powder, granule, solution, suspension, cream, gel, paste, aerosol or a transdermal patch.

9. The pharmaceutical composition according to claim 7, wherein the pharmaceutically acceptable salt is selected from Li, Na, K, Ca, Mg, Fe, Cu, Zn, sulphates, nitrates, phosphates, perchlorates, borates, hydrohalides (HC1, HBr, HI), acetates, tartrates, maleates, citrates, succinates, palmoates, methanesulphonates, benzoates, salicylates, hydroxynaphthoates, benzenesulfonates, ascorbates, glycerophosphates, or ketoglutarate salts.

10. A pharmaceutical composition comprising compound of formula (I) in a medicament for the treatment of cancer.