WO2016199172A2

WO2016199172A2 - Novel compounds and uses thereof

Info

Publication number: WO2016199172A2
Application number: PCT/IN2016/050179
Authority: WO
Inventors: Hanumant Bapurao Borate; Subhash Prataprao Chavan; Mahesh Madanrao PISAL; Ritesh Ashok ANNADATE; Dhiman Sarkar; Meghana Chintan ATHALYE
Original assignee: Council Of Scientific & Industrial Research
Priority date: 2015-06-10
Filing date: 2016-06-10
Publication date: 2016-12-15
Also published as: WO2016199172A3

Abstract

The present invention disclosed a novel compound of formula (I), (II) and (III) and process for preparation thereof. Further, the present invention provides a pharmaceutical composition comprising compound of formula (I) or (II) or (III) and use of said compounds for the treatment of cancer and in cell imaging applications.

Description

NOVEL COMPOUNDS AND USES THEREOF

FIELD OF THE INVENTION:

The present invention relates to a novel compound of formula (I), (II) and (III). More particularly, the present invention relates to a novel compound of formula (I), (II) and (III) or a pharmaceutically acceptable salt thereof, process for preparation thereof and use of these compounds for the treatment of cancer and in cell imaging application.

BACKGROUND AND PRIOR ART OF THE INVENTION:

Cancer is a generic term for a large group of diseases caused by uncontrolled growth and spread of cells that can affect any part of the body. Chemotherapy is one of the most common forms of treatment for cancer which involves use of anticancer drugs that can destroy the cancer cells. Currently numerous treatment options are available for cancer, including chemotherapy, surgery and radiation for localized disease or a combination of said treatments. With the development of chemotherapy, survival and recovery rates of cancer patients have improved. However, anticancer agents are problematic in terms of being highly toxic and thus severely damaging to normal cells. To overcome such a side effect of anticancer agents, many recent studies have focused on developing alternative anticancer substances capable of specifically suppressing proliferation of tumor cells. Unfornately, however, due to the prevalence of many different types of cancers and due to the complexity of cancers, there still remains a need to develop new anti-cancer therapeutics, including the development of compounds displaying anticancer activity.

Substituted 2,6-dicyanoanilines are an important class of compounds with acceptor- donor- acceptor (A-D-A) systems having varied and diverse applications. The compounds find application in optical materials, in dyes, as intermediates in the synthesis of polymers, for chiral phases in chromatography, as precursors and reagents for regio selective or asymmetric syntheses. Further, the 2,6-dicyanoaniline compounds with 2,6-dicyanoaniline as core group have been studied for various therapeutic activities and also find use as herbicides and insecticides. They also constitute molecular skeleton of a number of compounds with an array of structural variations some of which have been studied for potential medicinal use. The numerous synthetic methods to prepare these moieties and their applications have been reviewed recently and the continued interest in these compounds has resulted in further publications. A review article titled 'Synthesis of substituted 2,6-Dicyanoanilines and related compounds' by Borate et al. published in organic Preparations and Procedures International, 2012, 44, pp 467-521 reports monosubstituted, disubstituted and trisubstituted 2,6 dicyanoanilines and their preparation methods. The monosubstituted 2,6- dicyano aniline as disclosed includes mono substitution at 3 or 4 position; the disubstituted 2,6-dicyanoaniline includes 3,4(4,5) -disubstituted 2,6-dicyano aniline. In the disubstituted 2,6-dicyanoaniline compounds, a variety of substituents such as alkyl, aryl, furyl and thienyl moieties are substituted at 3,5 or 4,5 positions.

Article titled "A simple and clean synthesis of polysubstituted 2,6-Dicyanoanilines catalyzed by KF/alumina" by S Jain et al. published in Journal of the Korean Chemical Society, 2012, 56(6), pp.712-715 reports a simple and clean synthesis of polysubstituted 2,6- dicyanoanilines has been developed via the reaction of arylidene malonodinitriles with 1- arylethylidenemalonodinitriles in ethanol catalyzed by KF/ alumina. Use of non-hazardous solid base as a catalyst, operational simplicity and improved product yields are the key advantages of the present protocol.

Article titled "Regioselective cyclization of unsymmetrical dicyanoanilines to novel 2,3-bifunctionalised indole regioisomers and their use in the synthesis of 4,5- dihydro[l,3]oxazino[5,4- ]indole-6-carbonitriles" by B. Narsaiah et al. published in Tetrahedron, 2005, 61 (16), pp 3999-4008 reports synthesis of novel-2,3-bifunctionalised indole regioisomers (2/3 and 6/7) from unsymmetrical dicyanoanilines 1 by regioselective cyclization in two independent ways. Regioisomers 6 are further utilized in synthesis of novel 4,5-dihydro[l,3]oxazino[5,4- ] indole-6-carbonitriles 9.

Article titled "One-step synthesis of 4-alkyl-3-aryl-2,6-dicyanoanilines and their use in the synthesis of highly functionalized 2,3,5,6,7- and 2,3,4, 5, 7 -substituted indoles" by H Borate et al. published in Tetrahedron Letters, 2011, 52, pp 5491-5493 reports a three- component, one-step method for the synthesis of 4-alkyl-3-aryl-2,6-dicyanoanilines involving reaction of alkyl aldehyde, malononitrile and aryl aldehyde in presence of morpholine. Highly functionalized 2,3,5,6,7- and 2,3,4,5,7-substituted indoles were prepared from these dicyanoanilines by reaction with ethyl bromoacetate. These substituted dicyanoanilines and indoles have a potential to be converted into various other compounds taking advantage of various functional groups present in these molecules.

Article titled "Multicomponent synthesis of 3,5-diaryl-2,6-dicyanoanilines under thermal solvent-free conditions" by HR Shaterian et al. published in Monatsh Chem, 2010, 141 (5), pp 557-560 reports a facile parallel synthesis of 3,5-diaryl-2,6-dicyanoanilines via three-component reaction of aryl aldehydes, acetophenone derivatives, and malononitrile under thermal green solvent-free conditions in the presence of potassium carbonate and also potassium bicarbonate without using any hazardous materials.

Article titled "Parallel synthesis of strongly fluorescent polysubstituted 2,6- dicyanoanilines via microwave-promoted multicomponent reaction" by SL Cui et al. published in J. Org. Chem., 2005, 70 (7), pp 2866-2869 reports a facile parallel synthesis of polysubstituted 2,6-dicyanoanilines via microwave-promoted three-component reaction of aldehydes, ketones, and propanedinitrile in solution and also on polymer support has been developed. The screening for optical properties identified two new compounds with high fluorescence quantum yields.

Article titled "2,6-Dicyanoaniline based donor- acceptor compounds: the facile synthesis of fluorescent 3,5-diaryl/hetaryl-2,6-dicyanoanilines" by E Yalcina et al. published in Arkivoc, april 2015, pp 202-218 reports a series of new 3,5-diaryl/hetaryl-2,6- dicyanoaniline derivatives synthesized by three component one -pot procedure at room temperature to 80°C. The experimental procedure in the preparation of the target compounds is simple, reproducible and it includes short reaction times and easy-isolation/purification of the products. The synthesized compounds are fluorescent active and show wavelength of maximum absorption

in UV or visible region in DMSO at room temperature.

Article titled "Organocatalyzed straightforward synthesis of highly fluorescent 3,5- disubstituted 2,6-dicyanoanilines via domino annulation of a-enolicdithioesters with malononitrile" by Singh et al. RSC Adv., 2013, 3, pp 5345-5349 reports Piperidine mediated a robust, efficient, and selective one-pot synthesis of previously inaccessible and highly fluorescent 3,5-disubstituted 2,6-dicyanoanilines. This was achieved via the domino carboannulation of a-enolic dithioesters with malononitrile by dehydrative C=0/C=S bond functionalization.

Article titled "Novel fluoro substituted benzo[b]pyran with anti-lung cancer activity" by AEFG Hammam et al. published in IJC-B, September 2005, Vol.44B (09); pp 1887-1893 reports the dicarbonitrile derivative 12 and the synthesized compound has been tested against three cell lines of human cancer (lung, breast and CNS cancer), and these compounds show anticancer activity at low concentration as compared to reference drug 5- fluorodeoxyuridine .

The pyrrole-fused benzene (indole) derivatives have been considered as useful intermediates in drugs, pesticides and also as potential pharmaceuticals. A large number of methods for the construction of the indole nucleus have been reported. However, synthesis of indole and indole fused derivatives by novel approach is of current interest due to their promising activity.

PCT application no. 2003091214 disclosed substituted 3-amino-2-carboxylic acid indole and benzo(thiophene derivatives for use in treating allergy, asthma, rhinitis, dermatitis, B-cell lymphomas, tumors and diseases associated with bacterial, rhinovirus or respiratory syncytial virus (RSV) infections.

X and Y are the same or different and are independently selected from the group consisting of hydrogen, halogen, nitro, amino, hydroxy, Ci_₆alkyl, C₂-₆alkenyl, C₂-₆alkynyl, Ci_₆alkoxy, Ci_₆ perfluoroalkyl, Ci_₆perfluoroalkoxy, phenyl and benzyl, wherein phenyl or benzyl is optionally substituted with one or two substituent's each independently selected from Cj- ₆alkyl, Ci-₆perfluoroalkyl, halogen, hydroxy or Ci_₆perfluoroalkyl or Ci_₆perfluoroalkoxy;

PCT application no. 2000046199 disclosed the use of a 3-substituted indole compound of formula (I) ;

or a pharmaceutically acceptable salt, amide or ester thereof; X is CH₂ or S0₂ and Ri, R₂, R₃, R4, R5, R₆ and R₇ are certain specified organic moieties, for use in the preparation of a medicament for the inhibition of monocyte chemoattractant protein- 1 and/or RANTES induced chemotaxis.

Since cancer is a leading cause of death in animals and humans, several efforts have been and are still being undertaken in order to obtain an anticancer therapy active and safe to be administered to patients suffering from a cancer. The problem to be solved by the present invention is to provide compounds that are useful in the treatment of cancer and in cell imaging applications.

OBJECTIVE OF THE INVENTION:

The main objective of the present invention is to provide a novel compound of formula (I) or a pharmaceutically acceptable salt thereof and process for preparation thereof. Another objective of the present invention is to provide a novel compound of formula (II) or a pharmaceutically acceptable salt thereof and process for preparation thereof.

Yet another objective of the present invention is to provide a novel compound of formula (III) or a pharmaceutically acceptable salt thereof and process for preparation thereof.

Still another objective of the present invention is to provide a pharmaceutical composition comprising compound of formula (I) or (II) or (III) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, diluent and/or carrier.

Yet still another objective of the present invention is to provide a method for the treatment of cancer in a subject in need thereof; comprising administering to the said subject a therapeutically effective amount of the compound of formula (I) or (II) or (III) or a pharmaceutically acceptable salt thereof.

Still another objective of the present invention is to provide use of compounds of formula (I) for cell imaging applications.

Yet still another objective of the present invention is to provide use of compounds of formula (I) in cell imaging applications.

Yet still another objective of the present invention is to provide use of compounds of formula (I), (II), (III) for the treatment of cancer.

SUMMARY OF THE INVENTION:

Accordingly, the present invention provides a compound of formula (I);

Formula (I)

Wherein;

R and R¹ are selected independently from hydrogen, (un)substituted alkyl,

(un)substituted aryl, 1,2,3-triazolyl, 1,2,4-triazolyl, imidazolyl, thienyl, furanyl, thienopyrimidinonyl, benzimidazolyl or benzofuranyl, (un)substituted 4-oxothieno[2,3- d]pyrimidin-3(4H)-yl;

R and R¹ together may form a cyclic ring; 2

R is selected from (un)substituted 1,2,3-triazolyl, 1,2,4-triazolyl, mono, di or tri methoxy or halo substituted phenyl ; (benzyl)triazolyl , thienyl, benzofuranyl; 4-((l-(5-iodo- 2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)phenyl;

R³, R⁴ is selected from hydrogen, alkyl, benzyl or allyl;

With the proviso that;

2 1

When R is thienyl, R is (un) substituted 4-oxothieno[2,3-d]pyrimidin-3(4H)-yl; and When R is mono, di or tri methoxy or halo substituted phenyl,

R¹ is not hydrogen and R, R¹ together may not form a cyclic ring;

or a pharmaceutically acceptable salt thereof.

The term ' (un)substituted' refers to ' substituted or unsubstituted' .

In preferred embodiment, said compound of formula (I) is selected from 2-amino-4- (l-benzyl-lH-l,2,3-triazol-4-yl)-5-(4-oxo-6-propylthieno[3,2-<i]pyrimidin-3(4H)-yl)-6- (thiophen-2-yl)isophthalonitrile (1-1), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(6- hexyl-4-oxothieno[3,2-<i]pyrimidin-3(4H)-yl)-6-(thiophen-2-yl)isophthalonitrile (1-2), 2- amino-4-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-6-(thiophen-2-yl)-5-( 1H- 1 ,2,4-triazol- 1 - yl)isophthalonitrile (1-3), 2-amino-4-(benzofuran-2-yl)-6-(l-benzyl-lH-l,2,3-triazol-4-yl)- 5-(lH-imidazol-l-yl)isophthalonitrile (1-4), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)- 2',4'-difluoro-6-( 1H- 1 ,2,4-triazol- 1 -yl)- [ 1 , 1 '-biphenyl] -2,4-dicarbonitrile (1-5), 3-amino-5- ( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-4'-fluoro-6-( 1H- 1 ,2,4-triazol- 1 -yl)- [ 1 , 1 '-biphenyl] -2,4- dicarbonitrile (1-6), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(4-oxo-6- pentylthieno [2,3-<i]pyrimidin-3(4H)-yl)-[l, -biphenyl]-2,4-dicarbonitrile (1-7), 3-amino-5- (l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(6-methyl-4-oxothieno[2,3-<i]pyrimidin- 3(4H)-yl)-[l,l'-biphenyl] -2,4-dicarbonitrile (1-8), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4- yl)-2',4'-difluoro-6-(lH-imidazol-l-yl)-[l,r-biphenyl]-2,4-dicarbonitrile (1-9), 3-amino-5- ( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-4'-fluoro-6-( lH-imidazol- 1 -yl)-[ 1 , 1 '-biphenyl] -2,4- dicarbonitrile (1-10), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)isophthalonitrile (1-11), 2- amino-4-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-5-methylisophthalonitrile (1-12), 2-amino-4-( 1 - benzyl- lH-1, 2,3 -triazol-4-yl)-5-ethylisophthalonitrile (1-13), 2-amino-4-( 1 -benzyl- 1H- l,2,3-triazol-4-yl)-5-propylisophthalonitrile (1-14), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4- yl)-5-butylisophthalonitrile (1-15), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- pentylisophthalonitrile (1-16), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- hexylisophthalonitrile (1-17), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro- [Ι,Γ-biphenyl] -2,4-dicarbonitrile (1-18), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(6- butyl-4-oxothieno[2,3-<i]pyrimidin-3(4H)-yl)isophthalonitrile (1-19), 5-(l-benzyl-lH-l,2,3- triazol-4-yl)-3-(dimethylamino)-2',4'-difluoro-6-( 1H- 1 ,2,4-triazol-l -yl)-[ 1 , l'-biphenyl]-2,4- dicarbonitrile (1-20), 5-(l-benzyl-lH-l,2,3-triazol-4-yl)-3-(dimethylamino)-4'-fluoro-6-(lH- l,2,4-triazol-l-yl)-[l,r-biphenyl]-2,4-dicarbonitrile (1-21), 4-(l-benzyl-lH-l,2,3-triazol-4- yl)-2-(dimethylamino)-5-methylisophthalonitrile (1-22), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)- 2-(dimethylamino)-5-ethylisophthalonitrile (1-23), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2- (dimethylamino)-5-propylisophthalonitrile (1-24), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- butyl-2-(dimethylamino)isophthalonitrile (1-25), 4-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-2- (dimethylamino)-5-pentylisophthalonitrile (1-26), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2- (dimethylamino)-5-hexylisophthalonitrile (1-27), 5-amino-7-(l-benzyl-lH-l,2,3-triazol-4- yl)-2,3-dihydro-lH-indene-4,6-dicarbonitrile (1-28), 2-amino-4-(l-benzyl-5-

(hydroxymethyl)-lH-l,2,3-triazol-4-yl)-5-methylisophthalonitrile (1-29), 3-amino-3',4',5'- trimethoxy-6-pentyl-[l, -biphenyl]-2,4-dicarbonitrile (1-30), 3-amino-6-hexyl-3',4',5'- trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-31), 3-amino-6-heptyl-3',4',5'-trimethoxy- [l,l'-biphenyl]-2,4-dicarbonitrile (1-32), 3-amino-6-decyl-3',4',5'-trimethoxy-[l,r- biphenyl]-2,4-dicarbonitrile (1-33), 5'-amino-3,4,4",5-tetramethoxy-[l,l':3',l"-terphenyl]- 4',6'-dicarbonitrile (1-34), 5'-amino-2,3",4",5"-tetramethoxy-[l,r:3',l"-terphenyl]-4',6'- dicarbonitrile (1-35), 3-amino-5-(furan-2-yl)-3',4',5'-trimethoxy-[l, -biphenyl]-2,4- dicarbonitrile (1-36), 3-amino-3',4',5'-trimethoxy-5-(thiophen-2-yl)-[l, -biphenyl]-2,4- dicarbonitrile (1-37), 3-amino-6-heptyl-4'-methoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-38), 3-amino-6-decyl-4'-methoxy-[l,r-biphenyl]-2,4-dicarbonitrile (1-39), 3-amino-6-(6-butyl- 4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)-4'-methoxy-[l,r-biphenyl]-2,4-dicarbonitrU^ (1-40), 3-amino-4'-methoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)-[l, - biphenyl]-2,4-dicarbonitrile (1-41), 3-amino-3',5'-dimethoxy-6-(2-(4-oxo-6- pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)-[l,r-biphenyl]-2,4-dicarbonitrile (1-42), 3- amino-3 4^5'-trimethoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)-[l,r- biphenyl]-2,4-dicarbonitrile (1-43), 2-amino-5-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin- 3(4H)-yl)ethyl)-4-(thiophen-2-yl)isophthalonitrile (1-44), 3-(dimethylamino)-6-heptyl- 3',4',5'-trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-45), 3-(dibenzylamino)-6-heptyl- 3',4',5'-trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-46), 3-(diallylamino)-6-heptyl- 3',4',5'-trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-47), 6-decyl-3-(dibenzylamino)- 3',4',5'-trimethoxy-[l,r-biphenyl]-2,4-dicarbonitrile (1-48), 5'-(dibenzylamino)-2,3",4",5"- tetramethoxy-[l,r:3',l"-terphenyl]-4',6'-dicarbonitrile (1-49) or 3-amino-4'-((l-(5-iodo-2- methoxybenzyl)- 1H- 1 ,2,3-triazol-4-yl)methoxy)-6-methyl-[ 1 , -biphenyl]-2,4-dicarbonitrile (1-50). In yet another preferred embodiment, said compound of formula (I) shows fluorescence upon radiation.

In still another preferred embodiment, said compound of formula (I) is used in cell imaging applications.

In yet still another preferred embodiment, said compound of formula (I) is used for the treatment of cancer.

In another embodiment, the present invention provides a novel substituted indole of formula (II);

Formula (II)

Wherein;

R⁵ and R⁵ is selected from hydrogen, (un) substituted alkyl, benzyl, formyl, (un)substituted acetyl, (un)substituted allyl,

R⁶ is selected from hydrogen, (un) substituted alkyl, (un)substituted triazolyl, (un)substituted aryl, imidazolyl, thienyl,

R 7 and R 8 is selected from hydrogen, (un)substituted alkyl, alkoxy, (un)substituted aryl, imidazolyl, thienyl, (un)substituted 1,2,3 -triazolyl, 1,2,4-triazolyl;

or a pharmaceutically acceptable salt thereof.

In preferred embodiment, said compound of formula (II) is selected from ethyl 3- amino-6-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-7-cyano-4-(2,4-difluorophenyl)- 1 -(2-ethoxy-2- oxoethyl)-5-(lH-l,2,4-triazol-l-yl)-lH-indole-2-carboxylate (2-1), ethyl 3-amino-4-(l- benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-6-(2,4-difluorophenyl)-l-(2-ethoxy-2-oxoethyl)-5- (lH-l,2,4-triazol-l-yl)-lH-indole-2-carboxylate (2-2), ethyl 3-amino-6-(l-benzyl-lH-l,2,3- triazol-4-yl)-7-cyano- l-(2-ethoxy-2-oxoethyl)-5-propyl- lH-indole-2-carboxylate (2-3), ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)- lH-indole-2-carboxylate (2-4), ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-l- (2-ethoxy-2-oxoethyl)-5-hexyl-lH-indole-2-carboxylate (2-5), ethyl l-amino-5-(l-benzyl- lH-l,2,3-triazol-4-yl)-4-cyano-3-(2-ethoxy-2-oxoethyl)-6,7,8,9-tetrahydro-3H- benzo[e]indole-2-carboxylate (2-6), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5- methyl-6-(thiophen-2-yl)-lH-indole-2-carboxylate (2-7), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-methyl-4-(thiophen-2-yl)-lH-indole-2-carboxylate (2-8), ethyl 7- cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-3-(methylamino)-6-(thiophen-2-yl)-lH-indole-2- carboxylate (2-9), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(thiophen-2-yl)-6- (3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-10), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-hexyl-6-(thiophen-2-yl)-lH-indole-2-carboxylate (2-11), ethyl 3- amino-6-(benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-lH-indole-

2- carboxylate (2-12), ethyl 3-amino-4-(benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-methyl-lH-indole-2-carboxylate (2-13), ethyl 3-amino-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-methyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-14), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-4-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-15), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-16), ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)- 5-ethyl-3-(methylamino)-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-17), ethyl 7-cyano-3-(dimethylamino)-l-(2-ethoxy-2-oxoethyl)-5-ethyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-18), ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-3- formamido-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-19), ethyl 3-amino-7- cyano-l-(2-ethoxy-2-oxoethyl)-5-hexyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-20), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-21), ethyl 7-cyano-3-(dibenzylamino)-l-(2- ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-22), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-octyl-6-(3,4,5-trimethoxyphenyl)-lH- indole-2-carboxylate (2-23), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6- (3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-24), ethyl 7-cyano-l-(2-ethoxy-2- oxoethyl)-3-(methylamino)-5-nonyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-25), ethyl 3-(allylamino)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-26), ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-

3- formamido-5-nonyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-27), ethyl 3- amino-7-cyano-5-decyl-l-(2-ethoxy-2-oxoethyl)-6-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-28), ethyl 3-amino-7-cyano-5-decyl-l-(2-ethoxy-2-oxoethyl)-4-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-29), ethyl 3-amino-7-cyano-l-(2-ethoxy-2- oxoethyl)-4-(4-methoxyphenyl)-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2- 30), ethyl 3-amino-7-cyano- l-(2-ethoxy-2-oxoethyl)-6-(4-methoxyphenyl)-5-methyl- 1H- indole-2-carboxylate (2-31), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4- methoxyphenyl)-5-methyl-lH-indole-2-carboxylate (2-32), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-6-(4-methoxyphenyl)-5-propyl-lH-indole-2-carboxylate (2-33), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-5-propyl-lH-indole-2- carboxylate (2-34), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(4- methoxyphenyl)-lH-indole-2-carboxylate (2-35), ethyl 3-amino-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-methyl-6-phenyl-lH-indole-2-carboxylate (2-36), ethyl 3-amino-6-(2- chlorophenyl)-7-cyano- l-(2-ethoxy-2-oxoethyl)-5-methyl- lH-indole-2-carboxylate (2-37), ethyl 3-amino-7-cyano- l-(2-ethoxy-2-oxoethyl)-6-(4-hydroxyphenyl)-5-methyl- lH-indole- 2-carboxylate (2-38), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-fluorophenyl)-5- methyl-lH-indole-2-carboxylate (2-39), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4- (4-fluorophenyl)-5-methyl-lH-indole-2-carboxylate (2-40), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-6-(4-nitrophenyl)-5-pentyl-lH-indole-2-carboxylate (2-41), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-nitrophenyl)-5-pentyl-lH-indole-2- carboxylate (2-42), ethyl 6-(4-(allyloxy)phenyl)-3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-

5- methyl-lH-indole-2-carboxylate (2-43), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)- 5-methyl-6-(4-(prop-2-yn-l-yloxy)phenyl)-lH-indole-2-carboxylate (2-44), ethyl 3-amino-

7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-4-(4-(prop-2-yn-l-yloxy)phenyl)-lH-indole-2- carboxylate (2-45), ethyl 3-amino-6-(4-((l-benzyl-lH-l,2,3-triazol-4-yl)methoxy)phenyl)- 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-46), ethyl 3-amino-

6- butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-47) or ethyl 3-amino-4-butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-

48).

In yet another preferred embodiment, said compound of formula (II) is used for the treatment of cancer.

In yet another embodiment, the present invention provides a compound of formula (III);

Formula (III)

Wherein

R is selected from (un) substituted 4-oxothieno [2,3-d]pyrimidin-3(4H)-yl, 4-formyl- phenoxymethyl or 4-acetylphenoxymethyl, or a pharmaceutically acceptable salt thereof.

In preferred embodiment, said compound of formula (III) is selected from 4-((l-(5- iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)benzaldehyde (3-1), l-(4-((l-(5- iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)phenyl)ethan-l-one (3-2) or 6-ethyl- 3-((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methyl)thieno[2,3-d]pyrimidin- 4(3H)-one (3-3).

In yet another preferred embodiment, said compound of formula (III) is used for the treatment of cancer.

In still another embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) or (II) or (III) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, diluent and/or carrier.

In yet still another embodiment, the present invention provides a method for the treatment of cancer in a subject in need thereof; comprising administering to the said subject a therapeutically effective amount of the compound of formula (I) or (II) or (III) or a pharmaceutically acceptable salt thereof.

BRIEF DESCRIPTION OF THE DRAWINGS:

Fig 1: depicts the absorption spectra of compounds 1-15, 1-3 and 1-5.

Fig 2: depicts the emission spectra of compounds 1-15, 1-3 and 1-5 indicating the optical properties.

Fig 3: UV-visible absorption spectra of compounds 1-5, 1-6, 1-20 and 1-21.

Fig 4: Fluorescence spectra of compounds 1-5, 1-6, 1-20 and 1-21.

Fig 5: UV-visible absorption spectra of compounds 1-12, 1-14, 1-17, 1-22, 1-24 and 1-27. Fig 6: Fluorescence spectra of compounds 1-12, 1-14, 1-17, 1-22, 1-24 and 1-27.

Fig 7: MCF-7 cells stained with compound 1-17 (100 μ νην> and SYTO 9 (A) Bright field; (B) Blue - compound 1-17, Green - SYTO 9 (Nucleus); (C) Merge image of (A) and (B). Fig 8: MCF-7 cells stained with compound 1-17 (100 aglmL), SYTO 9 and Nile red (A) Bright field; (B) Blue - compound 1-17, Green - SYTO 9 (Nucleus); (C) Red - Nile red (Cell membrane), Green -SYTO 9; (D) Merge image of (A), (B) and (C).

Fig 9: MCF-7 cells stained with compound 1-18 (100 aglmL), SYTO 9 and Nile red (A) Bright field; (B) Blue - compound 1-18, Green - SYTO 9 (Nucleus); (C) Red - Nile red (Cell membrane), Green - SYTO 9 (Nucleus). Fig 10: MCF-7 cells stained with compound 1-7 (100 ug/mL), SYTO 9 and Nile red (A) Bright field; (B) Blue - compound 1-7, Green - SYTO 9 (Nucleus); (C) Red - Nile red (Cell membrane), Green - SYTO 9 (Nucleus); (D) Merge image of (A), (B) and (C).

Fig 11: MDM-MB-231 cells stained with compound 1-17 (100 μg/mL) and SYTO 9 (A) Bright field with Blue - compound 1-17; (B) Blue - compound 1-17, Green - SYTO 9 (Nucleus); (C) Blue - compound 1-17; (D) Merge image of (A), (B) and (C).

Fig 12: THP-1 cells stained with compound 1-19 (100 μg/mL), Annexin-V-FITC and Propidium iodide (PI) (A) Bright field; (B) Green - Annexin-V-FITC (apoptosis), Red - PI (dead); (C) Blue - compound 1-19, Red - PI (dead); (D) Bright field with blue - compound 1-19 (E) - Merge image of (A), (B) and (C); (F) - Merge image of (B) and (C).

Fig 13: THP-1 cells with induced apoptosis using Paclitaxel IC90 concentration, stained with compound 1-19 (100 μ§/ναν), Annexin-V-FITC and Propidium iodide (PI) (A) Bright field; (B) Green - Annexin-V-FITC (apoptosis), Red - Pl(dead); (C) Blue - compound 1- 19, Red - PI (dead); (D) Bright field with blue - compound 1-19; (E) Blue - compound 1- 19; (F) Merge image of (A) and (C).

Fig 14: MCF-7 cells stained with compound 1-19 (100 μ§/ηιΙ_/), Annexin-V-FITC and Propidium iodide (PI) (A) Bright field; (B) Green - Annexin-V-FITC (apoptosis), Red - Pl(dead); (C) Blue - compound 1-19, Red - PI (dead); (D) Blue - compound 1-19; (E) - Merge image of (A) and (B); (F) Merge image of (A) and (C).

Fig 15: MCF-7 cells with induced apoptosis using Doxorubicin IC50 concentration, stained with compound 1-19 (100 μ§/ναν), Annexin-V-FITC and Propidium iodide (PI) (A) Bright field; (B) Blue - compound 1-19 (C) Green - Annexin-V-FITC (apoptosis), Red - PI (dead) and Blue - compound 1-19; (D) - Merge image of (A) and (B); (E) - Merge image of (A) and (C).

Fig 16: MDM-MB-231 cells with induced apoptosis using Doxorubicin IC90 concentration, stained with compound 1-19 (100 \aglmL), Annexin-V-FITC and Propidium iodide (PI) (A) Bright field; (B) Green - Annexin-V-FITC (apoptosis); (C) Green - Annexin-V-FITC (apoptosis), Red - PI (dead; (D) - Merge image of (A) and (B); (E) Bright field with blue - compound 1-19 and red - PI (dead); (F)- Merge image of (A) and (E).

Fig 17: Growth curve for human prostate cancer cell line DU-145 treated with compounds

2- 24, 1-50, 3-1 and 2-23 and standard drug adriamycin. The compound NCL-ACT-SPC- 0025 is 2-24, compound NCL-ACT-SPC-0028 is 1-50, compound NCL-ACT-SPC-0029 is

3- 1 and compound NCL-ACT-SPC-0030 is 2-23 of present invention and ADR is adriamycin. DETAILED DESCRIPTION OF THE INVENTION:

The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

In the view of above, the present invention provides to a novel compound of formula (I), (II) and (III) or a pharmaceutically acceptable salt thereof, process for preparation thereof and use of these compounds for the treatment of cancer. Further, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) or (II) or (III) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, diluent and/or carrier.

In an embodiment, the present invention provides a compound of formula (I);

Formula (I)

Wherein;

R and R¹ are selected independently from hydrogen, (un)substituted alkyl, (un)substituted aryl, 1,2,3-triazolyl, 1,2,4-triazolyl, imidazolyl, thienyl, furanyl, thienopyrimidinonyl, benzimidazolyl or benzofuranyl, (un)substituted 4-oxothieno[2,3- d]pyrimidin-3(4H)-yl;

R and R¹ together may form a cyclic ring;

R is selected from (un)substituted 1,2,3-triazolyl, 1,2,4-triazolyl, mono, di or tri methoxy or halo substituted phenyl; (benzyl)triazolyl, thienyl, benzofuranyl; 4-((l-(5-iodo- 2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)phenyl;

R³, R⁴ is selected from hydrogen, alkyl, benzyl or allyl;

With the proviso that;

When R 2 is thienyl, R 1 is (un) substituted 4-oxothieno[2,3-d]pyrimidin-3(4H)-yl; and When R is mono, di or tri methoxy or halo substituted phenyl,

R¹ is not hydrogen and R; R¹ together may not form a cyclic ring;

or a pharmaceutically acceptable salt thereof. In preferred embodiment, said compound of formula (I) is selected from 2-amino-4- (l-benzyl-lH-l,2,3-triazol-4-yl)-5-(4-oxo-6-propylthieno[3,2-<i]pyrimidin-3(4H)-yl)-6- (thiophen-2-yl)isophthalonitrile (1-1), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(6- hexyl-4-oxothieno[3,2- ]pyrimidin-3(4H)-yl)-6-(thiophen-2-yl)isophthalonitrile (1-2), 2- amino-4-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-6-(thiophen-2-yl)-5-( 1H- 1 ,2,4-triazol- 1 - yl)isophthalonitrile (1-3), 2-amino-4-(benzofuran-2-yl)-6-(l-benzyl-lH-l,2,3-triazol-4-yl)- 5-(lH-imidazol-l-yl)isophthalonitrile (1-4), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)- 2',4'-difluoro-6-( 1H- 1 ,2,4-triazol- 1 -yl)- [ 1 , 1 '-biphenyl] -2,4-dicarbonitrile (1-5), 3-amino-5- ( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-4'-fluoro-6-( 1H- 1 ,2,4-triazol- 1 -yl)- [ 1 , 1 '-biphenyl] -2,4- dicarbonitrile (1-6), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(4-oxo-6- pentylthieno [2,3-<i]pyrimidin-3(4H)-yl)-[l, -biphenyl]-2,4-dicarbonitrile (1-7), 3-amino-5- (l-benzyl-lH-l,2,3-triazol-4-yl)-2^4'-difluoro-6-(6-methyl-4-oxothieno[2,3-<i]pyrimidin- 3(4H)-yl)-[l,l'-biphenyl] -2,4-dicarbonitrile (1-8), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4- yl)-2',4'-difluoro-6-(lH-imidazol-l-yl)-[l,r-biphenyl]-2,4-dicarbonitrile (1-9), 3-amino-5- (1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-4'-fluoro-6-( lH-imidazol- 1 -yl)-[ 1 , 1 '-biphenyl] -2,4- dicarbonitrile (1-10), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)isophthalonitrile (1-11), 2- amino-4-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-5-methylisophthalonitrile (1-12), 2-amino-4-( 1 - benzyl- lH-1, 2,3 -triazol-4-yl)-5-ethylisophthalonitrile (1-13), 2-amino-4-( 1 -benzyl- 1H-

1.2.3- triazol-4-yl)-5-propylisophthalonitrile (1-14), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4- yl)-5-butylisophthalonitrile (1-15), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- pentylisophthalonitrile (1-16), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- hexylisophthalonitrile (1-17), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro- [Ι,Γ-biphenyl] -2,4-dicarbonitrile (1-18), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(6- butyl-4-oxothieno[2,3-<i]pyrimidin-3(4H)-yl)isophthalonitrile (1-19), 5-(l-benzyl-lH-l,2,3- triazol-4-yl)-3-(dimethylamino)-2',4'-difluoro-6-(lH-l,2,4-triazol-l-yl)-[l,r-biphenyl]-2,4- dicarbonitrile (1-20), 5-(l-benzyl-lH-l,2,3-triazol-4-yl)-3-(dimethylamino)-4'-fluoro-6-(lH-

1.2.4- triazol-l-yl)-[l,l'-biphenyl] -2,4-dicarbonitrile (1-21), 4-(l-benzyl-lH-l,2,3-triazol-4- yl)-2-(dimethylamino)-5-methylisophthalonitrile (1-22), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)- 2-(dimethylamino)-5-ethylisophthalonitrile (1-23), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2- (dimethylamino)-5-propylisophthalonitrile (1-24), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- butyl-2-(dimethylamino)isophthalonitrile (1-25), 4-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-2- (dimethylamino)-5-pentylisophthalonitrile (1-26), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2- (dimethylamino)-5-hexylisophthalonitrile (1-27), 5-amino-7-(l-benzyl-lH-l,2,3-triazol-4- yl)-2,3-dihydro-lH-indene-4,6-dicarbonitrile (1-28), 2-amino-4-(l-benzyl-5- (hydroxymethyl)-lH-l,2,3-triazol-4-yl)-5-methylisophthalonitrile (1-29), 3-amino-3',4',5'- trimethoxy-6-pentyl-[l, -biphenyl]-2,4-dicarbonitrile (1-30), 3-amino-6-hexyl-3',4',5'- trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-31), 3-amino-6-heptyl-3',4',5'-trimethoxy- [l,l'-biphenyl]-2,4-dicarbonitrile (1-32), 3-amino-6-decyl-3',4',5'-trimethoxy-[l,r- biphenyl]-2,4-dicarbonitrile (1-33), 5'-amino-3,4,4",5-tetramethoxy-[l,r:3',l"-terphenyl]- 4',6'-dicarbonitrile (1-34), 5'-amino-2,3",4",5"-tetramethoxy-[l,r:3',l"-terphenyl]-4',6'- dicarbonitrile (1-35), 3-amino-5-(furan-2-yl)-3',4',5'-trimethoxy-[l, -biphenyl]-2,4- dicarbonitrile (1-36), 3-amino-3',4',5'-trimethoxy-5-(thiophen-2-yl)-[l, -biphenyl]-2,4- dicarbonitrile (1-37), 3-amino-6-heptyl-4'-methoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-38), 3-amino-6-decyl-4'-methoxy-[l,r-biphenyl]-2,4-dicarbonitrile (1-39), 3-amino-6-(6-butyl- 4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)-4'-^^ (1-40), 3-amino-4'-methoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)-[l, - biphenyl]-2,4-dicarbonitrile (1-41), 3-amino-3',5'-dimethoxy-6-(2-(4-oxo-6- pentylthieno[2,3-d]pyrimidin-3(4¾^ (1-42), 3- amino-3 4^5' rimethoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)eA biphenyl]-2,4-dicarbonitrile (1-43), 2-amino-5-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin- 3(4H)-yl)ethyl)-4-(thiophen-2-yl)isophthalonitrile (1-44), 3-(dimethylamino)-6-heptyl- 3',4',5'-trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-45), 3-(dibenzylamino)-6-heptyl- 3',4',5'-trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-46), 3-(diallylamino)-6-heptyl- 3',4',5'-trimethoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-47), 6-decyl-3-(dibenzylamino)- 3',4',5'-trimethoxy-[l,r-biphenyl]-2,4-dicarbonitrile (1-48), 5'-(dibenzylamino)-2,3",4",5"- tetramethoxy-[l,r:3',l"-terphenyl]-4',6'-dicarbonitrile (1-49) or 3-amino-4'-((l-(5-iodo-2- methoxybenzyl)- 1H- 1 ,2,3-triazol-4-yl)methoxy)-6-methyl-[ 1 , -biphenyl]-2,4-dicarbonitrile (1-50).

In another more preferred embodiment, said compound of formula (I) is selected from 3-amino-5-(l -benzyl- lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(4-oxo-6-pentylthieno [2,3-<i]pyrimidin-3(4H)-yl)-[l, -biphenyl]-2,4-dicarbonitrile (1-7), 2-amino-4-(l-benzyl- lH-l,2,3-triazol-4-yl)-5-hexylisophthalonitrile (1-17), 3-amino-5-(l-benzyl-lH- 1,2,3- triazol-4-yl)-2',4'-difluoro-[l, -biphenyl]-2,4-dicarbonitrile (1-18), 2-amino-4-(l-benzyl- lH-l,2,3-triazol-4-yl)-5-(6-butyl-4-oxothieno[2,3- ]pyrimidin-3(4H)-yl)isophthalonitrile (1- 19), 3-amino-4'-((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)-6-methyl- [1,1 '-biphenyl] -2,4-dicarbonitrile (1-50) . In another preferred embodiment, said compound of formula (I) shows fluorescence upon radiation.

In yet another preferred embodiment, said compound of formula (I) is used in cell imaging applications.

In still another preferred embodiment, said compound of formula (I) is used for the treatment of cancer.

In another embodiment, the present invention provides a process for the synthesis of novel compounds of formula (I) which comprises stirring the reaction mixture of two carbonyl compounds and malononitrile in solvent in presence of morpholine at temperature in the range of 75 to 85°C for the period in the range of 8 to 16 hrs to afford compound of formula (I).

In yet another embodiment, said process may optionally further comprise stirring the compound of formula (I) in tetrahydrofuran (THF) with sodium hydride (NaH) at temperature in the range of 50 to 60°C for the period in the range of 10 to 12 hrs followed by addition of methyl iodide and again stirred at temperature in the range of 25 to 30°C for the period in the range of 10 to 12 hrs to afford N,N-dimethylated compound of formula (I).

In preferred embodiment, said carbonyl compound is selected from 1-benzyl-lH- l,2,3-triazole-4-carbaldehyde, 3-(2-oxo-2-(thiophen-2-yl)ethyl)-6-propylthieno[2,3- d]pyrimidin-4(3H)-one, 3-(2-oxo-2-(thiophen-2-yl)ethyl)-6-hexylthieno[2,3-d]pyrimidin- 4(3H)-one, l-(thiophen-2-yl)-2-(lH-l,2,4-triazol-l-yl)ethan-l-one, l-(2,4-difluorophenyl)- 2-( 1 H- 1 ,2,4-triazol- 1 -yl)ethan- 1 -one, 1 -(4-fluorophenyl)-2-( 1 H- 1 ,2,4-triazol- 1 -yl)ethan- 1 - one, 3-(2-(2,4-difluorophenyl)-2-oxoethyl)-6-pentylthieno[2,3-d]pyrimidin-4(3H)-one, 3-(2- (2,4-difluorophenyl)-2-oxoethyl)-6-methylylthieno[2,3-d]pyrimidin-4(3H)-one, l-(2,4- difluorophenyl)-2-( lH-imidazol- 1 -yl)ethan- 1 -one, 1 -(4-fluorophenyl)-2-( lH-imidazol- 1 - yl)ethan-l-one, acetaldehyde, propionaldehyde, butyraldehyde, valeraldehyde, hexanal, heptanal, octanal, 2,4-difluoroacetophenone, 2-(6-butyl-4-oxothieno[2,3-d]pyrimidin-3(4H)- yl)acetaldehyde, cyclopentanone, l-benzyl-5-(hydroxymethyl)-lH-l,2,3-triazole-4- carbaldehyde, 3,4,5-trimethoxybenzaldehyde, dodecanal, 4-methoxyacetophenone, 2- methoxyacetophenone, 2-acetylfuran, 2-acetylthiophene, nonanal, 4-methoxybenzaldehyde, 4-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)butanal, 3,5-dimethoxybenzaldehyde, thiophene-2-carboxaldehyde or 4-(( 1 -(5-iodo-2-methoxybenzyl)- 1 H- 1 ,2,3-triazol-4- yl)methoxy)benzaldehyde. In yet another preferred embodiment, said solvent is selected from dimethylformamide (DMF), acetonitrile or ethyl acetate.

In still another preferred embodiment, said reaction is carried out under argon atmosphere.

In yet another embodiment, the present invention provides a novel substituted indole of formula (II);

Formula (II)

Wherein;

R⁵ and R⁵ is selected from hydrogen, (un)substituted alkyl, benzyl, formyl,

(un)substituted acetyl, (un)substituted allyl,

or a pharmaceutically acceptable salt thereof.

In preferred embodiment, said compound of formula (II) is selected from ethyl 3- amino-6-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-7-cyano-4-(2,4-difluorophenyl)- 1 -(2-ethoxy-2- oxoethyl)-5-(lH-l,2,4-triazol-l-yl)-lH-indole-2-carboxylate (2-1), ethyl 3-amino-4-(l- benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-6-(2,4-difluorophenyl)-l-(2-ethoxy-2-oxoethyl)-5-

(lH-l,2,4-triazol-l-yl)-lH-indole-2-carboxylate (2-2), ethyl 3-amino-6-(l-benzyl-lH-l,2,3- triazol-4-yl)-7-cyano- l-(2-ethoxy-2-oxoethyl)-5-propyl- lH-indole-2-carboxylate (2-3), ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)- lH-indole-2-carboxylate (2-4), ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-l- (2-ethoxy-2-oxoethyl)-5-hexyl-lH-indole-2-carboxylate (2-5), ethyl l-amino-5-(l-benzyl- lH-l,2,3-triazol-4-yl)-4-cyano-3-(2-ethoxy-2-oxoethyl)-6,7,8,9-tetrahydro-3H- benzo[e]indole-2-carboxylate (2-6), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5- methyl-6-(thiophen-2-yl)-lH-indole-2-carboxylate (2-7), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-methyl-4-(thiophen-2-yl)-lH-indole-2-carboxylate (2-8), ethyl 7- cyano- l-(2-ethoxy-2-oxoethyl)-5-methyl-3-(methylamino)-6-(thiophen-2-yl)- lH-indole-2- carboxylate (2-9), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(thiophen-2-yl)-6- (3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-10), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-hexyl-6-(thiophen-2-yl)-lH-indole-2-carboxylate (2-11), ethyl 3- amino-6-(benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-lH-indole- 2-carboxylate (2-12), ethyl 3-amino-4-(benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-methyl-lH-indole-2-carboxylate (2-13), ethyl 3-amino-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-methyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-14), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-4-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-15), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-16), ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)- 5-ethyl-3-(methylamino)-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-17), ethyl 7-cyano-3-(dimethylamino)-l-(2-ethoxy-2-oxoethyl)-5-ethyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-18), ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-3- formamido-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-19), ethyl 3-amino-7- cyano-l-(2-ethoxy-2-oxoethyl)-5-hexyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-20), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-21), ethyl 7-cyano-3-(dibenzylamino)-l-(2- ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-22), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-octyl-6-(3,4,5-trimethoxyphenyl)-lH- indole-2-carboxylate (2-23), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6- (3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-24), ethyl 7-cyano-l-(2-ethoxy-2- oxoethyl)-3-(methylamino)-5-nonyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-25), ethyl 3-(allylamino)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-26), ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)- 3-formamido-5-nonyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-27), ethyl 3- amino-7-cyano-5-decyl-l-(2-ethoxy-2-oxoethyl)-6-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-28), ethyl 3-amino-7-cyano-5-decyl-l-(2-ethoxy-2-oxoethyl)-4-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-29), ethyl 3-amino-7-cyano-l-(2-ethoxy-2- oxoethyl)-4-(4-methoxyphenyl)-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2- 30), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-methoxyphenyl)-5-methyl-lH- indole-2-carboxylate (2-31), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4- methoxyphenyl)-5-methyl-lH-indole-2-carboxylate (2-32), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-6-(4-methoxyphenyl)-5-propyl-lH-indole-2-carboxylate (2-33), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-5-propyl-lH-indole-2- carboxylate (2-34), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(4- methoxyphenyl)-lH-indole-2-carboxylate (2-35), ethyl 3-amino-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-methyl-6-phenyl-lH-indole-2-carboxylate (2-36), ethyl 3-amino-6-(2- chlorophenyl)-7-cyano- l-(2-ethoxy-2-oxoethyl)-5-methyl- lH-indole-2-carboxylate (2-37), ethyl 3-amino-7-cyano- l-(2-ethoxy-2-oxoethyl)-6-(4-hydroxyphenyl)-5-methyl- lH-indole- 2-carboxylate (2-38), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-fluorophenyl)-5- methyl-lH-indole-2-carboxylate (2-39), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4- (4-fluorophenyl)-5-methyl-lH-indole-2-carboxylate (2-40), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-6-(4-nitrophenyl)-5-pentyl-lH-indole-2-carboxylate (2-41), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-nitrophenyl)-5-pentyl-lH-indole-2- carboxylate (2-42), ethyl 6-(4-(allyloxy)phenyl)-3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)- 5-methyl-lH-indole-2-carboxylate (2-43), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-

5- methyl-6-(4-(prop-2-yn-l-yloxy)phenyl)-lH-indole-2-carboxylate (2-44), ethyl 3-amino- 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-4-(4-(prop-2-yn-l-yloxy)phenyl)-lH-indole-2- carboxylate (2-45), ethyl 3-amino-6-(4-((l-benzyl-lH-l,2,3-triazol-4-yl)methoxy)phenyl)- 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-46), ethyl 3-amino-

6- butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-47), ethyl 3- amino-4-butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-48).

In another more preferred embodiment, said compound of formula (II) is selected from ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-octyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-23) or ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl- 6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-24).

In another preferred embodiment, said compound of formula (II) is used for the treatment of cancer.

In another embodiment, the present invention provides a process for the synthesis of novel compounds of formula (II) which comprises stirring the reaction mixture of compound of formula (I), ethyl bromoacetate and base in solvent at temperature in the range of 25 to 30°C and for the period in the range of 2 to 4 hrs to afford compound of formula (II).

In another preferred embodiment, said solvent is selected from acetonitrile or dimethylformamide (DMF).

In yet another preferred embodiment, said base is selected from potassium hydroxide, sodium hydroxide, potassium carbonate or sodium carbonate.

In still another preferred embodiment, said reaction is carried out under argon atmosphere. In still another embodiment, the present invention provides a compound of formula

(HI);

Formula (III)

Wherein;

R is selected from (un) substituted 4-oxothieno[2,3-d]pyrimidin-3(4H)-yl,

4-formylphenoxymethyl or 4-acetylphenoxymethyl

or a pharmaceutically acceptable salt thereof.

In preferred embodiment, said compound of formula (III) is selected from 4-((l-(5- iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)benzaldehyde (3-1), l-(4-((l-(5- iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)phenyl)ethan-l-one (3-2), 6-ethyl-3- ((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methyl)thieno[2,3-d]pyrimidin-4(3H)- one (3-3).

In another more preferred embodiment, said compound of formula (III) is 4-((l-(5- iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)benzaldehyde (3-1).

In another preferred embodiment, said compound of formula (III) is used for the treatment of cancer.

In yet still another embodiment, the present invention provides a process for the synthesis of novel compounds of formula (III) comprising click reaction of azido compound with propargyl compound in solvent in presence of copper(II) sulfate pentahydrate

(CuS0₄.5H₂0) and sodium ascorbate at temperature in the range of 20°C to 40°C for the period in the range of 6 to 12 hours.

In preferred embodiment, said azido compound is selected from 2-(azidomethyl)-4- iodo- 1 -methoxybenzene .

In another preferred embodiment, said propargyl compound is selected from 4- propargyloxybenzaldehyde, 4-propargyloxyacetophenone, substituted 3-propargyl- thieno[2,3-d]pyrimidin-3(4H)-one. In yet another preferred embodiment, said solvent is selected from t-butanol, water or mixture thereof.

In one embodiment, the present invention provides compounds of formula (I) which show fluorescence properties. The fluorescence properties of compounds of formula (I) are summarized in Table 1.

Table 1: Fluorescence properties of compounds of formula (I)

25 1-25 379 449 70 0.21

26 1-26 380 450 70 0.22

27 1-27 380 450 70 0.14

The UV-visible absorption spectra for compounds 1-5, 1-15 and 1-3 are given in Fig. 1 while fluorescence spectra for these compounds are shown in Fig. 2.

The UV-visible absorption spectra, of 2.5 x 10^"5 M solutions in acetonitrile, for representative compounds 1-5 and 1-6 and their corresponding N,N-dimethylated derivatives 1-20 and 1-21 are shown in Fig. 3 while fluorescence spectra for these compounds are shown in Fig. 4. Similarly, the UV-visible absorption spectra, of 2.5 x 10^"5 M solutions in acetonitrile, for compounds 1-12, 1-14, 1-17, 1-22, 1-24 and 1-27 are shown in Fig. 5 while fluorescence spectra for these compounds are shown in Fig. 6.

The _max values for amino compounds 1-5 and 1-6 are 367 and 365 nm while those for their corresponding N,N-dimethylated derivatives 1-20 and 1-21 are 395 and 390 nm showing that there is a red shift in absorption maxima due to enhanced electron-donating ability of the amino group after methylation. It is observed that the Stokes shifts for the amino compounds 1-5 and 1-6 are 47 and 46 nm while the stokes shifts for the corresponding N,N-dimethylated derivatives 1-20 and 1-21 are 74 and 75 nm indicating that the Stokes shift is increased after N,N-dimethylation of amino group. Similar trend is observed in case of the compounds 1-12 to 1-17 and 1-22 to 1-27. The _max values of both absorption and emission for all the compounds are given in Table 1 which shows that Stokes shifts for amino compounds are in the range of 42-52 nm while the Stokes shifts for the N,N-dimethylated derivatives are in the range of 70-75 nm. The quantum yields for these compounds are determined using 0.1 M quinine sulphate solution in sulphuric acid as a reference. It is observed that compounds 1-12 to 1-17 having alkyl chains at 4 position of 5- ( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-2,6-dicyanoaniline and 5-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)- 2,6-dicyanoaniline (1-11) had maximum quantum yields of -0.5 while all the di/tri- heterocyclyl-2,6-dicyanoanilines 1-1 to 1-10, 1-18 and 1-19 had less quantum yields. All the Ν,Ν-dimethylated compounds 1-20, 1-21 and 1-22 to 1-27 had quantum yields in the range of 0.11 to 0.23.

In another embodiment, the present invention provides novel compounds of formula (I) which are used for cell imaging applications. From the cell imaging analysis it is observed that some compounds are able to stain eukaryotic cells. The compounds 1-21, 1-18 and 1-7 are found to stain all the cells in contact. These compounds are found to specifically stain only the cytoplasm of the cells but not the nucleus. This is verified by using known counter stains like SYTO 9 (for nucleus) and Nile red (lipid molecules and cell membrane) as shown in figures 7 to 11.

However, one compound 1-19 is found to stain differently only some cells out of total cells. This differential staining was studied further using some known markers and inducers. In order to study the differential staining property of compound 1-19, the cells are seeded and apoptosis / cell death is induced using known anti-cancer, cytotoxic compounds namely Paclitaxel and Doxorubicin at their IC50 and IC90 concentrations. Known markers like Annexin-VFITC for apoptosis and propidium iodide for dead cells are used along with the compound 1-19. Standard staining protocol for Apoptosis/Necrosis using Annexin-V- FITC/PI is carried out with addition of this new compound 1-19. Healthy cells were used as negative control. Interestingly, it is found, that the compound 1-19 staining (blue fluorescence) coincided with Annexin-V-FITC (green fluorescence). This shows a possible affinity of compound 1-19 to apoptotic / dead cells (figures 12 to 16).

In one embodiment, the present invention provides a pharmaceutical composition comprising the compound of formula (I) or (II) or (III) or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, diluent and/or carrier.

The carrier is typically used when the composition is prepared, and includes, but not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybezoate, talcum, magnesium stearate, mineral oil, or the like.

The composition can additionally comprise stability improving material, viscosity improving or adjusting material, solubility improving material, sweetener, dye, palatability improving material, osmotic pressure variable salt, buffer solution, antioxidant and so on.

The pharmaceutical compositions of the present invention can be oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, local or rectal administration, the active principle, alone or in combination with another active principle, can be administered in a unit administration form, as a mixture with conventional pharmaceutical supports, to animals and human beings. Suitable unit administration forms comprise oral-route forms such as tablets, gel capsules, powders, granules and oral suspensions or solutions, sublingual and buccal administration forms, aerosols, implants, subcutaneous, transdermal, topical, intraperitoneal, intramuscular, intravenous, subdermal, transdermal, intrathecal and intranasal administration forms and rectal administration forms.

The pharmaceutical compositions contain vehicles which are pharmaceutically acceptable for a formulation capable of being injected. These may be in particular isotonic, sterile, saline solutions (monosodium or disodium phosphate, sodium, potassium, calcium or magnesium chloride and the like or mixtures of such salts), or dry, especially freeze-dried compositions which upon addition, depending on the case, of sterilized water or physiological saline, permit the constitution of injectable solutions.

Solutions comprising compounds of the invention as free base or pharmacologically acceptable salts can be prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. For parenteral administration in an aqueous solution, for example, the solution should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose.

Typically, the inventive pharmaceutical composition is administered in the form of a unit dose containing its effective ingredient at an amount between about 1 mg and about 50 mg. The total dose per day of the inventive pharmaceutical composition is within a range from about 1 mg to about 50 mg, and preferably from about 1 mg to about 30 mg. However, in comprehensive consideration of the situation of a patient, and in consideration of the activity of an administered medication, a specific dose beyond such a range can be administered. An optimal dose administered under a specific situation must be decided experimentally.

The inventive compounds can be administered once or several times at a dose.

Preferably, a dose per day is administered once or twice per day. The inventive compounds can be administered alone or in conjunction with a pharmaceutically acceptable carrier and excipient. The inventive pharmaceutical composition can be formulated into excipient known in the art as well as a pharmaceutically acceptable carrier and diluents. This formulation can take the form of a unit dose by a method known in the pharmaceutical field for convenience.

The inventive pharmaceutical composition can be used in conjunction with one or more other therapeutically useful materials, for instance other anti-cancer drugs. In another embodiment, the present invention provides a method for the treatment of cancer in a subject in need thereof; comprising administering to the said subject a therapeutically effective amount of the compound of formula (I) or (II) or (III) or a pharmaceutically acceptable salt thereof.

From Table 2 and Table 3 and Figure 17 it is observed that the compounds of present invention exhibit anticancer activity comparable to standard drug adriamycin and the compounds of present invention have potential as anticancer drugs.

The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

Examples:

Example 1: Synthesis of compound of formula (I):

a) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(4-oxo-6-propylthieno[3,2- rf]pyrimidin-3(4H)-yl)-6-(thioph n-2-yl)isophthalonitrile (1-1):

1-1

To a mixture of 3-(2-oxo-2-(thiophen-2-yl)ethyl)-6-propylthieno[2,3-d]pyrimidin- 4(3H)-one (200 mg, 0.62 mmol), l-benzyl-lH-l,2,3-triazole-4-carbaldehyde (176 mg, 0.94 mmol) and malononitrile (104 mg, 1.57 mmol) in dry DMF (3 ml) taken in round bottom flask equipped with reflux condenser under argon atmosphere, was added morpholine (0.1 ml, 1 mmol) at 0°C. The mixture was allowed to come to RT and then stirred at 80 °C for 12 h. It was then cooled to room temperature, diluted with ice cold water (30 ml), extracted with ethyl acetate (3 x 20 ml) dried over Na₂S0_4i concentrated and purified by column chromatography on silica gel (60-120 mesh) using pet ether- ethyl acetate (30% ethyl acetate in pet ether) as an eluent to afford 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(4- oxo-6-propylthieno[3,2- ]pyrimidin-3(4H)-yl)-6-(thiophen-2-yl)isophthalonitrile (1-1) as a white solid, 156 mg, 43%. Melting point: 211°C. 1H NMR (500 MHz, CDC1₃): S 1.01 (t, = 7Hz, 3H), 1.70-1.86 (m, 2H), 2.79 (t, = 8Hz, 2H), 5.49 (q, 2H), 5.62 (s, 2H, D₂0 exchangeable), 6.95-7.10 (m, 4H), 7.26-7.32 (m, 4H), 7.42 (d, = 5Hz, 1H), 7.66 (s, 1H), 7.78 (d, = 9Hz, 1H). ¹³C NMR (125 MHz, CDC1₃): δ 13.70, 24.14, 32.61, 54.31, 97.82, 99.39, 114.48, 114.58, 118.37, 123.89, 124.46, 124.91, 127.57 (2C), 128.79, 129.11 (2C), 129.92, 130.49, 130.68, 132.07, 133.65, 138.61, 139.95, 143.35, 144.87, 145.99, 152.49, 157.52, 162.22. IR (CHCI₃): 3490, 3398, 2218, 1682, 1631, 1571, 1268 cm^"1. HRMS (ESI) m/z calculated for [C₃oH₂₂N₈OS₂+H]: 575.1431, found: 575.1417.

Following compounds were prepared by above procedure reacting corresponding carbonyl compounds.

b) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(6-hexyl-4-oxothieno[3,2- rf]pyrimidin-3(4H)-yl)-6-(thiophen-2-yl)isophthalonitrile (1-2):

1-2

Yield: 45%. Melting point: 185°C. 1H NMR (200 MHz, CDCI₃): S 0.90 (t, = 7Hz, 3H), 1.28-1.49 (m, 6H), 1.68-1.80 (m, 2H), 2.81 (t, = 7Hz, 2H), 5.49 (d, = 2Hz, 2H), 5.65 (s, 2H), 6.93-7.10 (m, 4H), 7.23-7.33 (m, 4H), 7.39 (d, J = lHz, 1H), 7.66 (s, 1H), 7.78 (s, 1H). ¹³C NMR (100 MHz, CDCI₃): δ 14.02, 22.49, 28.75, 30.61, 30.84, 31.45, 54.27, 97.82, 99.37, 114.47, 114.57, 118.22, 123.88, 124.47, 124.90 127.55 (2C), 127.72, 128.74, 129.08 (2C), 129.84, 130.46, 132.12, 133.70, 138.63, 139.96, 143.34, 145.10, 145.95, 152.54, 157.55, 162.33. IR (CHC1₃): 3395, 3021, 2220, 1673, 1635, 1584, 1269 cm^"1. HRMS (ESI) m/z calculated for [C₃₃H₂₈N₈OS₂+H]: 617.1900, found: 617.1894; [C₃3H₂₈N₈OS₂ +Na]: 639.1720, found: 639.1713.

c) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-6-(thiophen-2-yl)-5-(lH-l,2,4-triazol-l- yl)isophthalonitrile (1-3):

1-3

Yield: 44%. Melting Point: 242 °C. 1H NMR (500 MHz, CDC1₃ +DMSO-d₆): δ 5.42 (s, 2H), 6.69 (s, 2H), 6.92 (t, = 4Hz, 1H), 7.03 (d, = 6Hz, 2H), 7.08 (d, = 3Hz, 1H), 7.25- 7.31 (m, 3H), 7.37 (d, = 5Hz, 1H), 7.39 (s, 1H), 7.64 (s, 1H), 7.85 (s, 1H). ¹³C NMR (125 MHz, CDC1₃ + DMSO-d₆): δ 52.74, 96.59, 97.63, 114.62, 114.75, 123.41, 125.16, 127.04, 127.30 (2C), 128.02, 128.64 (2C), 129.90, 130.44, 132.49, 135.47, 138.47, 138.88, 142.41, 147.20, 151.46, 153.68. IR (CHC1₃): 3356, 3321, 2210, 1650, 1562, 1506, 1287, 1217 cm^"1. HRMS (ESI) m/z calculated for [C₂₃Hi₅N₉S+H]: 450.1244, found: 450.1235; [C₂₃Hi₅N₉S +Na]:472.1063, found: 472.1053.

d) 2-Amino-4-(benzofuran-2-yl)-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(lH-imidazol-l- yl)isophthalonitrile (1-4):

1-4

Yield: 38%. Melting point: 227 °C. 1H NMR (400 MHz, CDC1₃): δ 5.45 (s, 2H), 5.83 (s, 2H), 6.45 (s, 1H), 6.72 (s, 2H), 7.02 (s, 1H), 7.10-7.25 (m, 3H), 7.30-7.60 (m, 7H). ¹³C NMR (100 MHz, CDC1₃): δ 54.19, 95.35, 96.69, 110.53, 111.48, 114.82, 114.91, 120.89, 122.11, 122.48, 123.03, 123.67, 126.81, 127.38, 127.97 (2C), 128.85, 129.10 (2C), 129.96, 133.57, 136.25, 137.91, 137.97, 139.14, 146.18, 153.33, 154.80. IR (CHC1₃): 3669, 3460, 3350, 2219, 1634, 1561, 1265 cm^"1. HRMS (ESI) m/z calculated for [C₂₈Hi₈N₈0+H]: 483.1676, found: 483.1661; [C₂₈Hi₈N₈0 +Na]: 505.1496, found: 505.1473.

e) 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(lH-l,2,4-triazol-l-yl)- [l,l'-biphenyl]-2,4-dicarbonitrile (1-5):

1-5

Yield: 49%. Melting point: 222 °C. 1H NMR (200 MHz, DMSO-d₆): δ 5.60 (s, 2H), 6.98-7.11 (m, 2H), 7.12-7.24 (m, 2H), 7.28-7.49 (m, 6H), 7.78 (s, 1H), 7.99 (s, 1H), 8.38 (s, 1H). ¹³C NMR (125 MHz, CDC1₃ +DMSO-d₆): δ 53.89, 97.28, 98.46, 104.22 (t), 111.66 (d), 113.67, 114.24, 116.75, 123.65, 123.77, 127.64 (2C), 128.60, 128.86 (2C), 131.00, 133.33, 137.75, 138.97, 142.86, 145.63, 151.49, 153.05, 158.66 (dd), 163.44 (dd). IR (CHC1₃): 3490, 3397, 2223, 1632, 1592, 1268 cm^"1. HRMS (ESI) m/z calculated for [C₂₅H₁₅N9F₂+H]: 480.1491, found: 480.1585; [C₂₅Hi₅N9F₂+Na]:502.1311, found: 502.1409.

f) 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-4'-nuoro-6-(lH-l,2,4-triazol-l-yl)-[l,l'- biphenyl]-2,4-dicarbonitrile (1-6):

1-6

Yield: 52%. Melting point: 203 °C. 1H NMR (200 MHz, DMSO-d₆): δ 5.61 (s, 2H), 7- 7.16 (m, 3H), 7.22-747 (m, 6H), 7.54 (s, 2H), 7.79 (s, 1H), 8.02 (s, 1H), 8.44 (s, 1H). ¹³C NMR (125 MHz, CDCl₃ +DMSO-d₆): δ 52.54, 95.56, 96.60, 113.43, 113.61, 114.22, 114.39, 122.18, 123.38, 126.52 (2C), 127.36, 127.77 (2C), 129.24, 129.31, 133.32, 136.97, 138.15, 145.31, 147.44, 150.27, 150.30, 152.56, 161.68 (d). IR (CHC1₃): 3356, 2206, 1600, 1560, 1274 cm^"1. HRMS (ESI) m/z calculated for [C₂₅Hi₆N₉F+H]: 462.1585, found: 462.1579. g) 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(4-oxo-6-pentylthieno

[2,3-rf]pyrimidin-3(4H)-yl)-[l,l'-biphenyl]-2,4-dicarbonitrile (1-7):

1-7

Yield: 31%. Melting point: 196 °C. 1H NMR (200 MHz, CDC1₃): S 1.37 (t, J= 7Hz, 3H), 1.81 (s, 2H), 1.98-2.27 (m, 4H), 3.24 (t, J= 8Hz, 2H), 5.95 (s, 2H), 6.0 (bs, 2H), 7.23- 7.42 (m, 3H), 7.43-7.60 (m, 2H), 7.66-7.84 (m, 4H), 8.14 (s, 1H), 8.21 (s, 1H). ¹³C NMR (100 MHz, CDC1₃): δ 13.90, 22.31, 30.51, 30.53, 31.20, 54.32, 98.22, 99.70, 104.64 (t), 112.54 (d), 113.75, 114.53, 118.04, 123.58, 124.43, 125.18, 127.64 (2C), 128.78, 128.83, 129.13 (2C), 131.18, 131.28, 133.59, 138.41, 138.77, 139.75, 144.08, 145.20, 145.41, 152.36, 157.21, 162.35. IR (CHC1₃): 3341, 3231, 2220, 1691, 1573, 1509, 1271 cm^"1. HRMS (ESI) m/z calculated for [C₃₄H₂6N₈OSF₂+H]: 633.1991, found: 633.1980; [C₃₄H₂₆N₈OSF₂+Na]: 655.1811, found: 655.1797.

h) 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(6-methyl-4- oxothieno[2,3-rf]pyrimidin-3(4H)-yl)-[l,l'-biphenyl]-2,4-dicarbonitrile (1-8):

1-8

Yield: 37%. Melting point: 248°C. 1H NMR (500 MHz, CDC1₃): δ 2.50, (s, 3H), 5.49 (d, J= 2Hz, 2H), 5.65, (bs, 2H), 6.73-6.97 (m, 3H), 7.01- 7.14 (m, 2H), 7.22-7.36 (m, 4H), 7.68 (d, = 2Hz, 1H), 7.75 (t, = 5Hz, 1H). ¹³C NMR (125 MHz, CDC1₃ +DMSO-d₆): δ 15.97, 54.34, 98.21, 99.68, 104.64 (t), 112.54 (d), 113.75, 114.52, 119.35, 123.84, 124.41, 125.16, 127.63, 127.70 (2C), 128.79, 128.83, 129.12 (2C), 131.19 (dd), 133.55, 138.42, 139.16, 139.73, 144.07, 145.47, 145.97, 152.36, 157.08, 162.65. IR (CHC1₃): 3314, 3215, 2219, 1681, 1625, 1574, 1269, 1232 cm^"1. HRMS (ESI) m/z calculated for [C₃₀Hi₈N₈OSF₂+H]: 577.1365, found: 577.1359; [C₃₀Hi₈N₈OSF₂+Na]: 599.1185, found: 599.1176. i) 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(lH-imidazol-l-yl)- [l,l'-biphenyl]-2,4-dicarbonitrile (1-9):

1-9

Yield: 43%. Melting point: 164 °C. 1H NMR (200 MHz, DMSO-d₆): δ 5.60 (s, 2H), 6.66 (bs, 2H), 6.95-7.20 (m, 3H), 7.21-760 (m, 8H), 7.87 (s, 1H). ¹³C NMR (100 MHz, CDC1₃ +DMSO-d₆): δ 53.52, 96.93, 97.98, 104.01 (t), 111.51 (d), 113.64, 114.23, 116.95 (dd), 120.51 (d), 122.81, 123.49, 127.29 (2C), 128.22, 128.53 (2C), 128.93, 130.43 (d), 133.29, 137.02, 137.39, 138.82, 141.97, 152.49, 158.47 (dd), 163.07 (dd). IR (CHC1₃): 3434, 2217, 1648, 1563, 1500, 1299 cm^"1. HRMS (ESI) m/z calculated for [C₂₆Hi₆N₈F₂+H]: 479.1539, found: 479.1752; [C₂₆Hi₆N₈F₂+Na]: 501.1358, found: 501.1580. j) 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-4'-nuoro-6-(lH-imidazol-l-yl)-[l,l'- biphenyl]-2,4-dicarbonitrile (1-10):

1-10

Yield: 47%. Melting point: 120 °C. 1H NMR (200 MHz, DMSO-d₆): δ 5.59 (s, 2H), 6.63 (s, 1H), 6.88 (s, 1H), 6.95-7.08 (m, 2H), 7.10-7.47 (m, 10H), 7.83 (s, 1H). ¹³C NMR (125 MHz, CDCI₃ +DMSO-d₆): δ 53.60, 96.33, 97.54, 114.17, 114.39, 115.25, 115.43, 120.88, 122.80, 123.01, 127.36 (2C), 128.28, 128.59 (2C), 128.99, 129.03, 129.49, 129.56, 133.38, 136.90, 137.69, 139.06, 147.51, 152.59, 162.54 (d). IR (CHC1₃): 3437, 2726, 1647, 1560, 1303 cm^"1. HRMS (ESI) m/z calculated for [C₂₆Hi₇N₈F+H]: 461.1633, found: 461.1675; [C₂₆Hi₇N₈F +Na]:483.1452, found: 483.1496. k) 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-[l,l^,-biphenyl]-2,4- dicarbonitrile (1-18):

1-18

Yield: 55%. Melting point: 189 °C. 1H NMR (400 MHz, CDC1₃): S 5.34 (s, 2H), 5.64 (s, 2H), 6.90 -7.08 (m, 2H), 7.29-7.36 (m, 2H), 7.37-7.48 (m, 4H), 7.73 (s, IH), 8.37 (s, IH). ¹³C NMR (100 MHz, DMSO d6): δ 53.18, 92.36, 95.54, 104.64 (t), 112.23 (dd), 115.34, 115.78, 116.96, 121.77, 125.05, 128.06 (2C), 128.31, 128.84 (2C), 132.44 (dd), 135.62, 138.08, 142.59, 143.56, 153.90, 158.92 (dd), 163.03 (dd). IR (CHC1₃): 3274, 2403, 1532, 1217 cm^"1. HRMS (ESI) m/z calculated for [C₂ Hi₄N₆F₂+H]: 413.1321, found: 413.1319; [C₂₃Hi₄N₆F₂+Na]: 435.1140, found: 435.1137.

1) 5'-Amino-3,4,4 ,5-tetramethoxy-[l,l':3',l -terphenyl]-4',6'-dicarbonitrile (l-34)

1-34

1H NMR (200 MHz, CDC1₃): δ 3.88 (s, 3H), 3.92 (s, 9H), 5.40 (bs, 2H), 6.79 (s, 2H), 6.88 (s, IH), 7.06 (d, = 7Hz, 2H), 7.58 (d, = 7Hz, 2H). m) 5'-Amino-2,3 ,4 ,5 -tetramethoxy-[l,l':3',l -terphenyl]-4',6'-dicarbonitrile (1-

1-35

1H NMR (200 MHz, CDC1₃): δ 3.89 (s, 3H), 3.92 (s, 9H), 5.32 (bs, 2H), 6.78-6.90 ( 3H), 7.00-7.14 (m, 2H), 7.29-7.35 (m, IH), 7.39-7.53 (m, IH). n) 3-Amino-5-(furan-2-yl)-3',4',5'-trimethoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1-

1-36 1H NMR (200 MHz, CDC1₃): S 3.93 (s, 9H), 5.38 (bs, 2H), 6.63 (d, = 7Hz, 1H), 6.80

(s, 2H), 7.30 (s, 1H), 7.47 (d, J = 7Hz, 1H), 7.63 (s, 1H).

o) 3-Amino-3^4',5'-trimethoxy-5-(thiophen-2-yl)-[l,l'-biphenyl]-2,4-dicarbonitrile

1H NMR (200 MHz, CDCI₃): S 3.94 (s, 9H), 5.41 (bs, 2H), 6.79 (s, 2H), 7.01 (s, 1H), 7.21 (t, J = 7Hz, 1H), 7.52 (t, J = 7Hz, 1H), 7.75 (t, J = 7Hz, 1H).

Example 2: Preparation of 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl) isophthalonitrile (1-11):

To a mixture of 1 -benzyl- lH-l,2,3-triazole-4-carbaldehyde (100 mg, 0.53 mmol), acetaldehyde (0.05 ml, 0.8 mmol), and malononitrile (0.08 ml, 1.35 mmol) in dry DMF (3 ml) taken in round bottom flask equipped with reflux condenser under argon atmosphere, was added morpholine (0.055 ml, 0.65 mmol) at 0°C. The mixture was allowed to come to RT and then stirred at 80°C for 8 h. It was then cooled to room temperature, diluted with ice cold water (30 ml), extracted with ethyl acetate (3 x 30 ml), dried over Na₂S0_4i concentrated and purified by column chromatography on silica gel (60-120 mesh) using pet ether- ethyl acetate (15 % ethyl acetate in pet ether) as an eluent to give 2-amino-4-(l-benzyl-lH-l,2,3- triazol-4-yl)isophthalonitrile as a white solid, 80 mg, 50%. Melting point: 190 °C. 1H NMR (200 MHz, DMSO-d6): δ 5.74 (s, 2H) 6.82 (s, 2H), 7.28 (d, = 8 Hz, 1H), 7.31-7.45 (m, 5H), 7.85 (d, = 8 Hz, 1H), 8.84 (s, 1H). ¹³C NMR (125 MHz, CDC1₃): δ 54.52, 93.30, 95.94, 115.81, 116.16, 116.79, 123.09, 128.02 (2C), 129.01, 129.24 (2C), 134.04, 136.98, 138.62, 143.19, 152.12. IR (CHC1₃): 3401, 2213, 1586, 1540, 1284 cm^"1. HRMS (ESI) m/z calculated for [Ci₇Hi₂N₆+H]: 301.1196, found: 301.1202; [Ci₇Hi₂N₆+Na]: 323.1016, found: 323.1022.

a) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-methylisophthalonitrile (1-12):

1-12

Yield: 61%. Melting point: 174 °C. 1H NMR (200 MHz, CDC1₃): δ 2.28 (s, 3H), 5.08 (bs, 2H), 5.66 (s, 2H), 7.29-7.36 (m, 2H), 7.37-7.44 (m, 3H), 7.51 (s, 1H), 7.78 (s, 1H). ¹³C NMR (50 MHz, CDC1₃ + DMSO-d₆): δ 19.13, 53.69, 96.24, 97.47, 115.33, 115.56, 123.80, 126.13, 127.41 (2C), 128.29, 128.66 (2C), 133.95, 137.82, 138.05, 142.29, 150.16. IR (CHC1₃): 3460, 3344, 2225, 1641, 1597, 1556, 1273 cm^"1. HRMS (ESI) m/z calculated for [Ci₈Hi₄N₆+H]: 315.1353, found: 315.1361; [Ci₈Hi₄N₆+Na]: 337.1172, found: 337.1180. b) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-ethylisophthalonitrile (1-13):

1-13

Yield: 64%. Melting point: 168 °C. 1H NMR (200 MHz, CDC1₃): δ 1.08 (t, = 7Hz, 3H), 2.63 (q, = 7 Hz, 2H), 5.08 (bs, 2H), 5.66 (s, 2H), 7.28-7.35 (m, 2H), 7.36-7.48 (m, 3H), 7.54 (s, 1H) 7.75 (s, 1H). ¹³C NMR (100 MHz, CDC1₃): δ 15.07, 25.59, 54.39, 97.38, 98.43, 115.57, 115.78, 123.84, 127.95 (2C), 128.95, 129.26 (2C), 133.93, 134.15, 137.14, 137.92, 142.68, 149.77. IR (CHC1₃): 3437, 3313, 2220, 1637, 1600, 1221 cm^"1. HRMS (ESI) m/z calculated for [Ci₉Hi₆N₆+H]: 329.1509, found: 329.1502; [Ci₉Hi₆N₆+Na]: 351.1329, found: 351.1321. c) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-propylisophthalonitrile (1-14):

1-14 Yield: 59%. Melting point: 132 °C. 1H NMR (200 MHz, CDC1₃): S 0.81 (t, = 7Hz,

3H), 1.09-1.48 (m, 2H), 2.54 (t, = 7Hz, 3H), 5.10 (bs, 2H), 5.66 (s, 2H), 7.24-7.35 (m, 2H), 7.36-7.46 (m, 3H), 7.51 (s, 1H), 7.73 (s, 1H). ¹³C NMR (50 MHz, CDC1₃ +DMSO-d₆): δ 13.12, 23.48, 33.67, 53.62, 96.53, 97.91, 115.21, 115.60, 123.61, 123.68 127.21 (2C), 128.21, 128.61 (2C), 131.05, 134.08, 137.39, 137.74, 142.20, 149.99. IR (CHC1₃): 3437, 3313, 2221, 1636, 1220 cm^"1. HRMS (ESI) m/z calculated for [C₂oHi₈N₆+H]: 343.1666, found: 343.1661.

d) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-butylisophthalonitrile (1-15):

Yield: 60%. Melting point: 163 °C. 1H NMR (200 MHz, CDC1₃): δ 0.78 (t, J= 7Hz, 3H), 1.08-1.45 (m, 4H), 2.56 (t, = 8Hz, 2H), 5.10 (s, 2H), 5.66 (s, 2H), 7.28-7.35 (m, 2H), 7.36-7.46 (m, 3H), 7.51 (s, 1H), 7.73 (s, 1H). ¹³C NMR (125 MHz, CDC1₃): δ 13.68, 22.15, 31.98, 32.99, 54.34, 97.24, 98.49, 115.52, 115.77, 123.79, 127.86 (2C), 128.90, 129.21 (2C), 132.66, 134.24, 137.75, 138.04, 142.73, 149.79. IR (CHC1₃): 3401, 2224, 1629, 1528, 1217 cm^"1. HRMS (ESI) m/z calculated for [C₂iH₂oN₆+H]: 357.1822, found: 357.1819. e) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-pentylisophthalonitrile (1-16):

1-16 Yield: 61%. Melting point: 190 °C. 1H NMR (200 MHz, CDC1₃): S 0.81 (t, =7Hz, 3H), 1.05-1.25 (m, 4H), 2.56 (t, J= 8Hz, 2H), 5.07 (s, 2H), 5.66 (s, 2H), 7.26-7.34 (m, 2H), 7.35-7.47 (m, 3H), 7.51 (s, 1H), 7.72 (s, 1H). ¹³C NMR (100 MHz, CDC1₃): δ 13.80, 22.15, 30.46, 31.14, 32.15, 54.23 97.11, 98.36, 115.49, 115.77, 123.78, 127.78 (2C), 128.79, 129.11 (2C), 132.46, 134.23, 137.70, 137.97, 142.64, 149.87. IR (CHCI₃): 3490, 3395, 2224, 1630, 1215 cm^"1. HRMS (ESI) m/z calculated for [C₂₂H₂₂N₆+H] : 371.1979, found: 371.1973; [C₂₂H₂₂N₆+Na] : 393.1798, found: 393.1791.

f) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-hexylisophthalonitrile (1-17):

1-17

Yield: 63%. Melting point: 133 °C. 1H NMR (200 MHz, CDCI₃): S 0.84 (t, J= 7Hz, 3H), 1.08-1.45 (m, 8H), 2.46-2.65 (m, 2H), 5.08 (s, 2H), 5.66 (s, 2H), 7.28-7.35 (m, 2H), 7.36-7.46 (m, 3H), 7.51 (s, 1H), 7.72 (s, 1H). ¹³C NMR (50 MHz, CDC1₃): δ 13.93, 22.37, 28.70, 30.76, 31.32, 32.25, 54.26, 97.13, 98.39, 115.51, 115.78, 123.78, 127.81 (2C), 128.83, 129.14 (2C), 132.52, 134.23, 137.72, 137.99, 142.67, 149.85. IR (CHCI₃): 3490, 3398, 2221, 1634, 1219 cm^"1. HRMS (ESI) m/z calculated for [C₂3H₂₄N₆+H] : 385.2135, found: 385.2130.

g) 2-Amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(6-butyl-4-oxothieno[2,3- rf]pyrimidin-3(4H)-yl)isophthalonitrile (1-19):

1-19

Yield: 65%. Melting point: 202 °C. 1H NMR (400 MHz, CDC1₃): S 0.97 (t, J= 7Hz, 3H), 1.37-1.48 (m, 2H), 1.68-1.75 (m, 2H), δ 2.85 (t, J= 7Hz, 2H), 5.47 (A of ABq, J=16 Hz, 1H), 5.52 (B of ABq, J=16 Hz, 1H), 5.64 (s, 2H), 7.04 (s, 1H), 7.05-7.14 (m, 2H), 7.27- 7.34 (m, 3H), 7.62 (s, 1H), 7.79 (s, 1H), 7.84 (s, 1H). ¹³C NMR (100 MHz, CDCI₃): δ 13.71, 22.06, 30.28, 33.05, 54.32, 97.40, 98.13, 114.45, 114.62, 118.29, 124.21, 124.48, 125.37, 127.71 (2C), 128.83, 129.11 (2C), 133.61, 137.54, 138.09, 139.70, 145.38, 145.44, 152.39, 157.11, 162.43. IR (CHC1₃): 3494, 3398, 2225, 1684, 1635, 1569, 1532, 1322 cm^"1. HRMS (ESI) m/z calculated for [C₂₇H₂₂N₈OS+H]: 507.1710, found: 507.1778; [C₂₇H₂₂N₈OS +Na]: 529.1529, found: 529.1600.

h) 5-Amino-7-(l-benzyl-lH-l,2,3-triazol-4-yl)-2,3-dihydro-lH-indene-4,6- dicarbonitrile (1-28)

1-28

1H NMR (200 MHz, CDC1₃): δ 2.04-2.21 (m, 2H), 3.04-3.22 (m, 4H), 5.09 (bs, 2H), 5.63 (s, 2H), 7.29-7.49 (m, 5H), 8.07 (s, 1H).

i) 2-Amino-4-(l-benzyl-5-(hydroxymethyl)-lH-l,2,3-triazol-4-yl)-5- methylisophthalonitrile (1-29)

1-29

1H NMR (200 MHz, CDCI3): δ 1.96 (s, 3H), 1.43 (s, 2H), 5.56 (bs, 2H), 5.75 (s, 1H), 6.61 (s, 2H), 7.23 (s, 2H), 7.35 (s, 3H), 7.78 (s, 1H).

j) 3-Amino-3',4',5'-trimethoxy-6-pentyl-[l,l'-biphenyl]-2,4-dicarbonitrile (1-30)

1-30

1H NMR (200 MHz, CDC1₃): δ 0.81 (t, = 7Hz, 3H), 1.06-1.50 (m, 6H), 2.35 (t, 7Hz, 2H), 3.87 (s, 6H), 3.92 (s, 3H), 5.09 (bs, 2H), 6.44 (s, 2H), 7.49 (s, 1H).

k) 3-Amino-6-hexyl-3',4',5'-trimethoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1-31)

1H NMR (200 MHz, CDC1₃): S 0.83 (t, J = 7Hz, 3H), 1.10-1.26 (m, 6H), 1.34-1.43 (m,H), 2.36 (t, J = 7Hz, 2H), 3.87 (s, 6H), 3.92 (s, 3H), 5.08 (bs, 2H), 6.44 (s, 2H), 7.49 (s,H).

1) 3-Amino-6-heptyl-3',4',5'-trimethoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1-32)

1H NMR (200 MHz, CDC1₃): S 0.84 (t, J = 7Hz, 3H), 1.03-1.25 (m, 8H), 1.29-1.49 (iH), 2.35 (t, J = 7Hz, 2H), 3.86 (s, 6H), 3.91 (s, 3H), 5.12 (bs, 2H), 6.43 (s, 2H), 7.48 (s,H).

m) 3-Amino-6-decyl-3',4',5'-trimethoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1-33)

1H NMR (200 MHz, CDCI₃): S 0.87 (t, J = 7Hz, 3H), 1.10-1.45 (m, 16H), 2.35 (t, J -Hz, 2H), 3.86 (s, 6H), 3.92 (s, 3H), 5.09 (bs, 2H), 6.44 (s, 2H), 7.49 (s, 1H).

n) 3-Amino-6-heptyl-4'-methoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1-38)

1H NMR (200 MHz, CDC1₃): S 0.85 (t, J = 7Hz, 3H), 1.03-1.44 (m, 10H), 2.35 (t, J =Hz, 2H), 3.87 (s, 3H), 5.08 (bs, 2H), 7.02 (d, = 7Hz, 2H), 7.20 (d, = 7Hz, 2H), 7.48 (s,H).

o) 3-Amino-6-decyl-4'-methox '-biphenyl]-2,4-dicarbonitrile (1-39)

1-39

1H NMR (200 MHz, CDC1₃): S 0.88 (t, J = 7Hz, 3H), 1.03-1.44 (m, 16H), 2.36 (t, J =Hz, 2H), 3.87 (s, 3H), 5.08 (bs, 2H), 7.02 (d, = 7Hz, 2H), 7.20 (d, = 7Hz, 2H), 7.49 (s,H).

p) 3-Amino-6-(6-butyl-4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)-4'-methoxy-[l,l'- biphenyl] -2,4-dicarbonitrile (1-

1H NMR (200 MHz, CDC1₃): S 0.95 (t, J = 7Hz, 3H), 1.33-1.49 (m, 2H), 1.63-1.78 (m,H) 2.84 (t, J = 7Hz, 2H), 3.78 (s, 3H), 5.53 (bs 2H), 6.88 (d, J = 8Hz, 2H), 7.17 (d, / =Hz, 2H), 7.21 (s, 1H), 7.52 (s, 1H), 7.64 (s, 1H).

q) 3-Amino-4'-methoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)- [1,1' -biphenyl] -2,4-dicarbonitrile ( 1 -41 )

1-41

1H NMR (200 MHz, CDC1₃): δ 0.91 (t, J = 7Hz, 3H), 1.29-1.45 (m, 4H), 1.62-1.77 (m,H) 2.77-2.98 (m, 4H), 3.85 (s, 3H), 5.22 (bs 2H), 6.96 (d, J = 8Hz, 2H), 7.03-7.18 (m, 3H),.30 (s, 1H), 7.51 (s, 1H). r) 3-Amino-3',5'-dimethoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)- yl)ethyl)-[l,l'-biphenyl]-2 4-dicarbonitrile (1-42)

1-42

1H NMR (200 MHz, CDC1₃): S 0.91 (t, / = 7Hz, 3H), 1.16-1.50 (m, 4H), 1.68 (t, J =Hz, 2H), 2.75-3.02 (m, 4H), 3.80 (s, 6H), 3.91 (t, = 7Hz, 2H), 5.21 (bs 2H), 6.35 (s, 2H),.55 (s, 1H), 7.10 (s, 1H), 7.37 (s, 1H), 7.50 (s, 1H).

s) 3-Amino-3 ' ,4' ,5 ' -trimethoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)- yl)ethyl)-[l,l'-biphenyl]-2,4-dicarbonitrile (1-43)

1-43

1H NMR (200 MHz, CDC1₃): δ 0.90 (t, J = 7Hz, 3H), 1.16-1.50 (m, 6H), 1.70 (t, =Hz, 2H), 2.75-3.02 (m, 4H), 3.84 (s, 6H), 3.92 (s, 3H), 5.23 (bs 2H), 6.44 (s, 2H), 7.08 (s,H), 7.44 (s, 1H), 7.48 (s, 1H).

t) 2-Amino-5-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)-4-(thiophen- 2-yl)isophthalonitrile (1

1-44

1H NMR (200 MHz, CDC1₃): δ 0.91 (t, = 7Hz, 3H), 1.23-1.47 (m, 4H), 1.72 (t, =Hz, 2H), 2.84 (t, = 7Hz, 2H), 3.01 (t, = 7Hz, 2H), 3.94 (t, = 7Hz, 2H), 5.24 (bs 2H),.06-7.018 (m, 3H), 7.43 (s, 1H), 7.52-7.58 (m, 2H).

u) 3-Amino-4'-((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)-6- methyl-[l,l'-biphenyl]-2,4-dicarbonitrile (1-50)

1-50

Yield: 49%. Melting point: 87.4 °C.

1H NMR (200 MHz, CDC1₃): δ 2.03 (s, 3H), 3.83 (s, 3H), 5.10 (bs, 2H), 5.24 (s, 2H), 5.49 (s, 2H), 6.69 (d, = 7Hz, 1H), 7.08 (d, = 7Hz, 2H), 7.19 (d, = 7Hz, 2H), 7.46 (s, 1H), 7.52 (d, = 2Hz, 1H), 7.61 (dd, = 2Hz, 1H), 7.65 (s, 1H).

Example 3: Preparation of N-alkylated compounds of formula (I):

a) Preparation of 5-(l-benzyl-lH-l,2,3-triazol-4-yl)-3-(dimethylamino)-2',4'-difluoro- 6-(lH-l,2,4-triazol-l-yl)-[l,l'-biphenyl]-2,4-dicarbonitrile (1-20):

1-20 3-Amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(lH-l,2,4-triazol-l-yl)- [l,l'-biphenyl]-2,4-dicarbonitrile (1-5) (100 mg, 0.2 mmol) in dry THF (10 ml) was stirred with NaH (19 mg, 0.83 mmol) at 60 °C for 12 h. It was then cooled to RT, methyl iodide (0.14 ml, 340 mg, 2.4 mmol) was added and the reaction mixture was stirred at RT for 12 h. It was then quenched with methanol (2 ml), solvent was removed on rotavapor, water (2 ml) was added and the product was extracted with ethyl acetate (3 x 15 ml). The organic layer was dried with sodium sulphate, concentrated and the residue obtained was purified by column chromatography to obtain 5-(l-benzyl-lH-l,2,3-triazol-4-yl)-3-(dimethylamino)- 2',4'-difluoro-6-(lH-l,2,4-triazol-l-yl)-[l,r-biphenyl]-2,4-dicarbonitrile (1-20) as yellow solid (70 mg, 66%). Melting point: 205 °C. 1H NMR (400 MHz, CDC1₃): δ 3.41 (s, 6H), 5.48 (s, 2H), 6.79-6.88 (m, 2H), 7.05-7.14 (m, 3H), 7.28 (s, 1H), 7.35-7.41 (m, 3H), 7.61 (s, 1H), 7.85 (s, 1H). ¹³C NMR (100 MHz, CDC1₃): δ 44.47 (2C), 54.34, 104.71 (t), 106.91, 107.53, 112.12 (d), 115.25, 115.77, 116.91 (d), 123.99, 127.61, 127.96 (2C), 129.02, 129.25 (2C), 131.08, 133.50, 139.22, 139.99, 144.72, 145.68, 151.92, 159.00, 159.09 (dd), 163.91 (dd). IR (CHC1₃): 2229, 1608, 1557, 1512, 1433 cm^"1. HRMS (ESI) m z calculated for [C27H19N9F2+H]: 508.1804, found: 508.1988; [C27H19N9F2 +Na]: 530.1624, found: 530.1815.

b) 5-(l-Benzyl-lH-l,2,3-triazol-4-yl)-3-(dimethylamino)-4'-fluoro-6-(lH-l,2,4-triazol- l-yl)-[l,l'-biphenyl]-2,4-dicarbonitrile (1-21):

This compound was prepared by procedure described for 1-20.

Yield: 70%. Melting Point: 226°C. 1H NMR (400 MHz, CDCI₃): δ 3.39 (s, 6H), 5.47 (s, 2H), 6.93-7.06 (m, 2H), 7.07-7.19 (m, 4H), 7.32-7.42 (m, 4H), 7.61 (s, 1H), 7.73 (s, 1H). ¹³C NMR (100 MHz, CDCI₃): δ 44.39 (2C), 54.22, 106.41, 106.99, 115.67, 115.81 (2C), 116.03, 124.06, 127.17, 127.83 (2C), 128.80 (d), 128.91, 129.16 (2C), 130.20, 130.28, 133.61, 139.33, 139.89, 145.80, 150.20, 151.67, 159.29, 163.21 (d). IR (CHC1₃): 2226, 1659, 1558, 1510, 1447 cm^"1. HRMS (ESI) m z calculated for [C₂₇H₂₀N9F+H] : 490.1898, found: 490.1899; [C₂₇H₂₀N9F +Na]: 512.1718, found: 512.1721.

Following compounds were prepared by using the procedure similar to 1-20 with slight modification. The compounds were stirred with NaH at room temperature and reacted further with methyl iodide at RT. c) 4-(l-Benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-methylisophthalonitrile (1- 22):

1-22

Yield: 75%. Melting point: 127 °C. 1H NMR (400 MHz, CDCI₃): δ 2.15 (s, 3H), 3.07 (s, 6H), 5.53 (s, 2H), 7.11-7.22 (m, 2H), 7.23-7.33 (m, 3H), 7.45 (s, 1H), 7.64 (s, 1H). ¹³C NMR (100 MHz, CDC1₃): δ 19.94, 43.86 (2C), 54.32, 106.52, 108.43, 116.87, 117.46, 124.09, 127.92 (2C), 128.88, 129.19 (2C), 131.71, 134.16, 139.86, 140.25, 142.61, 156.76. IR (CHCI₃): 2228, 1587, 1507, 1343 cm^"1. HRMS (ESI) m/z calculated for [C₂oHi₈N₆+H]: 343.1666, found: 343.1656; [C₂oHi₈N₆+Na]: 365.1485, found: 365.1475.

d) 4-(l-Benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-ethylisophthalonitrile (1- 23):

Yield: 73%. Melting point: 121 °C. 1H NMR (200 MHz, CDC1₃): δ 1.08 (t, J= 7Hz, 3H), 2.60 (q, J= 7Hz, 2H), 3.20 (s, 6H), 5.66 (s, 2H), 7.28-7.33 (m, 2H), 7.34-7.44 (m, 3H), 7.60 (s, 1H), 7.73 (s, 1H). ¹³C NMR (125 MHz, CDCI₃): δ 14.88, 25.80, 43.86 (2C), 54.32, 106.85, 108.70, 116.79, 117.60, 124.05, 127.85 (2C), 128.86, 129.20 (2C), 134.22, 137.79, 138.97, 139.57, 142.44, 156.54. IR (CHCI₃): 2229, 1584, 1507, 1340 cm^"1. HRMS (ESI) m/z calculated for [C₂iH₂iN₆+H]: 357.1822, found: 357.1820.

e) 4-(l-Benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-propylisophthalonitrile (1- 24):

1-24 Yield: 70%. Melting point: 140 °C. 1H NMR (500 MHz, CDCI₃): S 0.81 (t, J= 7Hz,

3H), 1.38-1.50 (m, 2H), 2.53 (t, J= 7Hz, 2H), 3.21 (s, 6H), 5.67 (s, 2H), 7.24-7.33 (m, 2H), 7.33-7.48 (m, 3H), 7.58 (s, 1H), 7.71 (s, 1H). ¹³C NMR (125 MHz, CDC1₃): δ 13.66, 23.88, 34.56, 43.88 (2C), 54.34, 106.78, 108.85, 116.79, 117.60, 124.03, 127.80 (2C), 128.88, 129.22 (2C), 134.34, 136.43, 139.61, 139.79, 142.58, 156.58. IR (CHC1₃): 2229, 1583, 1507, 1345 cm^"1. HRMS (ESI) m/z calculated for [C22H22N6+H] : 371.1979, found: 371.2009; [C₂₂H₂2N6+Na] : 393.1798, found: 393.1830.

f) 4-(l-Benzyl-lH-l,2,3-triazol-4-yl)-5-butyl-2-(dimethylamino)isophthalonitrile (1- 25):

1-25

Yield: 72%. Melting point: 122 °C. 1H NMR (500 MHz, CDC1₃): S 0.79 (t, = 7Hz, 3H), 1.14-1.24 (m, 2H), 1.32-1.41 (m, 2H), 2.55 (t, = 8Hz, 2H), 3.21 (s, 6H), 5.67 (s, 2H), 7.27-7.31 (m, 2H), 7.35-7.43 (m, 3H), 7.58 (s, 1H), 7.71 (s, 1H). ¹³C NMR (125 MHz, CDC1₃): δ 13.69, 22.22, 32.24, 32.86, 43.89 (2C), 54.33, 106.71, 108.74, 116.81, 117.63, 123.98, 127.81 (2C), 128.88, 129.21 (2C), 134.32, 136.62, 139.63, 139.76, 142.56, 156.53. IR (CHC1₃): 2228, 1583, 1506, 1458, 1344 cm^"1. HRMS (ESI) m/z calculated for [C₂ H₂₄N₆+H]: 385.2135, found: 385.2299; [C₂₃H₂₄N₆+Na] : 407.1955, found: 407.2128. g) 4-(l-Benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-pentylisophthalonitrile (1- 26):

1-26

Yield: 69%. Melting point: 90 °C. 1H NMR (200 MHz, CDC1₃): δ 0.81 (t, = 7Hz, 3H), 1.03-1.24 (m, 4H), 1.29-1.49 (m, 2H), 2.54 (t, = 7Hz, 2H), 3.21 (s, 6H), 5.66 (s, 2H), 7.27-7.34 (m, 2H), 7.34-7.46 (m, 3H), 7.57 (s, 1H), 7.70 (s, 1H). ¹³C NMR (125 MHz, CDC1₃): δ 13.84, 22.21, 30.40, 31.28, 32.52, 43.87 (2C), 54.33, 106.82, 108.85, 116.77, 117.59, 123.97, 127.82 (2C), 128.86, 129.19 (2C), 134.33, 136.73, 139.58, 139.71, 142.56, 156.53. IR (CHC1₃): 2227, 1582, 1504, 1456, 1345 cm^"1. HRMS (ESI) m/z calculated for [C₂₄H₂₆N₆+H]: 399.2292, found: 399.2284; [C₂₄H₂₆N₆+Na] : 421.2111, found: 421. 2102. h) 4-(l-Benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-hexylisophthalonitrile (1- 27):

1-27 Yield: 77%. Melting point: 83 °C. 1H NMR (200 MHz, CDC1₃): S 0.85 (t, J= 7Hz, 3H), 1.05-1.28 (m, 6H), 1.28-1.49 (m, 2H), 2.55 (t, J= 7Hz, 2H), 3.21 (s, 6H), 5.67 (s, 2H), 7.23-7.33 (m, 2H), 7.33-7.46 (m, 3H), 7.57 (s, 1H), 7.71 (s, 1H). ¹³C NMR (50 MHz, CDCI₃): δ 13.93, 22.36, 28.75, 30.62, 31.30, 32.52, 43.81 (2C), 54.24, 106.67, 108.73, 116.73, 117.55, 123.95, 127.74 (2C), 128.79, 129.12 (2C), 134.29, 136.62, 139.53, 139.64, 142.48, 156.45. IR (CHCI₃): 2228, 1582, 1505, 1345 cm^"1. HRMS (ESI) m/z calculated for [C25H28N6+H]: 413.2448, found: 413.2439; [C₂5H₂8N₆+Na] : 435.2268, found: 435.2258. i) 3-(Dimethylamino)-6-heptyl-3^4',5'-trimethoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1-45)

1-45

1H NMR (200 MHz, CDCI₃): δ 0.85 (t, J = 7Hz, 3H), 1.03-1.44 (m, 10H), 2.36 (t, = 7Hz, 2H), 3.23 (s, 6H), 3.86 (s, 6H), 3.92 (s, 3H), 6.42 (s, 2H), 7.56 (s, 1H).

The following compounds were prepared by using the procedure similar to 1-20 with slight modification. The compound was stirred with NaH at room temperature and reacted further with benzyl bromide at RT. j) 3-(Dibenzylamino)-6-heptyl-3^4',5'-trimethoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1-46)

1-46

1H NMR (200 MHz, CDC1₃): S 0.87 (t, J = 7Hz, 3H), 1.10-1.50 (m, 10H), 2.41 (t, J = 7Hz, 2H), 3.88 (s, 6H), 3.94 (s, 3H), 4.55 (s, 4H), 6.36 (s, 2H), 7.25-7.40 (m, 10H), 7.58 (s, 1H).

k) 3-(Diallylamino)-6-heptyl-3^4',5'-trimethoxy-[l,l'-biphenyl]-2,4-dicarbonitrile (1- 47)

This compound was prepared by using the procedure similar to 1-20 with slight modification. The compound was stirred with NaH at room temperature and reacted further with allyl bromide at RT.

1H NMR (200 MHz, CDC1₃): δ 0.85 (t, J = 7Hz, 3H), 1.03-1.44 (m, 10H), 2.40 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.92 (s, 3H), 4.07 (d, J = 6Hz, 4H), 5.14-5.38 (m, 4H), 5.74-5.99 (m, 2H), 6.41 (s, 2H), 7.61 (s, 1H).

1) 6-Decyl-3 -(dibenzylamino) -3 ' ,4 ' ,5 ' - trimethoxy- [1,1' -biphenyl] -2,4-dicarbonitrile ( 1 - 48)

1-48

1H NMR (200 MHz, CDC1₃): δ 0.88 (t, J = 7Hz, 3H), 1.10-1.45 (m, 16H), 2.40 (t, = 7Hz, 2H), 3.87 (s, 6H), 3.99 (s, 3H), 4.54 (s, 4H), 6.35 (s, 2H), 7.28-7.45 (m, 10H), 7.60 (s, 1H).

m) 5'-(Dibenzylamino)-2,3",4",5"-tetramethoxy-[l,l':3',l"-terphenyl]-4',6'- dicarbonitrile (1-49)

1-49

1H NMR (200 MHz, CDCI₃): δ 3.77 (s, 3H), 3.97 (s, 9H), 4.71 (s, 4H), 6.77 (s, 2H), 7.14 (t, J = 7Hz, 2H), 7.28-7.63 (m, 13H).

Example 4: Preparation of ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-butyl-7- cyano-l-(2-ethoxy-2-oxoethyl)-lH-indole-2-carboxylate (2-4) :

The 2-amino-4-(l -benzyl- lH-1, 2, 3-triazol-4-yl)-5-butylisophthalonitrile (1 gm, 0.002 mol), and ethyl bromoacetate (1.54 ml, 0.014 mol) were dissolved in acetonitrile (5 ml), in a two necked RB flask under argon atmosphere at RT and the pellets of potassium hydroxide (0.90 gm, 0.016 mol) were added. The reaction mixture was stirred at room temperature for 2 h. It was then diluted with excess of cold water and extracted with ethyl acetate (3 x 10 ml), dried over Na₂S0₄, concentrated and purified by column chromatography on silica gel (60:120) using pet ether-ethyl acetate as eluent. Ethyl 3- amino-6-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-5-butyl-7-cyano- 1 -(2-ethoxy-2-oxoethyl)- 1H- indole-2-carboxylate was obtained as a yellow solid. 1H NMR (200 MHz, CDCI₃): δ 0.76 (t, = 7Hz, 3H), 1.07-1.46 (m, 10H), 2.63 (t, =8Hz, 2H), 4.23 (q, =7Hz, 2H), 4.38 (q, =7Hz, 2H), 5.00 (bs, 2H), 5.56 (s, 2H), 5.67 (s, 2H), 7.29-7.60 (m, 5H), 7.64 (s, 1H), 7.69 (s, 1H).

The following compounds were prepared by using procedure similar to compound 2-4: a) Ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-4-(2,4-difluorophenyl)-l- (2-ethoxy-2-oxoethyl)-5-(lH-l,2,4-triazol-l-yl)-lH-indole-2-carboxylate (2-1)

1H NMR (200 MHz, CDCI₃): S 0.30 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 4.21- 4.48 (m, 4H), 5.43 (s, 2H), 5.71 (s, 2H), 5.88 (s, 2H), 6.69-6.90 (m, 2H), 7.00 (s, 1H), 7.04- 7.23 (m, 3H), 7.33-7.44 (m, 3H), 7.55 (s, 1H), 7.72 (s, 1H).

b) Ethyl 3-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-6-(2,4-difluorophenyl)-l- (2-ethoxy-2-oxoethyl)-5-(lH-l,2,4-triazol-l-yl)-lH-indole-2-carboxylate (2-2)

2-2

1H NMR (200 MHz, CDC1₃): S 0.30 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 4.21- 4.48 (m, 4H), 5.43 (s, 2H), 5.71 (s, 2H), 5.88 (s, 2H), 6.69-6.90 (m, 2H), 7.00 (s, 1H), 7.04- 7.23 (m, 3H), 7.33-7.44 (m, 3H), 7.55 (s, 1H), 7.72 (s, 1H).

c) Ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5- propyl- lH-indole-2-carboxylate (2-3)

2-3

1H NMR (200 MHz, CDCI₃): δ 0.79 (t, = 7Hz, 3H), 1.2-1.5 (m, 8H), 2.60 (t, = 7Hz, 2H), 4.16-4.46 (m, 4H), 5.00 (bs, 2H), 5.56 (s, 2H), 5.67 (s, 2H), 7.23-7.34 (m, 2H), 7.34-7.47 (m, 3H), 7.64 (s, 1H), 7.69 (s, 1H).

d) Ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5- hexyl- lH-indole-2-carboxylate (2-5)

2-5

1H NMR (200 MHz, CDC1₃): δ 0.84 (t, = 7Hz, 3H), 1.07-1.45 (m, 14H), 2.62 (t, = 7Hz, 2H), 4.15-4.45 (m, 4H), 5.00 (bs, 2H), 5.56 (s, 2H), 5.67 (s, 2H), 7.28-7.33 (m, 2H), 7.34-7.42 (m, 3H), 7.63 (s, 1H), 7.69 (s, 1H).

e) Ethyl l-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-4-cyano-3-(2-ethoxy-2-oxoethyl)- 6,7,8,9-tetrahydro-3H-benzo[e]indole-2-carboxylate (2-6)

1H NMR (200 MHz, CDC1₃): S 1.20-1.45 (m, 6H), 1.65-1.95 (m, 4H), 2.59 (t, = 7Hz, 2H), 3.33 (t, J = 7Hz, 2H), 4.15-4.45 (m, 4H), 5.33 (bs, 2H), 5.53 (s, 2H), 5.65 (s, 2H), 7.28-7.34 (m, 2H), 7.35-7.45 (m, 3H), 7.65 (s, IH).

f) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-6-(thiophen-2-yl)-lH- indole-2-carboxylate (2-7)

2-7

1H NMR (200 MHz, CDC1₃): δ 1.29 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 2.27 (s, 3H), 4.17-4.47 (m, 4H), 4.97 (bs, 2H), 5.60 (s, 2H), 7.04-7.10 (m, IH), 7.12-7.19 (m, IH), 7.46-7.52 (m, IH), 7.62 (s, IH).

g) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-4-(thiophen-2-yl)-lH- indole-2-carboxylate (2-8)

1H NMR (200 MHz, CDC1₃): δ 1.23-1.40 (m, 6H), 2.19 (s, 3H), 4.21-4.40 (m, 4H), 4.63 (bs, 2H), 5.58 (s, 2H), 7.03-7.07 (m, IH), 7.18-7.24 (m, IH), 7.53-7.58 (m, 2H).

h) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(thiophen-2-yl)-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-10)

1H NMR (200 MHz, CDC1₃): S 1.20-1.47 (m, 6H), 3.92 (s, 9H), 4.22-4.45 (m, 4H), 4.73 (bs, 2H), 5.71 (s, 2H), 6.69 (s, IH), 6.79 (s, IH), 7.04-7.34 (m, 3H), 7.38-7.55 (m, IH). i) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-hexyl-6-(thiophen-2-yl)-lH- indole-2-carboxylate (2-11)

2-11

1H NMR (200 MHz, CDCI₃): δ 0.85 (t, = 7Hz, 3H), 1.15-1.60 (m, 14H), 2.57 (t, = 7Hz, 2H), 4.17-4.48 (m, 4H), 4.97 (bs, 2H), 5.60 (s, 2H), 7.05-7.09 (m, IH), 7.11-7.18 (m, IH), 7.45-7.51 (m, IH), 7.63 (s, IH).

j) Ethyl 3-amino-6-(benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5- methyl- lH-indole-2-carboxylate (2-12)

1H NMR (200 MHz, CDC1₃): δ 1.29 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 2.19 (s 3H), 4.16-4.47 (m, 4H), 4.97 (bs, 2H), 5.59 (s, 2H), 6.05 (d, = 2Hz, 2H), 6.70-6.79 (m 2H), 6.94 (d, = 7Hz, 2H) 7.62 (s, IH).

k) Ethyl 3-amino-4-(benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5 methyl- lH-indole-2-carboxylate (2-13)

2-13

1H NMR (200 MHz, CDC1₃): δ 1.20-1.40 (m, 6H), 2.10 (s, 3H), 4.10-4.36 (m, 4H), 4.57 (bs, 2H), 5.56 (s, 2H), 6.08 (s, 2H), 6.71-6.78 (m, 2H), 6.91-6.99 (m, IH) 7.54 (s, IH).

1) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-14)

2-14

1H NMR (200 MHz, CDC1₃): S 1.29 (t, = 7Hz, 3H), 1.42 (t, = 7Hz, 3H), 2.20 (s, 3H), 3.87 (s, 6H), 3.92 (s, 3H), 4.15-4.50 (m, 4H), 4.98 (bs, 2H), 5.60 (s, 2H), 6.49 (s, 2H), 7.63 (s, IH).

m) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-4-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-15)

1H NMR (200 MHz, CDC1₃): S 1.29-1.42 (m, 6H), 2.14 (s, 3H), 3.86 (s, 6H), 3.95 (s, 3H), 4.24-4.36 (m, 4H), 4.58 (bs, 2H), 5.58 (s, 2H), 6.51 (s, 2H), 7.56 (s, IH).

n) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-16)

2-16

1H NMR (200 MHz, CDC1₃): δ 1.12 (t, = 7Hz, 3H), 1.35-1.48 (m, 6H), 2.51 (t, = 7Hz, 2H), 3.87 (s, 6H), 3.93 (s, 3H), 4.18-4.47 (m, 4H), 5.61 (s, 2H), 6.51 (s, 2H), 7.66 (s, 1H).

o) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-hexyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-20)

2-20

1H NMR (200 MHz, CDCI₃): S 0.83 (t, = 7Hz, 3H), 1.10-1.55 (m, 14H), 2.48 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.93 (s, 3H), 4.16-4.48 (m, 4H), 5.00 (bs, 2H), 5.60 (s, 2H), 6.50 (s, 2H), 7.64 (s, 1H).

p) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-21)

2-21

1H NMR (200 MHz, CDCI₃): S 0.85 (t, = 7Hz, 3H), 1.10-1.52 (m, 16H), 2.48 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.93 (s, 3H), 4.18-4.48 (m, 4H), 5.00 (bs, 2H), 5.60 (s, 2H), 6.50 (s, 2H), 7.64 (s, 1H).

q) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-octyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-23)

2-23

Yield: 55%. Melting point: 90.4°C.

1H NMR (200 MHz, CDC1₃): δ 0.83 (t, = 7Hz, 3H), 1.10-1.55 (m, 18H), 2.48 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.93 (s, 3H), 4.15-4.50 (m, 4H), 5.01 (bs, 2H), 5.61 (s, 2H), 6.50 (s, 2H), 7.73 (s, 1H). ¹³C NMR (50 MHz, CDC1₃): δ 13.95, 14.11, 14.36, 17.69, 22.38, 28.91, 31.46, 31.65, 33.13, 46.55, 46.82, 56.14 (2C), 60.42, 60.95, 61.48, 95.00, 106.62 (2C), 110.57, 117.03, 119.87, 124.28, 132.44, 133.44, 135.95, 136.14, 137.80, 147.22, 152.95 (2C), 162.43, 169.63.

r) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-24)

2-24

Yield: 39%. Melting point: 102.4 °C.

1H NMR (200 MHz, CDC1₃): δ 0.85 (t, = 7Hz, 3H), 1.10-1.55 (m, 20H), 2.48 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.92 (s, 3H), 4.15-4.50 (m, 4H), 5.01 (bs, 2H), 5.59 (s, 2H), 6.50 (s, 2H), 7.64 (s, 1H).

s) Ethyl 3-amino-7-cyano-5-decyl-l-(2-ethoxy-2-oxoethyl)-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-28)

2-28

1H NMR (200 MHz, CDC1₃): δ 0.87 (t, = 7Hz, 3H), 1.10-1.54 (m, 22H), 2.48 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.93 (s, 3H), 4.18-4.48 (m, 4H), 5.00 (bs, 2H), 5.60 (s, 2H), 6.50 (s, 2H), 7.64 (s, 1H). t) Ethyl 3-amino-7-cyano-5-decyl-l-(2-ethoxy-2-oxoethyl)-4-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-29)

2-29

1H NMR (200 MHz, CDC1₃): δ 0.87 (t, = 7Hz, 3H), 1.10-1.54 (m, 22H), 2.48 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.93 (s, 3H), 4.18-4.48 (m, 4H), 5.00 (bs, 2H), 5.60 (s, 2H), 6.50 (s, 2H), 7.64 (s, 1H).

u) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-30)

2-30

1H NMR (200 MHz, CDC1₃): δ 1.12-1.54 (m, 6H), 3.90 (s, 12H), 4.12-4.50 (m, 4H), 4.84 (bs, 2H), 5.69 (s, 2H), 6.79 (s, 2H), 6.87-7.14 (m, 3H), 7.32-7.68 (m, 2H).

v) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-methoxyphenyl)-5-methyl-lH- indole-2-carboxylate (2-31)

1H NMR (200 MHz, CDC1₃): δ 1.28 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 2.18 (s, 3H), 3.87 (s, 3H),4.16-4.48 (m, 4H), 4.96 (bs, 2H), 5.60 (s, 2H), 7.03 (d, J = 7Hz, 2H), 7.25 (d, = 7Hz, 2H), 7.62 (s, 1H).

w) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-5-methyl-lH- indole-2-carboxylate (2-32)

1H NMR (200 MHz, CDC1₃): S 1.32 (t, = 7Hz, 3H), 1.34 (t, = 7Hz, 3H), 2.09 (s, 3H), 3.90 (s, 3H),4.24-4.35 (m, 4H), 4.49 (bs, 2H), 5.57 (s, 2H), 7.06 (d, J = 7Hz, 2H), 7.24 (d, = 7Hz, 2H), 7.56 (s, 1H).

x) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-methoxyphenyl)-5-propyl-lH- indole-2-carboxylate (2-33)

2-33

1H NMR (200 MHz, CDC1₃): δ 0.79 (t, = 7Hz, 3H), 1.28 (t, = 7Hz, 3H), 1.33- 1.55 (m, 5H), 2.47 (t, J = 7Hz, 2H), 3.88 (s, 3H),4.16-4.48 (m, 4H), 5.59 (s, 2H), 7.02 (d, J = 7Hz, 2H), 7.24 (d, = 7Hz, 2H), 7.63 (s, 1H).

y) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-5-propyl-lH- indole-2-carboxylate (2-34)

2-34

1H NMR (200 MHz, CDC1₃): δ 0.80 (t, = 7Hz, 3H), 1.28-1.52 (m, 8H), 2.36 (t, = 7Hz, 2H), 3.91 (s, 3H),4.38-4.22 (m, 4H), 4.43 (bs, 2H), 5.57 (s, 2H), 7.06 (d, J = 7Hz, 2H), 7.25 (d, J = 7Hz, 2H), 7.57 (s, 1H).

z) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(4-methoxyphenyl)-lH- indole-2-carboxylate (2-35)

2-35

1H NMR (200 MHz, CDC1₃): S 0.85 (t, = 7Hz, 3H), 1.06-1.48 (m, 16H), 2.47 (t, = 7Hz, 2H), 3.87 (s, 3H), 4.17-4.46 (m, 4H), 5.00 (bs, 2H), 5.59 (s, 2H), 7.02 (d, = 7Hz, 2H), 7.24 (d, = 7Hz, 2H), 7.62 (s, 1H).

aa) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-6-phenyl-lH-indole-2- carboxylate (2-36)

2-36

1H NMR (200 MHz, CDC1₃): S 1.20-1.47 (m, 6H), 2.16 (s, 3H), 4.13-4.48 (m, 4H), 5.60 (s, 2H), 7..22-7.35 (m, 2H), 7.42-7.52 (m, 3H), 7.64 (s, 1H).

bb) Ethyl 3-amino-6-(2-chlorophenyl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-lH- indole-2-carboxylate (2-37)

2-37

1H NMR (200 MHz, CDCI3): S 1.28 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 2.12 (s, 3H), 4.15-4.48 (m, 4H), 5.58 (s, 2H), 7.23-7.32 (m, 1H), 7.35-7.45 (m, 2H), 7.48-7.59 (m, 1H), 7.67 (s, 1H).

cc) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-hydroxyphenyl)-5-methyl-lH- indole-2-carboxylate (2-38)

2-38 1H NMR (200 MHz, CDC1₃): S 1.20-1.48 (m, 6H), 2.16 (s, 3H), 4.15-4.48 (m, 4H), 4.97 (bs, 2H), 5.59 (s, 2H), 7.04 (d, = 7Hz, 2H), 7.25 (d, = 7Hz, 2H), 7.62 (s, 1H).

dd) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-fluorophenyl)-5-methyl-lH- indole-2-carboxylate (2-39)

1H NMR (200 MHz, CDCI₃): S 1.28 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 2.15 (s, 3H), 4.16-4.47 (m, 4H), 4.99 (bs, 2H), 5.59 (s, 2H), 7.11-7.34 (m, 4H), 7.64 (s, 1H).

ee) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-fluorophenyl)-5-methyl-lH- indole-2-carboxylate (2-40)

1H NMR (200 MHz, CDC1₃): δ 1.28-1.40 (m, 6H), 2.08 (s, 3H), 4.22-4.39 (m, 4H), 5.58 (s, 2H), 7.23-7.31 (m, 4H), 7.57 (s, 1H).

ff) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-nitrophenyl)-5-pentyl-lH- indole-2-carboxylate (2-41)

2-41

1H NMR (200 MHz, CDC1₃): S 0.88 (t, = 7Hz, 3H), 1.07-1.50 (m, 12H), 2.43 (t, = 7Hz, 2H), 4.17-4.48 (m, 4H), 5.59 (s, 2H), 7.54 (d, = 7Hz, 2H), 7.71 (s, 1H), 8.38 (d, = 7Hz, 2H).

gg) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-nitrophenyl)-5-pentyl-lH- indole-2-carboxylate (2-42)

1H NMR (200 MHz, CDC1₃): S 0.81 (t, = 7Hz, 3H), 1.05-1.50 (m, 12H), 2.33 (t, = 7Hz, 2H), 4.23-4.41 (m, 4H), 5.60 (s, 2H), 7.50-7.66 (m, 3H), 8.82 (d, = 7Hz, 2H).

hh) Ethyl 6-(4-(allyloxy)phenyl)-3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-lH- indole-2-carboxylate (2-43)

1H NMR (200 MHz, CDC1₃): S 1.28 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 2.17 (s, 3H), 4.16-4.46 (m, 4H), 4.55-4.64 (m, 2H), 4.97 (bs, 2H), 5.27-5.38 (m, 1H), 5.39-5.53 (m, 1H), 5.60 (s, 2H), 5.99-6.22 (m, 1H), 7.04 (d, = 7Hz, 2H), 7.24 (d, = 7Hz, 2H), 7.62 (s, 1H).

ii) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-6-(4-(prop-2-yn-l- yloxy)phenyl)-lH-indole-2-carboxylate (2-44)

1H NMR (200 MHz, CDCI3): S 1.28 (t, = 7Hz, 3H), 1.41 (t, = 7Hz, 3H), 2.17 (s, 3H), 2.57 (t, = 2Hz, 1H), 4.16-4.48 (m, 4H), 4.76 (d, J = 2Hz, 2H), 4.97 (bs, 2H), 5.60 (s, 2H), 7.10 (d, = 7Hz, 2H), 7.26 (d, = 7Hz, 2H), 7.62 (s, 1H).

jj) Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-4-(4-(prop-2-yn-l- yloxy)phenyl)-lH-indole-2-carboxylate (2-45)

1H NMR (200 MHz, CDC1₃): δ 1.2 '- 1.39 (m, 6H), 2.18 (s, 3H), 2.59 (t, = 2Hz, 1H), 4.20-4.39 (m, 4H), 4.79 (d, J = 2Hz, 2H), 5.56 (s, 2H), 7.15 (d, J = 7Hz, 2H), 7.26 (d, = 7Hz, 2H), 7.55 (s, 1H).

kk) Ethyl 3-amino-6-(4-((l-benzyl-lH-l,2,3-triazol-4-yl)methoxy)phenyl)-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-46)

1H NMR (200 MHz, CDC1₃): δ 0.78 (t, = 7Hz, 3H), 1.2-1.5 (m, 8H), 2.44 (t, = 7Hz, 2H), 4.16-4.47 (m, 4H), 5.25 (s, 2H), 5.56 (s, 4H), 6.99-7.10 (m, 2H), 7.15-7.24 (m, 2H), 7.28-7.34 (m, 2H), 7.35-7.42 (m, 3H), 7.57 (s, 1H), 7.63 (s, 1H).

11) Ethyl 3-amino-6-butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2- carboxylate (2-47)

1H NMR (200 MHz, CDC1₃): δ 0.90-1.08 (m, 6H), 1.23-1.46 (m, 6H), 1.47-1.76 (m, 6H), 2.66 (t, = 7Hz, 2H), 2.93 (t, = 7Hz, 2H), 4.18-4.46 (m, 4H), 5.57 (s, 2H), 7.53 (s, 1H).

mm) Ethyl 3-amino-4-butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2- carboxylate (2-48)

1H NMR (200 MHz, CDC1₃): δ 0.93-1.08 (m, 6H), 1.24-1.46 (m, 6H), 1.48-1.72 (m, 6H), 2.62 (t, = 7Hz, 2H), 3.00 (t, = 7Hz, 2H), 4.19-4.46 (m, 4H), 5.50 (s, 2H), 7.46 (s, 1H).

Example 5: Preparation of ethyl 7-cyano-3-(dibenzylamino)-l-(2-ethoxy-2-oxoethyl)-5- heptyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-22)

Potassium carbonate (143 mg, 1.035 mmol) was taken in a 50 mL two-neck RB flask and heated under vacuum to remove the traces of moisture and flushed with nitrogen. Ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5-trimethoxyphenyl)-lH-indole- 2-carboxylate (2-21) (200 mg, 0.345 mmol) was added under nitrogen followed by dry DMF (4 mL) and stirred for 10 min. Benzyl bromide (120 mg, 0.690 mmol) was added drop wise and the reaction mixture was stirred at RT for 8 h. It was then diluted with water (40 mL) and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to afford ethyl 7-cyano-3-(dibenzylamino)-l-(2- ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5-trimethoxyphenyl)- lH-indole-2-carboxylate (2-22) as yellow thick gum 195 mg (84.38 %).

¹H NMR (200 MHz, CDC1₃): δ 0.86 (t, = 7Hz, 3H), 1.10-1.52 (m, 16H), 2.42 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.92 (s, 3H), 4.20-4.43 (m, 8H), 5.63 (s, 2H), 6.49 (s, 2H), 7.22- 7.32 (m, 10H), 7.57 (s, 1H).

Example 6: Ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-3-(methylamino)-6- (thiophen-2-yl)-lH-indole-2-carboxylate (2-9)

A mixture of ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-6-(thiophen- 2-yl)-lH-indole-2-carboxylate (2-7) (100 mg, 0.25 mmol), dry potassium carbonate (100 mg, 0.73 mmol), methyl iodide (103 mg, 0.73 mmol) and dry acetone (10 ml) was refluxed for 6 h. Acetone was distilled off, reaction mixture was diluted with water and extracted with ethyl acetate. Concentration of organic layer and purification by column chromatography gave compound 2-9 (40 mg, 38%). The corresponding dimethylamino compound was obtained in impure form.

1H NMR (200 MHz, CDC1₃): δ 1.17-1.50 (m, 6H), 2.26 (s, 3H), 3.32 (s, 3H), 4.15-4.45 (m, 4H), 5.53 (s, 2H), 7.02-7.21 (m, 2H), 7.50 (s, 1H), 8.05 (s, 1H).

The following two compounds (2-17 and 2-18) were obtained by similar procedure by reacting compound 2-16 with methyl iodide.

a) Ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-3-(methylamino)-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-17)

2-17

1H NMR (200 MHz, CDC1₃): δ 1.09 (t, = 7Hz, 3H), 1.19-1.47 (m, 6H), 2.5 (q, = 7Hz, 2H), 3.34 (s, 3H), 3.85 (s, 6H), 3.91 (s, 3H), 4.14-4.43 (m, 4H), 5.52 (s, 2H), 6.50 (s, 2H), 8.07 (s, 1H).

b) Ethyl 7-cyano-3-(dimethylamino)-l-(2-ethoxy-2-oxoethyl)-5-ethyl-6-(3,4,5- trimethoxyphenyl)- lH-indole-2-carboxylate (2-18)

2-18

1H NMR (200 MHz, CDC1₃): δ 1.13 (t, / = 7Hz, 3H), 1.30 (t, / = 7Hz, 3H), 1.44 (t, = 7Hz, 3H), 2.54 (q, = 7Hz, 2H), 3.07 (s, 6H), 3.86 (s, 6H), 3.93 (s, 3H), 4.16-4.53 (m, 4H), 5.57 (s, 2H), 6.50 (s, 2H), 7.99 (s, 1H).

c) Ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-3-(methylamino)-5-nonyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-25)

2-25

This compound was prepared by procedure given for compound 2-9.

1H NMR (200 MHz, CDC1₃): δ 0.85 (t, = 7Hz, 3H), 1.10-1.50 (m, 20H), 2.47 (t, = 7Hz, 2H), 3.35 (s, 3H) 3.87 (s, 6H), 3.93 (s, 3H), 4.19-4.43 (m, 4H), 5.53 (s, 2H), 6.50 (s, 2H), 8.05 (s, 1H).

d) Ethyl 3-(allylamino)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6-(3,4,5- trimethoxyphenyl)- lH-indole-2-carboxylate (2-26)

2-26

This compound was prepared by procedure given for compound 2-9 using allyl bromide in place of methyl iodide. 1H NMR (200 MHz, CDC1₃): S 0.85 (t, = 7Hz, 3H), 1.10-1.50 (m, 20H), 2.46 (t, = 7Hz, 2H), 3.86 (s, 6H), 3.92 (s, 3H), 4.19-4.44 (m, 4H), 5.15-5.29 (m, 1H), 5.30-5.46 (m, 1H), 5.54 (s, 2H), 5.95-6.18 (m, 1H), 6.50 (s, 2H), 7.91 (s, 1H).

Example 7: Ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-3-formamido-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-19)

2-19

A mixture of compound 2-16 (500 mg, 0. 98 mmol), formic acid (903 mg, 19.6 mmol) and ammonium acetate (76 mg, 0.98 mmol) was stirred at 120 °C for 10 h. The reaction mixture was then cooled to room temperature, ice was added and stirred for 30 min and extracted with ethyl acetate. The organic layer was concentrated and purified by column chromatography to get compound 2-19 (256 mg, 49%).

1H NMR (200 MHz, CDCI₃): δ 1.12 (t, J = 7Hz, 3H), 1.31 (t, J = 7Hz, 3H), 1.44 (t, J = 7Hz, 3H), 1.56 (q, J = 7Hz, 2H), 3.87 (s, 6H), 3.93 (s, 3H), 4.20-4.55 (m, 4H), 5.68 (s, 2H), 6.51 (s, 2H), 8.29 (s, 1H), 8.49 (s, 1H), 9.14 (s, 1H).

a) Ethyl 7-cyano-l-(2-ethoxy-2-oxoethyl)-3-formamido-5-nonyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-27)

2-27

This compound was prepared by procedure given for compound 2-19.

1H NMR (200 MHz, CDC1₃): δ 0.82 (t, J = 7Hz, 3H), 0.95-1.90 (m, 20H), 2.52 (t, J = 7Hz, 2H), 3.86 (s, 6H), 3.93 (s, 3H), 4.19-4.54 (m, 4H), 5.67 (s, 2H), 6.50 (s, 2H), 8.26 (s, 1H), 8.48 (s, 1H), 9.93 (s, 1H).

Example 8: Preparation of compounds of formula (III):

A) Preparation of 4-(prop-2-yn-l-yloxy)benzaldehyde

Anhydrous K₂CO₃ (18.147 gm, 0.1315 mol) was taken in a two neck round bottom flask and dried under inert atmosphere. Then /?-hydroxybenzaldehyde (4 gm, 0.0263 mol) was added followed by the addition of dry DMF (40 ml). Propargyl bromide (3.52 ml, 0.0236 mol) was added drop by drop to the reaction mixture at room temperature with constant stirring. The reaction mixture was stirred at room temperature for 14 hours, diluted with water, extracted with ethyl acetate, washed with cold, dilute NaOH solution followed by water, dried over sodium sulphate and concentrated to obtain the desired product as buff- white solid (3.53 gm, 93.13%).

1H NMR (200 MHz, CDC1₃): δ 2.58 (t, J= 3Hz, 1H), 4.79 (d, J= 3Hz, 2H), 7.10 (d,

J= 8Hz, 2H), 7.87 (d, J= 8Hz, 2H), 9.91(s, 1H). ¹³C NMR (50 MHz, CDC1₃): δ 55.79, 75.89, 77.00, 114.54, 129.92, 131.33, 161.81, 190.31.

B) Preparation of 2-azidomethyl-4-iodoanisole

In two necked round bottom flask, 2-bromomethyl-4-iodoanisole (Chem Asian J. 6, 1546-1556, 2011) (327 mg, 1 mmol) was dissolved in dimethyl formamide (5 ml) and sodium azide (78 mg, 1.2 mmol) was added to it under argon. Reaction mixture was stirred at 80°C for 4 hr, water was added in reaction mixture and extracted with ethyl acetate (2 x 15 ml). Organic layer was dried over Na₂S0₄ and concentrated to obtain 2-azidomethyl-4- iodoanisole (231 mg, 80%).

C) Preparation of 4-((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4- yl)methoxy)benzaldehyde

3-1

In a 100 ml round bottom flask, 4-(prop-2-yn-l-yloxy)benzaldehyde (160 mg, 1 mmol 3 gm, 0.01872 mol ) and 2-azidomethyl-4-iodoanisole (289 mg, 1 mmol) were taken and dissolved in DMF and water (1:1, 2 ml). An aqueous solution of CuS0₄ (6 mg, in 0.2 ml water) was added followed by sodium ascorbate (40 mg)). The reaction mixture was subjected to microwave (360 W) for 2 min and then it was diluted with water, extracted with ethyl acetate, concentrated and purified by column chromatography to obtain compound 3-1 (125 mg, 25%).

The following compounds were prepared by procedure used for compound 3-1. b) l-(4-((l-(5-Iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)phenyl)ethan-l- one (3-2)

¹H NMR (200 MHz, CDCI₃): S 2.55 (s, 3H), 3.82 (s, 3H), 5.24 (s, 2H), 5.47 (s, 2H), 6.71 (d, = 7Hz, 1H), 7.04 (d, = 7Hz, 2H), 7.48 (s, 1H), 7.56-7.67 (m, 2H), 7.95 (d, = 7Hz, 2H).

c) 6-Ethyl-3-((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methyl)thieno[2,3- d]pyrimidin-4(3H)-one (3-3)

1H NMR (200 MHz, CDC1₃): S 1.34 (t, = 7Hz, 3H), 2.78-2.91 (m, 2H), 3.83 (s, 3H), 5.26 (s, 2H), 5.43 (s, 2H), 6.70 (d, J = 7Hz, 1H), 7.13 (s, 1H), 7.50 (s, 1H), 7.63 (d, J = 7Hz, 1H), 7.75 (s, 1H), 8.30 (s, 1H).

Example 9: Experimental Procedure for SRB Assay (for anticancer activity):

The cell lines were grown in RPMI 1640 medium containing 10% fetal bovine serum and 2 mM L-glutamine. For present screening experiment, cells were inoculated into 96 well microtiter plates in 90 μΐ_^ at 5000 cells per well. After cell inoculation, the microtiter plates were incubated at 37°C, 5%C02, 95% air and 100 % relative humidity for 24 h prior to addition of experimental drugs. Experimental drugs were solubilized in appropriate solvent to prepare stock of 10^" concentration. At the time of experiment four 10-fold serial dilutions were made using complete medium. Aliquots of 10 μΐ of these different drug dilutions were added to the appropriate micro-titer wells already containing 90 μΐ of medium, resulting in the required final drug concentrations.

After compound addition, plates were incubated at standard conditions for 48 hours and assay was terminated by the addition of cold TCA. Cells were fixed in situ by the gentle addition of 50 μΐ of cold 30 % (w/v) TCA (final concentration, 10 % TCA) and incubated for 60 minutes at 4°C. The supernatant was discarded; the plates were washed five times with tap water and air dried. Sulforhodamine B (SRB) solution (50 μΐ) at 0.4 % (w/v) in 1 % acetic acid was added to each of the wells, and plates were incubated for 20 minutes at room temperature. After staining, unbound dye was recovered and the residual dye was removed by washing five times with 1 % acetic acid. The plates were air dried. Bound stain was subsequently eluted with 10 mM trizma base, and the absorbance was read on an Elisa plate reader at a wavelength of 540 nm with 690 nm reference wavelength.

Percent growth was calculated on a plate -by-plate basis for test wells relative to control wells. Percent Growth was expressed as the ratio of average absorbance of the test well to the average absorbance of the control wells * 100. Using the six absorbance measurements [time zero (Tz), control growth (C), and test growth in the presence of drug at the four concentration levels (Ti)], the percentage growth was calculated at each of the drug concentration levels. The dose response parameters were calculated for each test article. Growth inhibition of 50 % (GI50) was calculated from [(Ti-Tz)/(C-Tz)] x 100 = 50, which is the drug concentration resulting in a 50% reduction in the net protein increase (as measured by SRB staining) in control cells during the drug incubation. The drug concentration resulting in total growth inhibition (TGI) was calculated from Ti = Tz. The LC50 (concentration of drug resulting in a 50% reduction in the measured protein at the end of the drug treatment as compared to that at the beginning) indicating a net loss of cells following treatment is calculated from [(Ti-Tz)/Tz] x 100 = -50.

Values were calculated for each of these three parameters if the level of activity was 5 reached; however, if the effect was not reached or was exceeded, the values for that parameter were expressed as greater or less than the maximum or minimum concentration tested. [Vanicha Vichai et al. Sulforhodamine B colorimetric assay for cytotoxicity screening Nature Protocols. 2006, 1, - 1112 - 1116, Skehn et al. New colorimetric cytotoxicity assay for anticancer drug screening J. Natl. Cancer Inst. 1990, 82, 1107]. The 10 results of the same are summarized in Table 2 and Table 3.

Table 2: Molar concentrations of compounds of present invention and adriamycin

Table 3: Concentration values calculated from graph in Figure 17

LC50 = Concentration of drug causing 50% cell kill

GI50 : = Concentration of drug causing 50% inhibition of cell growth

TGI = Concentration of drug causing total inhibition of cell growth

15 Example 10: Cell imaging studies:

Cell imaging analysis was carried out on all of the 22 compounds submitted. Of those, total 4 compounds were found to stain eukaryotic cells. Three cell lines were tested for cell staining viz; differentiated THP-1, MCF-7 and MDA-MB-231.

The ATCC numbers of the same are as follows:

Human breast cancer cell line MCF-7: ATCC- HTB-22

Human breast cancer cell line MDA-MB-231: ATCC- HTB-26

Human monocytic cell line THP-1: ATCC-TIB-202

(A) Preparation of compound solutions: - The compounds were dissolved in DMSO at the concentration of lmg/mL. These solutions were then used for cell imaging studies.

(B) Materials: - Fetal bovine serum (FBS), Dulbecco's modified Eagle's medium (DMEM), Minimum Essential Medium and RPMI 1640 were purchased from Gibco ThermoFisher Scientific.

(C) Cell culture: - Human breast cancer cell lines - MCF-7 and MDA-MB-231 and human monocytic cell line - THP-1 were obtained from National Centre for Cell Science (NCCS),

India. MCF-7 cells were maintained in MEM supplemented with 10% and MDA-MB-231 were maintained in DMEM supplemented with 10% FBS at 37°C in C02 incubator. These two adherent cell lines were passaged using trypsin-EDTA (Gibco) and sub-cultured at 1:3 ratio routinely. THP-1 were maintained in RPMI 1640 supplemented with 12% FBS and 0.15% NaHC03. This suspension cell line was passaged at 1:5 ratio routinely and stimulated with PMA (Sigma) for differentiation whenever required.

(D) Cell staining protocol: - Approximately 1 x 106 cells/mL were seeded in 96 well plates with ΙΟΟμΕ in each well. In order to use THP-1 (monocytes), which is a suspension cell line, for cell imaging studies, the cells were first differentiated into macrophages by using phorbol 12-myristate 13-acetate (PMA) at a final concentration of lOOnM. The cells were incubated with PMA for 24h at 37°C in C0₂ incubator and allowed to adhere to the well bottom surface. Upon differentiation, the cells gain adherent property and get attached to the well surface. The cells were allowed to attach and proliferate for 1 to 2 days. The culture medium was then removed gently from the wells and replaced with pre- warmed PBS (pH 7.2) containing the desired compound to be screened at different concentrations (3, 10, 30 and

The plate containing the cells and compounds was incubated for 20 minutes at 37°C in C0₂ incubator. The cells were then washed with pre-warmed PBS twice and replaced with 50μΕ PBS and viewed under fluorescent microscope (EVOS FL, Invitrogen) at 20X and 60X objective magnification. (E) Apoptosis / Necrosis staining protocol: - Annexin-V-FITC conjugate (Invitrogen) was used for the assay along with Propidium iodide. A modified protocol was followed for Annexin-V-FITC staining. Briefly, Annexin binding buffer was prepared (lOmM HEPES, 140mM NaCl and 2.5mM CaC12, pH 7.4). Propidium iodide stock of lmg/mL (w/v) was prepared in DMSO. To 100 μΙ_, of binding buffer, 5 μΙ_, (v/v) Annexin-V-FITC and lpL (v/v) Propidium iodide (lmg/mL) was added and mixed. Culture media was gently removed from wells containing cells and 100 μΙ_, of this binding buffer containing conjugate and PI was added to the well along with addition of the desired compound viz, COMPOUND 1-19. This was incubated at 37°C in C02 incubator for 15 minutes. After incubation, the cells were gently washed with pre-warmed PBS twice and replaced with 50μΕ PBS and then observed under the fluorescent microscope EVOS FL, Invitrogen) at 20X and 60X objective magnification. Appropriate controls and blanks were used in the staining study. When required, apoptosis was induced using known anti-cancer agents like Paclitaxel and Doxorubicin at their IC50 and IC90 concentrations on given cell lines.

(F) Results: Four compounds (compounds 1-7, 1-17, 1-18 and 1-19) were found to stain the cells. Of these, compounds 1-7, 1-17 and 1-18 were found to stain all the cells in contact. These compounds were found to specifically stain only the cytoplasm of the cells but not the nucleus. This was verified by using known counter stains like SYTO 9 (for nucleus) and Nile red (lipid molecules and cell membrane) Figures 7 to 11.

However, one compound viz. compound 1-19 was found to stain differently only some cells out of total cells. This differential staining was studied further using some known markers and inducers. In order to study the differential staining property of compound 1-19, the cells were seeded and apoptosis / cell death was induced using known anti-cancer, cytotoxic compounds namely Paclitaxel and Doxorubicin at their IC50 and IC90 concentrations. Known markers like Annexin- VFITC for apoptosis and Propidium iodide for dead cells were used along with the compound 1-19. Standard staining protocol for Apoptosis/Necrosis using Annexin- V-FITC/PI was carried out with addition of this new compound 1-19. Healthy cells were used as negative control. Interestingly, it was found, that the compound 1-19 staining (blue fluorescence) coincided with Annexin-V-FITC (green fluorescence). This shows a possible affinity of compound 1-19 to apoptotic / dead cells Figures 12 to 16. Advantages of invention:

1. Novel compounds of formula (I), (II), (III) are provided.

2. The compounds of the present invention possess excellent optical properties and can be used in the synthesis of indole and related compounds.

3. The compounds of formula (I) show fluorescence and are used in cell imaging applications.

4. The compounds of the present invention are used for the treatment of cancer.

5. The compounds of formula (I), (II), (III) are used for the treatment of cancer.

Claims

CLAIMS:

1. A compound of formula (I);

Formula (I)

wherein;

R and R¹ are selected independently from hydrogen, (un)substituted alkyl,

R and R¹ together may form a cyclic ring;

R is selected from (un) substituted 1,2,3-triazolyl, 1,2,4-triazolyl, mono, di or tri methoxy or halo substituted phenyl; (benzyl)triazolyl, thienyl, benzofuranyl; 4-((l-(5- iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4-yl)methoxy)phenyl;

R³, R⁴ is selected from hydrogen, alkyl, benzyl or allyl;

with the proviso that;

2 1

when R is thienyl, R is (un)substituted 4-oxothieno[2,3-d]pyrimidin-3(4H)-yl; and when R is mono, di or tri methoxy or halo substituted phenyl,

R¹ is not hydrogen and R and R¹ together may not form a cyclic ring;

or a pharmaceutically acceptable salt thereof.

The compound of formula (I) as claimed in claim 1, wherein said compound of formula (I) is selected from 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(4-oxo-6- propylthieno[3,2- ]pyrimidin-3(4H)-yl)-6-(thiophen-2-yl)isophthalonitrile (1-1), 2- amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-(6-hexyl-4-oxothieno[3,2-<i]pyrimidin- 3(4H)-yl)-6-(thiophen-2-yl)isophthalonitrile (1-2), 2-amino-4-( 1 -benzyl- 1H- 1 ,2,3- triazol-4-yl)-6-(thiophen-2-yl)-5-( 1H- 1 ,2,4-triazol- 1 -yl)isophthalonitrile (1-3), 2- amino-4-(benzofuran-2-yl)-6-( 1 -benzyl- 1H- 1,2,3 -triazol-4-yl)-5-(lH-imidazol-l- yl)isophthalonitrile (1-4), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6- ( 1H- 1 ,2,4-triazol- 1 -yl)-[ 1 , 1 '-biphenyl] -2,4-dicarbonitrile (1-5), 3-amino-5-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-4'-iluoro-6-( 1H- 1 ,2,4-triazol- 1-yl)- [ 1 , 1 '-biphenyl] -2,4- dicarbonitrile (1-6), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(4-oxo- 6-pentylthieno [2,3- ]pyrimidin-3(4H)-yl)-[l,r-biphenyl]-2,4-dicarbonitrile (1-7), 3- amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-6-(6-methyl-4-oxothieno[2,3- <i]pyrimidin-3(4H)-yl)-[l, -biphenyl]-2,4-dicarbonitrile (1-8), 3-amino-5-(l-benzyl- lH-l,2,3-triazol-4-yl)-2 4'-diiluoro-6-(lH-imidazol-l-yl)-[l,r-biphenyl]-2,4- dicarbonitrile (1-9), 3-amino-5-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-4'-fluoro-6-( 1H- imidazol-l-yl)-[l,r-biphenyl]-2,4-dicarbonitrile (1-10), 2-amino-4-(l-benzyl-lH-l,2,3- triazol-4-yl)isophthalonitrile (1-11), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- methylisophthalonitrile (1-12), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- ethylisophthalonitrile (1-13), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- propylisophthalonitrile (1-14), 2-amino-4-( 1 -benzyl- 1H- 1 ,2,3-triazol-4-yl)-5- butylisophthalonitrile (1-15), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- pentylisophthalonitrile (1-16), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- hexylisophthalonitrile (1-17), 3-amino-5-(l-benzyl-lH-l,2,3-triazol-4-yl)-2',4'-difluoro-

[l,r-biphenyl]-2,4-dicarbonitrile (1-18), 2-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5- (6-butyl-4-oxothieno[2,3-<i]pyrimidin-3(4H)-yl)isophthalonitrile (1-19), 5-(l-benzyl- 1H- 1 ,2,3-triazol-4-yl)-3 -(dimethylamino)-2',4'-difluoro-6-( 1H- 1 ,2,4-triazol- 1 -yl)-[ 1 , Γ- biphenyl]-2,4-dicarbonitrile (1-20), 5-(l-benzyl-lH-l,2,3-triazol-4-yl)-3- (dimethylamino)-4'-nuoro-6-(lH-l,2,4-triazol-l-yl)-[l, -biphenyl]-2,4-dicarbonitrile

(1-21), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-methylisophthalonitrile (1-22), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-ethylisophthalonitrile (1-23), 4-(l -benzyl- lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-propylisophthalonitrile (1-24), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-5-butyl-2-(dimethylamino)isophthalonitrile (1-25), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-pentylisophthalonitrile

(1-26), 4-(l-benzyl-lH-l,2,3-triazol-4-yl)-2-(dimethylamino)-5-hexylisophthalonitrile (1-27), 5-amino-7-(l-benzyl-lH-l,2,3-triazol-4-yl)-2,3-dihydro-lH-indene-4,6- dicarbonitrile (1-28), 2-amino-4-(l-benzyl-5-(hydroxymethyl)-lH-l,2,3-triazol-4-yl)-5- methylisophthalonitrile (1-29), 3-amino-3',4',5'-trimethoxy-6-pentyl-[l, -biphenyl]- 2,4-dicarbonitrile (1-30), 3-amino-6-hexyl-3',4',5'-trimethoxy-[l,l'-biphenyl]-2,4- dicarbonitrile (1-31), 3-amino-6-heptyl-3',4',5'-trimethoxy-[l,r-biphenyl]-2,4- dicarbonitrile (1-32), 3-amino-6-decyl-3',4',5'-trimethoxy-[l,r-biphenyl]-2,4- dicarbonitrile (1-33), 5'-amino-3,4,4",5-tetramethoxy-[l,r:3',l"-terphenyl]-4',6'- dicarbonitrile (1-34), 5'-amino-2,3",4",5"-tetramethoxy-[l,r:3',l"-terphenyl]-4',6'- dicarbonitrile (1-35), 3-amino-5-(furan-2-yl)-3',4',5'-trimethoxy-[l, -biphenyl]-2,4- dicarbonitrile (1-36), 3-amino-3',4',5'-trimethoxy-5-(thiophen-2-yl)-[l, -biphenyl]-

2,4-dicarbonitrile (1-37), 3-amino-6-heptyl-4'-methoxy-[l,l'-biphenyl]-2,4- dicarbonitrile (1-38), 3-amino-6-decyl-4'-methoxy-[l, -biphenyl]-2,4-dicarbonitrile (1-

3-amino-6-(6-butyl-4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)-4'-methoxy-[l, yl] -2,4-dicarbonitrile (1-40), 3-amino-4'-methoxy-6-(2-(4-oxo-6 pentylthieno[2,3-d]pyrimidin-3(4¾^ (1-41), 3-amino-3\5'-dimethoxy-6-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)- [l,l'-biphenyl]-2,4-dicarbonitrile (1-42), 3-amino-3',4',5'-trimethoxy-6-(2-(4-oxo-6- pentylthieno[2,3-d]pyrimidin-3(4¾^ (1-43), 2-amino-5-(2-(4-oxo-6-pentylthieno[2,3-d]pyrimidin-3(4H)-yl)ethyl)-4-(thiophen-2- yl)isophthalonitrile (1-44), 3-(dimethylamino)-6-heptyl-3',4',5'-trimethoxy-[l, - biphenyl]-2,4-dicarbonitrile (1-45), 3-(dibenzylamino)-6-heptyl-3',4',5'-trimethoxy- [l,l'-biphenyl]-2,4-dicarbonitrile (1-46), 3-(diallylamino)-6-heptyl-3',4',5'-trimethoxy- [l,l'-biphenyl]-2,4-dicarbonitrile (1-47), 6-decyl-3-(dibenzylamino)-3',4',5'-trimethoxy- [l,l'-biphenyl]-2,4-dicarbonitrile (1-48), 5'-(dibenzylamino)-2,3",4",5"-tetramethoxy- [l,r:3',l"-terphenyl]-4',6'-dicarbonitrile (1-49) or 3-amino-4'-((l-(5-iodo-2- methoxybenzyl)- 1H- 1 ,2,3-triazol-4-yl)methoxy)-6-methyl-[ 1 , 1 '-biphenyl] -2,4- dicarbonitrile (1-50).

3. The compound as claimed in claim 1, wherein said compound of formula (I) is fluorescent upon radiation.

4. The compound as claimed in claim 1, wherein said compound of formula (I) is used in cell imaging applications.

5. The compound as claimed in claim 1, wherein said compound of formula (I) is used for the treatment of cancer.

6. A novel substituted indole of formula II);

Formula (II)

wherein; R⁵ and R⁵ is selected from hydrogen, (un) substituted alkyl, benzyl, formyl, (un)substituted acetyl, (un)substituted allyl,

R 7 and R 8 is selected from hydrogen, (un)substituted alkyl, alkoxy, (un)substituted aryl, imidazolyl, thienyl, (un)substituted 1,2,3-triazolyl, 1,2,4-triazolyl;

or a pharmaceutically acceptable salt thereof.

7. The compound as claimed in claim 6, wherein said compound of formula (II) is selected from ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-4-(2,4- difluorophenyl)-l-(2-ethoxy-2-oxoethyl)-5-(lH-l,2,4-triazol-l-yl)-lH-indole-2- carboxylate (2-1), ethyl 3-amino-4-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-6-(2,4- difluorophenyl)-l-(2-ethoxy-2-oxoethyl)-5-(lH-l,2,4-triazol-l-yl)-lH-indole-2- carboxylate (2-2), ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-3), ethyl 3-amino-6-(l- benzyl-lH-l,2,3-triazol-4-yl)-5-butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-lH-indole-2- carboxylate (2-4), ethyl 3-amino-6-(l-benzyl-lH-l,2,3-triazol-4-yl)-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-hexyl-lH-indole-2-carboxylate (2-5), ethyl l-amino-5-(l-benzyl- lH-l,2,3-triazol-4-yl)-4-cyano-3-(2-ethoxy-2-oxoethyl)-6,7,8,9-tetrahydro-3H- benzo[e]indole-2-carboxylate (2-6), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5- methyl-6-(thiophen-2-yl)-lH-indole-2-carboxylate (2-7), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-methyl-4-(thiophen-2-yl)-lH-indole-2-carboxylate (2-8), ethyl 7- cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-3-(methylamino)-6-(thiophen-2-yl)-lH- indole-2-carboxylate (2-9), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4- (thiophen-2-yl)-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-10), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-hexyl-6-(thiophen-2-yl)-lH-indole-2- carboxylate (2-11), ethyl 3-amino-6-(benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-methyl-lH-indole-2-carboxylate (2-12), ethyl 3-amino-4- (benzo[d][l,3]dioxol-5-yl)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-lH-indole-2- carboxylate (2-13), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-6- (3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-14), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-methyl-4-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2- 15), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-ethyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-16), ethyl 7-cyano-l-(2-ethoxy-2- oxoethyl)-5-ethyl-3-(methylamino)-6-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-17), ethyl 7-cyano-3-(dimethylamino)-l-(2-ethoxy-2-oxoethyl)-5-ethyl- 6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-18), ethyl 7-cyano-l-(2- ethoxy-2-oxoethyl)-5-ethyl-3-formamido-6-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-19), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-hexyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-20), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2- 21), ethyl 7-cyano-3-(dibenzylamino)-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-22), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-5-octyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2- 23), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-24), ethyl 7-cyano-l-(2-ethoxy-2- oxoethyl)-3-(methylamino)-5-nonyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2- carboxylate (2-25), ethyl 3-(allylamino)-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-nonyl-6- (3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-26), ethyl 7-cyano-l-(2-ethoxy-

2- oxoethyl)-3-formamido-5-nonyl-6-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-27), ethyl 3-amino-7-cyano-5-decyl-l-(2-ethoxy-2-oxoethyl)-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-28), ethyl 3-amino-7-cyano-5-decyl-l- (2-ethoxy-2-oxoethyl)-4-(3,4,5-trimethoxyphenyl)-lH-indole-2-carboxylate (2-29), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-6-(3,4,5- trimethoxyphenyl)-lH-indole-2-carboxylate (2-30), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-6-(4-methoxyphenyl)-5-methyl-lH-indole-2-carboxylate (2-31), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-5-methyl-lH- indole-2-carboxylate (2-32), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4- methoxyphenyl)-5-propyl-lH-indole-2-carboxylate (2-33), ethyl 3-amino-7-cyano-l- (2-ethoxy-2-oxoethyl)-4-(4-methoxyphenyl)-5-propyl-lH-indole-2-carboxylate (2-34), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-heptyl-6-(4-methoxyphenyl)-lH- indole-2-carboxylate (2-35), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl- 6-phenyl-lH-indole-2-carboxylate (2-36), ethyl 3-amino-6-(2-chlorophenyl)-7-cyano- l-(2-ethoxy-2-oxoethyl)-5-methyl-lH-indole-2-carboxylate (2-37), ethyl 3-amino-7- cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-hydroxyphenyl)-5-methyl-lH-indole-2- carboxylate (2-38), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4- fluorophenyl)-5-methyl-lH-indole-2-carboxylate (2-39), ethyl 3-amino-7-cyano-l-(2- ethoxy-2-oxoethyl)-4-(4-fluorophenyl)-5-methyl- lH-indole-2-carboxylate (2-40), ethyl

3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-6-(4-nitrophenyl)-5-pentyl-lH-indole-2- carboxylate (2-41), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-4-(4-nitrophenyl)- 5-pentyl-lH-indole-2-carboxylate (2-42), ethyl 6-(4-(allyloxy)phenyl)-3-amino-7- cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-lH-indole-2-carboxylate (2-43), ethyl 3- amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-methyl-6-(4-(prop-2-yn-l-yloxy)phenyl)- lH-indole-2-carboxylate (2-44), ethyl 3-amino-7-cyano-l-(2-ethoxy-2-oxoethyl)-5- methyl-4-(4-(prop-2-yn-l-yloxy)phenyl)-lH-indole-2-carboxylate (2-45), ethyl 3- amino-6-(4-((l-benzyl-lH-l,2,3-triazol-4-yl)methoxy)phenyl)-7-cyano-l-(2-ethoxy-2- oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-46), ethyl 3-amino-6-butyl-7-cyano-l- (2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-47) or ethyl 3-amino-4- butyl-7-cyano-l-(2-ethoxy-2-oxoethyl)-5-propyl-lH-indole-2-carboxylate (2-48).

8. The compound as claimed in claim 6, wherein said compound of formula (II) is used for the treatment of cancer.

9. A compound of formula (III);

Formula (III)

wherein;

R is selected from (un) substituted 4-oxothieno[2,3-d]pyrimidin-3(4H)-yl,

4-formylphenoxymethyl or 4-acetylphenoxymethyl;

or a pharmaceutically acceptable salt thereof.

10. The compound as claimed in claim 9, wherein said compound of formula (III) is selected from 4-((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4- yl)methoxy)benzaldehyde (3-1), l-(4-((l-(5-iodo-2-methoxybenzyl)-lH-l,2,3-triazol-4- yl)methoxy)phenyl)ethan-l-one (3-2) or 6-ethyl-3-((l-(5-iodo-2-methoxybenzyl)-lH- l,2,3-triazol-4-yl)methyl)thieno[2,3-d]pyrimidin-4(3H)-one (3-3).

11. The compound as claimed in claim 9, wherein said compound of formula (III) is used for the treatment of cancer.

12. A pharmaceutical composition comprising a therapeutically effective amount of the compound as claimed in any of the preceding claims or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient, diluent and/or carrier.

13. A method for the treatment of cancer in a subject in need thereof.; comprising administering to the said subject a therapeutically effective amount of the compound as claimed in any of the preceding claims or a pharmaceutically acceptable salt thereof.

14. Use of compounds of formula (I) in cell imaging applications.

15. Use of compounds as claimed in any of the preceding claims for the treatment of cancer.