Novel compounds to treat viral infections

Abstract

The present invention relates to novel compounds of the general formula (I) having the potential to treat viral infections especially those related to the dengue virus, their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts, their polymorphs, pharmaceutical compositions containing them and methods for their preparation. The compounds of the present invention are useful in the treatment of the human or animal body, by regulation of viral replication. The compounds of this invention are therefore suitable for the treatment of virus-related disorders such as Dengue.

Description

[0001] NOVEL COMPOUNDS TO TREAT VIRAL INFECTIONS

[0002] FIELD OF INVENTION

[0003] The present invention relates to novel compounds of the general formula (I) having potential to treat viral infections especially related to dengue virus, their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts, their polymorphs, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation. formula (I)

[0004] BACKGROUND OF THE INVENTION

[0005] Dengue, caused by dengue virus (DENV), is one of the most important arthropod-borne human viral infections in many tropical and subtropical areas. With approximately 390 million infections occurring each year, DENV infection puts global population at high health risk. The DENV genome encodes three structural proteins - the capsid (C), membrane (M), and envelope (E) proteins - and seven nonstructural proteins, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. There are four distinct DENV serotypes: DENV-1, DENV-2, DENV-3, and DENV-4 with each capable of infecting person in his life time. Infection with one serotype may provide lifelong immunity against infection with a homologous DENV strain; however, only short-term immunity is maintained against heterologous infections. Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the life-threatening outcomes of DENV infection. Severe dengue may lead to the plasma leakage, hemorrhagic tendencies, organ failure, shock, and occasionally death. Dengvaxia, is the approved tetravalent live-attenuated dengue vaccine candidate but its usage has been allowed with strict restrictions and it offers high effectiveness in preventing dengue disease caused by DENV serotypes 1^1 and is safe in people who have had a past dengue infection, i.e., those who are seropositive.

[0006] US 10550123 describes viral replication inhibitors and process to prepare same. WO2021094563, WO2018215315, WO2018178238, WO2017046255, WO2017046258, WO2017167951, WO2016180696 and WO2016113371 describe substituted indole and indoline derivatives for the treatment of dengue disease. WO2019244047 describes N- substituted tetrahydrothienopyridine derivatives and use thereof. WO2018178240 describes substituted indoline derivatives as dengue viral replication inhibitors. W02017102014 describes propenamide thiophene derivatives as flavivirus inhibitors and their use.

[0007] Despite the worldwide spread and the long existence of the dengue disease, there is still no specific antiviral drugs for the treatment or prevention of dengue fever virus infection. Hence, there is a great unmet medical need for therapeutics for the prevention or treatment of viral infections in animals, especially for viral infections caused by Dengue virus. Compounds with good pan anti-viral potency for DENV 1-4, minimal side-effects, a low toxicity and good ADME profile are highly needed.

[0008] SUMMARY OF THE INVENTION

[0009] The present invention relates to novel compounds of the general formula (I) having the potential to treat viral infections especially those related to the dengue virus, their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts, their polymorphs, pharmaceutical compositions containing them and methods for their preparation. The compounds of the present invention are useful in the treatment of the human or animal body, by regulation of viral replication. The compounds of this invention are therefore suitable for the treatment of virus-related disorders such as Dengue.

[0010] EMBODIMENTS OF THE INVENTION

[0011] The main objective of the present invention is to provide novel compounds of general formula (I), their tautomeric forms, their stereoisomers, novel intermediates involved in their synthesis, their suitable pharmaceutically acceptable salts and their polymorphs. In an embodiment is provided a process for the preparation of novel compounds of general formula (I), their tautomeric forms, their stereoisomers, novel intermediates involved in their synthesis, their suitable pharmaceutically acceptable salts and their polymorphs.

[0012] In another embodiment is provided pharmaceutical compositions comprising compounds of general formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs having pharmaceutically acceptable carriers, solvents, diluents, binder, disintegrant, coating agent, filler, glidant, and / or other suitable excipients.

[0013] In a further another embodiment is provided the use of the novel compounds of the present invention for the treatment of virus-related disorders such as dengue, by administering a therapeutically effective & non-toxic amount of the compound of formula (I) or their pharmaceutically acceptable salts, or their pharmaceutically acceptable compositions.

[0014] In yet another embodiment is provided a method of treating virus-related disorders such as dengue using compound of formula (I) or their pharmaceutically acceptable salts, or their pharmaceutically acceptable compositions.

[0015] DESCRIPTION OF THE INVENTION

[0016] In the first embodiment, the present invention relates to compounds of the general formula (I), formula (I) Wherein,

[0017] X represents aryl, heteroaryl or heterocyclyl ring;

[0018] Ri represents hydrogen , halogen, haloalkyl, (Ci-Ce)alkyl, heterocyclyl, -ORfl; where (Ci- Ce)alkyl, heterocyclyl are independently unsubstituted or substituted with one or more suitable substituents;

[0019] Y represents carbocyclic ring or heterocyclic ring, which are independently unsubstituted or substituted with one or more suitable substituents selected from (Ci-Ce)alkyl, -ORe, halogen;

[0020] A and B represent carbocyclic or heterocyclic ring;

[0021] R2 and R3 represents hydrogen, hydroxy, cyano, halo, nitro, haloalkyl, (Ci-Ce)alkyl, (C2- Ce)alkenyl, (C2-Ce)alkynyl, (CrC cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heterocyclylalkyl, alkylsulfonyloxy, -CORe, -COORe, -ORe, -OSO2CH3, -OCORe, - S(O)PR6, -NR6R7, -CONR6R7, -N(R6)COR7, -N(R6)COOR7, -N(R6)CONR6R7, -SO2NR6R7, - N(Re)SO2R7; which are independently unsubstituted or substituted with one or more suitable substituents;

[0022] R4 is selected from hydrogen, (Ci-Ce)alkyl, (C3-Ce)cycloalkyl, haloalkyl and heterocyclyl, which are independently unsubstituted or substituted with one or more suitable substituents; R5 is selected from haloalkyl, (Ci-Ce)alkyl, (C3-Ce)cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heterocyclylalkyl, which are independently unsubstituted or substituted with one or more suitable substituents;

[0023] Re and R7are independently selected from hydrogen, unsubstituted or substituted (Ci- Ce)alkyl, (C3-Ce)cycloalkyl, haloalkyl; Re and R7together with the N atom to which they are attached may form a 5-8 membered heterocyclyl or heteroaryl ring;

[0024] In an embodiment, when any of the (Ci-Ce)alkyl, (C2-Ce)alkenyl, (C2-Ce)alkynyl, (C3- Ce)cycloalkyl are substituted; the suitable substitutions on them may be selected from hydrogen, hydroxy, cyano, halo, nitro, haloalkyl, oxo, (Ci-Ce)alkyl, (C3-Ce)cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heterocyclylalkyl, alkylsulfonyloxy, -CORe, -COORe, - OR6, -S(O)PR6, -NR6R7, -CONR6R7, -CON(R6)OR7, -CON(R6)SO2R7, -N(R6)COR7, - N(Re)COOR7, -N(Re)CONReR7, -SO2NReR7, -N(Re)SO2R7derivatives; Re and R7are same as described above; p represents integers from 0-2; 1 represents integers from 1-4; m represents integers from 1-5; n represents integers from 1 -4.

[0025] In the second embodiment, the present invention relates to compounds of the general formula (I- A); formula (I-A) or pharmaceutically acceptable salt thereof, wherein the groups R R2, R3, R4, R5, A and Y in formula (I-A) are as described in formula (I).

[0026] Further preferred embodiments are those disclosed below:

[0027] Preferred X may be selected from aryl;

[0028] Preferred Y may be selected from carbocyclic ring;

[0029] Preferred A and B may be selected from carbocyclic or heterocyclic ring;

[0030] Preferred R|. R2 and R3 may be selected from the hydrogen, cyano, halogen, (Ci-Ce)alkyl, haloalkyl, heterocyclyl and -ORe;

[0031] Preferred R4 may be selected from hydrogen and unsubstituted or substituted (Ci-Ce)alkyl;

[0032] Preferred R5 may be selected from unsubstituted or substituted (Ci-Ce)alkyl;

[0033] Preferred substitutions on (Ci-Ce)alkyl may be selected from hydroxy, -COORe, -ORe, - CONR6R7, -CON(R6)OR7and -CON(R6)SO2R7;

[0034] 1 represents integers from 1-4; m represents integers from 1-5; n represents integers from 1 -4.

[0035] In a further embodiment the groups, radicals described above may be selected from: the “alkyl” group used either alone or in combination with other radicals, denotes a linear or branched radical containing one to six carbons, selected from methyl, ethyl, n- propyl, z’so-propyl, / i-butyl, sec-butyl, tert-butyl, amyl, t-amyl, n- pentyl, / i-hexyl, and the like; the “alkenyl” group used either alone or in combination with other radicals, is selected from a radical containing from two to six carbons, more preferably groups selected from vinyl, allyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3- hexenyl, 4-hexenyl and the like; the “alkenyl” group includes dienes and trienes of straight and branched chains; the “alkynyl” group used either alone or in combination with other radicals, is selected from a linear or branched radical containing two to six carbon atoms, more preferably thienyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2- pentynyl, 3-pentynyl, 4-pentynyl, 1 -hexynyl, and the like. The term “alkynyl” includes di- and tri-ynes; the “cycloalkyl”, or “alicyclic” group used either alone or in combination with other radicals, is selected from a cyclic radical containing three to six carbons, more preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; the “haloalkyl” group is selected from an alkyl radical, as defined above, suitably substituted with one or more halogens; such as fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, mono or polyhalo substituted methyl, ethyl, propyl, butyl, pentyl or hexyl groups;

[0036] "halo" or "halogen" by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom; the “aryl” or “aromatic” group used either alone or in combination with other radicals, is selected from a suitable aromatic system containing one, two or three rings wherein such rings may be attached together in a pendant manner or may be fused, more preferably the groups are selected from phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl, and the like; the “carbocyclic” group used either alone or in combination with other radicals, is selected from groups as described in “cycloalkyl” or “aryl” or “aromatic”. the “heterocyclyl” or “heterocyclic” group used either alone or in combination with other radicals, is selected from suitable saturated, partially saturated or unsaturated aromatic or non-aromatic mono, bi or tricyclic radicals, containing one or more heteroatoms selected from nitrogen, sulfur and oxygen, more preferably selected from aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, 4- methylpiprrazinyl, 4-hydroxypiperidinyl, 2-oxopiperidinyl, 4-oxopiperidinyl, 2- oxopiperazinyl, 3-oxopiperazinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, 2-oxomorpholinyl, azepinyl, diazepinyl, oxapinyl, thiazepinyl, oxazolidinyl, thiazolidinyl, dihydrothiophene, dihydropyran, dihydrofuran, dihydrothiazole, benzopyranyl, benzopyranonyl, benzodihydrofuranyl, benzodihydrothienyl, pyrazolopyrimidonyl, azaquinazolinoyl, thienopyrimidonyl, quinazolonyl, pyrimidonyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl, benzothiazinonyl, thieno piperidinyl, and the like; In one embodiment, the heterocycle group, wherever applicable, may consists of appropriate number of carbon atoms and include from 1 -4 heteroatoms selected from the group consisting of N, O, and S(O)p, p = 0-2; the “heteroaryl” or “heteroaromatic” group used either alone or in combination with other radicals, is selected from suitable single or fused mono, bi or tricyclic aromatic heterocyclic radicals containing one or more hetero atoms selected from O, N or S, more preferably the groups are selected from pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, isothiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, benzofuranyl, benzothienyl, indolinyl, indolyl, azaindolyl, azaindolinyl, pyrazolopyrimidinyl, azaquinazolinyl, pyridofuranyl, pyridothienyl, thienopyrimidyl, quinolinyl, pyrimidinyl, pyrazolyl, quinazolinyl, pyridazinyl, triazinyl, benzimidazolyl, benzotriazolyl, phthalazynil, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl, benzoxazolyl, benzothiazolyl and the like; the “aralkyl” group used either alone or in combination with other radicals, is selected from groups containing an aryl radical, as defined above, attached directly to an alkyl radical, as define above, more preferably groups selected from benzyl, phenethyl, and the like; the “heterocyclylalkyl” group used either alone or in combination with other radicals, is selected from groups containing an heterocyclyl radical, as defined above, attached directly to an alkyl radical, as define above; the “alkylsulfonyloxy” group used either alone or in combination, refers to an alkylsulfonyl group attached directly to an oxygen atom, wherein a suitable alkyl group as defined above is attached to a sulfonyl radical; the “one or more suitable substituents” used either one or more suitable substituents substituted on single carbon or it may be substituted on more than one carbon; the term "substituted," as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. Substitution selected from hydrogen, deuterium, hydroxy, cyano, halo, nitro, haloalkyl, oxo, (Ci-Ce)alkyl, (CrQ cycloalkyl, aminoalkyl, alkoxyalkyl, alkenyl, alkynyl, aryl, heterocyclyl, heteroaryl, aralkyl, heterocyclylalkyl, alkylsulfonyloxy; the term “stereoisomers” used anywhere in the specification indicates that compounds of the present invention show (R) and (S) configuration; the term "polymorph" refers to the ability of the compound of the invention to exist in more than one form or crystal structure.

[0037] Suitable groups and substituents on the groups may be selected from those described anywhere in the specification.

[0038] Preferred compounds according to the present invention include but are not limited to:

[0039] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0040] (+) 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0041] (-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0042] 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0043] (+) 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid; (-) 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0044] 2-(4-chlorophenyl)-2-((3-(l-((2-hydroxyethoxy)imino)ethyl)-5-methoxyphenyl)amino)-l- (6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - 1 '-yl)ethan- 1 -one;

[0045] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]- r-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0046] (+) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0047] (-) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0048] 2-(((l-(3-((l-(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'- yl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0049] 2-(((3-((l-(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)- 2-oxoethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0050] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2-methylpropanoic acid;

[0051] (+) 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2-methylpropanoic acid;

[0052] (-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2-methylpropanoic acid;

[0053] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)-2-methylpropylidene)amino)oxy)-2- methylpropanoic acid;

[0054] 2-((((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)(cyclopropyl)methylene)amino)oxy)-2- methylpropanoic acid; 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)-2,2,2-trifluoroethylidene)amino)oxy)-2- methylpropanoic acid;

[0055] 2-((( 1 -(3-methoxy-5-((2-oxo- 1 -phenyl-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0056] 2-((( 1 -(3-(( 1 -(4-fluorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0057] 2-((( 1 -(3-(( 1 -(2,4-dichlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-r-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0058] 2-(((l-(3-((l-(5-chloropyridin-2-yl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0059] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-methoxyspiro[cyclopropane- 1 ,3'-indolin] - 1 '-yl)-2- oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0060] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-morpholinospiro[cyclopropane- 1 ,3'-indolin] - 1 '-yl)-2- oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0061] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)acetic acid;

[0062] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0063] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)butanoic acid;

[0064] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-3-methylbutanoic acid;

[0065] 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)cyclobutane- 1 - carboxylic acid; 4-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)butanoic acid;

[0066] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0067] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopentane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0068] 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0069] 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopentane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0070] 3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)ethyl)amino)-5-methoxybenzaldehyde O-(2-hydroxyethyl) oxime;

[0071] 2-(4-chlorophenyl)-2-((3-(l-(((l-hydroxy-2-methylpropan-2-yl)oxy)imino)ethyl)-5- methoxyphenyl)amino)- 1 -(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethan-l-one;

[0072] 3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)ethyl)amino)-5-methoxybenzaldehyde O-( 1 -hydroxy-2-methylpropan-2-yl) oxime;

[0073] 2-(4-chlorophenyl)-2-((3-(l-((2-hydroxy-2-methylpropoxy)imino)ethyl)-5- methoxyphenyl)amino)- 1 -(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethan-l-one;

[0074] 2-(4-chlorophenyl)-2-((3-(l-((3-hydroxypropoxy)imino)ethyl)-5-methoxyphenyl)amino)-l- (6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - 1 '-yl)ethan- 1 -one;

[0075] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0076] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0077] 2-((( 1 -(3-(( 1 -(4-chloro-2-(2-hydroxyethoxy)phenyl)-2-oxo-2-(6'- (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid; 3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0078] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0079] (+) 3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0080] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0081] (-) -3-((( 1 -(3-(( l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0082] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0083] 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-

[0084] 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0085] 2-((( 1 -(3-methoxy-5-(( l-(4-methoxyphenyl)-2-oxo-2-(6'-

[0086] ( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1' - yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0087] 2-((( 1 -(3-(( 1 -(4-cyanophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0088] 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;

[0089] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0090] (trifluoromethoxy)spiro[cyclopentane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0091] 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane- 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0092] 3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0093] (trifluoromethoxy)spiro[cyclopentane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid; 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3'- indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0094] (+) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3'- indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0095] (-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3'- indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0096] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3'- indolin]-l'-yl) ethyl) amino) -5-methoxybenzylidene) amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0097] (+) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3'- indolin]-l'-yl) ethyl) amino) -5-methoxybenzylidene) amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0098] (-) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3'- indolin]-l'-yl) ethyl) amino) -5-methoxybenzylidene) amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0099] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclobutane- 1,3'- indolin]-l'-yl) ethyl)amino)-5 -methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0100] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopentane- 1,3'- indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0101] 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0102] 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)propenamide; 3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0103] (trifluoromethoxy)spiro[cyclopentane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)propenamide;

[0104] 3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0105] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)propenamide;

[0106] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N-isopropyl-2- methylpropanamide ;

[0107] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl- 1 - morpholinopropan- 1 -one ;

[0108] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanamide; 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N-hydroxy-2- methylpropanamide ;

[0109] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanenitrile ;

[0110] 2-((3-(l-(((2-(lH-tetrazol-5-yl)propan-2-yl)oxy)imino)ethyl)-5-methoxyphenyl)amino)-2- (4-chlorophenyl)- 1 -(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethan- 1 - one;

[0111] 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-r-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanenitrile;

[0112] 2-((3-(l-((2-(lH-tetrazol-5-yl)ethoxy)imino)ethyl)-5-methoxyphenyl)amino)-2-(4- chlorophenyl)- 1 -(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - 1 '-yl)ethan- 1 -one;

[0113] 3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)ethyl)amino)-5-methoxybenzaldehyde O-methyl oxime;

[0114] 2-(4-chlorophenyl)-2-((3-methoxy-5-(l-(methoxyimino)ethyl)phenyl)amino)-l-(6'- (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethan-l-one; 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)acetic acid;

[0115] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)propanoic acid;

[0116] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)butanoic acid;

[0117] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0118] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin]- 1 yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)acetic acid;

[0119] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]- r-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)propanoic acid;

[0120] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]- r-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)butanoic acid;

[0121] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]- r-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-3-methylbutanoic acid;

[0122] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0123] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0124] 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)propanoic acid;

[0125] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0126] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)butanoic acid;

[0127] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0128] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-3-methylbutanoic acid;

[0129] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)propanamide; 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0130] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)propan amide;

[0131] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)butan amide;

[0132] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0133] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)butanamide;

[0134] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0135] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-3-methyl-N-(methylsulfonyl)butan amide;

[0136] 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(spiro[cyclopropane-l,3'-indolin]-r- yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0137] 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propan amide;

[0138] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0139] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propan amide;

[0140] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0141] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0142] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)propylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propanamide;

[0143] 2-(4-chloro-2-methoxyphenyl)-2-((3-(l-((2-hydroxy-2-methylpropoxy)imino)ethyl)-5- methoxyphenyl)amino)- 1 -(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethan-l-one;

[0144] 2-(4-chloro-2-methoxyphenyl)-2-((3-(l-(((l-hydroxy-2-methylpropan-2- yl)oxy)imino)ethyl)-5-methoxyphenyl)amino)-l-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '-yl)ethan- 1 -one; 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0145] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)acetamide ;

[0146] 4-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0147] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)butanoic acid;

[0148] 2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0149] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-r-yl)ethyl)amino)-5- methoxyphenyl)propylidene)amino)oxy)-2-methylpropanoic acid;

[0150] 2-(((3-methoxy-5-((2-oxo-l-phenyl-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]- 1 '-yl)ethyl)amino)benzylidene)amino)oxy)-2-methylpropanoic acid;

[0151] 2-(((3-methoxy-5-((l-(4-methoxyphenyl)-2-oxo-2-(6'-

[0152] ( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1' - yl)ethyl)amino)benzylidene)amino)oxy)-2-methylpropanoic acid;

[0153] 2-(((3-((l-(2,4-dichlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]- 1 '-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;

[0154] 2-((( 1 -(3-methoxy-5-((2-oxo- 1 -(tetrahydro-2H-pyran-4-yl)-2-(6'-

[0155] ( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1' - yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0156] 2-((( 1 -(3-(( 1 -(4-fluorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0157] 2-((( 1 -(3-methoxy-5-((2-oxo- 1 -phenyl-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0158] 2-((( 1 -(3-methoxy-5-(( l-(4-methoxyphenyl)-2-oxo-2-(6'-

[0159] ( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1' - yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propanamide; 2-((( 1 -(3-(( 1 -(4-cyanophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0160] 2-((( 1 -(3-(( 1 -(2,4-dichlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0161] 2-(((l-(3-((l-(5-chloropyridin-2-yl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0162] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethyl)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0163] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(5'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-r-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;

[0164] 2-(((l-(3-((l-(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'- yl)-2-oxoethyl)amino)-5-methoxyphenyl)-2,2,2-trifluoroethylidene)amino)oxy)-2- methylpropanoic acid;

[0165] 2-(((l-(3-((l-(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'- yl)-2-oxoethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2-methylpropanoic acid;

[0166] 2-((( 1 -(3-((2-(6'-chloro-7'-methoxyspiro[cyclopropane- 1 ,3'-indolin]- 1 ’-yl) - 1 -(4- chlorophenyl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;

[0167] 3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-(6'-methoxyspiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;

[0168] 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-methoxyspiro[cyclopropane- 1 ,3'-indolin] - 1 '-yl)-2- oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;

[0169] 2-((( 1 -(3-methoxy-5-(( l-(6-methoxypyridin-3-yl)-2-oxo-2-(6'-

[0170] ( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1' - yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid; 2-((( 1 -(3-methoxy-5-(( l-(6-methoxypyridin-3-yl)-2-oxo-2-(6'-

[0171] ( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - T - yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propanamide.

[0172] The novel compounds of this invention may be prepared using the reactions and techniques as shown in scheme below and described in this section. The reactions are performed in solvents appropriate to the reagents and materials employed and are suitable for the transformations being affected. It is understood by those skilled in the art that the nature and order of the synthetic steps presented may be varied for the purpose of optimizing the formation of the compounds of the present invention. It will also be well appreciated that one or more of the reactants may be protected and de -protected for facile synthesis by techniques known to persons skilled in the art. It will also be appreciated that one or more of the compounds of the present invention may exist in stereoisomeric and / or diastereomeric forms. Such stereoisomers and / or diastereoisomers as well as their optical antipodes are to be construed to be within the scope of the present invention. It will also be well appreciated that one or more of these compounds may be converted to their salts and other derivatives based on the specific groups present on the compounds, which can be well comprehended by persons skilled in the art. Such salts and / or other derivatives, as the case may be should also be construed to be within the scope of the present invention.

[0173] Scheme 1: Synthesis of compounds of general formula (I)

[0174] L = leaving group such as halogen

[0175] The compounds of the general formula (II) can be prepared using general techniques available in the literature to prepare spirocyclic compounds (J. Med. Chem. 2021, 64, 7, 3658-3676 and J. Med. Chem. 2012, 55, 7667-7685). Compounds of the general formula (HI) can be prepared by alpha halogenation of corresponding acetic acid derivatives using various techniques available in the literature. Compounds of the general formula (IV) can be obtained by coupling (II) with (III) using various amide bond formation techniques known in the art such as described in Tetrahedron 2005, 61, 10827 with appropriate modifications as necessary. The compounds of the general formula (I) can be obtained by reacting compounds of the formula (IV) with (V) in the presence of bases such as triethyl amine, diisopropyl ethyl amine etc, in solvents such as DMF, acetonitrile etc.

[0176] Scheme 2: Synthesis of compounds of general formula (I)

[0177] Alternatively, compounds of the formula (I) can be obtained by following scheme 2. The compounds of the general formula (VII) can be prepared by coupling compounds of the general formula (VI) and (V) by following a similar method as described in scheme 1 for coupling of compounds of formula (IV) and (V). Compounds of the general formula (VIII) can be obtained by deprotection using alkaline hydrolysis (PG = Me or Et) or debenzylation (PG = Bn) using hydrogenation in the presence of Pd-C. Compounds of the general formula (I) are then obtained by coupling (II) with (VIII) using various amide bond formation techniques known in the art such as described in Tetrahedron 2005, 61, 10827 with appropriate modifications as necessary. Scheme 3: Synthesis of intermediates of general formula (V)

[0178] L = leaving group such as halogen

[0179] Compounds of the general formula (V) can be prepared as shown in scheme 3. Compounds of the formula (X) can be prepared by treating (IX) with hydroxylamine hydrochloride in an alcoholic solvent. The compound of the general formula (XII) can be obtained by coupling (X) with compound (XI) using general nucleophilic displacement techniques available in the literature. Compounds of the formula (V) are prepared by using a reducing agent like stannous chloride in ethyl acetate or hydrogenation in the presence of Pd-C.

[0180] The invention is explained in greater detail by the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.

[0181] The ’ id NMR spectra were recorded on a Brucker Avance-400 spectrometer (400 MHz). The chemical shifts (5) are reported in parts per million (ppm) relative to Tetramethyl silane (TMS), in either CDCI3 or DMSO-<5?6 solution. Mass spectra (ESI-MS) were obtained on Shimadzu LC-MS 2010- A spectrometer.

[0182] List of Abbreviations min: Minute(s)

[0183] RT: Room temperature (25-30°C)

[0184] HMPA: Hexamethylphosphoramide

[0185] DMF: Dimethyl formamide

[0186] DCM: Dichloromethane hrs: Hour(s)

[0187] BBT,: Boron tribromide

[0188] DMAP: Dimethyl amino pyridine

[0189] EDC.HC1: N-(3-Dimethyl aminoprop yl)-N’ -ethyl carbodiimide hydrochloride NBS: N-Bromo succinamide

[0190] LiHMDS: Lithium bis(trimethylsilyl)amide

[0191] THF: Tetrahydrofuran

[0192] AIBN: Azobisisobutyronitrile

[0193] TMS-C1: Trimethylsilyl chloride

[0194] CCI4: Carbon tetrachloride

[0195] DIBAL-H: Diisobutylaluminium hydride

[0196] HATU: Hexafluorophosphate azabenzotriazole tetramethyl uronium

[0197] DIPEA: N,N-Diisopropylethylamine

[0198] Pd / C: Palladium on carbon

[0199] ACN: Acetonitrile

[0200] CDCI3: Deuterated chloroform

[0201] CS2CO3: Cesium carbonate

[0202] DIPEA: Disopropyl ethyl amine

[0203] DMSO: Dimethyl sulfoxide

[0204] DMSO-df,: Hexadeuterodimethyl sulfoxide

[0205] HC1: Hydrochloric acid

[0206] NaOH: Sodium hydroxide

[0207] TPP: Triphenyl phosphine

[0208] TFA: Trifluoro acetic acid

[0209] 'H NMR: Proton Nuclear Magnetic Resonance

[0210] J Coupling constant in units of Hz

[0211] Hz: Hertz

[0212] Preparation of intermediates of formula (II)

[0213] Preparation of 6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indoline] (II-l)

[0214] Step 1: Preparation of diethyl 2-(2-nitro-4-(trifluoromethoxy)phenyl)malonate

[0215] To a stirring solution of 1 -chloro-2-nitro-4-(trifluoromethoxy)benzene (50 g, 207 mmol) and diethyl malonate (37.90 ml, 101 mmol) in dry DMF (500 ml) was added cesium carbonate (101 g, 310 mmol) and the resulting mixture was stirred at 80°C for 3-4 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 366.03 (M+H)+.

[0216] Step 2: Preparation of 2-(2-nitro-4-(trifluoromethoxy)phenyl)acetic acid

[0217] To a stirring solution of the product obtained from step 1 (46.35 g, 127 mmol) in methanol (400 mL) was added 100 ml aqueous solution of sodium hydroxide (20.30 g, 508 mmol) and the resulting mixture was stirred at 80°C for 4 hrs. After the complete conversion of starting material, the reaction mixture was diluted with cold water and acidified with dilute HC1. The solid obtained was filtered and washed with water to get the title product. ESI-MS (m / z): 266.03 (M+H)+.

[0218] Step 3: Preparation of methyl 2-(2-nitro-4-(trifluoromethoxy)phenyl)acetate rj^%^^COOMe F3CO^^^NO2

[0219] To a stirring solution of the product obtained from step 2 (33 g, 124 mmol) in DCM (330 mL) was added 0.9 ml DMF at 0°C. Oxalyl chloride (6.31 ml, 73.5 mmol) was added dropwise over a period of 10 mins and the resulting mixture was stirred for 2 hrs at room temperature. The reaction mixture was cooled to 0°C and 100 mL of methanol was added drop wise and stirred for 2 hrs at room temperature. After complete conversion of starting material, the reaction mixture was diluted with cold water. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 280.05 (M+H)+. Step 4: Preparation of methyl l-(2-nitro-4-(trifluoromethoxy)phenyl)cyclopropane-l- carboxylate

[0220] To a stirring solution of the product obtained from step 3 (31 g, 111 mmol) and 1,2- dibromoethane (11.54 ml, 133 mmol) in dry DMF (310 ml) was added cesium carbonate (109 g, 333 mmol) and the resulting mixture was stirred at 120°C for 2 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. MS (m / z): 306.07 (M+H)+.

[0221] Step 5: Preparation of 6'-(trifhioromethoxy)spiro[cyclopropane-l,3'-indolin]-2'-one

[0222] To a stirring solution of the product obtained from step 4 (12.3 g, 40.3 mmol) in acetic acid (120 ml) was added iron powder (11.25 g, 202 mmol) and the resulting mixture was stirred at 100°C for 2 hrs. After the complete conversion of starting material, the reaction mixture was filtered through celite and washed with ethyl acetate. The organic layer was distilled out and diluted with cold water. The solid obtained was filtered, washed with water, dried and column purified to get the title product. ESLMS (m / z): 244.04 (M+H)+.

[0223] Step 6: Preparation of 6'-(trifhioromethoxy)spiro[cyclopropane-l,3'-indoline]

[0224] To a stirring suspension of lithium aluminum hydride (4.92 g, 130 mmol) in dry THF (180 ml) at 0°C, solution of the product obtained from step 5 (9 g, 37 mmol) in dry THF (90 ml) was added dropwise and the resulting mixture was stirred at 60°C for 2 hrs. After the complete conversion of the starting material, the reaction mixture was diluted with 10% aq. NaOH and stirred for 1 h at RT. The reaction mixture was filtered through celite. Filtrate was washed with water, evaporated under reduced pressure, dried and column purified to get the title product. ESI-MS (m / z): NMR (CDCI3): 6.56-6.52 (m, 2H), 6.50-6.47 (d, 1H), 3.93 (s, 1H), 3.65 (s, 2H), 1.04-0.93 (m, 4H). ESI-MS (m / z): 230.12 (M+H)+.

[0225] Preparation of 6'-methoxyspiro[cyclopropane-l,3'-indoline] (II-2)

[0226] Step 1: Preparation of 6-methoxyindolin-2-one

[0227] To a stirring solution of ethyl 2-(4-methoxy-2-nitrophenyl) acetate (5.8 g, 24.24 mmol) in acetic acid (50 ml) was added iron powder (6.77 g, 121 mmol) and the resulting mixture was stirred at 100°C for 2 hrs. After the complete conversion of the starting material, the reaction mixture was filtered through celite and washed with ethyl acetate. The obtained filtrate was distilled out, diluted with water and filtered. The solid obtained was filtered, washed with water, dried and column purified to get the title product. ESI-MS (m / z): 164.07 (M+H)+.

[0228] Step 2: Preparation of 6'-methoxyspiro[cyclopropane-l,3'-indolin]-2'-one

[0229] To a stirring solution of the product obtained from step 1 (2.5 g, 15.32 mmol) in dry THF (25 ml) was added N,N,N',N'-tetramethyl ethylenediamine (3.45 ml, 22.98 mmol) and n- butyllithium (18.39 ml, 46.0 mmol) dropwise at -78°C and stirred for 30 min. 1,2- dibromoethane was added dropwise at -78°C. Resulting mixture was stirred at room temperature for 2 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. Organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by columnchromatography to get the title product. ESI-MS (m / z): 190.08 (M+H)+.

[0230] Step 3: Preparation of 6'-methoxyspiro[cyclopropane-l,3'-indoline] To a stirring solution of the product obtained from step 2 (610 mg, 3.22 mmol) in dry toluene (10 ml) was added vitride (39.0 mg, 1.028 mmol) at 60°C and the resulting mixture was stirred at 60°C for 2 hrs. After completion of the reaction, the reaction mixture was diluted with sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column-chromatography to get the title product. ESI-MS (m / z): 176.09 (M+H)+.

[0231] Using appropriate starting materials and suitable modifications of the process described for the preparation of intermediate II-I and II-2, including suitable addition and / or deletion of steps as may be necessary, well within the scope of a person skilled in the art; the following intermediates (Table 1) were prepared in an analogues manner.

[0232] Table 1

[0233] Preparation of intermediates of formula (III)

[0234] Preparation of 2-bromo-2-(4-chlorophenyl)acetic acid (III-l) To a stirring solution of the 2-(4-chlorophenyl)acetic acid (10 g, 58.6 mmol) in dry CCI4 (100 ml) was added NBS (11.48 g, 64.5 mmol) followed by AIBN (0.48 g, 2.93 mmol) and the resulting mixture was refluxed for 12 hrs. After the complete conversion of the starting material, the reaction mixture was cooled at 0°C and the precipitated solid was filtered, filtrate was separated, washed with water and dried under reduced pressure to get the title product. ESI-MS (m / z): 248.96 (M-H).

[0235] Using appropriate starting materials and suitable modifications of the process described for the preparation of intermediates III-l, including suitable addition and / or deletion of steps as may be necessary, well within the scope of a person skilled in the art; the following intermediates (Table 2) were prepared in an analogues manner. Preparation of intermediates of formula (VI)

[0236] Preparation of methyl 2-bromo-2-(4-chlorophenyl)acetate (VI-1)

[0237] To a stirring solution of 2-bromo-2-(4-chlorophenyl)acetic acid (2.5 g, 10.02 mmol) in dry DCM (15 ml) was added oxalyl chloride (1.03 mL, 12.02 mmol) and the resulting mixture was stirred at RT for 1 hr. The reaction mixture was cooled to 0°C and methanol (0.64 mL, 20.04 mmol) was added to the reaction mixture and stirred for 4 hrs at RT. After the complete conversion of the starting material, the reaction mixture was diluted with cold water and the organic layer was separated. The organic layer was distilled out to get the title product. ESLMS (m / z): 263.03 (M+H)+.

[0238] Preparation of benzyl 2-bromo-2-(4-chloro-2-methoxyphenyl)acetate (VI-2)

[0239] Step 1: Preparation of benzyl 2-(4-chloro-2-methoxyphenyl)acetate

[0240] To a stirring solution of the 2-(4-chloro-2-methoxyphenyl)acetic acid (5 g, 24.95 mmol) and benzyl bromide (3.26 ml, 27.4 mmol) in acetone (50 ml) was added potassium carbonate (6.89 g, 49.8 mmol) and the resulting mixture was stirred at 60°C for 4 hrs. After completion of reaction, the reaction mixture was filtered. The organic layer was distilled out to get the crude product which was purified by column chromatography to get the title product. ESLMS (m / z): 291.06 (M+H)+.

[0241] Step 2: Preparation of benzyl 2-bromo-2-(4-chloro-2-methoxyphenyl)acetate

[0242] To a stirring solution of the product obtained from step 1 (3.6 g, 12.38 mmol) in dry THF (40 ml) was added LiHMDS in THF (27.5 ml, 27.5 mmol) dropwise at -78°C. To this was added TMS-C1 (2.2 g, 20.64 mmol) in dry THF (4 ml) at -78°C and the reaction mixture was stirred for 15 min. at the same temperature. NBS (3.67 g, 20.64 mmol) in dry THF (30 ml) was added dropwise at -78°C to the reaction mixture and stirred for 1 at -78°C. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was distilled out to get the crude product which was purified by column chromatography to get the title product.

[0243] Preparation of methyl 2-bromo-2-(4-chloro-2-methoxyphenyl)acetate (VI-3)

[0244] PXprepared using a similar process as described for step 2 of the intermediate VI-2 using methyl 2-(4-chloro-2-methoxyphenyl) acetate as starting material. ESI-MS (m / z): 292.95 (M+H)+.

[0245] Preparation of ethyl 2-bromo-2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4- chlorophenyl)acetate (VI-4)

[0246] Step 1: Preparation of ethyl 2-(4-chloro-2-hydroxyphenyl)acetate To a stirring solution of the ethyl 2-(4-chloro-2-methoxyphenyl)acetate (3.6 g, 15.74 mmol) in dry DCM (50 ml) was added BBn (31.5 mF, 31.5 mmol) at -30°C and the resulting mixture was stirred at room temperature for 2 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 215.05 (M+H)+.

[0247] Step 2: Preparation of ethyl 2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4- chlorophenyl)acetate

[0248] To a stirring solution of the product obtained from step 1 (2.6 g, 12.11 mmol) in dry DMF (30 ml) was added (2-bromoethoxy)(tert-butyl)dimethylsilane (4.5 gm, 18.17 mmol) followed by cesium carbonate (7.89 mg, 24.23 mmol) and the resulting mixture was stirred at RT for 12 hrs. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 373.10 (M+H)+.

[0249] Step 3: ethyl 2-bromo-2-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)acetate

[0250] To a stirring solution of the product obtained from step 2 (2.8 g, 7.5 mmol) in dry THF (20 ml) was added LiHMDS in THF (15 ml, 15.01 mmol) dropwise at -78°C. To this was added TMS-C1 (1.31 g, 12.01 mmol) in dry THF (4 ml) at -78°C and the reaction mixture was stirred for 15 min. at the same temperature. NBS (2.01 g, 11.24 mmol) in dry THF (10 ml) was added dropwise at -78°C to the reaction mixture and stirred for 1 at -78°C. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 451.05 (M+H)+.

[0251] Preparation of ethyl 2-bromo-2-(4-methoxyphenyl)acetate (VI-5)

[0252] Eto Br

[0253] To a stirring solution of ethyl 2-(4-methoxyphenyl) acetate (1.0 g, 5.15 mmol) in CCI4 (15 ml) was added Benzoyl peroxide (0.062 g, 0.257 mmol). To this was added NBS (1.833 g, 10.30 mmol) portion wise and the reaction mixture was stirred at 75-80°C for 3.0 h. After completion of reaction, the reaction mixture was cooled to 25 °C and the solid was filtered through celite pad and solid was washed by 2x10 ml CCI4. The filtrate was washed with 10 ml water and 10 ml brine solution and the organic layer was dried and evaporated to get title product.

[0254] Preparation of ethyl 2-bromo-2-(4-cyanophenyl)acetate (VI-6)

[0255] Prepared using similar process as described for VI-5 using ethyl 2-(4-cyanophenyl)acetate as starting material. ESI-MS (m / z): 265.97 (M-H).

[0256] Preparation of methyl 2-bromo-2-(6-methoxypyridin-3-yl)acetate (VI-7)

[0257] Prepared using similar process as described for VI-5 using methyl 2-(6-methoxypyridin-3- yl)acetate as starting material ESI-MS (m / z): 261.95 (M+H)+.

[0258] Preparation of intermediates of formula (IV)

[0259] Preparation of 2-bromo-2-(4-chlorophenyl)-l-(6'-(trifluoromethoxy)spiro

[0260] [cyclopropane- 1 ,3 ' -indolin] - 1 ' -yl)ethan- 1 -one (IV - 1 )

[0261] To a stirring solution of the intermediate (III-l) (1.796 g, 7.20 mmol) in dry DCM (20 ml) was added EDC.HC1 (1.380 g, 7.20 mmol) portion-wise at 0°C followed by DMAP (0.080 g, 0.654 mmol) and intermediate (II-l) (1.5 g, 6.54 mmol) and the resulting mixture was stirred at room temperature for 2 hrs. After the complete conversion of the starting material, the reaction mixture was diluted with cold water and the organic layer was separated. The organic layer was washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ’ H NMR (DMSO- e): 8.02 (s, 1H), 7.62- 7.59 (m, 2H). 7.58-7.58 (m, 2H) 7.05-7.04 (m, 1H), 7.03-6.93 (m, 1H), 6.15 (s, 1H), 4.47- 4.44 (m, 1H), 4.09-4.07 (m, 1H), 1.17-1.06 (m, 4H). ESI-MS (m / z): 461.95 (M+H)+.

[0262] Preparation of 2-bromo-2-(5-chloropyridin-2-yl)-l-(6'-

[0263] (trifluoromethoxy)spiro [cyclopropane- 1 ,3 ' -indolin] - 1 ' -yl)ethan- 1 -one (I V-2)

[0264] Step 1: Preparation of ethyl 2-(5-chloropyridin-2-yl)acetate

[0265] To a stirring solution of 2-bromo-5 -chloropyridine (2.50 g, 12.99 mmol) and diethyl malonate (4.56 ml, 29.9 mmol) in Dioxane (30 ml) was added CS2CO3 (13.97 g, 42.9 mmol). To this was added picolinic acid (0.720 g, 5.85 mmol) and copper(I) oxide (0.744 g, 5.20 mmol) at RT. Reaction mixture was heated to 135°C and stirred for 24 hrs. After completion of reaction, the reaction mixture was diluted with Ethyl acetate and cold water. Organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESI-MS (m / z): 200.04 (M+H)+.

[0266] Step 2: Preparation of sodium 2-(5-chloropyridin-2-yl)acetate

[0267] To a stirring solution of the product obtained from step-1 (0.500 g, 2.505 mmol) in methanol (1.00 ml) was added a solution of NaOH (0.150 g, 3.76 mmol) in water (5.00 ml) and stirred for 3 hrs at RT. After completion of the reaction, the reaction mixture was freeze-dried to get the title product.

[0268] Step 3: Preparation of 2-(5-chloropyridin-2-yl)-l-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '-yl)ethan- 1 -one

[0269] To a stirring solution of product obtained from step-2 (0.338 g, 1.745 mmol) in DCM (15 ml) was added EDC:HC1 (0.502 g, 2.62 mmol) at 0°C followed by II-l (0.200 g, 0.873 mmol) and DMAP (0.075 g, 0.611 mmol). The reaction was stirred at RT for 3 hrs. After completion of the reaction, the reaction mixture was diluted with cold water and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESI-MS (m / z): 383.07 (M+H)+.

[0270] Step 4: Preparation of 2-bromo-2-(5-chloropyridin-2-yl)-l-(6'- (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-T-yl)ethan-l-one To a stirring solution of product obtained from step-3 (100 mg, 0.261 mmol) in DCM (5.00 ml ) was charged NBS (46.5 mg, 0.261 mmol) portion wise at RT and stirred for 4 hrs. After completion of the reaction, the reaction mixture was diluted with cold water and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESI-MS (m / z): 462.98 (M+H)+.

[0271] Using appropriate starting materials and suitable modifications of the process described for the preparation of intermediate IV-1 and IV-2 including suitable addition and / or deletion of steps as may be necessary, well within the scope of a person skilled in the art; the following intermediates (Table 3) were prepared in an analogues manner.

[0272] Table- 3

[0273] Preparation of tert-butyl 2-(((l-(3-amino-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoate (V-l)

[0274] Step 1: Preparation of 3-methoxy-5-nitrobenzoic acid

[0275] To a stirring solution of the 3, 5 -dinitrobenzoic acid (20 g, 94 mmol) in dry HMPA (200 ml) was added lithium methanolate (14.32 g, 377 mmol) and the resulting mixture was stirred for 16 hrs at RT and then at 100°C for 8 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidified with dil. HC1 and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 196.06 (M-H).

[0276] Step 2: Preparation of 3-methoxy-5-nitrobenzoyl chloride

[0277] To a stirring solution of the product obtained from step 1 (2.4 g, 12.17 mmol) in dry DCM (20 ml) was added oxalyl chloride (1.3 ml, 18.26 mmol) and the resulting mixture was stirred for 2 hrs at RT. Excess solvent was distilled out to get the crude product which was directly used for the next step.

[0278] Step 3: Preparation of l-(3-methoxy-5-nitrophenyl)ethan-l-one

[0279] To a stirring solution of diethyl malonate (2.03 ml, 13.36 mmol) in toluene (30 ml) was added magnesium chloride (0.74 g, 7.79 mmol) followed by triethyl amine (0.72 ml, 27.8 mmol) and the reaction mixture was stirred at RT for Ih. To this, the product obtained from step 2 (2.4 g, 11.13 mmol) in toluene (12 mL) was added and the reaction mixture was stirred at RT for 12 hrs. After the complete conversion of the starting material, the reaction mixture was diluted with cold water and the organic layer was separated. The organic layer was distilled out to get the crude product which was dissolved in a mixture of DMSO (30 ml) and water (5 ml) and heated at 150°C for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, and precipitated solid was filtered and dried to get title product. ESI-MS (m / z): 196.02 (M+H)+.

[0280] Step 4: Preparation of l-(3-methoxy-5-nitrophenyl)ethan-l-one oxime

[0281] To a stirring solution of the product obtained from step 3 (700 mg, 3.59 mmol) in water (15 ml) was added sodium acetate (0.915 g, 16.38 mmol) followed by hydroxylamine hydrochloride (1.2 g, 17.93 mmol) and the resulting mixture was stirred at 100°C for 2 hrs. After the complete conversion of the starting material, the reaction mixture was cooled up to 10°C and the precipitated solid was filtered to get the title product. ESI-MS (m / z): 211.07 (M+H)+.

[0282] Step 5: Preparation of tert-butyl 2-(((l-(3-methoxy-5-nitrophenyl)ethylidene)amino)oxy)-2- methylpropanoate To a stirring solution of the product obtained from step 4 (2.5 g, 11.8 mmol) and tert-butyl 2-bromo-2-methylpropanoate (3.98 g, 17.8 mmol) in dry DMF (10 ml) was added potassium carbonate (2.96 g, 21.41 mmol) and the resulting mixture was stirred at 90°C for 4 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. Organic layer was separated, washed with water and evaporated under reduced pressure to get title product. ESI-MS (m / z): 353.15 (M+H)+.

[0283] Step 6: Preparation of tert-butyl 2-(((l -(3 -amino-5 -methoxyphenyl) ethylidene) amino) oxy) -2-methylpropanoate

[0284] To a stirring solution of the product obtained from step 5 (0.5 g, 1.542 mmol) in rectified spirit (10 ml) was added iron powder (2.046 g, 10.79 mmol) followed by ammonium chloride (2.046 g, 10.79 mmol) and the resulting mixture was stirred at 80°C for 4 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get the title product. NMR (DMSO-de): 6.44-6.43 (t, 1H), 6.35-6.34 (d, 1H), 6.18-6.17 (d, 1H), 5.17 (s, 2H), 3.65 (s, 3H), 2.10 (s, 3H), 1.44 (s, 6H), 1.37 (s, 9H). ESI-MS (m / z): 323.21 (M+H)+. ESI-MS (m / z): 323.21 (M+H)+.

[0285] Preparation of tert-butyl -2-(((3-amino-5-methoxybenzylidene)amino)oxy)-2- methylpropanoate (V-2)

[0286] Step 1: Preparation of methyl 3-methoxy-5-nitrobenzoate

[0287] To a stirring solution of the 3-methoxy-5-nitrobenzoic acid (10 g, 150.7 mmol) in dry DCM (100 mL) was added oxalyl chloride (11.12 ml, 152 mmol) portion-wise over 10 mins and the resulting mixture was stirred for 2 hrs at RT. The reaction mixture was cooled to 0°C and 15 mL of methanol was added dropwise and it was stirred for 2 hrs at RT. After the complete conversion of the starting material, the reaction mixture was diluted with cold water and the organic layer was separated. The organic layer was distilled out to get the title product.

[0288] Step 2: Preparation of 3-methoxy-5-nitrobenzaldehyde

[0289] To a stirring solution of obtained from step 1 (36 g, 170.1 mmol) in dry THF (300 ml) was added DIBAL-H in toluene (107 g, 188.2 mmol) dropwise at -78°C. The reaction mixture was stirred for 1 hr at the same temperature. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 182.06 (M+H)+.

[0290] Step 3: Preparation of 3-methoxy-5-nitrobenzaldehyde oxime

[0291] To a stirring solution of the product obtained from step 2 (0.5 g, 2.76 mmol) in water (5 ml) was added sodium acetate (1.83 g, 27.6 mmol) followed by hydroxylamine hydrochloride (0.959 g, 13.8 mmol) and the resulting mixture was stirred at 100°C for 2 hrs. After complete conversion of starting material, the reaction mixture was cooled up to 10°C and the precipitated solid was filtered to get the title product. ESI-MS (m / z): 197.05 (M+H)+.

[0292] Step 4: Preparation of tert-butyl -2-(((3-methoxy-5-nitrobenzylidene)amino)oxy)-2- methylpropanoate To a stirring solution of the product obtained from step 3 (15 g, 76 mmol) and tert-butyl 2- bromo-2-methylpropanoate (21.4 ml, 115 mmol) in dry DMF (100 ml) was added potassium carbonate (19.02 g, 138 mmol) and the resulting mixture was stirred at 90°C for 4 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product.

[0293] Step 5: Preparation of tert-butyl -2-(((3-amino-5-methoxybenzylidene)amino)oxy)-2- methylpropanoate

[0294] To a stirring solution of the product obtained from step 4 (9 g, 26.6 mmol) in rectified spirit (100 ml) was added iron powder (8.91 g, 160 mmol) followed by ammonium chloride (8.54 g, 160 mmol) and the resulting mixture was stirred at 80°C for 4 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get the title product.1H NMR (CDC13): 7.97 (s, 1H), 6.55-6.52 (m, 2H), 6.27-6.26 (t, 1H), 3.75 (s, 3H), 3.73(s, 2H), 1.58 (s, 6H), 1.52 (s, 9H). ESI-MS (m / z): 309.1 (M+H)+.

[0295] Preparation of l-(3-amino-5-methoxyphenyl)ethane-l-one O-(2-hydroxyethyl) oxime (V-3)

[0296] Step 1: Preparation of l-(3-methoxy-5-nitrophenyl)ethan-l-one O-(2-hydroxyethyl) oxime

[0297] To a stirring solution of l-(3-methoxy-5-nitrophenyl)ethan-l-one oxime (1.0 g, 4.76 mmol) and 2-bromoethan-l-ol (0.4 ml, 5.71 mmol) in dry DMF (10 ml) was added cesium carbonate (3.88 g, 11.82 mmol) and the resulting mixture was stirred at 90°C for 4 hrs. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get the title product. ESI-MS (m / z): 255.09 (M+H)+.

[0298] Step 2: Preparation of l-(3-amino-5-methoxyphenyl)ethan-l-one O-(2-hydroxyethyl) oxime

[0299] To a stirring solution of the product obtained from step 1 (1 g, 3.93 mmol) in ethyl acetate (20 ml) was added stannous chloride (4.46 g, 19.67 mmol) and the resulting mixture was stirred at 60°C for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with aqueous ammonia and the organic layer was decanted. The organic layer was dried and distilled out to get the title product ’ H NMR (DMSO-7e): 6.49-6.48 (t, J=1.6 Hz, 1H), 6.35-6.34 (t, 7=1.6 Hz, 1H), 6.18-6.17 (t, 7=2 Hz, 1H), 5.18 (s, 2H), 4.69-4.67 (t, 7=5.6 Hz, 1H), 4.12-4.09 (t, 7=5.2 Hz, 2H), 3.68 (s, 3H), 3.66-3.62 (q, 7=5.5 Hz, 2H), 2.11 (s, 3H). ESI-MS (m / z): 225.2 (M+H)+. Using appropriate starting materials and suitable modifications of the process described for the preparation of intermediates V-l to V-3 including suitable addition and / or deletion of steps as may be necessary, well within the scope of a person skilled in the art; the following intermediates (Table 4) were prepared in an analogues manner.

[0300] Table- 4

[0301]

[0302] Preparation of ethyl 3-(((l-(3-amino-5-methoxyphenyl)ethylidene)amino)oxy) propanoate (V-25) Step 1: Preparation of ethyl 3-(((l-(3-methoxy-5-nitrophenyl) ethylidene) amino)oxy) propanoate

[0303] To a stirring solution of l-(3-methoxy-5-nitrophenyl)ethan-l-one oxime (30 g, 143 mmol) and ethyl acrylate (15.46 ml, 143 mmol) in dry ACN (300 ml) was added TPP (7.49 g, 28.5 mmol) and the resulting mixture was stirred at 100°C for 45 hrs. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 311.7 (M+H)+.

[0304] Step 2: Preparation of ethyl 3-(((l -(3 -amino-5 -methoxyphenyl) ethylidene) amino) oxy) propanoate

[0305] To a stirring solution of the product obtained from step 1 (12.0 g, 38.7 mmol) in ethyl acetate (120 ml) was added stannous chloride (36.7 g, 193 mmol) and the resulting mixture was stirred at 60°C for 4 hrs. After completion of the reaction, the reaction mixture was diluted with aq. ammonia and the organic layer was decanted. The organic layer was dried and distilled out to get the title product. ’ H NMR (DMSO-7e): 6.48-6.47 (t, 7=1.6 Hz, 1H), 6.35-6.34 (t, 7=1.6 Hz, 1H), 6.19-6.18 (t, 7=1.6 Hz, 1H), 5.19 (s, 2H), 4.33-4.30 (t, 7=6 Hz, 2H), 4.11-4.06 (q, 7=7.2 Hz, 2H), 3.72 (s, 3H), 2.70-2.67 (t, 7=6 Hz, 2H), 2.08 (s, 3H), 1.20- 1.16 (t, 7=6.8 Hz, 3H). ESI-MS (m / z): 281.15 (M+H)+.

[0306] Preparation of 3-(((l -(3-amino-5-methoxyphenyl)ethylidene)amino)oxy)propanenitrile (V-26)

[0307] Prepared using a similar process as described for V-25 by using acrylonitrile instead of ethyl acrylate. ESI-MS (m / z): 234.14 (M+H)+. Preparation of 2-(((l-(3-amino-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanenitrile (V-27)

[0308] Prepared using a similar process as described for V-3 by using 2-bromo-2- methylpropanenitrile instead of 2-bromoethanol. ESLMS (m / z): 248.40 (M+H)+.

[0309] Preparation of compounds

[0310] EXAMPLE 1

[0311] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid

[0312] Step 1: Preparation of tert-butyl 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoate

[0313] To a stirring solution of intermediate IV-1 (300 mg, 0.651 mmol) in DMF (5 ml) was added intermediate V-l (230 mg, 0.781 mmol) followed by triethylamine (0.13 ml, 0.977 mmol) and the resulting mixture was stirred at 80°C for 14 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESI-MS (m / z): 702.20 (M+H)+.

[0314] Step 2: Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1 ,3 ' -indolin] - 1 ' -yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid

[0315] To a stirring solution of the product obtained from step-1 (15 g, 21.36 mmol) in DCM (150 mL) was added TFA (11.52 mL, 150 mmol) and the resulting mixture was stirred at RT for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ’ H NMR (DMSO-de): 8.03 (s, 1H), 7.56-7.54 (d, 2H), 7.45-7.43 (d, 2H), 7.00-6.98 (m, 1H), 6.92-6.90 (m, 1H), 6.63-6.61 (m, 2H), 6.39 (s, 1H), 6.32 (s, 1H), 5.50-5.48 (m, 1H), 4.56-4.54 (m, 1H), 4.08-4.05 (m, 1H), 3.65 (s, 3H), 2.08 (s, 3H), 1.42-1.41 (d, 6H), 1.12-1.04 (m, 4H). ESI-MS (m / z): 646.5 (M+H)+.

[0316] EXAMPLE 2

[0317] Preparation of (+) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid

[0318] Enantiomer of example 1 was separated by preparative HPLC (YMC-Choral Amylose-C (250X4.6 mm) 5.0u)’ 0.1%TFA in Methanol-Hexane (20.20), Wavelength-220nm). (t=20.20 min; ee=93.20%). ’ H NMR (DMSO-d6): 8.03 (s, 1H), 7.56-7.54 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (m, 1H), 6.93-6.92 (m, 1H), 6.65-6.61 (m, 1H), 6.39 (s, 1H), 6.32 (s, 1H), 5.51- 5.49 (m, 1H), 4.56-4.54 (m, 1H), 4.07-4.05 (m, 1H), 3.65 (s, 3H), 2.09 (s, 3H), 1.44-1.13 (d, 6H), 1.15-1.08 (m, 4H). ESI-MS (m / z): 646.30 (M+H)+.

[0319] EXAMPLE 3

[0320] Preparation of (-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid

[0321] Enantiomer of example 1 was separated by preparative HPLC (YMC-Choral Amylose-C (250X4.6 mm) 5.0u)’ 0.1%TFA in Methanol-Hexane (8.764), Wavelength-220nm). (t=8.764 min; ee=95.74%). ’ H NMR (DMSO-d6): 8.03 (s, 1H), 7.55-7.54 (d, 2H). 7.45-7.44 (d, 2H) 7.01-6.99 (m, 1H), 6.93-6.91 (m, 1H), 6.66-6.64 (m, 1H), 6.39 (s, 1H), 6.32 (s, 1H), 5.50- 5.48 (m, 1H), 4.56-4.54 (m, 1H), 4.07-4.05 (m, 1H), 3.65 (s, 3H), 2.09 (s, 3H), 1.44-1.42 (s, 6H), 1.14-1.06 (m, 4H). ESI-MS (m / z): 646.30 (M+H)+.

[0322] EXAMPLE 4

[0323] Preparation of 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoic acid

[0324] Step 1: Preparation of ethyl 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoate.

[0325] To a stirring solution of intermediate IV-1 (300 mg, 0.651 mmol) in DMF (5 ml) was added intermediate V-25 (230 mg, 0.781 mmol) followed by triethylamine (0.13 ml, 0.977 mmol) and the resulting mixture was stirred at 80°C for 3 hrs. After completion of the reaction, the reaction mixture was diluted with cold water and extracted with ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product. ESLMS (m / z): 660.12 (M+H)+.

[0326] Step 2: Preparation of 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoic acid

[0327] To a stirring solution of the product obtained from step 1 (100 mg, 0.155 mmol) in 50% methanol :THF (5 mL) was added 4 ml aqueous solution of sodium hydroxide (18.57 mg, 0.46 mmol) and the resulting mixture was stirred at RT for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidified with aqueous HC1 and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. NMR (DMSO-de): 8.03 (s, 1H), 7.57-7.55 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (m, 1H), 6.93-6.91 (d, 1H), 6.64-6.62 (d, 1H), 6.45-6.43 (m, 1H), 6.33 (m, 1H), 5.52 (s, 1H), 4.58-4.55 (d, 1H), 4.27 (t, 2H), 4.13-4.07 (d, 1H), 3.67 (s, 3H), 2.58 (t, 2H), 2.05 (s, 3H), 1.17-1.07 (m, 4H). ESLMS (m / z): 632.2 (M+H)+.

[0328] EXAMPLE 5 Preparation of (+) 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoic acid

[0329] Enantiomer of example 4 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 0.1%TFA in 2-Propanol:0.1%TFA in Hexane, Isocratic Elution (40:60), Wavelength-2 lOnm). (t=12.990 min; ee=100%). ’ H NMR (DMSO-d6): 8.03 (s, 1H), 7.57-7.55 (m, 2H), 7.46-7.44 (m, 2H), 6.99-6.98 (m, 1H), 6.93-6.91 (d, 1H), 6.64 (s, 1H), 6.43-6.42 (m, 1H), 6.33-6.32 (m, 1H), 5.52 (s, 1H), 4.58-4.55 (d, 1H), 4.27 (t, 2H), 4.10-4.07 (d, 1H), 3.67 (s, 3H), 2.58 (t, 2H), 2.05 (s, 3H), 1.15-1.07 (m, 4H). ESI-MS (m / z): 632.22 (M+H)+.

[0330] EXAMPLE 6

[0331] Preparation of (-) 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoic acid

[0332] Enantiomer of example 4 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 0.1%TFA in 2-Propanol:0.1%TFA in Hexane, Isocratic Elution (40:60), Wavelength-2 lOnm). (t=9.347 min; ee=100%). ’H NMR (DMSO-d6): 8.03 (s, 1H), 7.57-7.55 (m, 2H), 7.46-7.44 (m, 2H), 7.01-6.98 (m, 1H), 6.93-6.91 (d, 1H), 6.64 (s, 1H), 6.43-6.42 (m, 1H), 6.33 (m, 1H), 5.52 (s, 1H), 4.58-4.55 (d, 1H), 4.27 (t, 2H), 4.10- 4.07 (d, 1H), 3.67 (s, 3H), 2.58 (t, 2H), 2.05 (s, 3H), 1.15-1.07 (m, 4H). ESI-MS (m / z): 632.21 (M+H)+. EXAMPLE 7

[0333] Preparation of 2-(4-chlorophenyl)-2-((3-(l-((2-hydroxyethoxy) imino) ethyl)-5- methoxyphenyl) amino)-l-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'- yl)ethan-l-one

[0334] To a stirring solution of intermediate IV-1 (400 mg, 0.89 mmol) in DMF (5 ml) was added intermediate V-3 (200 mg, 0.89 mmol) followed by triethylamine (0.14 ml, 1.07 mmol) and the resulting mixture was stirred at 80°C for 3 hrs. After completion of the reaction, the reaction mixture was diluted with cold water and extracted with ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get the title product.1H NMR (DMSO-d6): 8.03 (s, 1H), 7.58-7.56 (d, 2H), 7.46-7.44 (d, 2H), 6.96- 6.92 (m, 2H), 6.72 (br, 1H), 6.64 (s, 1H), 6.43 (s, 1H), 6.32 (s, 1H), 5.52 (s, 1H), 4.64-4.58 (d, 1H), 4.10-4.07 (m, 3H), 3.84 (s, 3H), 3.74-3.60 (m, 2H), 2.09 (s, 3H), 1.24-1.09 (m, 4H). ESLMS (m / z): 604.2 (M+H)+.

[0335] Using appropriate starting materials and suitable modifications of the process described for the preparation of Examples 1-7 including suitable addition and / or deletion of steps as may be necessary, well within the scope of a person skilled in the art; the following compounds were prepared in an analogues manner.

[0336] EXAMPLE 8

[0337] Preparation of 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino) -5-methoxy benzylidene) amino) oxy)-2-methyl propanoic acid

[0338] prepared using intermediat 12.53 (br, 1H), 8.02 (s, 2H), 7.56-7.54 (d, 2H), 7.46-7.44 (d, 2H), 7.01-7.07 (d, 1H), 6.99-6.93 (t, 1H), 6.63 (s, 1H), 6.38 -6.33 (d, 2H), 5.49 (s, 1H), 4.56-4.53 (d, 1H), 4.07-4.04 (d, 1H), 3.66 (s, 3H), 1.44-1.43 (s, 6H), 1.17-1.07 (m, 4H). ESI-MS (m / z): 632.15 (M+H)+.

[0339] EXAMPLE 9

[0340] Preparation of (+) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino) -5-methoxy benzylidene) amino) oxy)-2-methyl propanoic acid

[0341] Enantiomer of example 8 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 2-Propanol-Hexane, Isocratic Elution (40:60), Wavelength- 210nm). (t=21.069 min; ee=97.15%). ’ H NMR (DMSO-d6): H-55 (br, 1H), 8.02 (s, 2H), 7.55-7.54 (d, 2H), 7.46-7.44 (d, 2H), 7.43-7.42 (d, 1H), 7.01-7.07 (d, 1H), 6.99-6.93 (t, 1H), 6.62 (s, 1H), 6.40 (d, 1H), 6.38 (d, 1H), 5.49 (s, 1H), 4.56-4.53 (d, 1H), 4.07-4.04 (d, 1H), 3.66 (s, 3H), 1.44-1.43 (s, 6H), 1.17-1.07 (m, 4H). ESI-MS (m / z): 632.20 (M+H)+.

[0342] EXAMPLE 10

[0343] Preparation of (-) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino) -5-methoxy benzylidene) amino) oxy)-2-methyl propanoic acid

[0344]

[0345] Enantiomer of example 8 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 2-Propanol-Hexane, Isocratic Elution (40:60), Wavelength- 210nm). (t=17.093 min; ee=94.02%). ’ H NMR (DMSO-d6): 12.53 (br, 1H), 8.02 (s, 2H), 7.56-7.54 (d, 2H), 7.46-7.44 (d, 2H), 7.01-7.07 (d, 1H), 6.99-6.93 (t, 1H), 6.62 (s, 1H), 6.39 (s, 1H), 6.33 (s, 1H), 5.49 (s, 1H), 4.56-4.53 (d, 1H), 4.07-4.04 (d, 1H), 3.66 (s, 3H), 1.44- 1.43 (d, 6H), 1.17-1.07 (m, 4H). ESI-MS (m / z): 632.20 (M+H)+.

[0346] EXAMPLE 11

[0347] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-(6'-(difluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl)-2-oxoethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl propanoic acid

[0348] Prepared using intermed 12.45(s, 1H), 7.92(s, 1H), 7.56-7.54(d, 2H), 7.46-7.44(d, 2H), 7.31-7.12(m, 1H), 6.94-6.86 (m, 2H), 6.84-6.80 (m, 2H), 6.62-6.36 (m, 2H), 5.50-5.48 (d, 1H), 4.55-4.52 (d, 1H), 4.03-4.00 (d, 1H), 3.65 (s, 3H ), 2.09 (s, 3H), 1.45-1.43 (d, 6H), 1.10-0.85 (m, 4H). ESI-MS (m / z): 628.20 (M+H)+

[0349] EXAMPLE 12

[0350] Preparation of 2-(((3-((l-(4-chlorophenyl)-2-(6'-(difluoromethoxy) spiro[cyclopropane- l,3'-indolin]-l'-yl)-2-oxoethyl) amino)-5-methoxy benzylidene) amino) oxy)-2-methyl propanoic acid Prepared using intermediat 12.60 (s, 1H),

[0351] 8.02(s, 1H), 7.91(s, 1H), 7.56-7.54(d, 2H), 7.46-7.44(d, 2H), 7.31-7.095(m, 1H), 6.95-6.94

[0352] (m, 1H), 6.85-6.80 (m, 2H), 6.67 (s, 1H), 6.60 (s, 1H), 6.38-6.34 (m, 2H), 5.48 (s, 1H), 4.54-4.52 (d, 1H), 4.02-3.99 (d, 1H), 3.73 (s, 3H), 1.44 (s, 6H), 1.04-0.91 (m, 4H). ESI-MS (m / z): 614.18 (M+H)+

[0353] EXAMPLE 13

[0354] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) propylidene) amino) oxy)-2-methyl propanoic acid

[0355] Prepared using intermediate IV-1 and intermediate V-16. NMR (DMSO-de): 12.68 (br, 1H), 8.03 (s, 1H), 7.57-7.55 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (d, 1H), 6.96-6.92 (t, 1H), 6.61 (s, 1H), 6.58 (s, 1H), 6.38-6.33 (d, 2H), 5.50 (s, 1H), 4.58-4.55 (d, 1H), 4.29-4.21 (d, 2H), 2.68-2.65 (d, 1H), 1.44-1.41 (d, 6H), 1.29-1.27 (m, 3H), 1.26-1.25 (m, 1H), 1.15-1.09 (m, 3H), 0.98-0.96 (m, 3H). ESI-MS (m / z): 660.22 (M+H)+.

[0356] EXAMPLE 14

[0357] Preparation of (+) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) propylidene) amino) oxy)-2-methyl propanoic acid

[0358] Enantiomer of example 13 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 2-Propanol-Hexane, Isocratic Elution (40:60), Wavelength- 210nm). (t=14.496 min; ee=95.32%). ’ H NMR (DMSO-d6): 12.55 (br, 1H), 8.03 (s, 1H), 7.57-7.55 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (d, 1H), 6.96-6.92 (t, 1H), 6.61 (s, 1H), 6.58 (s, 1H), 6.38-6.33 (d, 2H), 5.50 (s, 1H), 4.58-4.55 (d, 1H), 4.29-4.21 (d, 2H), 2.68-2.65 (d, 1H), 1.44-1.41 (d, 6H), 1.29-1.27 (m, 3H), 1.26-1.25 (m, 1H), 1.15-1.09 (m, 3H), 0.98-0.96 (m, 3H). ESI-MS (m / z): 660.20 (M+H)+.

[0359] EXAMPLE 15

[0360] Preparation of (-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) propylidene) amino) oxy)-2-methyl propanoic acid

[0361] Enantiomer of example 13 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 2-Propanol-Hexane, Isocratic Elution (40:60), Wavelength- 210nm). (t=12.767 min; ee=94.73%). ’ H NMR (DMSO-d6): 12.55 (br, 1H), 8.03 (s, 1H), 7.57-7.55 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (d, 1H), 6.96-6.92 (t, 1H), 6.61 (s, 1H), 6.58 (s, 1H), 6.38-6.33 (d, 2H), 5.50 (s, 1H), 4.58-4.55 (d, 1H), 4.29-4.21 (d, 2H), 2.68-2.65 (d, 1H), 1.44-1.41 (d, 6H), 1.29-1.27 (m, 3H), 1.26-1.25 (m, 1H), 1.15-1.09 (m, 3H), 0.98-0.96 (m, 3H). ESI-MS (m / z): 660.20 (M+H)+. EXAMPLE 16

[0362] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl)-2- methylpropylidene) amino) oxy)-2-methyl propanoic acid prepared using intermediate IV-1 and intermediate V-14. ’ H NMR (DMSO-de): 12.56 (br, 1H), 8.03 (s, 1H), 7.56-7.54 (d, 2H), 7.46-7.44 (m, 2H), 7.01-6.99 (d, 1H), 6.93-6.91 (d, 1H), 6.32 (s, 1H), 6.30 (s, 1H), 6.21 (s, 1H), 5.49 (s, 1H), 4.55-4.53 (d, 1H), 4.07-4.05 (d, 1H), 3.64 (s, 3H), 1.41-1.40 (d, 3H), 1.27-1.24 (d, 6H) 1.14-1.02 (m, 5H), 0.93-0.89 (d, 4H). ESI-MS (m / z): 674.50 (M+H)+.

[0363] EXAMPLE 17

[0364] Preparation of 2-((((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) (cyclopropyl)methylene) amino) oxy)-2-methyl propanoic acid

[0365] Prepared using intermediat 12.26 (br, 1H), 8.05 (s, 3H), 7.72 (s, 2H), 7.53 (s, 1H), 7.44 (s, 1H), 7.03 (m, 1H), 7.01 (m, 1H), 6.93 (s, 1H), 6.52 (s, 1H), 5.55 (s, 1H), 3.63 (s, 1H), 1.35 (m, 1H), 1.26-1.27 (m, 2H), 1.33 (m, 4H), 1.23 (s, 6H), 1.14-1.02 (m, 3H), 0.93-0.89 (d, 3H). ESI-MS (m / z): 672.3 (M+H)+. EXAMPLE 18

[0366] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl)-2,2,2- trifluoroethylidene) amino) oxy)-2-methylpropanoic acid

[0367] Prepared using intermediate IV-1 and intermediate V-18. NMR (DMSO-de): 12.91 (s,lH), 8.03 (s, 1H), 7.56-7.54 (m, 2H). 7.46-7.44 (m, 2H) 7.01-6.99 (m, 1H), 6.96-6.91 (m, 1H), 6.45-6.43 (m, 2H), 6.31 (s, 1H), 5.51-5.49 (d, 1H), 4.55-4.52 (d, 1H), 4.05-4.06 (d, 1H), 3.67(s, 3H), 1.37 (s, 6H), 1.28-1.18 (m, 1H), 1.23-1.07 (m, 4H). ESI-MS (m / z): 700.08 (M+H)+

[0368] EXAMPLE 19

[0369] Preparation of 2-(((l-(3-methoxy-5-((2-oxo-l-phenyl-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1 ,3 ' -indolin] - 1 ' -yl)ethy l)amino)phenyl)ethy lidene)amino)oxy) -2- methylpropanoic acid prepared using intermediate IV-3 and intermediate V-l.

[0370] ’H NMR (DMSO-<76): 12.50 (br, 1H), 8.05 (s, 1H), 7.56-7.54 (m, 2H), 7.41-7.38 (m, 2H), 7.34-7.32 (d, 1H), 6.989-6.986 (d, 1H), 6.93-6.91 (d, 1H), 6.63 (s, 1H), 6.56-6.55 (d, 1H), 6.39-6.38 (m, 2H), 5.46-5.45 (d, 1H), 4.59 (s, 1H), 4.01-3.99 (d, 1H), 3.66 (s, 3H), 2.09 (s, 3H), 1.44-1.43 (d, 6H), 1.20-1.08 (m, 4H). ESI-MS (m / z): 612.2 (M+H)+. EXAMPLE 20

[0371] Preparation of 2-(((l-(3-((l-(4-fluorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl propanoic acid prepared using intermedia 12.44 (s, 1H), 8.04 (s, 1H), 7.59-7.57 (m, 2H), 7.24-7.01 (m, 2H), 6.987-6.984 (d, 1H), 6.93-6.91 (d, 1H), 6.61-6.59 (d, 2H), 6.4-6.34 (m, 2H), 5.49-5.47 (d, 1H), 4.58-4.55 (d, 1H), 4.05-4.02 (d, 1H), 3.66 (s, 3H), 2.11 (s, 3H), 1.45-1.43 (d, 6H), 1.18-1.10 (m, 4H). ESI-MS (m / z): 630.23 (M+H)+.

[0372] EXAMPLE 21

[0373] Preparation of 2-(((l-(3-((l-(2,4-dichlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid prepared using intermediate 8.01 (s, 1H), 7.67-7.66 (d, 1H). 7.49-7.44 (m, 2H) 7.03-7.01 (m, 1H), 6.95-6.93 (m, 1H), 6.57 (m, 2H), 6.43 (s, 1H), 6.17 (s, 1H), 5.59-5.57 (d, 1H), 4.40-4.37 (d, 1H), 4.26-4.24 (d, 1H), 3.65 (s, 3H), 2.08 (s, 3H), 1.43 (s, 6H), 1.24-1.07 (m, 4H). ESI-MS (m / z): 680.20 (M+H)+. EXAMPLE 22

[0374] Preparation of 2-(((l-(3-((l-(5-chloropyridin-2-yl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid prepared using intermediat 12.46 (br, 1H), 8.62-8.61 (d, 1H), 8.02-7.96 (m, 2H), 7.61-7.59 (d, 1H), 7.00-6.92 (m, 2H), 6.77-6.75 (d, 1H), 6.65 (s, 1H), 6.42 (s, 1H), 6.34 (s, 1H), 5.64-5.62 (d, 1H), 4.55-4.53 (d, 1H), 4.33- 4.31 (d, 1H), 3.66 (s, 3H), 2.09 (s, 3H), 1.45-1.44 (d, 6H), 1.18-1.09 (m, 4H). ESI-MS (m / z): 647.16 (M+H)+.

[0375] EXAMPLE 23

[0376] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-(6'-methoxyspiro[cyclopropane-l,3'- indolin]-l'-yl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid

[0377] Prepared using intermediate 12.44 (s, 1H), 7.77-7.76 (d, 1H), 7.57-7.55 (d, 2H), 7.46-7.43 (d, 2H), 6.72-6.70 (d, 1H), 6.62-6.57 (m, 3H), 6.40-6.39 (d, 2H), 5.49-5.47 (d, 1H), 4.51-4.48 (d, 1H), 4.04-3.97 (m, 1H), 3.70- 3.66 (d, 3H), 3.33 (s, 3H), 2.10 (s, 3H), 1.46-1.44 (d, 6H), 1.20-1.06 (m, 4H). ESI-MS (m / z): 592.19 (M+H)+. EXAMPLE 24

[0378] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-(6'-morpholinospiro[cyclopropane-l,3'- indolin]-l'-yl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid

[0379] Prepared using intermediat 12.55 (s, 1H), 8.02 (s, 1H), 7.86-7.56 (d, 1H), 7.54-7.45 (d, 2H), 7.43-7.42 (d, 2H), 6.61-6.39 (m, 2H), 6.32-6.32 (d, 1H), 6.42-6.34 (d, 1H), 5.46 (s, 1H), 4.45-4.44 (d, 2H), 4.01-3.97 (m, 2H), 3.76-3.74 (m, 2H), 3.73 (s, 3H), 3.73-3.72 (m, 2H), 3.03-3.02 (m, 2H), 2.09 (s, 3H), 1.24 (s, 6H), 1.12-1.13 (m, 1H), 0.96-0.95 (m, 4H). ESI-MS (m / z): 647.3 (M+H)+.

[0380] EXAMPLE 25

[0381] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)acetic acid

[0382] Prepared using intermediate IV-1 and intermediate V-10. NMR (DMSO-de): 12.8 (br, 1H), 8.03 (s, 1H), 7.57-7.48 (d, 2H), 7.46-7.44 (d, 2H), 7.01-7.0 (d, 1H), 6.96-6.94 (d, 1H), 6.64 (s, 2H), 6.41 (s, 1H), 6.33 (s, 1H), 5.53 (s, 1H), 4.63 (s, 2H), 4.57-4.54 (d, 1H), 4.10- 4.08 (d, 1H), 3.84 (s, 3H), 2.14 (s, 3H), 1.18-1.09 (m, 4H). ESI-MS (m / z): 618.22 (M+H)+. EXAMPLE 26

[0383] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)propanoic acid

[0384] Prepared using intermediate IV-1 and intermediate V-ll. NMR (DMSO-de): 12.65 (s, 1H), 8.03 (s, 1H), 7.56-7.54 (m, 2H), 7.47-7.43 (dd, 2H), 7.01-6.98 (m, 1H), 6.96-6.91 (m, 1H), 6.39 (s, 1H), 6.34-6.31 (m, 1H), 5.51 (s, 1H), 4.66-4.65 (m, 1H), 4.56-4.54 (m, 1H), 4.09-4.06 (m, 2H), 3.66 (s, 3H ), 3.17 (s, 1H ), 2.125-2.124 (d, 3H), 1.42-1.39 (m, 3H ), 1.24-1.08 (m, 4H). ESI-MS (m / z): 632.15 (M+H)+.

[0385] EXAMPLE 27

[0386] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)butanoic acid

[0387] Prepared using intermediate IV-1 and intermediate V-12. ’ H NMR (DMSO-de): 12.59(s, 1H), 8.70 (s, 1H), 8.03 (s, 1H), 7.56-7.54 (d, 2H), 7.45-7.43 (d, 2H), 7.03-7.01 (d, 1H), 6.93-6.91 (d, 1H), 6.63-6.62 (d, 1H), 6.40-6.39 (m, 1H), 6.34-6.31 (m 1H), 5.51 (s 1H), 4.57-4.47 (m, 1H), 4.14-4.06 (m, 2H), 3.66 (s, 3H), 2.137-2.135 (d, 3H), 1.83-1.76 (m, 2H), 1.18-1.12 (m, 2H), 1.08 (s, 2H), 0.97-0.93 (m, 3H). ESI-MS (m / z): 646.2 (M+H)+. EXAMPLE 28

[0388] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-3-methylbutanoic acid

[0389] Prepared using intermedia 12.63 (s, 1H), 8.033 (s, 1H), 7.56-7.54 (m, 2H), 7.45-7.43 (m, 2H), 7.01-6.99 (d, 1H), 6.93-6.91 (d, 1H), 6.68-6.63 (m, 2H), 6.39 (s, 1H), 6.33-6.31 (d, 1H), 5.52-5.50 (m, 1H), 4.57-4.53 (m, 1H), 4.32-4.30 (m 1H), 4.10-4.06 (m, 1H), 3.66 (s, 3H), 2.11 (s, 4H ), 1.36-1.35 (m, 1H), 1.08 (S, 3H), 0.99-0.85 (m, 6H). ESI-MS (m / z): 660.25 (M+H)+.

[0390] EXAMPLE 29

[0391] Preparation of 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)cyclobutane-l-carboxylic acid

[0392] Prepared using intermediate IV-1 and intermediate V-17. NMR (DMSO-<76): 12.20 (br, 1H), 8.03 (s, 1H), 7.57-7.55 (d, 2H), 7.46-7.44 (d, 2H), 6.92-6.90 (m, 2H), 6.64-6.62 (d, 2H), 6.42-6.33 (m, 2H), 5.52-5.50 (d, 1H), 4.81-4.55 (m, 2H), 4.10- 4.06 (m, 1H), 3.66 (s, 3H), 2.97-2.67 (m, 1H), 2.55-2.52 (m, 4H), 2.20-2.08 (m, 3H), 1.16- 1.09 (m, 4H). ESI-MS (m / z): 658.19 (M+H)+. EXAMPLE 30

[0393] Preparation of 4-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)butanoic acid

[0394] Prepared using intermed 12.2 (br, 1H), 8.03 (s, 1H), 7.58-7.55 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (m, 1H), 6.94-6.92 (d, 1H), 6.64-6.63 (d, 1H), 6.433-6.428 (d, 1H), 6.33-6.32 (d, 2H), 5.53-5.50 (d, 1H), 4.8-4.55 (d, 1H), 4.10-4.06 (m, 3H), 3.67 (s, 3H), 2.31-2.27 (t, 2H), 2.29 (s, 3H), 1.86-1.83 (m, 2H), 1.21-1.10 (m, 4H). ESI-MS (m / z): 646.17 (M+H)+.

[0395] EXAMPLE 31

[0396] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclobutane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoic acid

[0397] Prepared using intermediate IV-10 and intermediate V-l. NMR (DMSO-de): 12.59 (s, 1H), 7.98 (s, 1H), 7.65-7.63 (d, 1H), 7.60-7.58 (d, 2H), 7.46-7.44 (dd, 2H), 7.11-7.09 (dd, 1H), 6.64-6.60 (m, 2H), 6.40-6.36 (m 2H), 5.64-5.63 (d, 1H), 4.70-4.67 (d, 1H ), 4.11-4.09 (d, 1H), 3.66 (s, 3H), 2.33-2.26 (m, 3H), 2.10 (s, 3H), 1.99 (s, 3H ), 1.44-1.442 (d, 6H).

[0398] ESI-MS (m / z): 660.25(M+H)+. EXAMPLE 32

[0399] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopentane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid

[0400] Prepared using intermediate IV-11 and intermediate V-l. NMR (DMSO-de): 12.59 (s, 1H), 8.00 (s, 1H), 7.59-7.57 (d, 2H), 7.46-7.44 (dd, 2H), 7.37-7.35(d, 1H), 7.06-7.04 (dd, 1H), 6.65(s, 2H), 6.40-6.36 (m 2H), 5.61 (s, 1H), 4.34-4.31 (d, 1H), 3.82-3.80 (d, 1H), 3.66 (s, 3H), 2.10 (s, 3H), 1.87- 1.71 (m, 6H), 1.70-1.61 (m, 1H), 1.53-1.49 (m, 1H), 1.448-1.446 (d, 6H). ESI-MS (m / z): 674.20 (M+H)+.

[0401] EXAMPLE 33

[0402] Preparation of 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclobutane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoic acid

[0403] Prepared using intermediate IV-10 and intermediate V-25.1H NMR (DMSO- fJ: 12.40 (br, 1H), 7.98 (s, 1H), 7.64-7.60 (m, 3H), 7.47-7.45 (d, 2H), 7.11-7.09 (d, 1H), 6.67 (s, 1H), 6.60-6.58 (d, 1H), 6.43-6.37 (d, 2H), 5.68-5.66 (d, 1H), 4.73-4.70 (d, 1H), 4.28-4.25 (t, 2H), 4.12-4.09 (d, 1H), 3.68 (s, 3H), 2.60-2.57 (t, 2H), 2.35-2.29 (m, 3H), 2.06-2.03 (m, 4H), 2.01-1.96 (m, 2H). ESI-MS (m / z): 646.20 (M+H)+. EXAMPLE 34

[0404] Preparation of 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopentane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoic acid

[0405] Prepared using intermediate IV-11 and intermediate V-25. ’H NMR (DMSO-de): 12.23 (s, 1H), 8.00 (s, 1H), 7.61-7.59 (m, 2H). 7.47-7.45 (m, 2H) 7.37-7.39 (m, 1H), 7.06-7.04 (m, 1H), 6.67 (s, 1H), 6.57-6.55 (m, 1H), 6.43-6.37 (d, 2H), 5.66-5.64 (d, 1H), 4.36-4.34 (d, 1H), 4.29 (m, 2H), 3.82-3.80 (d, 1H), 3.67 (s, 3H), 2.08 (s, 3H), 1.77-1.76 (m, 6H), 1.54- 1.50 (m, 2H), 1.30-1.23 (m, 2H). ESI-MS (m / z): 660.25 (M+H)+.

[0406] EXAMPLE 35

[0407] Preparation of 3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxybenzaldehyde O-(2- hydroxyethyl) oxime

[0408] Prepared using intermediate IV-1 and intermediate V-7.1H NMR (DMSO-de): 8.02 (s, 2H), 7.57-7.54 (d, 2H), 7.46-7.44 (d, 2H), 6.99-6.92 (t, 1H), 6.90-6.80 (d, 1H), 6.59 (s, 1H), 6.42- 6.34 (m, 2H), 5.51 (s, 1H), 4.56-4.54 (d, 1H), 4.10-4.06 (m, 3H), 3.73 (s, 3H), 3.63-3.60 (t, 3H), 1.24-1.09 (m, 4H). ESI-MS (m / z): 590.5 (M+H)+.

[0409] EXAMPLE 36

[0410] Preparation of 2-(4-chlorophenyl)-2-((3-(l-(((l-hydroxy-2-methylpropan-2-yl) oxy) imino) ethyl) -5-methoxyphenyl) amino) -l-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin]-l'-yl) ethan-l-one

[0411] Prepared using intermediate IV-1 and intermediate V-5.1H NMR (DMSO-de): 8.04 (s, 1H),

[0412] 7.57-7.55 (d, 2H), 7.47-7.45 (d, 2H), 7.01-6.99 (d, 1H), 6.93-6.91 (d, 1H), 6.62 (s, 1H), 6.42

[0413] (s, 1H), 6.33 (s, 1H), 5.49 (s, 1H), 4.58-4.55 (d, 1H), 4.07-4.04 (d, 1H), 3.71 (s, 3H), 3.64 (s, 1H), 3.39 (s, 2H), 2.05 (s, 3H), 1.28-1.09 (m, 10 H). ESI-MS (m / z): 632.21 (M+H)+.

[0414] EXAMPLE 37

[0415] Preparation of 3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxybenzaldehyde O-(l- hydroxy-2-methylpropan-2-yl) oxime

[0416] Prepared using intermediate IV-1 and intermediate V-8. NMR (DMSO-de): 8.06-8.01 (m, 1H), 7.73-7.70 (m, 1H), 7.58-7.53 (m, 2H), 7.47-7.45 (d, 2H), 7.23-7.13 (m, 1H), 7.03- 6.96 (m, 1H), 6.88 (br, 1H), 6.67 (s, 1H), 6.42-6.35 (m, 2H), 5.48 (s, 1H), 4.59-4.56 (d, 1H), 4.14-4.09 (d, 1H), 3.85 (br, 1H), 3.67 (s, 3H), 3.39 (s, 2H), 1.35-1.30 (d, 6H), 1.22-1.02 (m, 4H). ESI-MS (m / z): 618.17 (M+H)+.

[0417] EXAMPLE 38

[0418] Preparation of 2-(4-chlorophenyl)-2-((3-(l-((2-hydroxy-2-methylpropoxy) imino) ethyl)-5-methoxyphenyl) amino)-l-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'- indolin]-l'-yl) ethan-l-one Prepared using intermediate IV-1 and intermediate V-6.1H NMR (DMSO-de): 8.03 (s, 1H),

[0419] 7.57-7.55 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (m, 1H), 6.94-6.91 (d, 1H), 6.64-6.63 (d, 2H), 6.43-6.42 (t, 1H), 6.33-6.32 (t, 1H), 5.52-5.50 (d, 1H), 4.58-4.55 (d, 1H), 4.46 (s, 1H), 4.10-4.07 (d, 1H), 3.89 (s, 2H), 3.33 (s, 3H), 2.11 (s, 3H), 1.16-1.08 (m, 10 H). ESI-MS (m / z): 632.20 (M+H)+.

[0420] EXAMPLE 39

[0421] Preparation of 2-(4-chlorophenyl)-2-((3-(l-((3-hydroxypropoxy)imino)ethyl)-5- methoxy pheny l)amino)- 1 -(6 ' -(trifluoromethoxy )spiro[cy clopropane- 1 ,3 ' -indolin] - 1 ' - yl)ethan-l-one

[0422] Prepared using intermediate IV-1 and intermediate V-4.1H NMR (DMSO-de): 8.03 (s, 1H), 7.58-7.56 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (d, 2H), 6.94-6.92 (d, 2H), 6.64-6.62 (d, 1H), 6.32 (s, 1H), 5.53-5.50 (d, 1H), 4.58-4.55 (d, 1H), 4.47 (s, 1H), 4.14-4.08 (m, 3H), 3.67 (s, 3H), 3.49-3.48 (d, 2H), 2.07 (s, 3H), 1.80-1.74 (m, 2H), 1.24-1.02 (m, 4H). ESI-MS (m / z): 618.18 (M+H)+.

[0423] EXAMPLE 40

[0424] Preparation of 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid

[0425] Step 1: Preparation of tert-butyl 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-methoxy-2- oxoethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoate.

[0426] To a stirring solution of VI-3 (400 mg, 1.36 mmol) in DMF (15 mL) was added intermediate V-l (439 mg, 1.36 mmol) followed by triethyl amine (0.28 mL, 2.04 mmol) and the resulting mixture was heated at 80°C for 3 hr. After the complete conversion of starting material, the reaction mixture was diluted with cold water and extracted with ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESI-MS (m / z): 535.03 (M+H)+.

[0427] Step 2: Preparation of 2-((3-(l-(((l-(tert-butoxy)-2-methyl-l-oxopropan-2- yl)oxy)imino)ethyl)-5-methoxyphenyl)amino)-2-(4-chloro-2-methoxyphenyl)acetic acid.

[0428] To a stirring solution of the product obtained from step 1 (600 mg, 1.12 mmol) in 50% methanol: THF (10 mL) was added 4 ml aqueous solution of sodium hydroxide (135 mg, 3.36 mmol) and the resulting mixture was stirred at 40°C for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidified with aqueous HC1 and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESI-MS (m / z): 521.03 (M+H)+.

[0429] Step 3: Preparation of tert-butyl 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoate

[0430] To a stirring solution of the product obtained from step 2 (250 mg, 0.48 mmol) in DMF (5 ml) was added intermediate II-l (110 mg, 0.48 mmol) followed by HATU (146 mg, 1.44 mmol) and DIPEA (0.25 mL, 1.44 mmol) at 0-10°C. the resulting mixture was stirred at the same temperature for 1 hr. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESI-MS (m / z): 733.10 (M+H)+.

[0431] Step 4: Preparation of 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanoic acid.

[0432] To a stirring solution of the product obtained from step 3 (300 mg, 0.445 mmol) in DCM (15 mL) was added TFA (39.2 mg, 0.979 mmol) and the resulting mixture was stirred at room temperature for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ’H NMR (DMSO- d6) 12.60-12.39 (br, 1H), 8.02 (s, 1H), 7.35-7.33 (d, 1H), 7.15-7.14 (d, 1H), 7.05-7.02 (m, 2H), 6.99-6.98 (d, 1H), 6.66-6.64 (d, 1H), 6.58 (s, 1H), 6.40 (s, 1H), 6.23 (s, 1H), 5.60-5.58 (d, 1H), 4.42-4.40 (d, 1H), 4.09-4.06 (d, 1H), 3.65 (s, 3H), 3.34 (s, 3H), 2.12 (s, 3H), 1.44 (s, 6H), 1.18-1.09 (m, 4H). ESI-MS (m / z): 676.2 (M+H)+. EXAMPLE 41

[0433] Preparation of 2-(((l-(3-((l-(4-chloro-2-(2-hydroxyethoxy) phenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5- methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoic acid

[0434] Step 1: Preparation of tert-butyl 2-(((l-(3-((l-(2-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-4- chlorophenyl)-2-ethoxy-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoate. To a stirring solution of intermediate VI-4 (1.3 g, 2.88 mmol) in DMF (15 mL) was added intermediate V-l (0.83 mg, 2.59 mmol) followed by triethyl amine (1.28 mL, 8.64 mmol) and the resulting mixture was heated at 80°C for 12 hr. After the complete conversion of starting material, the reaction mixture was diluted with cold water, and extracted with ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESLMS (m / z): 693.34 (M+H)+.

[0435] Step 2: Preparation of 2-((3-(l-(((l-(tert-butoxy)-2-methyl-l-oxopropan-2- yl)oxy)imino)ethyl)-5-methoxyphenyl)amino)-2-(2-(2-((tert- butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)acetic acid.

[0436] To a stirring solution of the product obtained from step 1 (600 mg, 1.15 mmol) in 50% methanol: THF (10 mL) was added 4 ml aqueous solution of sodium hydroxide (131 mg, 3.39 mmol) and the resulting mixture was stirred at RT for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidified with citric acid and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESI-MS (m / z): 665.32 (M+H)+.

[0437] Step 3: Preparation of tert-butyl (E)-2-(((l-(3-((l-(2-(2-((tert- butyldimethylsilyl)oxy)ethoxy)-4-chlorophenyl)-2-oxo-2-(6'- (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-T-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoate.

[0438] To a stirring solution of the product obtained from step 2 (1.5 g, 2.25 mmol) in DMF (20 ml) was added product obtained from intermediate II-l (0.517 g, 2.25 mmol) followed by HATU (1.28 g, 3.38 mmol) and DIPEA (1.18 mL, 6.76 mmol) at 0-10°C and the resulting mixture was stirred at RT for 1 hr. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure and purified by column chromatography to get the title product. ESI-MS (m / z): 876.38 (M+H)+.

[0439] Step 4: Preparation of 2-(((l-(3-((l-(4-chloro-2-(2-hydroxyethoxy)phenyl)-2-oxo-2-(6'- (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-T-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methyl propanoic acid.

[0440] To a stirring solution of the product obtained from step 3 (0.8 g, 0.913 mmol) in DCM (10 mL) was added TFA (0.70 mL, 9.13 mmol) at 0°C and the resulting mixture was stirred at RT for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ’H NMR (DMSO- : 12.6 (br, 1H), 8.03 (s, 1H), 7.41-7.39 (d, 1H), 7.146-7.141 (d, 1H), 7.04-7.02 (m, 2H), 6.982-6.979 (d, 1H), 6.69 (br, 1H), 6.62 (s, 1H), 6.40-6.396 (d, 1H), 6.29 (s, 1H), 5.73 (s, 1H), 4.46-4.44 (d, 1H), 4.19-4.15 (d, 1H), 4.09-4.04 (m, 2H), 3.99 (br, 1H), 3.78-3.73 (m, 2H), 3.65 (s, 3H),

[0441] 2.09 (s, 3H), 1.44 (s, 6H), 1.18-1.10 (m, 4H). ESLMS (m / z): 706.22 (M+H)+.

[0442] EXAMPLE 42

[0443] Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy) propanoic acid

[0444] Step 1: Preparation of ethyl 3-(((l-(3-((2-(benzyloxy)-l-(4-chloro-2-methoxyphenyl)-2- oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoate To a stirring solution of the intermediate VI-2 (400 mg, 1.36 mmol) in DMF (15 mL) was added V-25 (439 mg, 1.36 mmol) followed by triethyl amine (0.28 mL, 2.04 mmol) and the resulting mixture was heated at 80 °C for 4 hr. After the complete conversion of starting material, the reaction mixture was diluted with cold water, and extracted with ethyl acetate. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESLMS (m / z): 569.20 (M+H)+.

[0445] Step 2: Preparation of 2-(4-chloro-2-methoxyphenyl)-2-((3-(l-((3-ethoxy-3-oxopropoxy) imino) ethyl)-5 -methoxyphenyl) amino) acetic acid

[0446] To a stirring solution of the product obtained from step 1 (500 mg, 0.879 mmol) in 50% methanol: THF (5 mL) was added Pd / C (94 mg, 0.879 mmol) and the resulting mixture was stirred at RT under hydrogen pressure for 4 hrs. After complete conversion of starting material, the reaction mixture was filtered through Hyflow and filtrate was evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ESLMS (m / z): 479.16 (M+H)+.

[0447] Step 3: Preparation of ethyl 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino)oxy)propanoate.

[0448] To a stirring solution of the product obtained from step 2 (250 mg, 0.48 mmol) in DMF (5 ml) was added intermediate II-l (110 mg, 0.48 mmol) followed by HATU (146 mg, 1.44 mmol) and DIPEA (0.27 mL, 1.44 mmol) at 0-10°C at the resulting mixture was stirred at same temperature for 1 hr. After completion of the reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure and purified by column chromatography to get the title product. ESI-MS (m / z): 690.23 (M+H)+.

[0449] Step 4: Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-T-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid.

[0450] To a stirring solution of the product obtained from step 3 (270 mg, 0.391 mmol) in THF (2 mL) was added 2 ml aqueous solution of sodium hydroxide (49.3 mg, 1.174 mmol) and the resulting mixture was stirred at RT for 4 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidifyiedwith aqueous HC1 and extracted with DCM. The organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. ’H NMR (DMSO-d6): 8.02 (s, 1H), 7.36-7.34 (d, 1H), 7.148-7.143 (d, 1H), 7.04-6.98 (m, 2H), 6.95-6.91 (m, 1H), 6.60 (s, 1H), 6.43 (s, 1H), 6.24 (s, 1H), 5.60 (s, 1H), 4.44-4.38 (m, 1H), 4.27 (t, 2H), 4.13-4.08 (d, 1H), 3.90 (s, 3H), 3.66 (s, 3H), 2.60 (t, 2H), 2.04 (s, 3H), 1.19-1.10 (m, 4H). ESI-MS (m / z): 662.20 (M+H)+.

[0451] EXAMPLE 43

[0452] Preparation of (+) 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0453] (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5- methoxyphenyl)ethylidene) amino)oxy)propanoic acid Enantiomer of example 42 was separated by preparative HPLC (Column YMC-Choral cellulose-SZ (250X4.6 mm) 5.0u), 0.1%TFA in Ethanol-Hexane (05:95), Wavelength- 220nm).(t=22.898 min; ee=93.60 %).1H NMR (DMSO-d6): 8.02 (s, 1H), 7.36-7.34 (d, 1H), 7.148-7.143 (d, 1H), 7.04-6.99 (m, 2H), 6.93-6.91 (d, 1H), 6.61 (s, 1H), 6.43 (s, 1H), 6.24 (s, 1H), 5.61 (s, 1H), 4.44-4.41 (d, 1H), 4.27 (t, 2H), 4.11-4.08 (d, 1H), 3.90 (s, 3H), 3.66 (s, 3H), 2.58 (t, 2H), 2.04 (s, 3H), 1.20-1.08 (m, 4H). ESI-MS (m / z): 662.24 (M+H)+.

[0454] EXAMPLE 44

[0455] Preparation of (-) 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0456] (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5- methoxyphenyl)ethylidene)amino)oxy) propanoic acid

[0457] Enantiomer of example 42 was separated by preparative HPLC (Column- YMC-Choral cellulose-SZ (250X4.6 mm) 5.0u), 0.1%TFA in Ethanol-Hexane (05:95), Wavelength- 220nm). (t=15.205 min; ee=99.14 %). ’ H NMR (DMSO-d6): 8.02 (s, 1H), 7.36-7.34 (d, 1H), 7.147-7.142 (d, 1H), 7.04-6.98 (m, 2H), 6.93-6.91 (d, 1H), 6.61 (s, 1H), 6.43 (s, 1H), 6.24 (s, 1H), 5.61 (s, 1H), 4.44-4.41 (d, 1H), 4.27 (t, 2H), 4.11-4.08 (d, 1H), 3.90 (s, 3H), 3.66 (s, 3H), 2.58 (t, 2H), 2.04 (s, 3H), 1.18-1.08 (m, 4H). ESI-MS (m / z): 662.21 (M+H)+.

[0458] EXAMPLE 45

[0459] Preparation of 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5- methoxybenzylidene)amino)oxy)-2-methylpropanoic acid Step 1: Preparation of tert-butyl 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-methoxy-2- oxoethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoate

[0460] Prepared using intermediates V-2 and VI-3 using a similar process as described for step 1, Example 42. ESI-MS (m / z): 521.1 (M+H)+.

[0461] Step 2: Preparation of 2-((3-((((l-(tert-butoxy)-2-methyl-l-oxopropan-2- yl)oxy)imino)methyl)-5-methoxyphenyl)amino)-2-(4-chloro-2-methoxyphenyl)acetic acid

[0462] Prepared using a similar process as described for step 2, Example 42. ESI-MS (m / z): 507.1 (M+H)+.

[0463] Step 3: Preparation of tert-butyl 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0464] (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)-2-methylpropanoate. Prepared using a similar process as described for step 3, Example 42. ESI-MS (m / z): 718.2 (M+H)+.

[0465] Step 4: Preparation of 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5- methoxybenzylidene) amino)oxy)-2-methylpropanoic acid.

[0466] Prepared using a similar process as described for step 4, Example 42.1H NMR (DMSO-de): 12.64-12.49 (br, 1H), 8.02 (s, 2H), 7.34-7.32 (d, 1H), 7.21-7.17 (d, 1H), 7.09-7.02 (m, 2H), 6.95-6.93 (d, 1H), 6.83-6.71(br, 1H), 6.54 (s, 1H), 6.39 (s, 1H), 6.26(s, 1H), 5.57 (s, 1H), 4.42-4.40 (d, 1H), 4.12-4.08 (d, 1H), 3.90 (s, 3H), 3.77 (s, 3H), 1.44 (s, 6H), 1.19-1.08 (m,

[0467] 4H). ESI-MS (m / z): 662.27 (M+H)+.

[0468] EXAMPLE 46

[0469] Preparation of 2-(((l-(3-methoxy-5-((l-(4-methoxyphenyl)-2-oxo-2-(6'-

[0470] (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino) phenyl) ethylidene)amino)oxy)-2-methylpropanoic acid

[0471] Step 1: Preparation of tert-butyl 2-(((l-(3-((2-ethoxy-l-(4-methoxyphenyl)-2- oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoate Prepared using intermediates V-l and VI-5 by following a similar process as described for step 1, Example 40. ESI-MS (m / z): 515.20 (M+H)+.

[0472] Step 2: Preparation of 2-((3-(l-(((l-(tert-butoxy)-2-methyl-l-oxopropan-2- yl)oxy)imino)ethyl)-5-methoxyphenyl)amino)-2-(4-methoxyphenyl)acetic acid prepared using a similar process as described for step 2, Example 40.

[0473] Step 3: Preparation of tert-butyl 2-(((l-(3-methoxy-5-((l-(4-methoxyphenyl)-2-oxo-2-(6'-

[0474] (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino) phenyl) ethylidene) amino)oxy)-2-methylpropanoate

[0475] Prepared using a similar process as described for step 3, Example 40. ESI-MS (m / z):

[0476] 698.20 (M+H)+.

[0477] Step 4: Preparation of 2-(((l-(3-methoxy-5-((l-(4-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy )spiro [cyclopropane- 1,3' -indolin] - 1' - yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid

[0478] Prepared using a similar process as described for step 4, Example 40.1H NMR (DMSO-de): 8.04 (s, 1H), 7.46-7.45 (m, 2H). 6.99-6.89 (m, 4H) 6.61 (s, 1H), 6.44-6.34 (m, 3H), 5.38- 5.36 (d, 1H), 4.59-4.57 (d, 1H), 3.97-3.95 (d, 1H), 3.66 (s, 3H), 3.32 (s, 3H), 2.09 (s, 3H),

[0479] 1.44 (s, 6H), 1.16-1.07 (m, 4H). ESI-MS (m / z): 642.2 (M+H)+. EXAMPLE 47

[0480] Preparation of 2-(((l-(3-((l-(4-cyanophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoic acid

[0481] Step 1: Preparation of tert-butyl 2-(((l-(3-((l-(4-cyanophenyl)-2-ethoxy-2- oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoate.

[0482] Prepared using intermediates V-l and VI-6 by following a similar process as described for step 1, Example 40. ESI-MS (m / z): 510.26 (M+H)+.

[0483] Step 2: Preparation of 2-((3-(l-(((l-(tert-butoxy)-2-methyl-l-oxopropan-2- yl)oxy)imino)ethyl)-5-methoxyphenyl)amino)-2-(4-cyanophenyl)acetic acid

[0484] Prepared using a similar process as described for step 2, Example 40. ESI-MS (m / z): 482.23 (M+H)+.

[0485] Step 3: Preparation of tert-butyl 2-(((l-(3-((l-(4-cyanophenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoate

[0486] Prepared using a similar process as described for step 3, Example 40. ESI-MS (m / z): 693.34 (M+H)+.

[0487] Step 4: 2-(((l-(3-((l-(4-cyanophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spirofcyclopropane- l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene)amino)oxy)-2- methylpropanoic acid

[0488] Prepared using a similar process as described for step 4, Example 40.1H NMR (DMSO-de): 12.50 (br, 1H), 8.02 (s, 1H), 7.86-7.84 (d, 2H), 7.73-7.71 (d, 2H), 7.00-6.98 (m, 1H), 6.94- 6.92 (d, 1H), 6.84 (br, 1H), 6.60 (s, 1H), 6.40 (s, 1H), 6.31 (s, 1H), 5.62 (s, 1H), 4.53-4.50

[0489] (d, 1H), 4.18-4.15 (d, 1H), 3.65 (s, 3H), 2.08 (s, 3H), 1.45-1.43 (d, 6H), 1.18-1.09 (m, 4H). ESI-MS (m / z): 637.24 (M+H)+.

[0490] EXAMPLE 48

[0491] Preparation of 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclobutane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene)amino)oxy)-2-methylpropanoic acid Step 1: Preparation of tert-butyl 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclobutane-l,3'-indolin]-l'-yl) ethyl) amino) -5 -methoxyphenyl) ethylidene)amino)oxy)-2-methylpropanoate Prepared using intermediates II-6 and a product obtained in step 2, example 40 using similar process as described for step 3, Example 40. ESI-MS (m / z): 746.30 (M+H)+.

[0492] Step 2: Preparation of 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclobutane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene) amino) oxy)-2-methylpropanoic acid

[0493] Prepared using similar process as described for step 4, Example 40. NMR (CDCI3): 8.10 (s, 1H), 7.40-7.37 (m, 2H), 6.98- 6.96 (m, 3H), 6.55-6.53 (m, 2H), 6.32-6.31 (m, 1H), 5.71 (s, 1H), 4.34-4.31 (d, 1H), 4.05 (s, 3H), 4.03 (s, 1H), 3.77 (s, 3H), 2.33-2.02 (m, 9H), 1.60- 1.59 (d, 6H), 1.29-1.28 (t, 1H). ESI-MS (m / z): 690.27 (M+H)+.

[0494] EXAMPLE 49

[0495] Preparation of 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0496] (trifluoromethoxy)spiro [cyclopentane- 1 ,3 ' -indolin] - 1 ' -y l)ethyl)amino)-5 - methoxyphenyl)ethylidene) amino)oxy)-2-methylpropanoic acid Step 1: Preparation of tert-butyl 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy)spiro[cyclopentane-l,3'-indolin]-r-yl)ethyl) amino)-5 -methoxyphenyl) ethylidene)amino) oxy)-2-methylpropanoate

[0497] Prepared using intermediate II-7 and a product obtained in step 2, example 40 using similar process as described for step 3, Example 40. ESI-MS (m / z): 760.30 (M+H)+.

[0498] Step 2: Preparation of 2-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro[cyclopentane-l,3'-indolin]-l'-yl)ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-2-methylpropanoic acid

[0499] Prepared using similar process as described for step 4, Example 40. NMR (CDCI3): 8.10 (s, 1H), 7.41-7.39 (d, 1H), 7.11-7.09 (m, 1H), 6.99-6.93 (m, 3H), 6.54-6.52 (d, 2H), 6.30 (s,

[0500] 1H), 5.66 (s, 1H), 4.02-4.00 (m, 4H), 3.76-3.73 (m, 4H), 2.26 (s, 3H), 1.92-1.27 (m, 14H).

[0501] ESI-MS (m / z): 704.26 (M+H)+.

[0502] EXAMPLE 50

[0503] Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclobutane-l,3'-indolin]-l'-yl) ethyl) amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid Step 1: Preparation of ethyl 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0504] (trifluoromethoxy)spiro[cyclobutane- 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoate

[0505] Prepared using intermediate II-6 and a product obtained in step 2, example 42 using a similar process as described for step 3, Example 42. ESI-MS (m / z): 704.2 (M+H)+.

[0506] Step 2: Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- methoxyphenyl)ethylidene) amino)oxy)propanoic acid

[0507] Prepared using similar process as described for step 4, Example 42.1H NMR (DMSO-de) ■ 12.24 (s, 1H), 7.96(s, 1H), 7.65-7.633 (d, 1H), 7.36-7.634 (d, 1H), 7.17-7.16(m, 1H), 7.117- 6.113 (m, 1H), 7.096-7.093 (m, 1H), 7.04-7.01 (m, 1H), 6.63 (s, 1H), 6.59-6.577 (d, 1H), 6.43-630 (m, 1H), 5.73-5.71 (d, 1H), 4.52-4.50 (d, 1H ), 4.29-4.26 (t, 2H), 4.19-4.16 (m 1H), 3.96 (s, 3H), 3.67 (s, 3H), 2.61-2.52 (m, 2H), 2.33-2.77 (m, 4H), 2.05 (s, 3H ), 2.00- 1.96 (m, 2H ).ESI-MS (m / z): 676.20 (M+H)+

[0508] EXAMPLE 51

[0509] Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopentane-l,3'-indolin]-l'-yl) ethyl) amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid

[0510] Step 1: Preparation of ethyl 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0511] (trifluoromethoxy)spiro[cyclopentane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoate

[0512] Prepared using intermediates II-7 and a product obtained in step 2, example 42 using similar process as described for step 3, Example 42

[0513] Step 2: Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro [cyclopentane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)propanoic acid

[0514] Prepared using similar process as described for step 4, Example 42.1H NMR (DMSO-de) ■ 12.21 (s, 1H), 8.00(s, 1H), 7.38-7.35 (m, 2H), 7.17-7.16(d, 1H), 7.06-7.02 (m, 2H), 6.62 (s, 1H), 6.56-6.54(d, 1H), 6.43 (s, 1H), 6.30 (s, 1H), 5.69-5.67 (d, 1H), 4.29-4.26 (t, 1H), 4.19- 4.17 (d, 2H), 3.94 (s, 3H), 3.83-3.80 (d, 2H), 3.67 (s, 3H), 2.60-2.57 (t, 1H), 2.04 (s, 3H), 1.88-1.80 (m, 3H), 1.62-1.24 (m, 5H). ESI-MS (m / z): 690.20 (M+H)+

[0515] EXAMPLE 52

[0516] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide

[0517]

[0518] To a stirring solution of the product obtained from example 1 (400 mg, 0.619 mmol) in DCM (15 mL) was added EDC.HC1 (237 mg, 1.24 mmol) followed by DMAP (7.6 mg, 0.062 mmol) and the resulting mixture was stirred at RT for 1 hr. To this was added Methane sulfonamide (118 mg, 1.24 mmol) and the resulting mixture was stirred at RT for 12 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidify with aqueous HC1 and extracted with DCM. Organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. NMR (DMSO- d6. 11.44 (s, 1H), 8.03 (s, 1H), 7.56-7.54 (d, 2H), 7.45-7.43 (d, 2H), 6.99-6.91 (m, 1H), 6.93-6.91 (d, 1H), 6.63 (s, 1H), 6.42-6.37 (m, 2H), 5.47 (s, 1H), 4.54-4.51 (d, 1H), 4.09-4.06 (d, 1H), 3.65 (s, 3H), .3.20 (s, 3H), 3.21 (s, 3H), 1.45-1.44 (d, 6H), 1.15-1.07 (m, 4H). ESIMS (m / z): 723.4 (M+H)+.

[0519] EXAMPLE 53

[0520] Preparation of (+) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide

[0521] Enantiomer of example 52 was separated by preparative HPLC (Column YMC-Choral cellulose-SZ (250X4.6 mm) 5.0u), 0.1%TFA in Ethanol-Hexane (10:90), Wavelength- 220nm). (t=9.658 min; ee=99.74%) ’ H NMR (DMSO-d6): 1E44 (s, 1H), 8.03 (s, 1H), 7.56- 7.54 (d, 2H), 7.45-7.43 (d, 2H), 6.99-6.91 (m, 1H), 6.93-6.91 (d, 1H), 6.63 (m, 2H), 6.32 (s, 1H), 6.42-6.37 (m, 1H), 5.47 (s, 1H), 4.54-4.51 (d, 1H), 4.09-4.06 (d, 1H), 3.65 (s, 3H), 3.21 (s, 3H), 2.15 (s, 3H), 1.45-1.44 (d, 6H), 1.15-1.07 (m, 4H). ESI-MS (m / z): 723.15 (M+H)+.

[0522] EXAMPLE 54

[0523] Preparation of (-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide

[0524] Enantiomer of example 52 was separated by preparative HPLC (Column YMC-Choral cellulose-SZ (250X4.6 mm) 5.0u), 0.1%TFA in Ethanol-Hexane (10:90), Wavelength- 220nm). (t=7.814 min; ee=98.58%). ’ H NMR (DMSO-d6): 11.44 (s, 1H), 8.03 (s, 1H), 7.56- 7.54 (d, 2H), 7.45-7.43 (d, 2H), 6.99-6.91 (m, 1H), 6.93-6.91 (d, 1H), 6.63 (s, 2H), 6.42- 6.37 (m, 2H), 5.47 (s, 1H), 4.54-4.51 (d, 1H), 4.09-4.06 (d, 1H), 3.65 (s, 3H), 3.21 (s, 3H), 2.16 (s, 3H), 1.45-1.44 (d, 6H), 1.15-1.07 (m, 4H). ESI-MS (m / z): 723.15 (M+H)+.

[0525] EXAMPLE 55

[0526] Preparation of 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino) -5-methoxybenzylidene) amino)oxy)-2- methyl-N-(methylsulfonyl)propanamide

[0527] Prepared using product obtained from Example 8 by following similar procedure as described for Example 52.1H NMR (DMSO-d6):1H NMR (DMSO-d6): 12.52 (s, 1H), 8.08- 8.02 (d, 2H), 7.55-7.53 (d, 2H), 7.45-7.43 (d, 2H), 7.01-6.93 (m, 1H), 6.93-6.91 (d, 1H), 6.74-6.72 (m, 1H), 6.60 (s, 1H), 6.40-6.36 (m, 2H), 5.47-4.45 (d, 1H), 4.54-4.51 (d, 1H), 4.07-4.04 (d, 1H), 3.65 (s, 3H), 3.16 (s, 3H), 1.43-1.42 (d, 6H), 1.15-1.11 (m, 4H).. ESI-MS (m / z): 709.18 (M+H)+.

[0528] EXAMPLE 56

[0529] Preparation of (+) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxybenzylidene)amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide

[0530] Enantiomer of example 55 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 2-Propanol-Hexane, Isocratic Elution (40:60), Wavelength- 210nm). (t=l 1.926 min; ee=98.43%). ’ H NMR (DMSO-d6): 12.52 (s, 1H), 8.08-8.03 (d, 2H), 7.56-7.54 (d, 2H), 7.45-7.43 (d, 2H), 6.99-6.91 (m, 1H), 6.93-6.91 (d, 1H), 6.74-6.72 (m, 1H), 6.63 (s, 1H), 6.42-6.37 (m, 2H), 5.47 (s, 1H), 4.54-4.51 (d, 1H), 4.09-4.06 (d, 1H), 3.65 (s, 3H), 3.21 (s, 3H), 1.45-1.44 (d, 6H), 1.15-1.07 (m, 4H). ESI-MS (m / z): 709.18 (M+H)+.

[0531] EXAMPLE 57

[0532] Preparation of (-) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxybenzylidene)amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide

[0533] Enantiomer of example 55 was separated by preparative HPLC (Column-Chiral PAK IG(250*30) mm*10p(Diacel), 2-Propanol-Hexane, Isocratic Elution (40:60), Wavelength- 210nm). (t=9.295 min; ee=100%). ’H NMR (DMSO-d6): 11.52 (s, 1H), 8.08 (d, 2H), 7.55- 7.53 (d, 2H), 7.45-7.43 (d, 2H), 6.99-6.91 (m, 1H), 6.93-6.91 (d, 1H), 6.74-6.72 (m, 1H), 6.60 (s, 1H), 6.29-6.28 (m, 2H), 5.47 (s, 1H), 4.54-4.51 (d, 1H), 4.09-4.06 (d, 1H), 3.65 (s, 3H), 3.21 (s, 3H), 1.45-1.44 (d, 6H), 1.15-1.09 (m, 4H). ESI-MS (m / z): 709.18 (M+H)+.

[0534] EXAMPLE 58

[0535] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclobutane-l,3'-indolin]-l'-yl) ethyl)amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide

[0536] Prepared using Example 31 by following similar procedure as described for example 52.1H NMR (DMSO-<76): U.47(S, 1H), 7.98 (s, 1H), 7.65-7.58 (q, 3H), 7.45-7.43(d, 2H), 7.12-7.09 (dd, 1H), 6.65-6.60 (m, 2H), 6.416-6.412 (d, 2H), 5.60-5.58 (d, 1H), 4.67-4.64 (d, 1H ), 4.13-4.11 (d, 1H), 3.65 (s, 3H), 3.22 (s, 3H), 2.33-2.29 (m, 3H), 2.17 (s, 3H), 2.08-1.98 (m, 3H ), 1.45-1.44 (d, 6H). ESI-MS (m / z): 737.20 (M+H)+

[0537] EXAMPLE 59

[0538] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro[cyclopentane-l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-2-methyl-N-(methylsulfonyl)propanamide

[0539] Prepared using Example 32 by following similar procedure as described for example 52.1H NMR (DMSO-J6): U.47(S, 1H), 8.01 (s, 1H), 7.59-7.57 (d, 2H), 7.45-7.42 (d, 2H), 7.38- 7.35(d, 1H), 7.06-7.04 (dd, 1H), 6.64-6.58 (m, 2H), 6.42-6.40 (m, 2H), 5.57-5.54 (d, 1H), 4.30-4.27 (d, 1H ), 3.84-3.81 (d, 1H), 3.65 (s, 3H), 3.21 (s, 3H), 2.16 (s, 3H), 1.88 (s, 1H), 1.85- 1.76 (m, 3H), 1.74-1.63 (m, 3H), 1.53-1.48 (m, 1H), 1.45-1.44 (d, 6H).

[0540] ESI-MS (m / z): 751.25 (M+H)+.

[0541] EXAMPLE 60 Preparation of 2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxybenzylidene) amino)oxy)-2-methyl-N-(methylsulfonyl)propenamide

[0542] Prepared using Example 45 by following similar procedure as described for example 52.

[0543] ’H NMR (DMSO-J6): U-56 (S, 1H), 8.09 (s, 1H), 8.01 (s, 1H), 8.01 (d, 1H), 7.33-7.31 (d,

[0544] 1H), 7.01-7.02 (m, 1H), 6.8 (s, 1H), 6.55 (s, 1H), 6.55 (s, 1H), 6.41 (s, 1H), 6.29 (s, 1H),

[0545] 5.57 (s, 1H), 4.41-4.38 (d, 1H), 4.08-4.07 (d, 1H), 3.89 (s, 3H), 3.65 (s, 3H), 3.17 (s, 3H),

[0546] 1.44-1.43 (d, 6H), 1.12-1.07 (m, 4H). ESI-MS (m / z): 739.30 (M+H)+.

[0547] EXAMPLE 61

[0548] Preparation of 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-N-(methylsulfonyl)propanamide

[0549] Prepared using product obtained from Example 4 by following similar procedure as described for example 52. ’H NMR (DMSO-d6): 11.78 (s, 1H), 8.04 (s, 1H), 7.58-7.56 (d, 2H), 7.46-7.44 (d, 2H), 7.01-6.99 (d, 1H), 6.96-6.92 (t, 1H), 6.65 (s, 1H), 6.44 (s, 1H), 6.33 (s, 1H), 5.53 (s, 1H), 4.58-4.55 (d, 1H), 4.32-4.29 (t, 2H), 4.10-4.07 (d, 2H), 3.67 (s, 3H), 3.21 (s, 3H), 2.68-2.65 (t, 2H), 2.06 (s, 3H), 1.20-1.09 (m, 4H). ESI-MS (m / z): 709.19 (M+H)+.

[0550] EXAMPLE 62

[0551] Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopentane- 1 ,3 ' -indolin] - 1 ' -yl) ethyl) amino)-5-methoxyphenyl) ethylidene)amino)oxy)-N-(methylsulfonyl)propanamide

[0552] Prepared using Example 51 by following similar procedure as described for example 52.1H

[0553] NMR (DMSO-<76): U-47 (S, 1H), 8.00(S, 1H), 7.36 (s, 2H), 7.29 (s, 1H), 7.17(s, 1H), 7.04

[0554] (s, 2H), 6.62 (s, 1H), 6.56-6.54(d, 1H), 6.43 (s, 1H), 6.31 (s, 1H), 5.69-5.67 (d, 1H), 4.30 (s, 2H), 4.19-4.17 (d, 1H), 3.94 (s, 3H), 3.82-3.81 (d, 1H), 3.67 (s, 3H), 3.20 (s, 3H), 2.67 (s, 1H), 2.05 (s, 3H), 1.88-1.81 (m, 3H), 1.70-1.56 (m, 5H). ESI-MS (m / z): 767.26 (M+H)+

[0555] EXAMPLE 63

[0556] Preparation of 3-(((l-(3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-

[0557] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)propanamide

[0558] Prepared using Example 42 by following similar procedure as described for example 52. ’H NMR (DMSO-J6): U-78 (S, 1H), 8.03 (s, 1H), 7.36-7.34 (d, 1H), 7.149-7.144 (d, 1H), 7.05-7.01 (m, 2H), 6.99-6.986 (d, 1H), 6.61 (s, 1H), 6.44 (s, 1H), 6.25 (s, 1H), 5.61 (s, 1H), 4.44-4.42 (d, 1H), 4.32-4.29 (t, 2H), 4.10-4.08 (d, 2H), 3.91 (s, 3H), 3.67 (s, 3H), 3.20 (s, 3H), 2.68-2.65 (t, 2H), 2.05 (s, 3H), 1.17-1.09 (m, 4H). ESI-MS (m / z): 740.2 (M+H)+.

[0559] EXAMPLE 64

[0560] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-N-isopropyl-2-methylpropanamide

[0561] To a stirring solution of the product obtained from example 1 (75 mg, 0.11 mmol) in dry DCM (5 ml) was added DMAP (1.42 mg, 0.012 mmol) and propan-2-amine (8.23 mg, 0.139 mmol) followed by EDC.HC1 (33.4 mg, 0.174 mmol) and the resulting mixture was stirred at RT for 2 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidify with aqueous HC1 and extracted with DCM. Organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product.1H NMR (DMSO-J6): 8.02 (s, 1H), 7.55-7.53 (d, 2H), 7.45-7.43 (d, 2H), 6.98-6.90 (m, 3H), 6.60 (s, 1H), 6.40 (s, 1H), 6.33 (s, 1H), 5.47 (s, 1H), 4.65-4.54 (d, 1H), 4.05-4.03 (d, 1H), 3.83-3.94 (m, 2H), 3.65 (s, 3H), 2.15 (s, 3H), 1.38-1.36 (d, 6H), 1.17-1.08 (m, 4H), 1.03-1.02 (d, 6H). ESI-MS (m / z): 687.27 (M+H)+.

[0562] EXAMPLE 65

[0563] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methyl-l-morpholinopropan-l-one

[0564] Prepared using Example 1 by following similar procedure as described for example 64.

[0565] ’H NMR (DMSO-J6): 8.02 (s, 1H), 7.55-7.53 (d, 2H), 7.46-7.44 (d, 2H), 6.98-6.91 (t, 1H), 6.90 (m, 1H), 6.61 (s, 1H), 6.35 (d, 2H), 5.47 (s, 1H), 4.65-4.54 (d, 1H), 4.06-4.03 (d, 1H), 3.65 (s, 3H), 3.35 (m, 4H), 3.12 (m, 4H), 2.10 (s, 3H), 1.47-1.46 (d, 6H), 1.18-1.07 (m, 2H), 1.03-1.02 (d, 3H). ESI-MS (m / z): 715.26 (M+H)+.

[0566] EXAMPLE 66

[0567] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanamide

[0568] Prepared using Example 1 by following similar procedure as described for example 64.

[0569] 1H NMR (DMSO-J6): 8.03 (s, 1H), 7.56-7.54 (m, 2H). 7.46-7.44 (m, 2H) 7.05-6.99 (m, 1H), 6.98 (m, 1H), 6.93-6.91 (m, 1H), 6.86 (m,lH), 6.64-6.62 (m, 2H), 6.41 (s, 1H), 6.33 (s, 1H), 5.50-5.48 (d, 7 =8.0 Hz, 1H), 4.56-4.53 (d, 7 =10.8 Hz, 1H), 4.07-4.04 (d, 7 =10.4 Hz, 1H), 3.66 (s, 3H), 2.14 (s, 3H), 1.40 (s, 6H), 1.16-1.08 (m, 4H). ESI-MS (m / z): 645.40 (M+H)+

[0570] EXAMPLE 67

[0571] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane-1, 3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-N-hydroxy-2-methylpropanamide

[0572]

[0573] Step 1: Preparation of N-(benzyloxy)-2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'- (trifluoromethoxy) spiro [cyclopropane- 1 , 3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino) oxy)-2-methylpropanamide

[0574] To a stirring solution of the product obtained from example 1 (0.20 g, 0.316 mmol) in dry DMF (5 ml) was added DIPEA (0.09 ml, 0.475 mmol) and O-benzylhydroxylamine (0.061 g, 0.38 mmol) followed by HATU (0.132 g, 0.348 mmol) and the resulting mixture was stirred at RT for 2 hrs. After complete conversion of starting material, the reaction mixture was diluted with cold water, acidify with aqueous HC1 and extracted with ethyl acetate.

[0575] Organic layer was separated, washed with water and evaporated under reduced pressure to get crude product which was directly used for next step.

[0576] Step 2: Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5-methoxyphenyl)ethylidene) amino)oxy)-N-hydroxy-2-methylpropanamide To a stirring solution of the product obtained from step 1 (0.30 g, 0.408 mmol) in 50% methanol: THF (5 mL) was added Pd / C (0.043 g, 4.08 pmol) and the resulting mixture was stirred at room temperature under hydrogen pressure for 4 hrs. After complete conversion of starting material, the reaction mixture was filtered through Hyflow and filtrate was evaporated under reduced pressure to get crude product which was purified by column chromatography to get the title product. NMR (DMSO-de): 10.28 (s, 1H), 8.03 (s, 1H), 7.57-7.55 (d, 2H), 7.47-7.44 (d, 2H), 7.09-6.99 (t, 1H), 6.96-6.92 (m, 1H), 6.67 (s, 1H), 6.41 (s, 1H), 6.34 (s, 1H), 5.50 (s, 1H), 4.57-4.54 (d, 1H), 4.07-4.04 (d, 1H), 3.66 (s, 3H), 2.13 (s, 3H), 1.44-1.41 (d, 6H), 1.29-1.24 (d, 2H), 1.15-1.09 (m, 4H). ESI- ESI-MS (m / z): 661.21 (M+H)+.

[0577] EXAMPLE 68

[0578] Preparation of 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-

[0579] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanenitrile

[0580] To a stirring solution of the product obtained from intermediate IV-1 (100 mg, 0.19 mmol) in DMF (5 ml) was added intermediate V-27 (48.3 mg, 0.19 mmol) followed by triethylamine (0.082 ml, 0.59.3 mmol) and the resulting mixture was stirred at 80°C for 14 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product.1H NMR (DMSO-J6): 8.01 (s, 1H), 7.57 (d, 2H), 7.55-7.46 (d, 2H), 6.99-6.98 (d, 1H), 6.93- 6.91 (d, 1H), 6.72-6.70 (m, 2H), 6.47-6.46 (m, 1H), 6.39-6.38 (m, 1H), 5.52-5.50 (d, 1H), 4.57-4.55 (d, 1H), 4.07-4.04 (d, 1H), 3.68 (s, 3H), 2.14 (s, 3H), 1.65 (s, 6H), 1.15-1.08 (m, 4H). ESI- ESI-MS (m / z): 627.20 (M+H)+. EXAMPLE 69

[0581] Preparation of 2-((3-(l-(((2-(lH-tetrazol-5-yl)propan-2-yl)oxy)imino)ethyl)-5- methoxyphenyl)amino)-2-(4-chlorophenyl)-l-(6'-

[0582] (trifluoromethoxy)spiro [cyclopropane- 1 ,3 ' -indolin] - 1 ' -yl)ethan- 1 -one

[0583] To a stirring solution of the product obtained from Example 68 (150 mg, 0.23 mmol) in dry DMF (10 ml) was added sodium azide (78 mg, 1.19 mmol) followed by ammonium chloride (64 mg, 1.19 mmol) and the resulting mixture was stirred at 110°C for 14 hrs. After completion of reaction, the reaction mixture was diluted with cold water and extracted by ethyl acetate. The organic layer was separated, washed with water, evaporated under reduced pressure, and purified by column chromatography to get the title product.1H NMR (DMSO-J6): 7.52 (s, 1H), 7.50-7.44 (d, 2H), 7.42-7.41 (d, 2H), 6.99-6.93 (d, 1H), 6.91-6.90 (d, 1H), 6.72-6.70 (m, 1H), 6.63 (s, 1H), 6.61-6.60 (m, 2H), 5.44-5.42 (d, 1H), 4.54-4.51 (d, 1H), 4.06-4.04 (d, 1H), 3.63 (s, 3H), 2.14 (s, 3H), 1.74-1.72 (d, 6H), 1.15-1.08 (m, 4H). ESI- ESI-MS (m / z): 670.25 (M+H)+.

[0584] EXAMPLE 70

[0585] Preparation of 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-

[0586] (trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanenitrile

[0587] Prepared using intermediates IV-1 and V-26 by following a similar process as described for Example 68. ’H NMR (DMSO-d6): 7.57 (s, 1H), 7.55-7.46 (d, 2H), 7.44-7.43 (d, 2H), 6.99- 6.98 (d, 1H), 6.93-6.91 (m, 1H), 6.91-6.90 (m, 2H), 6.65 (s, 1H), 6.35 (s, 1H), 5.54-5.51 (d, 1H), 4.57-4.55 (d, 1H), 4.26-4.24 (t, 2H), 4.08-4.06 (d, 1H), 3.67 (s, 3H), 2.89-2.86 (t, 2H), 2.11 (s, 3H), 1.15-1.09 (m, 4H). ESI- ESI-MS (m / z): 613.20 (M+H)+.

[0588] EXAMPLE 71

[0589] Preparation of 2-((3-(l-((2-(lH-tetrazol-5-yl)ethoxy)imino)ethyl)-5- methoxyphenyl)amino)-2-(4-chlorophenyl)-l-(6'-

[0590] (trifluoromethoxy)spiro [cyclopropane- 1 ,3 ' -indolin] - 1 ' -yl)ethan- 1 -one

[0591] Prepared using product obtained from example 70 using a similar process as described for Example 69.1H NMR (DMSO-d6): 7.57 (s, 1H), 7.55-7.46 (d, 2H), 7.44-7.44 (d, 2H), 6.99- 6.98 (d, 1H), 6.93-6.91 (d, 1H), 6.59 (s, 1H), 6.36-6.32 (m, 2H), 5.51 (d, 1H), 4.58-4.56 (d,

[0592] 1H), 4.44-4.41 (t, 2H), 4.10-4.07 (d, 1H), 3.66 (s, 3H), 3,27-3,24 (t, 2H), 1.99 (s, 3H), 1.15- 1.09 (m, 4H). ESI- ESI-MS (m / z): 656.22 (M+H)+.

[0593] Using appropriate starting materials and suitable modifications of the process described for the preparation of the above examples including suitable addition and / or deletion of steps as may be necessary, well within the scope of a person skilled in the art; the following compounds were prepared in an analogues manner.

[0594]

[0595] Biological Data:

[0596] Assay protocol to screen compounds using RT-PCR VeroE6 cells, mycoplasma free are seeded at the density of 25,000 cells / well in lOO l / well in 96 well plate in Complete MEM (Plain MEM + 10% FBS+ IX antibiotics) and incubated overnight at 37°C, 5%CC>2. Next day, the required virus (DENV2 NGC Strain -New Guinea C) of 106PFU / mL in plain MEM at 0.05 MOI is added to the cells and incubated for 1 hour at 37°C, 5%CO2. After 1 hour, virus was removed and compounds were added at required concentrations. After 48 hours, RNA was isolated from the supernatant. It is then reverse transcribed to cDNA and amount of virus detected by RT-PCR. Following the denaturation at 95°C for 5 minutes, the RT-PCR was run for 45 cycles for 95°C for 10 second, 60°C 30sec. Delta delta CT was calculated for all CT values. %Inhibition was calculated by considering DMSO delta delta CT as 100-%Inhibition. Inhibitory concentration (50%) was derived from plotting the data in Graph pad prism and performing Non-linear regression analysis.

[0597] Compounds of the invention have shown excellent antiviral potency as reflected in their DENV2 IC50(Table 5). Table 5: Biological activity data

[0598] Examples 21, 32, 33, 34, 35, 37, 48, 49, 59, 62, 66, 68, 69, 70, 71, 72, 73, 76, 78, 98, 107, 108, 119 and 120 have shown DENV2 IC50 value in the range of less than 100 nM.

[0599] The novel compounds of formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients by techniques and processes and concentrations as are well known.

[0600] The novel compounds of formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs are useful as a medicament for the mammalian infections and suitable for humans and other warm-blooded animals, and may be administered either by oral, topical or parenteral administration.

[0601] The quantity of the active component, that is, the novel compounds of formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts, their polymorphs and unit dosage form thereof may be varied or adjusted widely depending upon several factors such as the particular application method, the potency of the particular compound and the desired concentration.

[0602] Use of the novel compounds of formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs for the treatment of virus- related disorders such as Dengue.

[0603] A method of treatment of virus-related disorders such as Dengue by administering to a subject in need thereof a therapeutically effective amount of formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs.

Claims

We claim:

1. A novel compound of the general formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs,formula (I)Wherein,X is selected from aryl, heteroaryl or heterocyclyl ring;Ri is selected from hydrogen, halogen, haloalkyl, (Ci-Ce)alkyl, heterocyclyl, -ORe; where (Ci-Qjalkyl, heterocyclyl are independently unsubstituted or substituted with one or more suitable substituents;Y is selected from carbocyclic ring or heterocyclic ring; which are independently unsubstituted or substituted with one or more suitable substituents selected from (Ci- Ce)alkyl, -ORe, halogen;A and B is selected from carbocyclic or heterocyclic ring;R2 and R3 are selected from hydrogen, hydroxy, cyano, halo, nitro, haloalkyl, (Ci- Ce)alkyl, (C2-C6) alkenyl, (C2-Ce)alkynyl, (C3-Ce)cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heterocyclylalkyl, alkylsulfonyloxy, -CORe, -COORe, -ORe, - OSO2CH3, -OCOR6, -S(O)PR6, -NR6R7, -CONR6R7, -N(R6)COR7, -N(R6)COOR7, - N(Re)CONReR7, -SO2NReR7, -N(Re)SO2R7; which are independently unsubstituted or substituted with one or more suitable substituents;R4 is selected from hydrogen, (Ci-Ce)alkyl, (C3-Ce)cycloalkyl, haloalkyl and heterocyclyl, which are independently unsubstituted or substituted with one or more suitable substituents;R5 is selected from haloalkyl, (Ci-Ce)alkyl, (CrC cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heterocyclylalkyl, which are independently unsubstituted or substituted with one or more suitable substituents;Re and R7 are independently selected from hydrogen, unsubstituted or substituted (Ci-Ce)alkyl, (C3-Ce)cycloalkyl, haloalkyl; Re and R7 together with the N atom to which they are attached to form a 5-8 membered heterocyclyl or heteroaryl ring; when any of the (Ci-Ce)alkyl, (C2-Ce)alkenyl, (C2-Ce)alkynyl, (C3-Ce)cycloalkyl are substituted; the suitable substitutions are selected from hydrogen, hydroxy, cyano, halo, nitro, haloalkyl, oxo, (Ci-Ce)alkyl, (C3-Ce)cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heterocyclylalkyl, alkylsulfonyloxy, -CORe, -COORe, -ORe, - S(O)PR6, -NR6R7, -CONR6R7, -CON(R6)OR7, -CON(R6)SO2R7, -N(R6)COR7, - N(R6)COOR7, -N(R6)CONR6R7, -SO2NR6R7, -N(R6)SO2R7derivatives; R6and R7are same as described above; p is selected from integers from 0-2;1 is selected from integers from 1-4; m is selected from integers from 1-5; n is selected from integers from 1 -4.

2. The compound of formula (I) as claimed in claim 1, wherein X is aryl; Y is carbocyclic ring; A and B is carbocyclic or heterocyclic ring; Ri R2 and R3 selected from hydrogen, cyano, halogen, (Ci-Ce)alkyl, haloalkyl, heterocyclyl and -ORe; R4 and R5 selected from (Ci-Ce)alkyl.

3. Compounds of the formula as claimed in claim 1:2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-T-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;(+) 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-T-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;(-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-T-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-T-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;(+) 3-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;(-) 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;2-(4-chlorophenyl)-2-((3-(l-((2-hydroxyethoxy)imino)ethyl)-5- methoxyphenyl) amino)- l-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 yl)ethan-l-one;2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;(+) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2- methylpropanoic acid;(-) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2- methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;2-(((3-((l-(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)-2-oxoethyl)amino)-5-methoxybenzylidene)amino)oxy)-2- methylpropanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2- methylpropanoic acid;(+) 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)propylidene) amino)oxy) -2-methylpropanoic acid ;(-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2- methylpropanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3' -indolin] - 1 '-yl)ethyl) amino) -5 -methoxyphenyl) -2- methylpropylidene)amino)oxy)-2-methylpropanoic acid;2-((((3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)(cyclopropyl)methylene)amino)oxy)- 2-methylpropanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)-2,2,2- trifluoroethylidene)amino)oxy)-2-methylpropanoic acid;2-(((l-(3-methoxy-5-((2-oxo-l-phenyl-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-(((l-(3-((l-(4-fluorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;2-((( 1 -(3-(( 1 -(2,4-dichlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-(( 1 -(5-chloropyridin-2-yl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-methoxyspiro[cyclopropane- 1 ,3'-indolin] - l'-yl)- 2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-morpholinospiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)acetic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)butanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-3- methylbutanoic acid;3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-1 ,3'-indolin] - 1 '-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)cyclobutane-l -carboxylic acid;4-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)butanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopentane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane-l,3'- indolin]-r-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid; 3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopentane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)propanoic acid;3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxybenzaldehyde O-(2-hydroxyethyl) oxime;2-(4-chlorophenyl)-2-((3-(l-(((l-hydroxy-2-methylpropan-2-yl)oxy)imino)ethyl)-5- methoxyphenyl) amino)- l-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 yl)ethan-l-one;3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin] - l'-yl)ethyl)amino)-5-methoxybenzaldehyde 0-( 1 -hydroxy-2-methylpropan- 2-yl) oxime;2-(4-chlorophenyl)-2-((3-(l-((2-hydroxy-2-methylpropoxy)imino)ethyl)-5- methoxyphenyl) amino)- l-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)ethan-l-one;2-(4-chlorophenyl)-2-((3-(l-((3-hydroxypropoxy)imino)ethyl)-5- methoxyphenyl) amino)- l-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)ethan-l-one;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chloro-2-(2-hydroxyethoxy)phenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;(+) 3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;(-) -3-((( 1 -(3-(( l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-methoxy-5-(( 1 -(4-methoxyphenyl)-2-oxo-2-(6'-( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1'- yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-(((l-(3-((l-(4-cyanophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane- 1 ,3'-indolin]- l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopentane- 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclobutane- 1 ,3'-indolin]- l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopentane- 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2- methyl-N-(methylsulfonyl)propanamide;(+) 2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide;(-) 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- l,3'-indolin]-l'-yl) ethyl) amino)-5 -methoxyphenyl) ethylidene) amino) oxy)-2-methyl-N-(methylsulfonyl)propanamide;2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- 1,3'- indolinj-l'-yl) ethyl) amino) -5-methoxybenzylidene) amino)oxy)-2-methyl-N- (methylsulfonyl)propan amide;(+) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- l,3'-indolin]-l'-yl) ethyl) amino) -5-methoxybenzylidene) amino)oxy)-2-methyl-N- (methylsulfonyl)propan amide;(-) 2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclopropane- l,3'-indolin]-l'-yl) ethyl) amino) -5-methoxybenzylidene) amino)oxy)-2-methyl-N- (methylsulfonyl)propan amide;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spiro [cyclobutane- l,3'-indolin]-l'-yl) ethyl)amino)-5-methoxyphenyl) ethylidene) amino) oxy)-2- methyl-N-(methylsulfonyl)propanamide;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy) spirofcyclopentane- l,3'-indolin]-l'-yl) ethyl) amino)-5-methoxyphenyl) ethylidene) amino)oxy)-2- methyl-N-(methylsulfonyl)propanamide;2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propan amide;3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)propenamide;3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopentane- 1 ,3'-indolin]- 1 '-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)propenamide;3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)propenamide;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- isopropyl-2-methylpropan amide;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl- 1 -morpholinopropan- 1 -one;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanamide ;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- hydroxy-2-methylpropan amide;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanenitrile ;2-((3-(l-(((2-(lH-tetrazol-5-yl)propan-2-yl)oxy)imino)ethyl)-5- methoxyphenyl) amino) -2-(4-chlorophenyl)(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethan- 1 -one;3-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-1 ,3'-indolin] - 1 '-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanenitrile;2-((3-(l-((2-(lH-tetrazol-5-yl)ethoxy)imino)ethyl)-5-methoxyphenyl)amino)-2-(4- chlorophenyl)- 1 -(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin]- l'-yl)ethan-1-one;3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)-5-methoxybenzaldehyde O-methyl oxime;2-(4-chlorophenyl)-2-((3-methoxy-5-(l-(methoxyimino)ethyl)phenyl)amino)-l-(6'- (trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethan- 1 -one;2-(((3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)acetic acid;2-(((3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)propanoic acid;2-(((3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)butanoic acid;2-(((3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin]- 1 yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)acetic acid;2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-r-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)propanoic acid;2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-r-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)butanoic acid;2-(((3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-r-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-3-methylbutanoic acid;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;2-(((3-((l-(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxybenzylidene)amino)oxy)propanoic acid;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)butanoic acid;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-3-methylbutanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)propan amide;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)propanamide;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)butan amide;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-N-(methylsulfonyl)butanamide;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-3-methyl-N-(methylsulfonyl)butan amide; 2-(((3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin]- 1 yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methylpropanoic acid;2-(((3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin] - 1'- yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propan amide;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propanamide; 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2- methyl-N-(methylsulfonyl)propanamide;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethyl)amino)-5- methoxyphenyl)propylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propan amide; 2-(4-chloro-2-methoxyphenyl)-2-((3-(l-((2-hydroxy-2-methylpropoxy)imino)ethyl)- 5 -methox yphenyl)amino)- 1 -(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]- l'-yl)ethan-l-one;2-(4-chloro-2-methoxyphenyl)-2-((3-( !-(((! -hydroxy-2-methylpropan-2- yl)oxy)imino)ethyl)-5-methoxyphenyl)amino)-l-(6'-(trifluoromethoxy)spiro[cyclopropane- 1 ,3'-indolin] - l'-yl)ethan- 1 -one;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(spiro[cyclopropane- 1 ,3'-indolin]- 1 '- yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methylpropanoic acid; 2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-N- (methylsulfonyl)acetamide;4-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)butanoic acid;2-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)propylidene) amino)oxy) -2-methylpropanoic acid ;2-(((3-methoxy-5-((2-oxo-l-phenyl-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'- indolin]-l'-yl)ethyl)amino)benzylidene)amino)oxy)-2-methylpropanoic acid;2-(((3-methoxy-5-((l-(4-methoxyphenyl)-2-oxo-2-(6'-( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1'- yl)ethyl)amino)benzylidene)amino)oxy)-2-methylpropanoic acid;2-(((3-((l-(2,4-dichlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxybenzylidene)amino)oxy)-2- methylpropanoic acid;2-((( 1 -(3-methoxy-5-((2-oxo- 1 -(tetrahydro-2H-pyran-4-yl)-2-(6'-( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1'- yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-(((l-(3-((l-(4-fluorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl- N-(methylsulfonyl)propanamide;2-(((l-(3-methoxy-5-((2-oxo-l-phenyl-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propanamide;2-((( 1 -(3-methoxy-5-(( 1 -(4-methoxyphenyl)-2-oxo-2-(6'-( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1'- yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propan amide;2-(((l-(3-((l-(4-cyanophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl- N-(methylsulfonyl)propanamide;2-((( 1 -(3-(( 1 -(2,4-dichlorophenyl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propanamide;2-((( 1 -(3-(( 1 -(5-chloropyridin-2-yl)-2-oxo-2-(6'-(trifluoromethoxy)spiro[cyclopropane-l,3'-indolin]-l'-yl)ethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N-(methylsulfonyl)propanamide;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-oxo-2-(6'-(trifluoromethyl)spiro[cyclopropane- 1,3'- indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;2-(((l-(3-((l-(4-chlorophenyl)-2-oxo-2-(5'-(trifluoromethoxy)spiro[cyclopropane- l,3'-indolin]-l'-yl)ethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)-2-oxoethyl)amino)-5-methoxyphenyl)-2,2,2- trifluoroethylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-(difluoromethoxy)spiro[cyclopropane- 1,3'- indolin]-l'-yl)-2-oxoethyl)amino)-5-methoxyphenyl)propylidene)amino)oxy)-2- methylpropanoic acid;2-((( 1 -(3-((2-(6'-chloro-7'-methoxyspiro[cyclopropane- 1 ,3'-indolin] - 1 ’-yl)- 1 -(4- chlorophenyl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2- methylpropanoic acid;3-((( 1 -(3-(( 1 -(4-chloro-2-methoxyphenyl)-2-(6'-methoxyspiro[cyclopropane- 1,3'- indolin] - l'-yl)-2-oxoethyl)amino)-5- methoxyphenyl)ethylidene)amino)oxy)propanoic acid;2-((( 1 -(3-(( 1 -(4-chlorophenyl)-2-(6'-methoxyspiro[cyclopropane- 1 ,3'-indolin] - l'-yl)-2-oxoethyl)amino)-5-methoxyphenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propan amide;2-((( 1 -(3-methoxy-5-(( 1 -(6-methoxypyridin-3-yl)-2-oxo-2-(6'-( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1'- yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methylpropanoic acid;2-((( 1 -(3-methoxy-5-(( 1 -(6-methoxypyridin-3-yl)-2-oxo-2-(6'-( trifluoromethoxy) spiro [cyclopropane- 1,3' -indolin] - 1'- yl)ethyl)amino)phenyl)ethylidene)amino)oxy)-2-methyl-N- (methylsulfonyl)propan amide.

4. Use of the novel compound of general formula (I) as claimed in claim 1 for the treatment of virus-related disorder selected from dengue.

5. Use of the compound of general formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs as claimed in claim 1 in the manufacture of a medicament for the treatment of virus- related disorder selected from dengue.

6. Pharmaceutical compositions comprising compounds of general formula (I), their tautomeric forms, their stereoisomers, their suitable pharmaceutically acceptable salts and their polymorphs as claimed in claim 1 and their mixtures having pharmaceutically acceptable carriers, solvents, diluents, binder, disintegrant, coating agent, filler, glidant, and / or other suitable excipients.

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