WO2010086878A2

WO2010086878A2 - Thyroid receptor modulators

Info

Publication number: WO2010086878A2
Application number: PCT/IN2010/000009
Authority: WO
Inventors: Saurin Raval; Preeti Raval; Mukul R. Jain
Original assignee: Cadila Healthcare Limited
Priority date: 2009-01-09
Filing date: 2010-01-06
Publication date: 2010-08-05
Also published as: WO2010086878A3; AR077726A1

Abstract

The present invention relates to novel compounds of general formula (I) which are thyroid receptor ligands and are preferably selective for the thyroid hormone receptor beta. Further, the present invention relates to processes of preparing such compounds, their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, methods for using such compounds and pharmaceutical compositions containing them.

Description

THYROID RECEPTOR MODULATORS

FIELD OF INVENTION

BACKGROUND OF THE INVENTION

Thyroid hormones (TH) are synthesized in the thyroid in response to thyroid stimulating hormone (TSH), which is secreted by the pituitary gland. Production of T4, and T3, by the thyroid gland is under negative feedback control. TSH, also known as thyrotropin, is responsible for normal thyroid gland function and thyroid hormone secretion. It is synthesized in the anterior pituitary gland, and its secretion is controlled by thyroid releasing hormone (TRH) that is synthesized in the hypothalamus. The natural thyroid hormones (TH) T₃ and T₄ are important endocrine signaling hormones. Thyroid hormones are iodinated tyrosine analogues excreted into the circulation primarily as T₄. T₄ is converted to T₃ rapidly by deiodination in local tissues which is the most potent thyroid hormone, ft plays important role in normal development, differentiation and maintenance of metabolic balance, control of cholesterol levels through interaction with thyroid hormone receptors (THR). Natural thyroid hormone, T₃ exhibit its physiological effect by acting on a Thyroid Hormone Receptor (THR), which belongs to the nuclear hormone receptor super family. There are two different isoforms of thyroid Hoπnone Receptors, THR-α and THR-β. Further, these two isoforms are sub-classified as cci; α₂ and βι ; β₂ subtypes. THRβi is prevalent in liver (85%), while THR ct| is mainly present in cardiac tissue (Yen P. M.. Physiol. Rev; 2001; 81:1097-1142). At normal levels, T3 maintains body weight, metabolic rate, body temperature, mood and regulate serum cholesterol. Hypothyroidism is associated with weight gain, high levels of low-density lipoproteins (LDL) cholesterol and depression. Hyperthyroidism leads to weight loss, hypermetabolism, lowering of serum LDL levels, cardiac arrhythmia, heart failure, muscle weakness, bone loss and anxiety.

The natural thyroid hormone T₃ mediates its pharmacological and physiological effect via activation of THR αι and THR β| . However T3 does not show any selectivity in binding to both of the THR isoforms (THR αι and THR βi ). Thus, administration of T₃ lowers plasma cholesterol, low-density lipoprotein (LDL) and triglyceride levels in animal models and humans while at the same time it also causes cardiac side effects such as tachycardia and arrhythmia. Hence, T₃ cannot be used therapeutically to treat hypercholesterolemia and obesity. Some effects of T₃ may be therapeutically useful in non-thyroid disorders if adverse effects can be minimized or eliminated. These potentially useful influences include weight reduction, lowering of serum LDL levels, amelioration of depression and stimulation of bone formation (Cheng S. Steroids; 2005: 70: 450-454). Knockout animal studies as well as results with some selective ligands suggest that cardiac side effects of T₃ can be attributed to the activation of THR ocι isoform.

Development of specific and selective thyroid hormone receptor ligands, particularly THR β agonist could lead to specific therapies for disorders such as obesity and hyperlipidemia, while avoiding the cardiovascular and other toxicities of native thyroid hormones. Thus, compounds mimicking only the beneficial effects of the thyroid hormone and lacking their cardiac side effects (tachycardia and arrhythmia) potentially could be used to treat a number of conditions such as obesity and dyslipidemia. (J. D. Baxter. Trends Endocrinol. Metab. 2004, 15 : 154-157).

TSH regulates thyroid hormone production. Thyromimetics can negatively regulate TSH secretion which ultimately leads to suppression of TSH levels and decreased levels of endogenous T₃ Knockout studies (Abel et al, J. Clin. Invest. 104:291 -300 ( 1999)) have also proved that negative regulation of TSH is through activation of the thyroid receptor beta, which is highly expressed in the pituitary. So there is possibility that selective Thyroid beta agonist can suppress TSH levels. Selective THR β agonist exhibit modest cardiac sparing in rodents and primates and lower lipids but it may induce the THR β mediated suppression of the THA.

Two strategies have been attempted for the development of novel thyromimetics. One is by making isoform selective compounds (Johan Malm, J. Med. Chem. 2003, 46, 1580-1588) and another is by making liver selective thyromiinetics (Mark D. Erion, PNAS 2007 15490-15495). Liver selective compounds are expected not to suppress the thyroid hormone axis (THA). Thus thyromimetic which has β isoform selectivity incorporated with liver selectivity can be expected to be devoid of cardiac toxicity and will not suppress THA.

Various compounds have been disclosed as possible agonists of THR β including those which claim to be liver selective. Some of the more relevant ones for the present invention includes WO 0039077, WO 2004067482, US 6,344,481 , US 6787652, US20070173548, WO2006128058, WO 20080221210 and WO 2009089093 which are incorporated herein as reference.

Improved therapeutic index achieved by Selective THR β agonists can be devoid of cardiac toxicities but it may have effects on THR β mediated suppression of the THA in the pituitary. Therefore, in the present invention we have concentrated on enhancing activation of thyroid Receptor in liver. US2002OO35153 describes compounds of the following general formula as thyromimetics

Various compounds have been disclosed as liver selective Thyromimetics. Some of the more relevant ones for the present invention include US20060046980, WO 200505 1298 A2 WO2006128056 which are incorporated herein as reference.

US20060046980 describes compounds of the following general formula as liver selective thyromimetics

WO/2008/062469 and WO/2007/132475 disclsoes selective TR beta agonists compounds of following general formula respectively:

However, none of these compounds have been commercially developed and looking at the beneficial potential and medical need for such compounds, specifically compounds having better liver selectivity while retaining its therapeutic efficacy, there remains a need for developing further compounds with better therapeutic and/or safety profile. Herein, we disclose novel compounds which shows activity as THR β agonists, some of which also have better liver selectivity. SUMMARY OF THE INVENTION The present invention discloses novel compounds as defined by the general formula (1) that are thyroid receptor ligands and are preferably selective for the thyroid hormone receptor beta 1 , which are useful for the treatment of a number of conditions such as obesity and dyslipidemia. The compounds of the present invention are useful in the treatment of obesity and dyslipidemia. The compounds of this invention are therefore suitable for the treatment/mitigation/regulation or prophylaxis of obesity and dyslipidemia. EMBODIMENT(S) OF THE PRESENT INVENTION

In an embodiment of the present invention is provided novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts and pharmaceutical compositions containing them or their mixtures suitable for the treatment of diabetes, obesity or dyslipidemia.

In a further embodiment is provided process (s) for the preparation of novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them.

In another embodiment is provided pharmaceutical compositions containing compounds of general formula (I), their tautomeric foπns, their pharmaceutically acceptable salts, and their mixtures having pharmaceutically acceptable carriers, solvents, diluents, excipients and other media normally employed in their manufacture. In a still further embodiment is provided the use of the novel compounds of the present invention for the treatment of diabetes, obesity and dyslipidemia, by administering a therapeutically effective and non-toxic amount of the compound as defined by the general formula (I), or their pharmaceutically acceptable compositions to the mammals. Preferably the compounds of present invention have liver selectivity.

DETAILED DESCRIPTION OF THE INVElSfTION

Accordingly, the present invention relates to the compounds of the general formula (1),

(O wherein

R = ORu NHR₁ wherein R| may be selected from H or groups selected from (C|-C₆)alkyl, Ar(Cp C₆)alkyl groups, each of these groups may be further substituted by suitable substituents;R₂ represents hydrogen, hydroxyl, halo, acyl, oxo or optionally substituted groups selected from (C|-C₆)alkyl, alkoxy, (C₃-C₇)cycloalkyl, aryl, heteroaryl, aryloxy, aralkyl, aralkoxy, carboxylic acid and its derivatives selected from (C|-C₃)alkyl esters and amides, sulfenyl derivatives, sulfonyl derivatives or R₂ is selected from the groups representing -CONRsR₆ • -SO₂NR5R6, wherein R₅ and Re may be same or different and at each occurrence are independently selected from H, or groups selected from (C ₁- C6)alkyl, (C₃-C₇)cycloalkyl, bicycloalkyl, aryl groups, each of these groups may be further substituted by suitable substituents; or the groups R5 and R^ together with the nitrogen atom to which they are attached may form a five to eight membered cyclic ring which may further optionally contain one or more hetero atoms selected from N, S, O; The substituents on R₂ represents hydroxy, halo or groups selected from (C _r C_δ)alkyl, (Ci-Ce)haloalkyl, aryl or heteroaryl groups, each of these groups may be further substituted by suitable substituents; Rj, R_A may be same or different and at each occurrence are independently selected from H. halogen or (C|-C6)alkyl groups, each of these groups may be further substituted with suitable substituents; 'X' represents O, -CH₂-, CO; 1Z' represents either a bond or suitable linker selected from NH or -(CH:)_n wherein 'n' represents integer 0-2;

Υ' represents groups selected from alkyl, aryl, heteroaryl, heterocyclyl or cycloalkyl groups, each of these groups may be further substituted by suitable substituents; R₇ may be selected from H or groups selected from (C|-C₆)alkyl. (C₃-C?)cycloalkyl, acyl, aryl, aralkyl, heteroaryl groups, each of these groups may be further substituted by suitable substituents;

R₈ may be selected from ORg, NHR₉ or NHOH wherein; R₉ at each occurrence may be selected from H or groups selected from (C|-C₆)alkyl, which may be further substituted by suitable substituents; Fn a preferred embodiment R₂ is selected from (C|-C₆)alkyl, (C₃-C₇)cycloalkyl, aryl, aralkyl, carboxamide and sulfonamide or acyl groups, each of these groups when applicable may be further substituted by suitable substituents;

In another preferred embodiment the compound of formula I wherein Z represents a bond or the group NH; In another preferred embodiment the compound of formula t wherein R₇ represents H or (CrC₆)alkyl;

In another preferred embodiment the compound of formula I wherein R₈ is selected from OR₉, or NHOH wherein R₉ represents H or groups selected from (Ci- C₆)alkyl, which may be further substituted by suitable substituents; In another preferred embodiment the compound of formula I wherein X represents O or CH₂;

The substituents on alkyl, aryl, heteroaryl or cycloalkyl groups as defined earlier may be selected from hydroxyl, halo, cyano, optionally substituted groups selected from (C|-C6)alkyl, haloalkyl, alkoxy, oxo, aryl, aryloxy, aralkyl, acyl, alkylthio, thioalkyl groups.

When any of these groups are farther substituted, the substituents on these substitutes may be selected from those described above;

In another preferred 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, A?-propyl, /so-propyl, w-butyl, sec-butyl, te/7-butyl, amyl, /-amyl, /?-pentyl, n- hexyl, /.ro-hexyl and the like; - the '"alkoxy" group used either alone or in combination with other radicals, is selected from groups containing an alkyl radical, as defined above, attached directly to an oxygen atom, more preferably groups selected from methoxy, ethoxy, n- propoxy, /sopropoxy, w-butoxy, /-butoxy, /so-butoxy, pentyloxy, hexyloxy, and the like; - the '"halo" group is selected from Cl, Br, F or I; the "haloalkyl'^" group is selected from an alkyl radical, as defined above, suitably substituted with one or more halogens; such as perhaloalkyl, more preferably, perfluoro(C|-C₆)alkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, mono or polyhalo substituted methyl, ethyl, propyl, butyl, pentyl or hexyl groups; 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 '"aryloxy" group used either alone or in combination with other radicals, is selected from groups containing aryl radical, as defined above, attached directly to an oxygen atom; 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, quinolinyt, pyrimidinyl, pyrazolyl, quinazolinyl, pyridazinyl, triazinyl, benzimidazolyl, benzotriazolyl, phthalazynil, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl, benzoxazolyl, benzothiazolyl and the like; - the "heterocyclyl" group may be 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, 2-oxopiperidinyl, 4-oxopiperidinyl, 2-oxopiperazinyl, 3- oxopiperazinyl, moφholinyl, thiomorpholinyl, 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, thienopiperidinyl, groups, each of these groups may be optionally substituted with one or more substituents selected from hydrogen, halogen, alkyl, alkoxy, hydroxyl, haloalkyl, haloalkoxy, aryl, aralkyl, cyano, alkylthio, thioalkyl groups; - the '"cycloalkyl" group may be selected from a cyclic radical containing three to ten carbons, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; the substituents on the cycloalkyl group may be selected from hydrogen, halogen, alkyl, alkoxy, hydroxyl, haloalkyl. haloalkoxy, cyano, alkylthio, thioalkyl groups;

- the "'bicycloalkyl" group may be selected form two cycloalkyl groups pendantly attached to each other wherein the "cycloalkyl" gropus as defined earlier;

- the group "aralkyl" represents an aryl group as defined above attached to an alkyl group as described above; the "acyl" group used either alone or in combination with other radicals, is selected from a radical containing one to eight carbons, more preferably selected from formyl, acetyl, propanoyl. butanoyl, /so-butanoyl, pentanoyl, hexanoyl, heptanoyl, benzoyl and the like, which may be substituted;

- the "oxo" or "carbonyl" group used either alone (-C=O-) or in combination with other radicals such as alkyl described above, for e.g. "alkylcarbonyl", denotes a carbonyl radical (-C=O-) substituted with an alkyl radical described above such as acyl or alkanoyl;

- the "carboxylic acid" group, used alone or in combination with other radicals, denotes a -COOH group, and includes derivatives of carboxylic acid such as esters and amides; the "ester" group used alone or in combination with other radicals, denotes -COO- group, and includes carboxylic acid derivatives, more preferably the ester moieties are selected from alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl. and the like, which may optionally be substituted; aryloxycarbonyl group such as phenoxycarbonyl, napthyloxycarbonyl. and the like, which may optionally be substituted; aralkoxycarbonyl group such as benzyloxycarbonyl, phenethyloxycarbonyl, napthylmethoxycarbonyl, and the like, which may optionally be substituted; heteroaryloxycarbonyl, heteroaralkoxycarbonyl, wherein the heteroaryl group, is as defined above, which may optionally be substituted; heterocyclyloxycarbonyl, where the heterocyclic group, as defined earlier, which may optionally be substituted;

- the "amide"' group used alone or in combination with other radicals, represents an aminocarbonyl radical (H₂N-C=O-), wherein the amino group is mono- or di- substituted or unsubstituted, more preferably the groups are selected from methylamide, diethylamide, ethylamide, diethylamide, and the like;

- the "alkylthio" group used either alone or in combination with other radicals, denotes a straight or branched or cyclic monovalent substituent comprising an alkyl group as defined above, linked through a divalent sulfur atom having a free valence bond from the sulfur atom, more preferably the groups may be selected from methylthio, ethylthio, propylthio, butylthio, pentylthio and the like or cyclic alkylthio selected from cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio and the like, which may be optionally substituted;

- the '"thioalkyl" group used either alone or in combination with other radicals, denotes an alkyl group, as defined above, attached to a group of formula -SR", where R' represents hydrogen, alkyl or aryl group, e.g. thiomethyl, methylthiomethyl, phenylthiomethyl and the like, which may be optionally substituted;

- the "'sulfenyl" group or "sulfenyl derivatives" used alone or in combination with other radicals, represents a bivalent group, -SO- or R_xSO, where R_x is an optionally substituted alkyl, aryl, heteroaryl, heterocyclyl, group selected from those described above;

- the "sulfonyl" group or "sulfones derivatives" used either alone or in combination with other radicals, with other terms such as alkylsulfonyl, represents a divalent radical -SO₂-, or R_xSO₂-, where R_x is as defined above. More preferably, the groups may be selected from "alkylsulfonyl^1" wherein suitable alkyl radicals, selected from those defined above, is attached to a sulfonyl radical, such as methylsulfonyl, ethylsulfonyl, propylsulfonyl and the like, "arylsulfonyl" wherein an aryl radical, as defined above, is attached to a sulfonyl radical, such as phenylsulfonyl and the like.

Depending on the reactive groups present in the Compound of formula ([). it can be converted in to suitable pharmaceutically acceptable salts such as alkali metal salts, alkaline earth metal salts for example sodium, lithium, calcium, magnesium, potassium or suitable acid addition salts like hydrochloride, phosphate and sulfate. In another embodiment the compound of formula (I) or its salts can be prepared in its respective isomeric forms.

Preferable compounds according to the present invention include but are not limited to: 2-(N-(3,5-dichloro-4-((6-hydroxy-[ l J '-biphenyl]-3- yl)oxy)phenyl)benzamido) acetic acid; 2-(N-(3,5-dichloro-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-hydroxy benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2- phenylacetamido) acetic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzamido)acetic acid; 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)acetic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)-2- phenylacetamido)acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-phenyl acetamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-hydroxy benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)benzamido)acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ l, r-biphenyl]-3-yl)oxy)phenyl)benzamido) acetic acid; 2-(N-(3.5-dibromo-4-(3-(sec-butyl)-4-hydro.\yphenoxy)phenyl)-2-phenyl acetamido) acetic acid;

2-(N-(4-(3-(sec-buty!)-4-hydroxypheno\y)-3,5-dichlorophenyl)benzamido)acetic acid; 2-(N-(3.5-dibromo-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-2-phenyl acetamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)thiophene-2- carboxamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)thiophene-2-carbox amido)acetic acid;

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzaιnido) propanoic acid;

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)thiophene-2-carbox amido)acetic acid; 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)furan-2-carbox amido)acetic acid;

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)benzamido) propanoic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)furan-2-carbox amido)acetic acid;

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dimethylphenyl)benzamido)acetic acid;

2-(N-(4-(4-hydroxy-3-isopropylphenoxy)-3,5-dimethylphenyl)benzamido)acetic acid; 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropyIphenoxy)phenyl)benzamido) propanoic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido) butanoic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)-2-methyl propanoic acid; 2-(N-(3.5-dibromo-4-((6-hydroxy-[l , r-biphenyl]-3-yl)oxy)phenyl)benzamido) propanoic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromopheny!)benzamido)acetic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromophenyl)benzamido)propanoic acid;

2-(N-(3,5-dibromo-4-(3-ethyl-4-hydroxyphenoxy)phenyl)benzamido)acetic acid;

2-(N-(4-((6-hydroxy-[l, l'-biphenyl)-3-yl)oxy)-3.5-dimethylphenyl)benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(tert-butyl)-4-hydroxyphenoxy)phenyl)benzamido)acetic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromophenyl)thiophene-2- carboxamido)acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl) cyclohexane carboxamido) acetic acid; 2-(3-chloro-N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-methyl benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methyl benzamido) acetic acid;

2-(N-(3.5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl) cyclohexane carbox amido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-(trifluoromethyl) benzamido) acetic acid; 2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-methyl benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-methyl benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(4-hydro\y-3-isopropylphenoxy)phenyl) cyclopropane carboxamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-hydroxy benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-hydroxy benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ I , l '-biphenyl]-3-yl)oxy)phenyl)-3-hydroxy benzamido) acetic acid;

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)-4-methyl benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ I , l '-biphenyl]-3-yl)oxy)phenyl)-2-hydroxy benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , l '-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetic acid; 2-(N-(3,5-dichloro-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-hydroxy benzamido) acetic acid;

2-(4-chloro-N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-methyl benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , l '-biphenyl]-3-yl)oxy)phenyl)-2-methyl benzamido) acetic acid; 2-(N-(3,5-dibromo-4-((6-hydroxy-2'-methyl-[ l , r-biphenyl]-3-yl)oxy)phenyl) benzamido) acetic acid;

2-(2-chloro-N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-(trifluoro methyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-((2',6-dihydroxy-[ 1 , 1 '-biphenylj-3- yl)oxy)phenyl)benzamido) acetic acid;

2-(N-(3.5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-(tri fluoromethyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-(trifluoro methyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3,5-bis(trifluoro methyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-((6-hydroxy-[ 1 , l '-biphenyl]-3-yl)oxy)phenyl)-3,5-bis(trifluoro methyl) benzamido)acetic acid;

2-(N-(3,5-dibromo-4-((2'-fluoro-6-hydroxy-[ 1 , 1 '-bipheny l]-3-yl)oxy)pheny I) benzamido)acetic acid;

2-(N-(3,5-dichloro-4-(3-(N,N-diethylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(N,N-diethylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-(piperidin- 1 -ylsulfonyl) phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(N-cyclohexylsulfamoyl)-4-hydrox.yphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(diethylcarbamoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-(piperidine- l -carbonyl) phenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(4-hydroxy-3-(piperidine- l -carbonyl) phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-((4-chlorophenyl)(hydroxy)methy!)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(3-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3.5-dibromo-4-(3-((3-chlorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(4-fluorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-((4-fluorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(3-fluorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-((3-fluorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido)acetic acid;

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)morpholine-4- carbox amido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)morpholine-4- carbox amido) acetic acid;

2-(N-(3,5-dichloro-4-((6-hydroxy-[l,r-biphenyl]-3-yl)oxy)phenyl)moφholine-4- carboxamido) acetic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)morpholine-4-carbox amido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)morpholine-4- carboxamido) acetic acid;

2-(l-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3- phenylureido)acetic acid; 2-(l-(3,5-dichloro-4-((6-hydroxy-[l, l'-biphenyl]-3-yl)oxy)phenyl)-3-isopropyl ureido)acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4- hydroxypiperidine-1-carbox amido) acetic acid;

2-(3-cyclohexyl-l -(3,5-dichloro-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) ureido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[l,l'-biphenyl]-3-yl)oxy)phenyl)morpholine-4- carboxamido) acetic acid; 2-( l-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-isopropyl ureido) acetic acid;

2-( l -(3,5-dichloro-4-((6-hydroxy-[ l . l'-biphenyI]-3-yl)o\y)phenyl)-3-phenyl ureido) acetic acid; 2-( 1 -(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)pheny l)-3- phenylureido)acetic acid;

2-( 1 -(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido)acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methylpiperazine- 1 -carboxamido) acetic acid;

2-(3-cyclohexyl- l -(3,5-dibromo-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) ureido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methylpiperazine- 1 -carboxamido) acetic acid; 2-( l-(3,5-dibromo-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-3-isopropyl ureido) acetic acid;

2-( l -(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)-3- phenylureido)acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)- 4- hydroxypiperidine- 1-carboxamido) acetic acid;

N-(3,5-dichloro-4-((6-hydroxy-[ 1 , l'-biphenyl]-3-yl)oxy)phenyl)-N-(2-(hydroxyl amino)-2-oxoethyl) benzamide;

N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-N-(2-(hydroxyl amino)-2-oxoethyl) benzamide; N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-N-(2-(hydroxyamino)-

2-oxoethyl)benzamide;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ l , r-biphenyl]-3-yl) oxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l , r-biphenyl]-3-yl)oxy)phenyl)-4- methoxy benzamido) acetate; Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-phenyl acetamidό) acetate; Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5- dichlorophenyl)benzamido)acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dichlorophenyl)-2-phenyl acetamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-phenyl acetamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methoxy benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)-2-phenyl acetamido) acetate;

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl) benzamido) acetate;

Ethyl2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-bipheny l]-3-y l)oxy)phenyl)-2-phenyl acetamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ l , l '-biphenyl]-3- yl)oxy)phenyl)thiophene-2-carboxamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)thiophene-2- carboxamido) acetate;

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl) benzamido) propanoate; Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)thiophene-2- carboxamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)furan-2- carboxamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy) phenyl) benzamido) propanoate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)furan-2- carboxamido) acetate;

Ethyl 2-(N-(4-(3-(sec-bιιtyl)-4-methoxyphenoxy)-3,5-dimethylphenyl) benzamido) acetate;

Ethyl 2-(N-(4-(3-isopropyl-4-methoxyphenoxy)-3,5-dimethylphenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl) benzamido) propanoate; Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl) benzamido) butanoate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)benzamido)-2- methyl propanoate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-bipheny l]-3-yl)oxy) phenyl) benzamido) propanoate;

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5- dibromophenyl)benzamido)acetate;

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dibromophenyl) benzamido) propanoate; Ethyl 2-(N-(3,5-dibromo-4-(3-ethyl-4-methoxyphenoxy)phenyl)benzamido)acetate;

Ethyl 2-(N-(4-((6-methoxy-[l , ] '-biphenyl]-3-yl)oxy)-3,5-dimethylphenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(tert-butyl)-4-methoxyphenoxy) phenyl) benzamido) acetate; Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dibromophenyl)thiophene-2- carboxamido) acetate;

Ethyl 2-(N-(3,5-dibroιno-4-(3-isopropyl-4-methoxypheπoxy) phenyl) cyclohexane carboxamido) acetate; Ethyl 2-(3-chloro-N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyprιenoxy)phenyl)-4-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy) phenyl) cyclohexane carboxamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-

(trifluoromethyl) benzamido) acetate; Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3- methylbenzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) cyclopropane carboxamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4- methoxy benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methoxy benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3- methoxy benzamido) acetate;

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl)-4-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[l,r-biphenyl]-3-yl)oxy)phenyl)-2- methoxy benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ ] , l '-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ l , r-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-methoxy benzamido) acetate;

Ethyl 2-(4-chloro-N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-2-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-2'-methyl-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate; Ethyl 2-(2-chloro-N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ l , r-biphenyl]-3-yl)oxy)phenyl)-4-

(trifluoromethyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((2',6-dimethoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl)-4-(trifluoro methyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-

(trifluoro methyl) benzamido) acetate; Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3,5- bis(trifluoro methyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ l ,r-biphenyl]-3-yl)oxy)phenyl)-3,5-bis (trifluoromethyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((2'-fluoro-6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl) benzamido) acetate; Ethyl 2-(N-(3,5-dichloro-4-(3-(N,N-diethylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(N,N-diethylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(4-methoxy-3-(piperidin- l -ylsulfonyl) phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(N-cyclohexylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-(diethylcarbamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(4-methoxy-3-(piperidine-.l -carbonyl) phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(4-methoxy-3-(piperidine- l -carbonyl) phenoxy) phenyl) benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-(diethylcarbamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-((4-chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido)acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(3-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-((3-chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-(4-fluorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-((4-fluorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-{N-(3,5-dibromo-4-(3-(3-fluorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido)acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-((3-fluorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido)acetate;

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxypheno\y)-3,5-dichlorophenyl)moφholine- 4-carboxamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-ιnethoxyphenoxy)phenyl)moφholine-

4-carboxamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3- yl)oxy)phenyl)moφholine-4-carboxamido) acetate;

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dichlorophenyl)moφholine-4- carboxamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-ιnethoxyphenoxy)phenyl)morpholine-4- carboxam ido)acetate;

Ethyl 2-( 1 -(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3- phenylureido)acetate; Ethyl 2-( l -(3,5-dichloro-4-((6-methoxy-[ l J '-biphenyl]-3-yl)oxy)phenyl)-3- isopropyl ureido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-hydroxy p i perid i ne- 1 -carboxam ido) acetate;

Ethyl 2-(3-cyclohexyl- l-(3,5-dichloro-4-(3-isopropyl-4-methoxy phenoxy) phenyl) ureido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ l , r-biphenyl]-3- yl)oxy)phenyl)morpholine-4-carboxamido)acetate;

Ethyl 2-( 1 -(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-isopropyl ureido) acetate; Ethyl 2-(l -(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido) acetate;

Ethyl 2-( l-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-phenyl ureido) acetate;

Ethyl 2-( 1 -(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido) acetate; Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methyl piperazine-1-carboxamido) acetate;

Ethyl 2-(3-cyclohexyl-l -(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl) ureido)acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxypheπoxy)phenyl)-4-methyl piperazine-1-carboxamido) acetate;

Ethyl 2-( 1 -(3,5-dibromo-4-((6-methoxy-[ I , I '-biphenyl]-3-yl)oxy)phenyl)-3- isopropyl ureido) acetate;

Ethyl 2-( I -(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)-3-phenyl ureido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-hydroxy piperidine-1 -carboxamido) acetate;

N-(3,5-dichloro-4-((6-hydroxy-[l,l '-biphenyl]-3-yl)oxy)phenyl)-N-(2-oxo-2- (((tetrahydro-2H-pyran-2-yl) oxy)amino)ethyl)benzamide; N-(3,5-dibrorno-4-((6-hydroxy-[l,l '-biphenyl]-3-yl)oxy)phenyl)-N-(2-oxo-2-

(((tetrahydro-2H-pyran-2-yl)oxy)amino)ethyl)benzamide;

N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-N-(2-oxo-2- (((tetrahydro-2H-pyran-2-yl)oxy)amino)Ethyl)benzamide;

The compounds of the present invention can be prepared according to the following schemes 1 to 4 or their suitable combination including suitable variation and/or alteration which is well within the scope of a person skilled in the art

Scheme 1:

Preparation of the compound of formula l(a) wherein R₂ is alkyl, aryl, R5R6NCO- R₅R₆NSO₂-, Z= -(CH2)n-, R₈=OH,

l(a)

In the fi rst step suitable biaryl ether of formula 2 wherein 'PG' represents suitable protecting groups known to persons skilled in the art (for e.g. those described in T. W. Greene and P, G. M. Wuts "Protective groups in Organic Synthesis", John Wiley and Sons, Inc, 1999, 3^rd Ed., 201-245 along with references therein), and all other symbols are as defined elsewhere in the specification, was reduced to give corresponding amine of formula 3. Reduction may be carried out using suitable reducing agents such as Raney Ni, Pd/C. SnChJHiO and the like in solvents such as MeOH or EtOH. Preferably SnCb.2H2θ is used and reaction is carried out at a reflux temperature of the solvents used. The amine 3 may be reacted with suitable alkyl haloacetate in suitable base(s) such as diisopropyl ehtylamine (JPr₂-NEt), pyridine, N,N dimethyl aniline and the like in solvents selected from DMF,THF and the like or their suitable mixtures to give a compound of formula 4. Further compound of formula 4 can be reacted with CICO(CHj)_nY in presence of suitable base such as pyridine,^' EtjN etc in an inert solvents such as dichloromelhane or chloroform or their mixture to give compound of formula 5. Deprotection εnd hydrolysis of compound of formula 5 gives compound represented by structural formula (Ia) Scheme: 2

Preparation of compound of formula l (b) wherein R₂ represents ArCO or ArCHOH-, Z represents -(CHj)_n- and R₈ is OH,

In the first step suitable nitro compound of formula 2 was reacted with suitable aromatic acids or suitable aromatic acid chlorides and appropriate acylating agents to obtain compound represented by structural formula 3. Compound of formula 3 can be converted to compound of formula l(b) by a similar process as described in scheme 1 with suitable variations as necessary. In an alternate embodiment the compound of 7 was reduced using suitable reducing agent as is known in the art to obtain further compounds of formula l (b).

Scheme: 3 Preparation of compound of formula I (c)

represents alkyl, aryl, aralkyl, carboxamides, sulfonamides, Z represents NH and Rg is OH,

In the first step suitable biaryl ether of formula 2 wherein 'PG' represents suitable protecting groups known to persons skilled in the art (for e.g. those described in T. W. Greene and P. G. M. Wuts "Protective groups in Organic Synthesis", John Wiley and Sons, Inc, 1999, 3^rd Ed., 201 -245 along with references therein), and all other symbols are as defined elsewhere in the specification, was reduced to give corresponding amine represented by structural formula 3. Reduction may be carried out using suitable reducing agents such as Raney Ni. Pd/C, SnCb.2H₂O and the like in solvents such as MeOH or EtOH. Preferably SnCh.2H?O is used and reaction is carried out at a reflux temperature of the solvents used. Further amine 3 may be reacted with suitable alkyl haloacetate in suitable base(s) such as diisopropyl ethylamine (JPr₂-NEt), pyridine, N, N dimethyl aniline and the like in solvents such as DMF, THF and the like or their mixtures to give a compound of formula 4. Further compound of formula 4 can be reacted with triphosgene in presence of suitable base such as pyridine, Et₃N and the like in an inert solvents such as dichloromethane or chloroform or their mixture to afford intermediate carbamoyl chloride which was then reacted with corresponding amineCYNHi) in aprotic solvents such as dichloromethane or chloroform using appropriate base such as pyridine, triethylamine and the like or their mixtures to afford compound of formula 5. Finally suitable deprotection and hydrolysis of compound of formula 5 gives compound represented by structural formula (Ic] Scheme 4: Preparation of compound of formula l (d) wherein R₂ represents alkyl, aryl, aralkyl, carboxamides, sulfonamides, Z represents -(CH₂)_P- and R₈ is NHOH

¹Ak' represents suitable alkyl group

In the first step suitable biaryl ether of formula 2 wherein 'PG' represents suitable protecting groups known to persons skilled in the art (for e.g. those described in T. W. Greene and P. G. M. Wuts "Protective groups in Organic Synthesis", John Wiley and Sons, Inc, 1999, 3^rd Ed., 201 -245 along with references therein), and all other symbols are as defined elsewhere in the specification, was reduced to give corresponding amine represented by structural formula 3. Reduction may be carried out using suitable reducing agents such as Raney Ni, Pd/C, SnCk2H₂O and the like in solvents such as MeOH or EtOH. Preferably SnCI₂^H₂O is used and reaction is carried out at the reflux temperature of the solvents used. Further amine 3 may be reacted with suitable alkyl haloacetate in suitable base(s) such as diisopropyl ethylamine (JPr₂-NEt), pyridine, N,N dimethyl aniline and the like in solvents selected from DMF, THF and the like or their mixtures to give a compound of formula 4. Further compound of formula 4 can be reacted with CIC0(CH₂)_nY in presence of suitable base such as pyridine, Et₃N and the like in an inert solvents such as dichloromethane or chloroform to give compound of formula 5. Suitable deprotection and hydrolysis of compound of formula 5 gives compound of formula 6 which was coupled with protected hydroxylamine to afford compound represented by structural foπnula 7. Finally suitable deprotection was carried out using CSA (Camphor sulfonic acid) afforded compound represented by structural formula t(d).

It will be appreciated that the compound of formula I(a), I(b), l(c) and I(d) represent alternative embodiments of compound of formula (I) and are within the scope of compound of formula (I).

The novel compounds of the present invention (1) may be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients or carriers by techniques and processes and concentrations as are well known. The compounds of the present invention can be administered orally or parenterally, neat, or in combination with conventional pharmaceutical carriers. Applicable solid carriers can include one or more substances that can also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders, tablet-disintegrating agents, or encapsulating materials. In powders, the carrier is a finely divided solid that is in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99 % of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins. Liquid carriers can be used in preparing solutions, suspensions, emulsions, syrups and elixirs. The active ingredient can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both, or a pharmaceutically acceptable oil or fat. The liquid carrier can contain other suitable pharmaceutical additives such as, for example, solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (particularly containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols e.g. glycols) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil). For parenteral administration, the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration. The liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceutically acceptable propel lant

The compounds of formula (1) or pharmaceutical compositions containing them are useful as Thyroid hormone receptor ligands suitable for humans and other warm blooded animals, and may be administered either by oral, topical, mucosal, transdermal, subcutaneous or parenteral administration for the treatment of various disease conditions associated with dyslipidemia, obesity etc.

The pharmaceutical composition is provided by employing conventional techniques. Preferably the composition is in unit dosage form containing a therapeutically effective amount of the active component, that is, the compounds of formula (I) according to this invention. The term "therapeutically effective amount," as used herein, refers to the amount of a compound of the present invention that, when administered to a patient, is effective to at least partially treat a condition from which the patient is suffering or is suspected to suffer.

The term "pharmaceutically acceptable excipient" means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic, and desirable, and includes excipients that are acceptable for veterinary use as well as for human pharmaceutical use. Such excipients can be solid, liquid, semisolid, or, in the case of an aerosol composition, gaseous.

"Treat, ''treatment" and "treating," as used herein, refer to partially or completely alleviating, inhibiting, preventing, ameliorating and/or relieving a condition from which a patient is suspected to suffer.

The quantity of active component, that is, the compounds of formula (I) according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application method, the potency of the particular compound and the desired concentration. The usual daily dose is, for example, from 0.01 - 1000 mg/kg for oral application, preferably 0.5 - 500 mg/kg, either in a single dose or in subdivided doses, for example from one to three times daily and from about 0.1 to 100 mg/kg for parenteral application, preferably 0.5 - 50 mg/kg, from one to three times daily. The compounds of the present invention in addition to being selective to the THR beta isoform also are more specific to the liver in that they are targeted to the liver. Such surprising beneficial properties have been seen in appropriate animal experiments for several compounds of the present invention though the effective concentration of the compound necessary in the body to such effect varies with the compounds of the invention being tested.

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. IH NMR spectral data given in the examples (vide infra) are recorded using a 300 MHz spectrometer (Bruker AVANCE-300) or a 400 MHz spectrometer (Bruker AVANCE2) and reported in δ scale. Until and otherwise mentioned the solvent used for NMR is CDCI₃ using tetramethyl si lane as the internal standard EXAMPLE 1 Preparation of 2-(N-(3,5-dichloro-4-((6-hydroxy-[l,l'-biphenyl]-3- yl)oxy)phenyl)benzamido)aceCic acid Step 1 : Preparation of 3,5-dichloro-4-((6-methoxy-[ l, l'-biphenyl]-3-yl)oxy)aniline

A solution of stannous chloride dihydrate (165.69 g, 0.73 mol) in concentrated HCI (71.80 mL) was added to 5-(2,6-dichloro-4-nitrophenoxy)-2-methoxy-l , l '- biphenyl (71.80 g, 0.18 mol) in EtOH (359 mL).The reaction mixture was refluxed for about 2 h. The resulting mixture was brought at room temperature and diluted with ethyl acetate. The mixture was made alkaline with ammonia solution. Resulting solid was filtered through cellite. The organic phase was washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give 3,5-dichloro-4-((6-methoxy- [ 1 , 1 '-biphenyl]-3-y l)oxy)aniline (66 g; 99 % yield).

Step 2: Preparation of ethyl 2-((3,5-dichloro-4-((6-methoxy-[ l , l '-biphenyl]-3- yl) oxy) phenyl) amino) acetate

To 3,5-dichloro-4-((6-methoxy-[ l,l '-biphenyl]-3-yl)oxy)aniline (66 g, 0.18 mol) was added ethyl bromoacetate (33.81 g, 0.20 mol) and diisopropylethyl amine

(26.12 g, 0.20 mol) in DMF (500 mL) and stirred at 140 ⁰C for 18 h. The reaction mixture was poured in to ice-water. The product was taken up in ethyl acetate, washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography over flash silica gel (Hexane: Ethyl acetate 90: 10) to afford the pure product ethyl 2-((3,5- dichloro-4-((6-methoxy-[l ,l'-biphenyl]-3-yl) oxy) phenyl) amino) acetate (59.6 g, 73 % yield)

Step 3: Preparation of ethyl 2-(N-(3.5-dichloro-4-((6-methoxy-[l,l'-biphenyl]- 3-yl) oxy) phenyl) benzamido) acetate

To a solution of ethyl 2-((3,5-dichloro-4-((6-methoxy-[ l, l'-biphenyl]-3-yl) oxy) phenyl) amino) acetate (0.43 g, 0.79 mmol) in dichloromethane (4.3 mL), pyridine (0.23 g, 2.39 mmol) was added at 0-5 ⁰C. After IO min. to that mixture, benzoyl chloride (0.30 g, 2.39 mmol) was added dropwise over 10-15 min. The reaction mixture was stirred at 20-25 ⁰C for another 24h. The reaction mixture was poured in to ice- water. The product was taken up in ethyl acetate, washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography over flash silica gel (Hexane: Ethyl acetate 95:05) to afford the pure product ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l, l'- biphenyl]-3-yl) oxy) phenyl) benzamido) acetate (0.38 g, 71 % yield).

¹H NMR (CDCI₃, 400MHz): 1.26-I.33(3H, m), 4.24-4.29(2H, q, J=7.2Hz), 3.76(3H, s), 4.57(2H, s), 6.64(1 H, d, J=3.2Hz), 6.72 -6.75(1 H, dd, J=3.2Hz and 9.2Hz), 6.87- 6.89(1 H, d, J=9.2Hz), 7.16-7.20(3H, m), 7.27-7.29(I H, m), 7.33-7.36(2H, m), 7.39- 7.59(5H, m).

Step 4: Preparation of 2-(N-(3,5-dichloro-4-((6-hydroxy-[l ,l '-biphenyl]-3-yl) oxy) phenyl) benzamido) acetic acid

A solution of ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l,l'-biphenyl]-3-yl) oxy) phenyl) benzamido) acetate (0.34 g, 0.61 mmol), prepared above (Step 3), in dichloromethane (3.4 mL) was cooled to -60 ⁰C to -70 ⁰C under N₂ atmosphere. To this IM BBr₃ solution (2.47 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature and it was stirred at same temperature for 5 h. The reaction mixture was then diluted with CH₂CI₂ (20 mL) and quenched with H₂O. After stirring at room temperature for 30 min, organic phase was separated, washed with water, brine, dried over sodium sulphate, filtered and concentrated to give crude product. The crude product was purified by column chromatography over flash silica gel (chloroform: methanol) gradient elution from 99:01 to 95:05 to give pure 2-(N-(3,5- dichloro-4-((6-hydroxy-[l,l'-biphenyl]-3-yl) oxy) phenyl) benzamido) acetic acid. (93 mg, 30 %). ¹ H NMR (DMSO-D₆, 400MHz): 4.53(2H, s), 6.46( I H, d, J=3.2Hz), 6.60-

6.63(1 H, dd, J=3.2Hz and 9.2Hz), 6.87( 1 H, d, J=8.8Hz), 7.20-7.25(2H, m), 7.26-

7.32(4H, m), 7.39-7.41 (6H, m).

Using appropriate starting materials and suitable modifications of one or more of the processes described above, either alone or in suitable combination of the steps disclosed therein, 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

(Examples 2-70) were prepared in an analogous manner.

EXAMPLE 2 2-(N-(3,5-dichloro-4-((6-hydroxy-[l , l '-biphenyl]-3-yl)oxy)phenyl)-4-hydroxy benzamido) acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 4.40(2H, s), 6.54-6.57( 1 H, dd, J=2.8Hz and

8.4Hz), 6.62 -6.64(2H, m), 6.88( 1 H, d, J=9.2Hz), 7.17(2H, d, J=8.8Hz), 7.27-7.31(2H, m), 7.38-7.40(2H, m), 7.42(2H, s), 7.44-7.46(2H, m). % Yield: 40

EXAMPLE 3

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)acetic acid

¹ H NMR:(DMSO-D₆, 400MHz): 1.08(6H, d, J=6.8Hz), 3.06-3.1 7(1 H, m), 4.54(2H, s),

6.23-6.26( 1 H, dd, J=3.2Hz and 8.8Hz), 6.48( 1 H, d, J=2.8Hz), 6.65(1 H, d, J=8.4Hz), 7.31 -7.35(5H, m), 7.40(2H, s).

% Yield: 75

EXAMPLE 4

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2- phenylacetamido)acetic acid 1 H NMR(CD₃OD, 400MHz): I . 17(6H, d, J=6.8Hz), 3.23-3.26( I H, m), 3.64(2H, s), 4.35(2H, s), 6.34-6.33( I H, dd, J=2.8Hz and 8.4Hz), 6.67( 1 H, d, J=8.4Hz), 6.70( I H, d, J=2.8Hz), 7.05-7.07(2H, m), 7.20-7.25(3H, m), 7.42(2H, s).

% Yield: 73

EXAMPLE 5 2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzamido)acetic acid

¹H NMR (DMSO-D₆, 400MHz): 3.79(2H, s), 4.51 (2H, s), 6.28-6.3 1( 1 H, dd, J=3.2Hz and 8.8Hz), 6.45(1 H, d, J=3.2Hz), 6.69(1 H, d, J=8.8Hz), 7.12-7.16(3H, m), 7.21 -

7.25(2H, m), 7.27-7.29(5H, m), 7.37(2H, s).

% Yield: 66 EXAMPLE 6

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)acetic acid ¹ H NMR (DMSO-D₆, 400MHz): 1.06(6H, d, J=6.8Hz), 3. 1 O-3.13( 1 H, m), 4.54(2H, s), 6.19-6.22( 1 H, dd, J=2.8Hz and 8.8Hz), 6.45( 1 H, d, J=3.2Hz), 6.65( 1 H, d, J=8.8Hz). 7.3 1 -7.36(5H, m), 7.54(2H, s). % Yield: 64 EXAMPLE 7

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)-2- phenylacetamido)acetic acid 1H NMR (CD₃OD, 400MHz): 3.59(2H, s), 3.89(2H, s), 4.32(2H, s), 6.35( 1 H, s),

6.53( 1H, d, J=8.8Hz), 6.73(1 H, d, J=8.8Hz), 7.02(2H, d, J=6.8Hz), 7. 13-7.22(8H, m), 7.36(2H, s). % Yield: 28

EXAMPLE 8

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-phenyl acetamido) acetic acid

¹ H NMR (CD₃OD, 400MHz): 1 .17(6H, d, J=6.8Hz), 3.23-3.26( 1 H, m), 3.63(2H, s), 4.3 1 ( 2H, s), 6.33( 1 H, d, J=8.8Hz), 6.64 -6.67(2H, m), 7.06(2H, d, ;=7.2Hz), 7.20-7.27(3H, m), 7.62(2H, s). % Yield: 17 EXAMPLE 9

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-hydroxy benzamido) acetic acid 1H NMR (CD₃OD, 400MHz): 1 .13(6H, d, J=6.8Hz), 3.17-3.24( I H, m),

4.50(2H, s), 6.25-6.28( I H, dd, J=2.4Hz and 8.8Hz), 6.52( I H, d, J=2.0Hz), 6.61 ( 1 H, d, J=8.8Hz), 6.69(2H, d, J=8.0Hz), 7.25(2H, d, J=8.4Hz), 7.55(2H, s). % Yield: 28 EXAMPLE 10 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)benzamido)acetic acid

¹H NMR (CDCI₃, 400MHz): 0.84(3H, t, J=7.2Hz), I .17(3H, d, J=6.8Hz), 1.51- 1.59(2H, m), 2.89-2.94(1 H, m), 4.63(2H, s), 6.31 -6.34( 1 H, dd, J=3.2Hz and 8.8Hz), 6.58( 1 H, d, J=2.8Hz), 6.63( I H, d. J=8.4Hz), 7.25-7.27( 1 H, m), 7.29(2H, s), 7.33-7.37(2H, m), 7.39(2H, s). % Yield: 71 EXAMPLE 11 2-(Η-(3,5-dibromo-4-((6-hydroxy-[ l , l'-biphenyl]-3-yl)oxy)phenyl)benzamido)acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.41-4.46(2H, s), 6.44(I H, s), 6.56-6.59(I H, dd, J=2.8Hz and 8.8Hz), 6.87( 1 H, d, J=9.2Hz), 7.20(2H, d, J=7.2Hz), 7.24-7.34(4H, m), 7.40-7.44(4H, m), 7.57(2H, s). % Yield: 33 EXAMPLE 12

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)-2-phenyl acetamido) acetic acid

¹H NMR (CDCI₃, 400MHz): 0.85(3H, t, J=7.6Hz), 1.27(3H, d, J=7.2Hz), 1.57-I .63(2H, m), 2.88-2.93( 1 H, m), 3.60(2H, s), 4.37(2H, s), 6.40(1 H, dd, J=2.8Hz and 8.8Hz), 6.67(1 H, d, J= 8.4Hz), 6.76(1H, d, J=2.8Hz), 6.99-7.06(5H, m), 7.45(2H, s). % Yield: 47 EXAMPLE 13 2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzamido)acetic acid 1 H NMR (CDCl₃, 400MHz): 0.82-0.89(3H, m), 1.17(3H, d, J=7.2Hz), 1 .49-1.61(2H, m), 2.83-2.97(1 H, m), 4.61 (2H, s), 6.32-6.35(1 H, dd, J=2.8Hz and 8.4Hz), 6.58- 6.67(2H, m), 7.18(2H, s), 7.21 -7.23(1 H, m), 7.27-7.34(2H, m), 7.37(2H, d, J=7.2Hz). % Yield: 1 1 EXAMPLE 14 2-(M-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-2-pheny I acetamido) acetic acid

¹H NMR (CD₃OD, 400MHz): 3.62(2H, s), 4.29(2H, s), 6.65(2H, d, J=7.6Hz), 6.85(1H, d, J=8.4Hz), 6.99(2H, d, J=3.6Hz), 7.13(3H, s), 7.26(1 H, t, J=7.2Hz), 7.36(2H, t, J=7.6Hz), 7.50(2H, d, J=7.6Hz), 7.60(2H, s). % Yield: 38 EXAMPLE 15 2-(N-(3,5-dibromo-4-((6-hydroxy-[l, l'-biphenyl]-3-yl)oxy)phenyl)thiophene-2- carboxamido) acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 4.38(2H, s), 6.62( 1 H, d, J=2.8Hz), 6.70-6.73( I H, dd, J=3.2Hz and 8.8Hz), 6.86( 1 H, t, J=4.4Hz), 6.92( 1 H. d, J=8.8Hz), 6.98( I H, d, J=3.2Hz), 7.32( 1 H, d, J=7.2Hz), 7.40(2H, t, J=7.6Hz), 7.46(2H, d. J=7.2Hz), 7.53(1 H, d, J=4.8Hz), 7.84(2H, s). % Yield: 55 EXAMPLE 16

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)thiophene-2- carboxamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): I .1O(6H, d, J=6.8Hz), 3.12-3.19(1 H, m), 4.40(2H, s), 6.37-6.39( 1 H, dd, J=2.8Hz and 8.8Hz), 6.61 (1 H, d, J= 2.8Hz), 6.70( 1 H, d, J= 8.8Hz), 7.00( 1 H, t, J=4.8Hz), 7.05( 1 H, d, J= 3.2Hz), 7.73( 1 H, d, J=4.8Hz), 7.80(2H, s). % Yield: 27 ^' EXAMPLE 17

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzamido)propanoic acid

¹H NMR (DMSO-D₆, 400MHz): 0.72(3H, t, J=6.4Hz), 1.00(3H, d, J=6.8Hz), 1.36- 1.40(5H, m), 2.88-2.93( 1 H, m), 4.89-4.94(1 H, q, J=6.4Hz), 6.25-6.28(1 H, dd, J=3.2Hz and 8.8Hz), 6.31 ( 1 H, d, J=2.8Hz), 6.66( I H, d, J=8.8Hz), 7.29-7.32(5H, m), 7.7(2H, s). % Yield: 28 EXAMPLE 18

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)thiophene-2- carboxamido) acetic acid 1H NMR (CD₃OD, 400MHz): 0.82(3H, t, J=7.2Hz), 1.12(3H, d, J=7.2Hz),1.52-

1.56(2H, m), 3.02-3.08( 1 H, m), 4.55(2H, s), 6.47-6.50(1 H, dd, J=3.2Hz and 8.8Hz), 6.51 ( I H, d, J=2.8Hz), 6.69(I H, d, J=8.4Hz), 7.00-7.02(1 H, m), 7.20(1 H, d, J=3.6Hz), 7.61 (I H, d, J=4.8Hz), 7.80(2H, s). % Yield: 18 EXAMPLE 19

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)furan-2-carboxamido) acetic acid ¹ H NMR (DMSO-D₆, 400MHz): 0.84(3H, t, J=6.8Hz), 1 .07(3H, d, J=7.2Hz). 1 .44- 1.50(2H, m). 2.94-2.96( I H, m), 4.37(2H, s), 6.34-6.37( 1 H, dd, J=3.2Hz and 8.8Hz), 6.41 ( 1 H, s), 6.49-6.51 ( 1 H, dd, J= 1.6Hz and 3.2Hz). 6.54( I H, d, J=2.8Hz), 6.70( I H, d, J=8.4Hz), 7.72( 1 H, s), 7.75(2H, s). % Yield: 22 EXAMPLE 20

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)benzamido)propanoic acid

¹H NMR (DMSO-D₆, 400MHz): 0.72 (3H, t, J=7.2Hz), 1.0(3H, d, J=6.8Hz), 1.34(3H, d, J=6.0Hz), 1.37-1.41 (2H, m), 2.87-2.91(1 H, m), 4.90(I H, s), 6.23-6.27(2H, m),

6.66(1 H, d, J=8.8Hz), 7.28(5H, s), 7.66(2H, s).

% Yield: 48

EXAMPLE 21

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)furan-2-carboxamido) acetic acid

¹H NMR (CD₃OD, 400MHz): 1.17(6H, d, J=6.8Hz), 3.30-3.31(I H, m), 4.46(2H, s), 6.36-6.39( I H, dd, J=2.8Hz and 8.8Hz), 6.46-6.47(2H, m), 6.64-6.67(2H, m), 7.53(1 H, s), 7.80(2H, s). % Yield: 23 EXAMPLE 22

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dimethylphenyl)benzamido)acetic acid

¹H NMR (CDCI₃, 400MHz): 0.85(3H, t, J=7.6Hz), I . I 5(3H, d, J=6.8Hz), 1 .42-1.47(2H, m), 1.98(6H, s), 2.87-2.92( 1 H, m), 4.65(2H, s), 6.26-6.28( 1 H, m), 6.49( 1 H, d, J=2.8Hz), 6.60( 1 H, d, J=8.8Hz), 6.85(2H, s), 7.19-7.23(2H, m), 7.27( 1 H, s), 7.40(2H, d, J=7.6Hz). % Yield: 15 EXAMPLE 23 2-(N-(4-(4-hydroxy-3-isopropylphenoxy)-3,5-dimethylphenyl)benzamido)acetic acid

¹H NMR (CD₃OD, 400MHz): 1 . I 2(6H, d, J=6.8Hz), 1.95(6H, s), 3.19-3.22(1 H, m), 4.58(2H, s), 6.21(1 H, dd, J=3.2Hz and 8.8Hz), 6.45(1 H, d, J=2.4Hz), 6.59(1 H, d, J=8.4Hz), 6.96(2H, s), 7.24-7.27(2H, m), 7.31-7.32(1 H, m), 7.36-7.38(2H, m). % Yield: 72 EXAMPLE 24

2-(N-(3,5-dibromo-4-(4-hydrox>-3-isopropylphenoxy)phenyl)benzamido)propanoic acid

¹H NMR (DMSO-D₆, 400MHz): 1.05(6H, d, J=6.8Hz), 1.39(3H, d, J=7.2Hz), 3.09- 3.14( I H, m), 4.9-4.92( 1 H, m). 6.15-6.18(1 H, dd, J=3.2Hz and 8.8Hz), 6.40( 1 H, d, J=2.8Hz), 6.64 ( I H, d, J=8.8Hz), 7.29-7.30(5H, m). 7.63(2H, s). % Yield: 47 EXAMPLE 25 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)butanoic acid 1H NMR (DMSO-D₆, 400MHz): 0.95(3H, t, J=7.2Hz), 1.03- 1.06 (6H, m), 1.92-1.99

(2H, m), 3.06-3.15(1H, m), 4.73(1 H, bs), 6.16-6.19 (I H, dd, J=3.2Hz and 8.8Hz),

6.39(1 H, s), 6.65( 1 H, d, J=8.8Hz), 7.29(5H, s), 7.60(2H, s).

% Yield: 42

EXAMPLE 26 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)-2- methylpropanoic acid

¹ H NMR (DMSO-D₆, 400MHz): 1.02(6H, d, J=6.8Hz), 1.41(6H, s), 3.03-3.1 1 ( I H, m), 6.08-6.1 1 ( I H, dd, J=2.8Hz and 8.4Hz), 6.34( 1 H, d, J=3.2Hz), 6.61 ( 1 H, d, J=8.8Hz), 7.21 -7.26(5H, m), 7.67(2H, s). % Yield: 72 EXAMPLE 27

2-(N-(3,5-dibromo-4-((6-hydroxy-[ l, l'-biphenyl]-3-yl)oxy) phenyl) benzamido) propanoic acid

¹H NMR (DMSO-D₆, 400MHz): 1.28-1.33(3H, m), 4.87-4.90( 1H, m), 6.4O(1H, s), 6.52-6.54( I H, dd, J=2.8Hz and 8.4 Hz), 6.86( 1 H, d, J=8.8Hz), 7.15-7.23 (5H, m), 7.29- 7.34(1 H, m), 7.40-7.41 (4H, m), 7.67(2H, s). % Yield: 31 EXAMPLE 28 2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromophenyl)benzamido)acetic acid ¹H NMR (CD₃OD, 400MHz): 3.85(2H, s), 4.57(2H, s), 6.26(1H; d, J=2.8Hz), 6.37(1 H, dd, J=3.2Hz and 8.8Hz), 6.67(1 H, d, J=8.8Hz), 7.12-7.15(3H, m), 7.20-7.23(2H, m), 7.26-7.31(3H, m), 7.34-7.36(2H, m), 7.53(2H, s). % Yield: 71 EXAMPLE 29

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromophenyl)benzamido)propanoic acid

¹H NMR (CD₃OD, 400MHz): 1.47(3H, d, J=7.2Hz), 3.85(2H. s), 5.02( 1 H. m), 6.2(1 H, d, J=2.8Hz), 6.34( 1 H, dd, J=3.2Hz and 8.8Hz), 6.67( 1 H, d, J=8.8Hz), 7.13(3H, t, J=7.6Hz), 7.2-7.25(5H, m), 7.25-7.3(2H, m), 7.59(2H, s). % Yield: 14 EXAMPLE 30 2-(N-(3,5-dibromo-4-(3-ethyl-4-hydroxyphenoxy)phenyl)benzamido)acetic acid ¹H NMR (CD₃OD, 400MHz): I . I 2(3H, t, J=7.6Hz), 2.50-2.56(2H, q, J=7.2Hz),

4.59(2H, s), 6.27-6.30( 1 H, dd, J=2.8Hz and 8.4Hz), 6.38( I H, d, J=2.4Hz), 6.61 ( 1 H, d,

J=8.8Hz), 7.33-7.35(2H, m), 7.38-7.40(3H, m), 7.57(2H, s).

% Yield: 15

EXAMPLE 31 2-(N-(4-((6-hydroxy-[l, l '-biphenyl]-3-yl)oxy)-3,5-dimethyl phenyl) benzamido) acetic acid

¹H NMR (CD₃OD, 400MHz): 1.99(6H, s), 4.55(2H ,s), 6.38-6.40(1 H, m), 6.55(1 H, d, J= 7.6Hz), 6.79(1 H, d, J=8.4Hz), 6.96(2H, s), 7.08-7.1 1 (2H, m), 7.17-7.25( I H, m), 7.26-7.3 1 (3H, m), 7.37-7.41 (4H, m). % Yield: 18 EXAMPLE 32 2-(N-(3,5-dibromo-4-(3-(tert-butyl)-4-hydroxyphenoxy)phenyl)benzamido)acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 1.25(9H, s), 4.53(2H, s), 6.20-6.22( 1 H, dd, J=2.4Hz and 8.4Hz), 6.54( I H, d, J=2.4Hz), 6.64(1 H, d, J=8.4Hz), 7.30-7.36(5H, m), 7.54(2H, s). % Yield: 63 EXAMPLE 33

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromophenyl)thiophene-2-carboxamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 3.82(2H, s), 4.44(2H, s), 6.40-6.44(1 H, dd,

J=3.2Hz and 8.8Hz), 6.57(1 H, d, J=3.2Hz), 6.74(I H, d, J= 8.8Hz), 6.96-6.98(2H, m), 7.12-7.25(5H, m), 7.70-7.71 (IH, m), 7.78(2H, s). % Yield: 58 EXAMPLE 34

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy) phenyl) cyclohexane carboxamido) acetic acid 1H NMR (CD₃OD, 400MHz): l .O5-l .O8(2H, m), 1. I4(6H, d, J=6.8Hz), 1.29-1.38(2H, m), 1.43-1.53(2H, m), 1.71-1.80(4H, m), 2.25-2.27( 1 H, m), 3.2O-3.27(1 H, m), 4.20(2H, s), 6.39-6.42(1 H, dd, J=2.8Hz and 8.8Hz), 6.57( 1 H, d, J=2.4Hz), 6.66( 1 H, d, J=8.8Hz), 7.87(2H, s) % Yield: 43 EXAMPLE 35

2-(3-chloro-N-(3,5-dibromo-4-(4-hydroxy-3-isopropy phenoxy) phenyl) benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.08(6H, d, J=6.8Hz), 3.09-3.15( 1 H, m), 4.32(2H. s), 6.12-6.15( 1 H, dd, J=2.8Hz and 8.8Hz), 6.55( I H, s), 6.64( 1 H, d, J=8.8Hz), 7.33- 7.38(3H, m), 7.42-7.43(1 H, m), 7.65(2H, s). % Yield: 34 EXAMPLE 36

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-methyl benzamido) acetic acid 1 H NMR (DMSO-D₆, 400MHz): 1.07(6H, d, J=7.2Hz), 2.24(3H, s), 3.09-3.12( 1 H, m),

4.25(2H, s), 6.12-6.14( 1 H, dd, J=2.0Hz and 8.0HZ), 6.6( 1 H, s), 6.65(1 H, d, J=8.8Hz),

7.12-7.18(4H, m). 7.72(2H, s).

% Yield: 68

EXAMPLE 37 2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methyl benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.07(6H, d, J=6.8Hz), 2.26(3H, s), 3.09-3.18(1 H, m), 4.33(2H, s), 6.26-6.29( 1 H, dd, J=3.2Hz and 8.8Hz), 6.63(1 H, d, J=3.2Hz), 6.69(1 H, d, J=8.8Hz), 7.1 1 (2H, d, J=8.0Hz), 7.23(2H, d, J=8.0Hz), 7.43(2H, s). % Yield: 46 EXAMPLE 38 2-(N-(3,5-dichloro-4-(4-hydro\y-3-isopropyl phenoxy) phenyl) cyclohexane carboxamido) acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 0.96- 1 .02(2H, m), 1.07- 1.09(7H, m), 1.28- 1 .36(2H. m), 1.51 - 1.54( 1 H, m), 1.64(4H, d, J= 10.4Hz), 2.20(1 H, bs), 3.1 1 -3.18( I H, m), 4.25(2H, s), 6.42( 1 H, d, J=6.8Hz). 6.57(1 H, s), 6.69( 1 H, d, J=8.8Hz), 7.67(2H, s). % Yield: 49 EXAMPLE 39

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-(trifluoromethyl) benzamido) acetic acid 1 H NMR (DMSO-D₆, 400MHz): 0.93(6H, d, J=6.4Hz), 3.07-3.16(1 H, m), 4.55(2H, s),

6.19-6.22(1H, dd, J=3.2Hz and 8.8Hz), 6.46(1 H, s), 6.64( I H, d, J=8.4Hz), 7.46(2H, s),

7.56(2H, d, J=8.0Hz), 7.70(2H, d, J=8.0Hz).

% Yield: 15

EXAMPLE 40 2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-methyl benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.04(6H, d, J=6.8Hz), 2.28(3H, s), 3.07-3.14( 1 H, m), 4.54 (2H, s), 6.20( 1 H, d, J-8.0Hz), 6.36(1 H, s), 6.64 ( IH, d, J= 8.8Hz), 7.07-7.15(4H, m), 7.38(2H, s). % Yield: 64 EXAMPLE 41

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-rnethyl benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1 .07(6H, d, J=6.8Hz), 2.24(3H, s), 3.09-3.15(1 H, m), 4.53(2H, s), 6.16-6.19( 1 H, dd, J=3.2Hz and 8.8Hz), 6.54( 1 H, d, J=2.8Hz), 6.64(1 H, d, J=8.8Hz), 7.08(1 H, d, J=3.2Hz), 7.17-7.19(3H, m), 7.40(2H, s). Yield: 45 EXAMPLE 42

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) cyclopropane carboxamido) acetic acid ¹ H NMR (CD₃OD, 400MHz): 0.8(2H, bs), 0.90-0.95(2H, m), 1 .16(6H, d, J=6.8Hz), 1.5( 1 H, bs), 3.27-3.22( I H, m), 4.29(2H, s), 6.31 -6.34( 1 H, dd, J=3.2Hz and 8.8Hz), 6.62( I H, d, J=8.8Hz), 6.67( 1 H, d, J=3.2Hz). 7.88(2H, s). % Yield: 52 EXAMPLE 43

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-hydroxy benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.47(2H, s), 6.53( 1 H, d, J=8.4Hz), 6.61-6.64(3H, m), 6.88( I H, d, J=8.8Hz), 7.15(2H, d, J=8.4Hz), 7.27-7.31(1 H, m), 7.38-7.42(2H, m), 7.44- 7.46(2H, m), 7.51 (2Rs). % Yield: 78 EXAMPLE 44

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-hydroxybenzamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 1.05(6H, d, J=6.8Hz), 3.07-3.14(1 H, m), 4.49(2H, s),

6.13-6.15( 1 H, m), 6.52-6.56(1 H, m), 6.81(1 H, d, J=8.0Hz), 6.85-6.88(2H, m), 7.07-

7.1 1 (2H, m), 7.55(2H,s).

% Yield: 71

EXAMPLE 45 2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-hydroxy benzamido) acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 4.52(2H, s), 6.50-6.53( 1 H, dd, J=3.2Hz and 8.8Hz), 6.57( 1 H, d, J=2.8Hz), 6.64( 1 H, d, J=7.6Hz), 6.69( 1 H, d, J=8.0Hz), 6.73( 1 H, s), 6.86(1 H, d, J=8.8Hz), 6.97( 1 H, t, J=7.6Hz), 7.30( 1 H, t, J=7.2Hz), 7.39(2H, t, J=7.2Hz), 7.44(2H, d, J=7.2Hz), 7.53(2H, s). % Yield: 79 EXAMPLE 46

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)-4-methyl benzamido)acetic acid 1H NMR (DMSO-D₆, 400MHz): 0.72(3H, t, J=7.4Hz), 1.03(3H, d, J=6.8Hz), 1.41 - 1.43(2H, m), 2.26(3H, s), 2.88-2.96(1 H, m), 4.50(2H, s), 6.33(1 H, d, J=3.2Hz), 6.34- 6.36( 1 H, dd, J=2.8Hz and 6.4Hz), 6.68( I H, d, J=8.4Hz), 7.12(2H, d, J=8.4Hz), 7.22(2H, d, J=8.0Hz). 7.39(2H, s). % Yield: 56 EXAMPLE 47 2-(N-(3,5-dibromo-4-((6-hydroxy-[ l , l'-biphenyl]-3-yl)oxy)phenyl)-2-hydroxy benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.49(2H, s), 6.42( 1 H, s), 6.49-6.52( 1 H, dd, J=2.8Hz and 8.8Hz), 6.65(2H, s), 6.85(1 H, d, J=8.8Hz), 7.01-7.06(2H, m), 7.28-7.33(I H, m), 7.37-7.41 (4H, m), 7.54(2H, s). % Yield: 64 EXAMPLE 48

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-y l)oxy)pheny l)-4-methyl benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 2.15(3H, s), 4.52(2H, s), 6.49(1 H, d, J=7.6Hz), 6.56- 6.59(1 H, dd, J=3.2Hz and 8.8Hz), 6.88(1H, d, J=8.8Hz), 7.00(2H, d, J=8Hz), 7.17(2H, d, J=8.0Hz), 7.29-7.33(1 H, m), 7.38-7.45(4H, m), 7.54(2H, s).

% Yield: 74

EXAMPLE 49

2-(N-(3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-methy! benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 2.16(3H, s), 4.53(2H, s), 6.52(1 H, d, J=3.2Hz), 6.59- 6.62(I H, dd, J=3.2Hz and 8.8Hz), 6.88(1 H, d, J=8.8Hz), 7.01(2H, d, J=8.0Hz), 7.18(2H, d, J=8.0Hz), 7.3 1 (1 H, t, J=7.0Hz), 7.38-7.40(3H, m), 7.42-7.46(3H, m). % Yield: 73 EXAMPLE 50

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-hydroxy benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.07(6H, d, J=6.8Hz), 3.08-3.15(I H, m), 4.51(2H, s), 6.16-6.19( 1 H, dd, J=2.8Hz and 8.8Hz), 6.53(1 H, d, J=2.8Hz), 6.64(1 H, d, J=8.4Hz), 6.68-6.73(3H, m), 7.09( 1 H, t, J=7.8Hz), 7.52(2H, s). % Yield: 84 EXAMPLE 51 2-(4-chloro-N-(3,5-dichloro-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) benzamido) acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 1.06(6H, d, J=7.2Hz), 3.08-3.15(I H, m), 4.54(2H, s), 6.26-6.29( I H. dd, J=3.2Hz and 8.8Hz), 6.46( 1 H, d, J=2.8Hz), 6.67( I H, d, J=8.8Hz), 7.34-7.40(4H, m), 7.43(2H, s). % Yield: 67 EXAMPLE 52

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-methyI benzamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 1.03(6H, d, J=6.4Hz), 2.27(3H, s), 3.07-3.14(1 H, m),

4.54 (2H, s), 6.16( 1 H, d, J=7.2Hz), 6.32( I H, s), 6.63( 1 H, d, J= 8.4Hz), 7.07-7.18(4H, m), 7.54(2H, s).

% Yield: 36

EXAMPLE 53 2-(N-(3,5-dibromo-4-((6-hydroxy-[ l,r-biphenyl]-3-yl)oxy)phenyl)-2-methyl benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 2.25(3H, s), 4.54(2H, s), 6.32(1H, s), 6.52(1 H, d, J=5.2Hz), 6.85( I H, d, J=9.2Hz), 6.95-7.04 (4H, m), 7.32( 1 H, d, J=8.4Hz), 7.39- 7.43(4H, m), 7.52(2H, s). % Yield: 39 EXAMPLE 54

2-(N-(3,5-dibromo-4-((6-hydroxy-2'-methyl-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1 .68(3H, s), 4.47(2H, s), 6.30-6.33( 1 H, dd, J=2.8Hz and 8.8Hz), 6.36-6.44( 1H, m), 6.66(1 H, d, J=8.4Hz), 6.7O(1 H, d, J=6.4Hz), 6.93-

6.98(1 H, m), 7.00(1H, t, J=7.4Hz), 7.04-7.1 1(2H, m), 7.32-7.37(5H, m), 7.7O-7.74(1 H, m).

% Yield: 58

EXAMPLE 55 2-(2-chloro-N-(3,5-dibromo-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) benzamido) acetic acid ¹ H NMR (DMSO-D₆, 400MHz): 1.02(6H, d, J=6.8Hz), 3.08-3.1 1 ( 1 H, m), 4.56(2H, s), 6.12-6.15( I H, dd, J=3.2Hz and 8.8Hz), 6.30( 1 H, d, J=3.2Hz), 6.62( I H, d, J=8.8Hz), 7.28-7.40(4H, m), 7.65(2H, s). % Yield: 41 EXAMPLE 56

2-(N-(3,5-dichloro-4-((6-hydroxy-[ U'-biphenyl]-3-yl)oxy)phenyl)-4-(trifluoro methyl) benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.58(2H, s), 6.44-6.47( I H, dd, J=2.4Hz and 8.4Hz), 6.63 ( I H, d, J=2.8Hz), 6.84(1 H, d, J=8.8Hz), 7.29(1 H, t, J=7.2Hz), 7.38(2H, t, J=7.2Hz), 7.44-7.46 (4H, m), 7.54(2H, d, J=7.6Hz), 7.65(2H, d, J=8.0Hz). % Yield: 81 EXAMPLE 57

2-(N-(3,5-dibromo-4-((2',6-dihydroxy-[ l, r-biphenyl]-3-yl)oxy) phenyl) benzamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 4.54(2H, s), 6.37-6.40(1 H, dd, J=2.8Hz and 8.8Hz), 6.45(1 H, d, J=2.8Hz), 6.60(2H, d, J=7.2Hz), 6.68(1H, d, J=9.2Hz), 6.75(1 H, d, J=8.0Hz), 7.01 -7.05( I H, m), 7.1 1-7.12( 1 H, m), 7.30-7.35(4H, m), 7.38( I H, d, J=6.4Hz), 7.49( 1 H, d, J=2.0Hz). % Yield: 39 EXAMPLE 58

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-(trifluoromethyl) benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.04(6H, d, J=7.2Hz), 3.08-3.12(I H, m), 4.57(2H, s), 6.15-6.18( I H, dd, J=2.8Hz and 8.4Hz ), 6.42(1 H, s), 6.63(1 H, d, J=8.4Hz), 7.55(2H, d, J=8.4Hz), 7.59(2H, s), 7.71 (2H, d, J=8.0Hz). % Yield: 47 EXAMPLE 59

2-(N-(3,5-dibromo-4-((6-hydroxy-[l,l'-biphenyl]-3-yl)oxy)phenyl)-4-(tnfluoro methyl) benzamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 4.57(2H, s), 6.42(1 H, d, J=6.0Hz), 6.59(1 H, d,

J=2.8Hz), 6.84(1 H, d, J=8.8Hz), 7.30(1 H, d, J=7.2Hz), 7.38(2H, t, J=7.6Hz), 7.45(2H, d, J=7.2Hz), 7.52(2H, d, J=7.6Hz), 7.59(2H, s), 7.65(2H, d, J=7.6Hz). % Yield: 73 EXAMPLE 60

2-(N-(3,5-dichloro-4-(4-hydro\y-3-isopropylphenoxy)phenyl)-3,5-bis (trifluoromethyl),benzamido) acetic acid 1 H NMR (DMSO-D₆, 400MHz): 1.05(6H, d, J=6.8Hz), 3.07-3.16(1 H, m),

4.59(2H, s), 6.00(1 H, d, J=3.6Hz), 6.58-6.60(2H, m), 7.59(2H, s), 8.02(2H, s), 8.16( 1 H, s).

% Yield: 75 EXAMPLE 61 2-(N-(3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3,5-bis (trifluoromethyl) benzamido)acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.60(2H, s), 6.63(1 H, s), 6.69 ( I H, d, J=3.2Hz), 6.81(1 H, d, J=8.8Hz), 7.30(1 H, t, J=7.2Hz), 7.37(2H, t, J=7.2Hz), 7.44(2H, d, J=7.2Hz), 7.59(2H, s), 7.99(2H, s), 8.10( 1 H, s). % Yield: 19 EXAMPLE 62

2-(N-(3,5-dibromo-4-((2'-fluoro-6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl) benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.59(2H, s), 6.35-6.40(2H, m), 6.68(1 H, d, J=8.8Hz), 6.83( 1 H, m), 7.05-7.09( 1 H, m), 7.1 1 -7.15(2H, m). 7.30-7.33(4H, m), 7.35-7.40(2H, m),

7.66-7.67(1 H, m).

% Yield: 80

EXAMPLE 63

2-(N-(3,5-dichloro-4-(3-(N,N-diethylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid

¹H NMR (CDCI₃, 400MHz): 1.08(6H, t, J=7.2Hz), 3.21 (4H, q, J=7.2Hz), 4.63(2H, s),

6.79(1 H, s), 6.97(2H, s), 7.21(2H, s), 7.29-7.32(2H, m). 7.37-7.38(3H, m).

% Yield: 65

EXAMPLE 64 2-(N-(3,5-dibromo-4-(3-(N,N-diethylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid

¹H NMR (CDCI₃, 400MHz): 1.08(6H, t, J=7.2Hz), 3.2(4H, q, J=7.2Hz), 4.63(2H, s),

6.76(1 H, m), 6.97-6.99(2H, m), 7.31 -7.33(2H, m), 7.36-7.38(3H, m), 7.41(2H, s). % Yield: 64 EXAMPLE 65

2-(N-(3,5-dibromo-4-(4-hydro.\y-3-(piperidin-l-ylsulfonyi) phenoxy) phenyl) benzamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): i .41 -1.46(6H, m), 2.99-3.0(4H, m), 4.41 (2H, s), 6.77-

6.81 ( I H, m), 6.99-7.02(2H, m), 7.25-7.33(5H, m), 7.59(2H,s).

% Yield: 24

EXAMPLE 66

2-(N-(3,5-dibromo-4-(3-(N-cyclohexylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid

¹H NMR (CDCI₃, 400MHz): 1.05-1.27(6H, m), 1.59-1.63(2H, m), 1.69-1.72(2H, m),

1.54-1.55( 1 H, m), 3.05(1 H, bs), 4.67(2H, s), 6.76 (I H, d, J=2.8Hz), 7.00-7.06(2H, m),

7.31 -7.34(2H, m), 7.38-7.41 (3H, m), 7.46(2H, s).

% Yield: 16 EXAMPLE 67

2-(N-(3,5-dichloro-4-(3-(diethylcarbamoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid

¹H NMR (CD₃OD, 400MHz): 0.9- 1.29(6H, m), 3.13-3.31 (2H, m), 3.48-3.52(2H, m),

4.61 (2H, s), 6.30(1 H, s), 6.74-6.77( 1 H, dd, J=2.8Hz and 8.8Hz), 6.81( 1 H, d, J=8.8Hz), 7.29-7.31(2H, m), 7.33-7.39(5H, m).

% Yield: 37

EXAMPLE 68

2-(N-(3,5-dichloro-4-(4-hydroxy-3-(piperidine-l -carbonyl) phenoxy) phenyl) benzamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 1.44-1.46(6H, m), 1.56(4H, m), 3.56(2H, s), 6.29(1 H, d, J=3.2Hz), 6.66-6.69(1 H, dd, J=3.2Hz and 9.2Hz), 6.8O(1H, d, J=8.8Hz), 7.31(5H, m), 7.43(2H, s).

% Yield: 15

EXAMPLE 69 2-(N-(3,5-dibromo-4-(4-hydroxy-3-(piperidine- 1 -carbonyl) phenoxy) phenyl) benzamido) acetic acid ¹H NMR (CDCI₃, 400MHz): 1.45- 1.56 (4H, m), 1.68-1.69(2H, m), 3.58-3.59(4H, m), 4.62 (2H, s), 6.53(1 H, d, J=2.8Hz), 6.78-6.82(I H, dd, J=2.8Hz and 8.8Hz), 6.98(1 H, d, J=8.8Hz), 7.26-7.3 1 (2H, m), 7.36-7.39(3H, m), 7.41 (2H, s). % Yield: 63 EXAMPLE 70

2-(N-(3,5-dibromo-4-(3-(diethylcarbamoyl)-4- hydroxyphenoxy)phenyl)benzamido)acetic acid

¹ H NMR (DMSO-D₆, 400MHz): I . I 6-I .78(6H, m), 3.06(2H, s), 3.27(2H, s), 4.35(2H, s), 6.1 1( 1 H, s), 6.68-6.71(1H, dd, J=3.2Hz and 8.4Hz), 6.82(1 H, d, J=9.2Hz), 7.27- 7.33(5H, m), 7.59(2H, s). % Yield: 61 EXAMPLE 71

2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid Step I : Preparation of (4-chlorophenyl)(5-(2,6-dibromo-4-nitrophenoxy)-2-methoxy phenyl) methanone l,3-dibromo-2-(4-methoxyphenoxy)-5-nitrobenzene (5.8 g, 0.014 mol) and 4- chlorobenzoic acid (0.31 g, 1.99 mmol) was mixed with Eaton's reagent [prepared by stirring P₂O₅(4 g) and Methanesulfonic acid (22.8 mL) at 20-30 ⁰C for 3 hrs]. The reaction mixture was heated at 70-80 ⁰C for 16 h and then was poured over ice. The product was taken up in ethyl acetate, washed with water, brine, dried over sodium sulphate, filtered and concentrated to give the crude product, which was purified by column chromatography over flash silica gel (hexane : ethyl acetate 95:05) to afford pure product (4-chlorophenyl)(5-(2,6-dibromo-4-nitrophenoxy)-2-methoxy phenyl) methanone (2.8 g, 36 %).

Step 2: Preparation of (5-(4-amino-2,6-dibromophenoxy)-2-methoxyphenyl) (4-chloro phenyl) methanone

A solution of stannous chloride dihydrate (5.62 g, 0.024 mol) in concentrated HCl (2.7 mL) was added to (4-chlorophenyl)(5-(2,6-dibromo-4-nitrophenoxy)-2- methoxy phenyl) methanone) in EtOH (13.5 mL).The reaction mixture was refluxed for about 4 h. The resulting mixture was brought at room temperature and diluted with ethyl acetate. The mixture was made alkaline with ammonia solution. Resulting solid was filtered through cellite. The organic phase was washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give (5-(4-amino-2,6- dibromophenoxy)-2-methoxyphenyl) (4-chloro phenyl) methanone (2.6 g; 99 % yield).

Step 3: Preparation of Ethyl 2-((3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) amino) acetate To (5-(4-amino-2,6-dibromophenoxy)-2-methoxyphenyl)(4-chlorophenyl) methanone

(2.6 g, 5.08 mmol) was added ethyl bromoacetate (0.93 g, 5.59 mmol) and diisopropylethyl amine (0.72 g, 5.59 mmol) in DMF (26 mL) and stirred at 140 ⁰C for

24 h. The reaction mixture was poured in to ice-water. The product was taken up in ethyl acetate, washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography over flash silica gel (Hexane: Ethyl acetate 90: 10) to afford the pure product ethyl 2-((3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) amino) acetate (2.87 g, 94 % yield)

Step 4: Preparation of Ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate

To a solution of ethyl 2-((3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) amino) acetate (1.6 g, 2.67 mmol) in dichloromethane (8 mL), pyridine (0.42 g, 5.35 mmol) was added at 0-5 ⁰C. After 10 min. to that Benzoyl chloride (0.75 g, 5.35 mmol) was added dropwise to the mixture over 10-15 min. The reaction mixture was stirred at room temperature for another 24h. The reaction mixture was poured in to ice-water. The product was taken up in ethyl acetate, washed with

H₂O, brine and dried over sodium sulphate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography over flash silica gel (Hexane: Ethyl acetate) gradient elution from 99:01 to 90: 10 to afford the pure product ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate. (1.16 g, 62 % yield).

¹H NMR (CDCI₃, 400MHz): 1.31 (3 H, t, J=7.2Hz), 3.68(3H; s), 4.23-4.29(2H, q, J=7.2Hz), 4.56(2H, s), 6.63(1 H, s), 6.91(2H, d, J= 1.6Hz), 7.17-7.23(3H, m), 7.32(2H, d, J=6.8Hz), 7.38(2H, s), 7.40-7.42(2H, dd, J=I .6Hz and 6.8Hz), 7.72-7.75 (2H, dd,

J=1.6Hz and 6.8Hz).

Step 5: Preparation of 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid A solution of ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ( I . I I g. 1 .58 mmol), prepared above (Example 71 , Step-4), in dichloromethatne ( 1 1 mL) was cooled to -60 ⁰C to -70 ⁰C under N_: atmosphere. To this I M BBr₃ solution (6.32 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature and then it was stirred for 6 h. The reation mixture was then diluted further with CH₂CI₂ (50 mL) and quenched with H₂O. After stirring at room temperature for 30 min, organic phase was separated, washed with water, brine, dried over sodium sulphate, filtered and concentrated to give crude product. The crude product was stirred with a mixture of 20 % ethyl acetate in Hexane (5 mL) to give pure 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid (0.96 g, 92 %).

¹ H NMR (DMSO-D₆, 400MHz): 4.54(2H, s), 6.50( 1 H, d, J=3.2Hz), 6.85-6.88( 1 H, dd, J=3.2Hz and 9.2Hz), 6.93( 1 H, d, J=8.8Hz), 7.21 -7.26(5H, m), 7.53(2H, s), 7.59(2H, d, J=8.8Hz), 7.69(2H, d, J=8.8Hz). EXAMPLE 72

2-(N-(3,5-dibromo-4-(3-((4-chlorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido)acetic acid

Step 1 : Preparation of Ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate To a solution of ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ( 1.1 g, 1 .56 mmol, Example 71 , step 4 above) in dichloromethatne ( 1 1 mL) was cooled to -60 ⁰C to -70 ⁰C under N₂ atmosphere. To this I M BBr₃ solution (3.13 mL) was added dropwise. The reaction mixture was stirred at -40 ⁰C for 2 h, The reaction mixture was further diluted with CH₂Cb (50 mL) and quenched with ice-H₂O. After stirring at room temperature for 30 min, organic phase was separated, washed with water, brine, dried over sodium sulphate, filtered and concentrated to give crude product. The crude product was purified by column chromatography over flash silica gel (Hexane : Ethylacetate) gradient elution from 99:01 to 95:05 to afford the pure product ethyl 2-(N-(3,5-dibromo-4-(3-(4- chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate (0.96 g, 89 %).

Step 2: Preparation of Ethyl 2-(N-(3,5-dibromo-4-(3-((4- chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate

To ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate, prepared in step 1 of example 72, (0.91 g, 1.38 mmol) in MeOH (9.1 mL) was added NaBH₄ (44.25 mg. 1 .16 mmol) at -5 to - 10 ⁰C. The reaction was stirred at same temperature for 2-3 hrs. The product was taken up in ethyl acetate, washed with water, brine, dried over sodium sulphate, filtered and concentrated to give the crude product, which was purified by column chromatography over flash silica gel (hexane : ethyl acetate 90: 10) to afford pure ethyl 2-(N-(3,5-dibromo-4-(3- ((4-chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate (0.79 g, 86%).

¹H NMR (CDCI₃, 400MHz): 1.31(3H, t, J=7.2Hz), 3.02(I H, d, J=3.6Hz), 4.24- 4.29(2H, q, J=7.2Hz), 4.55(2H, s), 5.87( 1 H, d, J=3.6Hz), 6.40(1 H, d, J=2.8Hz), 6.47- 6.50 (I H, dd, J=3.2Hz and 9.2Hz), 6.77(1 H, d, J=8.8Hz), 7.19( 1 H, s), 7.24( 1 H, s), 7.28-7.31 (3H, m), 7.32-7.34(4H, m), 7.38(2H, s).

Step 3: Preparation of 2-(N-(3,5-dibromo-4-(3-((4-chlorophenyl)(hydroxy)methyl)-4- hydroxyphenoxy) phenyl) benzamido)acetic acid

To a solution of ethyl 2-(N-(3.5-dibromo-4-(3-((4- chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate (0.74 g, 1.07 mmol) in EtOH was added to (7.4 mL) NaOH (50 mg, 1 .25 mmol) in H₂O (2 mL) and it was stirred at 50 ⁰C for 2hr. Ethanol was evaporated from the reaction mixture and H₂O was added and was washed with diethyl ether. The aqueous layer was acidified to pH 4 using 10 % HCI solution and product was extracted with ethyl acetate The organic layer was washed with water, brine, dried over sodium sulphate, filtered and concentrated to give pure product 2-(N-(3,5-dibromo-4-(3-((4- chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid (0.47 g, 66%) 1H NMR (CD₃OD, 400MHz): 4.55(2H, s), 5.99( 1 H, s), 6.43-6.46( I H, dd, J=3.2Hz and 8.8Hz), 6.66( I H, d, J=8.8Hz). 6.74(I H, d. J=3.2Hz), 7.24-7.29(5H, m), 7.31 -7.34(2H, m), 7.39(2H, d, J=6.8Hz), 7.56(2H, s).

Using appropriate starting materials and suitable modifications of one or more of the processes described in Examples 71 and 72, either alone or in suitable combination of the steps disclosed therein, 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 analogous manner. EXAMPLE 73 2-(N-(3,5-dibromo-4-(3-(3-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid ¹H NMR (DMSO-D₆, 400MHz): 4.52(2H, s), 6.50-6.51 (1 H, m), 6.92-6.94(2H, m),

7.20-7.23(5H, m), 7.54-7.57(3H, m), 7.62-7.64(2H, m), 7.72( 1 H, d, J=8.4Hz).

% Yield: 64

EXAMPLE 74 2-(N-(3,5-dibromo-4-(3-((3-chlorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.63(2H, s), 5.87( 1 H, s), 6.39(1 H, d, J=3.2Hz), 6.52-

6.55( I H, dd, J=3.2Hz and 8.8Hz), 6.78(1 H, d, J=8.8Hz), 7.27-7.30(5H, m), 7.32-

7.35(3H, m), 7.37-7.38(3H,m). % Yield: 71

EXAMPLE 75

2-(N-(3,5-dibromo-4-(3-(4-fluorobenzoyl)-4- hydroxyphenoxy)phenyl)benzamido)acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 4.53(2H, s), 6.48(1 H, d, J=2.8Hz), 6.84-6.87(1 H, dd, J=2.8Hz and 8.8Hz), 6.93(1 H, d, J=8.8Hz), 7.20-7.25(5H, m), 7.35(2H, t, J=8.8Hz),

7.53(2H, s), 7.74-7.78(2H, m ).

% Yield: 70

EXAMPLE 76

2-(N-(3,5-dibromo-4-(3-((4-tluorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido)acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.54(2H, s), 5.78(1 H, d, J=4.4Hz), 5.85(1 H, d,

J=4.4Hz), 6.33-6.36(I H, dd, J=3.2Hz and 8.8Hz), 6.65(I H, d, J=8.4Hz), 6.82( 1 H, d,

J=3.2Hz), 7.06(2H, t, J=9.0Hz), 7.26-7.33(6H, m ), 7.53(2H, s).

% Yield: 69 EXAMPLE 77

2-(N-(3,5-dibromo-4-(3-(3-fluorobenzoyl)-4- hydroxyphenoxy)phenyl)benzamido)acetic acid

¹ H NMR (CDCl₃, 400MHz): 4.53(2H, s), 6.90(1 H, m), 6.97-7.04(2H, m), 7.15(2H, m),

7.29-7.30 (3H, m), 7.36-7.38(3H, m), 7.42-7.45(3H, m). % Yield: 86

EXAMPLE 78

2-(N-(3,5-dibromo-4-(3-((3-fluorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido)acetic acid ¹H NMR (DMSO-D₆, 400MHz): 4.55(2H, s), 5.87(1 H, s), 6.36-6.39(1 H, dd, J=3.2Hz and 8.8Hz), 6.67( I H, d, J=8.8Hz), 6.80( 1 H, d, J=3.2Hz), 6.96-7.04(2H, m), 7.12(1 H, d, J=7.6Hz), 7.25-7.33(6H, m), 7.53(2H, s). % Yield: 98 EXAMPLE 79

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)morpholine-4- carboxamido) acetic acid

Step 1 : Preparation of4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichloroaniline

A solution of stannous chloride dihydrate (8.51 g, 0.037mol) in concentrated HCl (3.5 mL) was added to 2-(3-(sec-butyI)-4-methoxyphenoxy)- l ,3-dichloro-5- nitrobenzene (3.5 g, 9.4 mmol) in EtOH (35 mL).The reaction mixture was refluxed for about 4h. The resulting mixture was brought at room temperature and diluted with ethyl acetate. The mixture was made alkaline with ammonia solution. Resulting solid was filtered through cellite. The organic phase was washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give 4-(3-(sec-butyl)-4- methoxyphenoxy)-3,5-dichloroaniline

(3.21 g; 99 % yield).

Step 2: Preparation of Ethyl 2-((4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichloro phenyl) amino) acetate To 4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichloroaniline ( 1.89 g, 5.5 mmol) was added ethyl bromoacetate ( 1 .1 1 g, 6.6 mmol) and diisopropylethyl amine (0.86 g, 6.6 mmol) in DMF ( 18.9 mL) and stirred at 140 ⁰C for 16 h. The reaction mixture was poured in to ice-water. The product was taken up in ethyl acetate, washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography over flash silica gel (Hexane: Ethyl acetate 90: 10) to afford the pure product ethyl 2-((4-(3-(sec-butyl)- 4-methoxyphenoxy)-3,5-dichlorophenyl)amino)acetate ( 1.1 g, 46 % yield) Step 3: Preparation of Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5- dichlorophenyl)morpholine-4-carboxamido)acetate Triphosgene (50 mg, 0.16 mmol) was added to a solution of Ethyl 2-((4-(3-(sec- butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl) amino) acetate (0.2 g, 0.46 mmol) in dichloromethane (2 mL) at 20-30 ⁰C. The reaction mixture was cooled to 0-5 ⁰C and pyridine (37 mg, 0.46 mmol) was added slowly maintaining the temperature below 5

⁰C. The reaction mixture was stirred at room temperature for 3-4 h. The reaction mixture was poured in to ice. The product was taken up in ethyl acetate, washed with cold H₂O, brine and dried over sodium sulphate, filtered and concentrated to give the crude carbamoyl chloride. The crude carbamoyl chloride was dissolved in dichloromethane (2 mL) and to that morpholine (0.1 g, 1.19 mmol) was added at 0- 10 ⁰C. The reaction mixture was stirred at room temperature for 1-2 h. The reaction mixture was poured in to ice-water. The product was taken up in ethyl acetate, washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography over flash silica gel (Hexane : Ethyl acetate) gradient elution from 98:02 to 90: 10 to afford the pure product ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5- dichlorophenyl)morpholine-4-carboxamido)acetate (0.22 g).

¹H NMR (CDCI₃, 400MHz): 0.88(3H, t, J=6.8Hz), 1.14(3H, d, J=7.2Hz), 1.29(3H, t, J=7.2Hz), l .46-1.60(2H, m), 3.04-3.09(1H, m). 3.29(4H, t. J=4.8Hz), 3.58(4H, t, J=4.6 Hz), 3.77(3H, s), 4.20-4.25(2H, q, J=7.2Hz), 4.37(2H, s), 6.45-6.48( 1 H, dd, J=3.2Hz and 8.8Hz), 6.72( 1 H, d, J=8.8Hz), 6.74(1 H, d, J=2.8Hz), 7. I 6(2H, s).

Step 4: Preparation of 2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5- dichlorophenyl)morpholine-4-carboxamido) acetic acid

A solution of ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5- dichlorophenyl) morpholine-4-carboxamido) acetate (0.22 g, 0.4 mmol) in dichloromethatne (2.2 mL) was cooled to -60 ⁰C to -70 ⁰C under NT atmosphere. To this I M BBr₃ solution ( 1.63 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature over 5 h. and then further diluted with CH₂Ch (20 mL) and quenched with H₂O. After stirring at room temperature for 30 min, organic phase was separated, washed with water, brine, dried over sodium sulphate, filtered and concentrated to give crude product. The crude product was purified by column chromatography over flash silica gel (chloroform: methanol) gradient elution from 99:01 to 90: 10 to give pure 2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5- dichlorophenyl)morpholine-4-carboxamido) acetic acid. (53 ing, 26 %). 1H NMR (DMSO-D₆, 400MHz): 0.75(3H, t, J=7.2Hz), l .O5(3H, d, J=6.8Hz), 1.44- 1.48(2H, m), 2.92-2.94(1 H, m), 3.14-3.15(4H, m), 3.43-3.45(4H, m), 4.27(2H, s), 6.34- 6.37(1H, dd, J=2.8Hz and 8.4Hz), 6.52 (IH, d, J=2.8Hz), 6.68(1H, d, J=8.8Hz), 7.37(2H, s).

Using appropriate starting materials and suitable modifications of one or more of the processes described in Example 79, either alone or in suitable combination of the steps disclosed therein, 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 analogous manner.

EXAMPLE 80 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)moφholine-4- carboxamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 0.75(3H, t, J=7.2Hz), 1.04(3H, d, J=6.8Hz), 1.40-

I .49(2H, m), 2.90-2.96( 1 H, m), 3. I 5-3.16(4H, m), 3.44-3.45(4H, m), 4.14(2H, s), 6.31-

6.34(1 H, dd, J=2.8Hz and 8.4Hz), 6.49 (IH, d, J=3.2Hz), 6.68(1 H, d, J=8.8Hz), 7.37(2H, s).

% Yield: 52

EXAMPLE 81

2-(N-(3,5-dichloro-4-((6-hydroxy-[ I , l'-biphenyl]-3-yl)oxy)phenyl)moφholine-4- carboxamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 3.1 1 -3.13(4H, m), 3.39-3.42(4H, m), 4.31 (2H, s),

6.62-6.66(2H, m), 6.89(1 H, d, J=8.8Hz), 7.29(1 H, d, J=7.2Hz), 7.34-7.38(2H, m),

7.40(2H, s), 7.45-7.47(2H, m).

% Yield: 50

EXAMPLE 82 2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)moφholine-4- carboxamido)acetic acid

¹H NMR (CD₃OD, 400MHz): 3.24-3.25(4H, m), 3.52-3.53(4H, m), 3.87(2H, s),

4.27(2H, s), 6.40( 1 H, d, J=2.8Hz), 6.45-6.48(1 H, dd, J=3.2Hz and 8.8Hz), 6.70(1 H, d,

J=8.4Hz), 7.12-7.16 (3H, m), 7.20-7.24(2H, m), 7.27(2H, s). % Yield: 27

EXAMPLE 83

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)moφholine-4- carboxamido) acetic acid

¹H NMR (CD₃OD, 400MHz): 1.15(6H, d, J=7.2Hz), 3.22-3.28(5H, m), 3.55-3.57(4H, m), 4.39(2H, s), 6.35-6.38(1 H, dd, J=3.2Hz and 8.8Hz)), 6.63-6.66(2H, m), 7.35(2H, s).

% Yield: 90

EXAMPLE 84

2-(l -(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-phenylureido)acetic acid ¹HNMR (DMSO-D₆.400MHz): 1.13(6H, d, J=6.8Hz), 3.12-3.19(IH, m), 4.18(2H, s), 6.31-6.34(1 H, dd, J=3.2Hzand 8.8Hz), 6.66(1 H, d, J=8.8Hz), 6.77(1 H, d, J=3.2Hz), 6.96(1 H, d, J=7.2Hz), 7.24(2H, t, J=7.6Hz and 8Hz).7.41(2H, d, J=7.6Hz), 7.63(2H, s). % Yield: 30 EXAMPLE 85

2-(l-(3,5-dichloro-4-((6-hydroxy-[l,l'-biphenyl]-3-yl)oxy)phenyl)-3-isopropyl ureido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): l.03(6H, d, J=6.4Hz), 3.74-3.78(1H, m), 4.24(2H, s), 6.36( 1 H, s), 6.66-6.69( 1 H, dd. J=3.2Hz and 8.8Hz), 6.79( 1 H, d, J=3.2Hz), 6.87( 1 H, d, J=8.8Hz) 7.26-7.3( I H, m), 7.35-7.39(2H, m), 7.47(2H, s), 7.48-7.5( 1 H, m). % Yield: 72 EXAMPLE 86

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-hydroxy piperidine- 1 - carboxamido) acetic acid 1H NMR (DMSO-D₆, 400MHz): l.08(6H, d, J=6.8Hz), 1.17-1.22(2H, m), 1.57- 1.59(2H, m), 2.82-2.87(2H, m), 3.1-3.17(1 H, m), 3.31-3.45(2H, m), 4.25(2H, s), 4.69(1H, s), 3.57-3.58(lH,m), 6.28-6.31(1 H, dd, J=3.2Hz and 8.8Hz), 6.57(lH,d, J=3.2Hz), 6.67(1 H, d, J=8.8Hz), 7.47(2H, s). %Yield: 78 EXAMPLE 87

2-(3-cyclohexyl-l-(3,5-dichloro-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) ureido) acetic acid

¹HNMR(DMSO-D₆, 400MHz): 1.09-1.13(2H, m), I.18(6H, d, J=6.8Hz), 1.19-

1.31(3H, m), 1.52-] .55(1H, m), 1.63-1.7l(4H, m), 3.11-3.18(1H. m), 3.31-3.42(1H, m), 4.26(2H, s), 6.29-6.32(1 H, dd, J=3.2Hz and 8.8Hz), 6.65(1 H, d, J=8.8Hz), 6.76(1 H, d,

J=3.2Hz), 7.25(2H, s).

% Yield: 70

EXAMPLE 88

2-(N-(3,5-dibromo-4-((6-hydroxy-[l,r-biphenyl]-3-yl)oxy)phenyl)moφholine-4- carboxamido) acetic acid ¹H NMR (DMSO-D₆, 400MHz): 3.1 1 (4H, m), 3.39(4H, m), 4.30(2H, s), 6.58 (I H, d, J=3.2Hz), 6.61 -6.64( 1 H, dd, J=3.2Hz and 8.8Hz), 6.89( I H, d, J=8.8Hz), 7.27( I H, t, J=7.2Hz), 7.36(2H, t, J=7.6Hz), 7.45(2H, t, J=7.2Hz), 7.56(2H, s). % Yield: 16 EXAMPLE 89

2-( I -(3,5-dichloro-4-(4-hydroxy-3-isopropy lphenoxy)pheny l)-3-isopropylureido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.03(6H, d, J=6.8Hz), 1.12(6H, d, J=7.2Hz), 3.1 1 - 3.31 (1 H, m), 3.72-3.81 ( I H, in), 4.24(2H, s), 6.29-6.32( 1 H, dd, J=2.8Hz and 8.4Hz), 6.65( I H, d, J=8.8Hz), 6.76( I H, d, J=3.2Hz), 7.45(2H, s). % Yield: 78 EXAMPLE 90

2-( 1 -(3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-bipheny l]-3-yl)oxy)phenyl)-3-phenylureido) acetic acid 1H NMR (DMSO-D₆, 400MHz): 4.36(2H, s), 6.72-6.75(1 H, dd, J=3.2Hz and 8.8Hz), 6.83(1 H, d, J= 3.2Hz), 6.89(1 H, d, J=9.2Hz), 6.97(1 H, t, J=7.2Hz), 7.24(2H, t, J=7.8Hz), 7.30(1 H, t, J=7.4Hz ), 7.36-7.42(4H, m), 7.50(2H, d, J=7.2Hz), 7.57(2H, s). % Yield: 17 EXAMPLE 91 2-( 1 -(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-phenylureido)acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.13(6H, d, J=6.8Hz), 3.12-3.19(1 H, m), 4.31 (2H, s), 6.29-6.33( 1H, dd. J=3.2Hz and 8.8Hz), 6.65(1 H, d, J=8.8Hz), 6.76(1 H, d, J=2.8Hz), 6.95-6.99( I H, m), 7.22-7.26(2H, m), 7.39-7.41(2H, m), 7.73(2H, s). % Yield: 81 EXAMPLE 92

2-( 1 -(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido)acetic acid

¹H NMR (DMSO-D₆, 400MHz): 4.36(2H, s), 6.62-6.71 (I H, m), 6.73-6.80(1 H, m), 6.89( I H, d, J=8.0Hz), 6.97-7.06(1 H, m), 7.22-7.31(3H, m), 7.35-7.45(4H, m), 7.47- 7.58(2H, m), 7.72(2H, s). % Yield: 12 EXAMPLE 93

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methylpiperazine-l- carboxamido) acetic acid

¹H NMR(DMSO-D₆, 400MHz): 1.10(6H, d, J=6.8Hz), 2.66(3H, s), 2.71-2.84(2H, m), 2.96-3.05(4H. tn), 3.1O-3.21(1H, m), 3.33-3.70(2H, m), 4.36(2H, s), 6.28-6.31(IH, dd, J=2.8Hzand 8.4Hz), 6.65-6.68(2H, m), 7.44(2H, s). % Yield: 43 EXAMPLE 94

2-(3-cyclohe.\yl-l-(3,5-dibromo-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) ureido) acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 1.12(6H, d, J=6.8Hz), 1.17-1.26(4H, m), 1.51 - 1.54(2H, m),1.63-l.71(4H, m), 3.11-3.18 (IH, m), 3.32-3.40(1 H, m), 4.21 (2H, s), 6.25-6.28 (IH, dd, J=2.8Hz and 8.8Hz), 6.64(IH, d, J=8.8Hz), 6.73(1 H, d, J=2.8Hz), 7.62 (2H, s). % Yield: 54 EXAMPLE 95

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methylpiperazine-l- carboxamido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): l.08(6H, d, J=6.8Hz), 2.11(3H, s), 2.16(4H, bs), 3.12- 3.17(5H, m), 4.29(2H, s), 6.31-6.34(1 H, dd, J=2.8Hzand 8.4Hz), 6.54(1 H, d,

J=3.2Hz), 6.68(1 H, d, J=8.4Hz), 7.51 (2H, s).

% Yield: 11

EXAMPLE 96

2-( 1 -(3,5-dibromo-4-((6-hydroxy-[ 1 , l'-biphenyl]-3-y l)oxy)pheny l)-3-isopropy lureido) acetic acid

¹H NMR (DMSO-D₆, 400MHz): 1.02(6H, d, J=6.4Hz), 3.72-3.79(1H, m), 4.26(2H, s), 6.26(1H, d, J=7.6Hz), 6.63-6.66(IH, dd, J=3.2Hzand 8.8Hz), 6.76(IH, d, J=3.2Hz), 6.87(1 H, d, J=8.8Hz), 7.26-7.30(1 H, m), 7.35-7.39(2H, m).7.48-7.50(1 H, m), 7.60(2H, s). % Yield: 49 EXAMPLE 97 2-( l -(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)-3-phenylureido)acetic acid

¹ H NMR (DMSO-D₆, 400MHz): 0.79(3H, t, J=7.4Hz), 1.1 (3 H, d. J=6.8Hz), 1.46- 1.57(2H, m), 2.92-2.97(1 H, q, J=6.8Hz and 7.2Hz), 4.35(2H. s), 6.33-6.37( 1 H, dd. J=3.2Hz and 8.8Hz), 6.66(1 H, d, J=8.8Hz), 6.69( 1 H, d, J=3.2Hz), 6.97( 1 H, t, J=7.2Hz), 7.24(2H, t, J=7.8Hz), 7.41(2H, d, J=8Hz), 7.7 I(2H, s). % Yield: 75 EXAMPLE 98 2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)- 4-hydroxypiperidine-l- carboxamido)acetic acid

¹H NMR (CD₃OD, 400MHz): 1.15(6H, d, J=6.8Hz), 1.37-1.45(2H, m), 1.74-1.77(2H, m), 2.97-3.018(2H, m), 3.17-3.23( 1 H, m), 3.34-3.52(2H, m), 3.71-3.76( 1 H, m), 4.23(2H, s), 4.6(1 H, s), 6.33-6.36( 1 H, dd, J=3.2Hz and 8.8Hz), 6.62-6.64(2H, m), 7.29(2H, s). % Yield: 17 EXAMPLE 99

N-(3,5-dichIoro-4-((6-hydroxy-[l,r-biphenyl]-3-yl)oxy)phenyl)-N-(2-(hydroxyl amino)-2-oxoethyl) benzamide Step 1 : Preparation of N-(3,5-dichloro-4-((6-hydroxy-[ l, l'-biphenyl]-3-yl)oxy)phenyl)- N-(2-oxo-2-(((tetrahydro-2H-pyran-2-yl) oxy) amino) ethyl) benzamide

To a solution of 2-(N-(3,5-dichloro-4-((6-hydroxy-[l , l '-biphenyl]-3-yl) oxy) phenyl) benzamido) acetic acid prepared as per example 1 (0.1 g, 0.19 mmol) in DMF (2 mL) was added l-Ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCI (45 mg, 0.23 mmol) followed by HOBT (Hydroxybenzotriazole) (39.8 mg, 0.29 mmol). The reaction was stirred for 2-3 minutes at room temperature and then to that NH₂-OTHP (tetrahydropyran) (34.5 mg, 0.29 mmol) was added at same temperature. The reaction mixture was heated to 50-60 ⁰C and stirred for 4-6 h at same temperature. The reaction mixture was poured in to ice-water. The product was taken up in ethyl acetate, washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to afford N- (3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-N-(2-oxo-2- (((tetrahydro-2H-pyran-2-yl) oxy) amino) ethyl) benzamide (0.12 g, 99 %). 1H NMR (CDCl₃, 400MHz): 1.20-1.27(3H, m), 1.7I -1.72(3H, m), 3.65-3.67(1 H, m), 3.98(1H, bs), 4.43(1H, bs), 5.01(2H, s), 6.56(1 H, d, J=2.8Hz), 6.67-6.70(1 H, dd, J=2.8Hz and 8.8Hz), 6.89(1 H, d, J=8.8Hz), 7.14-7.32(6H, m), 7.41 -7.43(3H, m), 7.48-

7.52(3H, m).

Step 2: Preparation of N-(3,5-dichloro-4-((6-hydroxy-[ l. r-biphenyl]-3-yl)oxy)phenyl)-

N-(2-(hydroxyamino)-2-oxoethyl)benzamide Camphor- 10-suIphonic acid (42 mg, 0.18 minol) was added to N-(3,5-dichloro-4-((6- hydroxy-[ l ,r-biphenyl]-3-yl)oxy)phenyl)-N-(2-oxo-2-(((tetrahydro-2H-pyran-2-yl) oxy) amino) ethyl) benzamide (0.1 g, 0.16 mmol) in MeOH (2 mL) at 20-25 ⁰C. The reaction mixture was stirred for 4-6 h. MeOH was evaporated under reduced pressure and residue was taken in ethyl acetate, washed with H₂O, brine and dried over sodium sulphate, filtered and concentrated to afford N-(3,5-dichloro-4-((6-hydroxy-[ l, l'- biphenyl]-3-yl)oxy)phenyl)-N-(2-(hydroxyamino)-2-oxoethyl)benzamide (60 mg, 70

%).

¹H NMR (DMSO-D₆, 400MHz): 4.40(2H, s), 6.46(1 H, d, J=2.8Hz), 6.59 -6.62( I H, dd,

J=3.2Hz and 8.8Hz), 6.87(1 H, d, J=8.8Hz), 7.19-7.25(3H, m), 7.27-7.34(3H, m), 7.40- 7.42(4H, m), 7.48(2H, s), 8.96(1 H, s), 9.36(1 H, s), 10.72(1 H, s).

Using appropriate starting materials and suitable modifications of one or more of the process described in Example 99, 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 analogous manner. EXAMPLE 100

N-(3,5-dibromo-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-N-(2-(hydroxyamino)-

2-oxoethyl) benzamide

¹H NMR (CD₃OD, 400MHz): 4.49(2H, s), 6.41(1 H, d, J=2.8 Hz), 6.58-6.61 (1 H, dd, J=2.8Hz and 8.8 Hz), 6.81 ( I H, d, J=8.8 Hz), 7.15-7.18 (2H, m), 7.23 (I H, d, J=7.2Hz), 7.31-7.34 (3H, m), 7.38-7.45 (2H, m), 7.59 (2H, s), 7.89 (2H, s). % Yield: 45 EXAMPLE 101

N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-N-(2-(hydroxyamino)-2- oxoethyl)benzamide 1H NMR (DMSO-D₆, 400MHz): 1.07(6H, d, J=7.2Hz), 3.08-3.15(1 H, m), 4.39(2H, s), 6.18 -6.21 (I H, dd, J=3.2Hz and 8.8Hz), 6.46(1 H, d, J=2.0Hz), 6.65(1H, d, J=8.8Hz), 7.32(5H, bs), 7.63(2H, s), 8.96(I H, s), 9.03(1 H, s), 10.72(1 H, s). % Yield: 40 Following intermediates, which are encompassed within the scope of compound of formula (I), and which are also suitable for the preparation of the compounds of examples (Example 1 - 101 ) of the present invention, were prepared. INTERMEDIATE 1 Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l, l'-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate

¹H NMR (CDCI₃, 400MHz): I .26- I .33(3H, m), 3.76(3H, s), 4.24-4.29(2H, q, J=7.2Hz), 4.57(2H, s), 6.64( I H, d, J=3.2Hz), 6.72 -6.75 ( I H, dd, J=3.2Hz and 9.2 Hz), 6.88( 1 H, d, J=9.2Hz), 7.16-7.20(3H, m), 7.27-7.29( 1 H, m), 7.33-7.36(2H, m), 7.39-7.59(5H, m), 8.09-8.10( 1 H, m). % Yield: 30 INTERMEDIATE 2

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l , l '-biphenyl]-3-yl)oxy)phenyl)-4-methoxy benzamido) acetate 1H NMR (CDCI₃, 400MHz): I .19(3H, t, J=7.2Hz), 3.68(3H, s), 3.71 (3H, s), 4.10-

4.16(2H, q, J=7.2Hz), 4.61(2H, s), 6.65(1 H, d, J=3.2Hz), 6.69 -6.72 (I H, dd, J=3.2Hz and 8.8Hz), 6.80(2H, d, J=8.8Hz), 7.07(1 H, d, J=9.2Hz), 7.28(2H, d, J=8.8Hz), 7.32- 7.34( l H, m), 7.38-7.4 l(6H, m). % Yield: 61 INTERMEDIATE 3

Ethyl 2-(N-(3.5-dichloro-4-(3-isopropyl-4-methoxypheno\y)phenyl)benzamido)acetate ¹ H NMR: (CDCI₃, 400MHz): 1 .56(6H, d, J=7.2Hz), 1.32(3H, t, J=7.2Hz), 3.23- 3.30( 1H, m), 3.78(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.58(2H, s), 6.38( 1 H, dd, J=2.8Hz and 8.8Hz), 6.69(1 H, d, J=8.8Hz), 6.70( 1 H, d, J=3.2Hz), 7.20(2H, s), 7.33- 7.39(5H, m). % Yield: 82 INTERMEDIATE 4

Ethyl2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-phenyl acetamido) acetate 1H NMR (CDCl₃, 400MHz): 1.20(6H, d, J=7.2Hz), 1 .26-1.30(3H, m), 3.28-3.32(1H, m), 3.60(2H, s), 3.79(3H, s), 4.19-4.25(2H, m), 4.34(2H, s), 6.43-6.46(1 H, dd, J=3.2Hz and 8.8Hz), 6.72( 1 H, d, J=8.8Hz), 6.82(1 H, d, J=3.2Hz), 6.97-6.99(2H, m), 7.23- 7.36(5H, m). % Yield: 97 INTERMEDIATE 5

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoλy)-3,5-dichlorophenyl)benzamido)acetate

¹ H NMR (CDCI₃, 400MHz): 1.23- 1.26(3H, m), 3.75(3H, s), 3.91 (2H, s), 4.24-4.30(2H, q, J=7.0Hz), 4.56(2H, s), 6.45-6.48( I H, dd, J=3.2Hz and 8.8Hz), 6.56( I H, d, J=2.8Hz),

6.72( I H, d, J=8.8Hz), 7. I4-7.19(5H, m), 7.22-7.24(2H, m). 7.30-7.34(2H, m), 7.35-

7.36(3H, m).

% Yield: 98

INTERMEDIATE 6 Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)benzamido)acetate

¹ H NMR (CDCl₃, 400 MHz): I .18(6H, d, J=6.8Hz), 1.21(3H, t, J=7.2Hz), 3.23-

3.3O( 1 H, m), 3.78(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.58(2H, s), 6.34-6.37(1 H, dd,

J=2.8Hz and J=8.8Hz), 6.68-6.70(2H, m), 7.28-7.31 (2H, m), 7.33-7.36( 1 H, m), 7.37-

7.40(4H, m). % Yield: 68

INTERMEDIATE 7

Ethyl2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dichlorophenyl)-2-phenyl acetamido) acetate

¹H NMR (CDCl₃, 400MHz): 1.21-1.24(3H, m), 3.54(2H, s), 3.78(3H, s), 3.94(2H, s), 4.19-4.24(2H, q, J=7.2Hz), 4.31 (2H, s), 6.57-6.60( I H, dd, J=3.2Hz and 8.8Hz),

6.62(1 H, d, J=3.2Hz), 6.77( 1 H, d, J=8.8Hz), 7.03(2H, d, J=6.4Hz), 7.13-7.18(3H, m),

7.22-7.30(3H, m), 7.33-7.35(2H, m), 7.6 l -7.70(2H, m).

% Yield:54

INTERMEDIATE 8 Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-phenyl acetamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.20(6H, d, J=6.8Hz), 1.26- 1.29(3H, m), 3.26-3.31(IH, m), 3.60(2H, s), 3.79(3H, s), 4.18-4.23(2H, m), 4.40(2H, s), 6.4O-6.43(1 H, dd, J=3.2Hz and 8.8Hz), 6.7O(1H, d, J=3.2Hz), 6.72(1 H, d, J=8.8Hz), 7.22-7.36(5H, m), 7.45(2H, S).

% Yield:79 INTERMEDIATE 9 Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methoxy benzamido) acetate

¹ H NMR (CDCl₃, 400MHz): 1.16 (6H, d, J=6.8Hz), l.31(3H, t, J=7.2Hz), 3.24- 3.30( 1 H, m), 3.78(3H, s), 3.79(3H, s), 4.23-4.28(2H, q, J=7.2Hz), 4.55(2H, s), 6.37- 6.40( 1 H, dd, J=2.8Hz and 8.8Hz), 6.70(1 H, d, J= 8.8Hz), 6.73 (I H, d, J=3.2Hz), 6.77(2H, d, J=8.8Hz), 7.34-7.38(2H, m), 7.41(2H, s). % Yield: 59 INTERMEDIATE 10

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxy phenoxy) phenyl) benzamido) acetate

¹H NMR (CDCI₃, 400MHz): 0.81 (3H, t, J=7.2Hz), 1.12(3H, d, J=6.8Hz), 1.32(3H, t, J=7.2Hz), 1.42-1.57(2H, m), 3.02-3.08(1 H, q, J=7.2Hz), 3.77(3H, s), 4,25-4.30(2H, q, J=7.2Hz), 4.58(2H, s), 6.39-6.42(1 H, dd, J=3.2Hz and 8.8Hz), 6.59(1 H, d, J=3.2Hz), 6.71(1 H, d, J=8.8Hz), 7.28-7.30(2H, m), 7.33-7.40(4H, m), 7.46-7.50( I H, m). % Yield:95

INTERMEDIATE 11

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[l, l'-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate

¹H NMR (CDCl₃, 400MHz): 1.31(3H, t, J=7.2Hz), 3.76(3H, s), 4.23-4.29(2H, q, J=7.2Hz), 4.56(2H, s), 6.62( 1 H, d, J=3.2Hz), 6.70-6.73( 1 H, dd, J=3.2Hz and 8.8Hz),

6.88(1 H, d, J=8.8Hz), 7.17(2H, t, J=7.6Hz), 7.24-7.26( 1 H, m), 7.32-7.36(3H, m), 7.39-

7.42(2H, m), 7.45-7.49(3H, m), 8.1 O-8.12(1H, m).

% Yield: 98

INTERMEDIATE 12 Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)-2-phenyl acetamido) acetate

¹H NMR (CDCI₃, 400MHz): 0.84(3H, t, J=7.2Hz), 1.15-1.17(3H, m), 1.25-1.30(5H, m), 3.07-3.09(1 H, m), 3.60(2H, s), 3.78(3H, s), 4.19-4.25(2H, m), 4.58(2H, s), 6.43- 6.46(1 H, dd, J=3.2Hz and 8.8Hz), 6.73( 1 H, d, J=8.8Hz), 6.80( I H, d, J=3.2Hz), 7.07(2H, d, J=8.8Hz), 7.22-7.30(3H, m), 7.45(2H, s). % Yield: 66 INTERMEDIATE 13 Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl) benzamido) acetate

¹ H NMR (CDCI₃. 400MHz): 0.81 (3H, t, J=7.2Hz), 1. I 2(3H, d, J=6.8Hz), 1 .32(3H, t, J=7.2Hz), 1.42-1.50(2H, m), 3.02-3.07( I H, q, J=7.2Hz), 3.77(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.58(2H, s), 6.4O-6.43(1 H, dd, J=3.2Hz and 8.8Hz), 6.2O( 1 H, d, J=3.2Hz), 6.71(1 H, d, J-8.8Hz), 7.19(2H, s), 7.26-7.29(2H, m), 7.33-7.34(1H, in), 7.35-7.39(2H, m).

% Yield: 90 INTERMEDIATE 14 EthyI2-(N-(3,5-dibromo-4-((6-methoxy-[ I , I '-biphenyl]-3-yl)oxy)phenyl)-2-phenyl acetamido) acetate

¹H NMR (CDCI₃, 400MHz): I .2 I -I .31(3H, m), 3.59(2H, s), 3.78(3H, s), 4.20-4.24(2H, m), 4.32(2H, s), 6.79-6.80(1 H, m), 6.91 -6.93(1 H, m), 7.02-7.04(2H, m), 7.1 1 -7.23(2H, m), 7.28-7.33(3H, m), 7.37-7.41(2H, m), 7.44(2H, s), 7.48-7.52(2H, m). % Yield:98

INTERMEDIATE 15

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ I , I '-biphenyl]-3-yl)oxy)phenyl)thiophene-2- carboxamido) acetate

¹H NMR (CDCI₃, 400MHz): I .3O(3H, t, J=7.2Hz), 3.78(3H, s), 4.23-4.28(2H, q, J=7.2Hz), 4.49(2H, s), 6.74( 1 H, d, J=2.8Hz), 6.81-6.83(1 H, m), 6.90( 1 H, d, J=3.2Hz),

6.94( 1 H, d, J=9.2Hz), 7.19-7.21 (2H, m), 7.32-7.36( I H, m), 7.39-7.42(2H, m), 7.48-

7.50(2H, m), 7.71 (2H, s).

% Yield: 96

INTERMEDIATE 16 Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)thiophene-2- carboxam ido)acetate

¹H NMR (CDCI₃, 400MHz): 1. I9(6H, d, J=7.2Hz), 1.30(3H, t, J=7.2Hz), 3.27-3.34( 1 H, m), 3.80(3H, s), 4.23-4.29(2H, q, J=7.2Hz), 4.50(2H, s), 6.54-6.57(1 H, dd, J=3.2Hz and 8.8Hz), 6.75( 1 H, d, J=8.8Hz), 6.80( 1 H, d, J=3.2Hz ), 6.94( 1 H, dd, J= 4.0Hz and 5.2Hz), 7.23( 1 H, dd, J= 1.2Hz and 4.0Hz), 7.43(1 H, dd, J=I .2Hz and 5.2Hz), 7.80(2H, s). % Yield: 79 INTERMEDIATE 17

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxypheno\y)-3,5-dichlorophenyl) benzamido) propanoate

¹ H NMR (CDCI₃, 400MHz): O.83(3H, t, J=7.2Hz), 1.1 1 (3H, d, J=6.8Hz), 1 .27(3H, t, J=7.2Hz), 1.48- 1.56(5H, m), 3.02-3.07( 1 H, m), 3.77(3H, s), 4.24-4.34(2H, m), 5.03- 5.09(1H, q, J=7.2Hz), 6.36-6.39( 1 H, dd, J=3.2 Hz and 8.8Hz), 6.58( 1 H, d, J=2.8Hz), 6.7( 1 H, d, J=8.8Hz), 7.23-7.33(6H, m), 7.48( 1 H, t, J=8Hz). % Yield: 71

INTERMEDIATE 18 Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)thiophene-2- carboxam ido)acetate

¹H NMR (CDCI₃, 400MHz): 0.91 (3H, t, J=6.8Hz), 1.15(3H, d, J=6.8Hz), 1.31 (3H, t,

J=7.2Hz), 1.47-1.49(2H, m), 3.07-3.12(1 H, m), 3.79(3H, s), 4.23-4.29(2H, q,

J=7.20Hz), 4.50(2H, s), 6.58-6.61 ( 1 H, dd, J=3.2Hz and 8.8Hz), 6.71 ( 1 H. d, J=2.8Hz), 6.77(I H, d, J=8.8Hz), 6.93-6.95(1 H, m), 7.23-7.24( 1 H, m), 7.41 -7.43(1 H, m), 7.70(2H, s).

% Yield: 88

INTERMEDIATE 19

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)furan-2- carboxamido) acetate

¹ H NMR (CDCI₃, 400MHz): 0.89(3H, t, J=7.2Hz), 1.15(3H, d, J=6.8Hz), 1 .31 (3H, t, J=7.2Hz), 1.48-1.62(2H, m) , 3.06-3.1 1 (1 H, m), 3.79(3H, s), 4.23-4.26(2H, q, J=7.2Hz), 4.50(2H, s), 6.36-6.38(1 H, dd, J=2.0Hz and 3.6Hz), 6.50-6.53(2H, m). 6.73- 6.76(2H, m), 7.35-7.36(1 H, m), 7.64(2H, s). % Yield: 92

INTERMEDIATE 20

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxy phenoxy) phenyl) benzamido) propanoate

¹H NMR (CDCI₃, 400MHz): 0.81 (3H, t, J=7.2Hz), 1.12(3H, d, J=7.2Hz), 1.34(3H, t, J=7.2Hz), 1.45-1.48(2H, m), 1.52(3H, d, J=7.2Hz), 3.02-3.07(1H, m), 3.77(3H, s), 4.24-4.33(2H, m), 5.02-5.08(1H, q, J=7.2Hz), 6.34-6.37(1 H, dd, J=2.8Hz and 8.8Hz), 6.55(1 H, d, J=3.2Hz), 7.27-7.33(4H, m), 7.43-7.50(3H, m), 8.1O-8.13(1 H, m). % Yield: 62 INTERMEDIATE 21

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)furan-2- carbo.xamido) acetate 1 H NMR (CDCI₃, 400MHz): 1.19(6H, d, J=6.8Hz), 1.23-1.29(3H, t, J=7.6Hz), 3.26- 3.33( 1 H, m), 3.80(3H, s), 4.23-4.28(2H, q, J=7.6Hz), 4.50(2H, s), 6.36-6.38(1 H, dd, J=I .6Hz and J=3.2Hz), 6.49(1 H, d, J=3.2Hz) , 6.52(1 H, d, J= 3.2Hz), 6.72( 1 H, d, J= 8.8Hz), 6.81(1 H, d, J=3.2Hz), 7.35-7.36(1 H, m), 7.64(2H, s). % Yield: 61 INTERMEDIATE 22

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dimethylphenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 0.80(3H, t, J=7.4Hz), 0.86-0.93(2H, m), I . I O(3H, d,

J=6.8Hz), 1.40-1.45(3H, m), I .94(6H, s), 2.24-3.04(1 H, m), 3.05(3H, s), 4.23-4.29(2H, q, J=7.2Hz), 4.59(2H, s), 6.32-6.35(1 H, dd, J=3.2Hz and 8.8Hz), 6.51( 1 H, d, J=2.8Hz),

6.68(1 H, d, J=8.8Hz), 6.86(2H, s), 7.20(2H, t, J=7.4Hz), 7.39(2H, d, J=7.2Hz),

7.48(1 H, t, J=8.4Hz).

% Yield:62

INTERMEDIATE 23 Ethyl 2-(N-(4-(3-isopropyI-4-methoxyphenoxy)-3,5-dimethylphenyl) benzamido) acetate

¹H NMR (CDCl₃, 400MHz): I .13(6H, d, J=7.2Hz), 1.31 (3H, t, J=7.2Hz), 1.98(6H, s), 3.2O-3.28(1 H, m), 3.77(3H, s), 4.26(2H, q, J=7.2Hz), 4.58(2H, s), 6.29(1 H, dd, J=2.8Hz and 8.8Hz), 6.60(1 H, d, J=2.8Hz), 6.66( 1 H, d, J=2.8Hz), 6.86(2H, s), 7.18- 7.22(2H, m), 126-12% 1 H, m), 7.38-7.39(2H, m). % Yield: 92 INTERMEDIATE 24

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl)benzamido) propanoate 1H NMR (CDCI₃, 400MHz): I .14(6H, d, J=6.8Hz), 1.34(3H, t, J=7.0Hz), 1.52(3H, d, J=7.2Hz), 3.23-3.29( 1H, m), 3.78(3H, s), 4.09-4.14(2H, q, J=7.2Hz), 5.02-5.07(1 H, q, J=7.2Hz), 6.30-6.33( 1 H, dd, J=3.2Hz and 8.8Hz), 6.53( 1 H, d, J=2.8Hz), 6.68( 1 H, d, J=8.8Hz), 7.24-7.33(5H, m), 7.44(2H, s). % Yield:81

INTERMEDIATE 25 Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl) benzamido) butanoate

¹ H NMR (CDCI₃, 400MHz): l.09(3H, t, J=7.4Hz), 1 .13-1.16(6H, m), l .32(3H, t, J=7.2Hz). 1.96-2.00(2H, m), 3.24-3.28( I H, m), 3.78(3H, s), 4.26-4.30(2H, m), 4.79- 4.83( I H, m), 6.31 -6.34( I H, dd, J=3.2Hz and 8.8Hz), 6.65( I H, d, J=2.8Hz), 6.69( 1 H, d, J=8.8Hz), 7.24-7.34(3H, m), 7.42-7.50(3H, m), 8.10-8.13( I H, m). % Yield:41

INTERMEDIATE 26

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)benzamido)-2- methyl propanoate 1H NMR (CDCl₃, 400MHz): 1.13(6H, d, J=6.8Hz), 1.37(3H, t, J=7.2Hz), 1.55(6H, s), 3.22-3.29( 1 H, m), 3.78(3H, s), 4.27-4.33(2H, q, J=7.2Hz), 6.23-6.26(1 H, dd, J=3.2Hz and 8.8Hz), 6.61 ( I H, d, J=2.8Hz), 6.67( 1 H, d, J=8.8Hz), 7.20-7.27(5H, m), 7.43(2H, s). % Yield:39 INTERMEDIATE 27

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ l, l '-biphenyl]-3-yl)oxy) phenyl) benzamido) propanoate

¹H NMR (CDCI₃, 400MHz): 1.24-1.39(3H, m), 1.53(3H, d, J=7.2Hz), 3.76(3H, s), 4.23-4.33(2H, m), 5.01-5.03(1 H, m), 6.6O( 1 H, d, J=2.8Hz), 6.65-6.68(1 H, dd, J=3.2Hz and 8.8Hz), 6.88( 1 H, d, J=8.8Hz), 7.13-7.17(3H, m), 7.26-7.28( I H, m), 7.35-7.36(1 H, m), 7.39-7.43(4H, m), 7.45-7.47(3H, m). % Yield:65

INTERMEDIATE 28 Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dibromophenyl)benzamido)acetate ¹H NMR (CDCI₃, 400MHz): 1.32(3H, t, J=7.2Hz), 3.75(3H, s), 3.91(2H, s), 4.24-

4.30(2H, q, J=7.2Hz), 4.56(2H, s), 6.44-6.46(1 H, dd, J=3.2Hz and 8.8Hz), 6.53(1H, d, J=3.2Hz), 6.73(1 H, d, J=8.8Hz), 7.15-7.19(3H, m), 7.22-7.28(3H, m), 7.30-7.36(4H, in), 7.38(2H, s). % Yield: 97 INTERMEDIATE 29 Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dibromophenyl) benzamido) propanoate

¹H NMR (CDCI₃, 400MHz): 1 .34(3H, t, J=7.0Hz), I .51 (3H, d, J=7.2Hz), 3.75(3H, s), 3.91(2H, s), 4.30-4.33(2H, m), 5.02-5.04( 1 H, m), 6.4O-6.43(1 H, dd, J=3.2Hz and 8.8Hz), 6.48( I H, d, J=3.6Hz), 6.72( I H, d, J=8.8Hz), 7.14-7.29( 1 OH, m), 7.41 (2H, s). % Yield: 54

INTERMEDIATE 30

Ethyl 2-(N-(3,5-dibromo-4-(3-ethyl-4-methoxyphenoxy)phenyl)benzamido)acetate

¹H NMR (CDCI₃, 400MHz): I . I 7(3H, t, J=7.2Hz), I .32(3H, t, J=7.2Hz), 2.55-2.61(2H, q, J=7.6Hz), 3.78(3H, s), 4.25-4.30(2H, q , J=7.2Hz), 4.58(2H, s), 6.39-6.42(1 H, dd, J=3.2Hz and 8.8Hz), 6.59(1 H, d, J=3.2Hz), 6.69( I H, d, J=9.2Hz), 7.27(2H, d,

J=7.6Hz), 7.30-7.35(3H, m), 7.40(2H, s).

% Yield: 59

INTERMEDIATE 31

Ethyl 2-(N-(4-((6-methoxy-[ I , l '-biphenyl]-3-yl)oxy)-3,5-dimethylphenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): I .3O(3H, t, J=7.2Hz), I .99(6H, s), 3.74(3H, s), 4.23- 4.28(2H, q, J=7.2Hz), 4.58(2H, s), 6.58-6.61 (1 H, m), 6.62-6.64(1 H, dd, J=2.4Hz and 8.0Hz), 6.84-6.85(3H, m), 7.09(2H, t, J=7.2Hz), 7.17( 1 H, t, J=7.2Hz), 7.33-7.38(3H, m), 7.40-7.50(4H, m). % Yield: 67

INTERMEDIATE 32

Ethyl 2-(N-(3,5-dibromo-4-(3-(tert-butyl)-4-methoxyphenoxy) phenyl)benzamido) acetate

¹H NMR (CDCI₃, 400 MHz): 1.29- 1 35(3H, m), 1.32(9H, s), 3.78(3H, s), 4.24-4.30 (2H, q, J=7.2Hz), 4.57(2H, s), 6.33-6.36(1 H, dd, J=2.8Hz and 8.8Hz), 6.70(1 H, d,

J=8.8Hz), 6.80(1 H, d, J=3.2Hz), 7.28(2H, d, J=7.6Hz), 7.34( 1 H, d, J=7.6Hz), 7.37(2H, d, J= 1.2Hz), 7.39 (2H, s). % Yield: 67 INTERMEDIATE 33

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dibromophenyl)thiophene-2- carboxamido) acetate 1H NMR (CDCI₃, 400MHz): 1.32(3H, t, J=7.0Hz), 3.76(3H, s), 3.94(2H, s), 4.23- 4.28(2H, q, J=7.2Hz), 4.48(2H, s), 6.59-6.61(1 H, dd, J=3.2Hz and 8.8Hz), 6.65( 1 H, d, J=2.8Hz), 6.77(1 H, d, J= 8.8Hz), 6.88-6.90(1 H, dd, J= 3.6Hz and 4.8Hz), 7.15- 7.18(4H, m), 7.23-7.27(2H, m), 7.35-7.36( I H, dd, J= 1.2Hz and 4.8Hz), 7.67(2H, s). % Yield: 78 INTERMEDIATE 34

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) cyclohexane carboxamido) acetate

¹H NMR (CDCI₃, 400MHz): 1. I 8(6H, d, J=7.2Hz), 1.29(3H, t, J=7.0Hz), 1.52- l .58(2H, m), 1.59-1.63(2H, m), 1.72- 1.77(5H, m), 1.92-1.95(1 H, m), 2.22-2.27(1 H, m), 3.26-

3.32(1H, m), 3.79(3H,s ), 4.20-4.25(2H, q, J=8.8Hz), 4.30(2H, s), 6.46-6.48(1H, dd,

J=2.8Hz and 8.8Hz), 6.73(1 H, d, J=8.8Hz), 6.80(1 H, d, J=3.2Hz), 7.64(2H, s).

% Yield: 75

INTERMEDIATE 35 Ethyl 2-(3-chloro-N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1.17(6H, d, J=6.8Hz), 1.32(3H, t, J=7.2Hz), 3.23-3.30(1 H, m), 3.78(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.56(2H, s), 6.29-6.32( 1 H, dd, J=3.2Hz and 8.8Hz), 6.68(1 H, d, J=8.8Hz), 6.76( 1H, d, J=3.8Hz), 7.20-7.26(2H, m), 7.32-7.34( 1 H, m), 7.40-7.42( 1 H, m), 7.44(2H, s). % Yield: 96 INTERMEDIATE 36

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-methyl benzamido) acetate 1H NMR(CDCI₃, 400MHz): 1.18(6H, d, J=8.4Hz), 1.32(3H, t, J=7.2Hz), 2 .30(3H, s), 3.23-3.30(1 H, m), 3.78(3H, s), 4.24-4.30(2H, q, J=7.2Hz), 4.56(2H, s), 6.30-6.33(1 H, dd, J=3.2Hz and 8.8Hz), 6.67( 1 H, d, J=8.8Hz), 6.74( 1 H, d, J=2.8Hz), 7.08-7.1 1 ( 1 H, m), 7.13-7.16(2H, m), 7.27( I H, s), 7.41 (2H, s). % Yield: 96

INTERMEDIATE 37 Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4- methylbenzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1. 15(6H, d, J= 6.8Hz), 1.31(3H, t, J=7.2Hz), 2.31 (3H, s), 3.25-3.28( I H, m), 3.78(3 H, s), 4.23-4.29(2H, q, J= 7.2Hz), 4.56(2H, s), 6.41 -6.44(1 H, dd, J=3.2Hz and 8.8Hz), 6.68-6.71 (2H, m), 7.06(2H, d, J=8.0Hz), 7.19(2H, s), 7.28(2H, d, J= 8.4Hz). % Yield: 94 INTERMEDIATE 38

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy) phenyl) cyclohexane carboxamido) acetate 1H NMR (CDCl₃, 400MHz): 1.07-1.10(3H, m), 1.18(6H, d, J=6.8Hz), 1.24-1.31(4H, m), 1.53-1.63(2H, m), 1.71-1.74(4H, m), 2.22-2.28(1 H, m), 3.25-3.32(1 H, m), 3.79(3H, s), 4.20-4.25(2H, q, J=7.2Hz), 4.30(2H, s), 6.48-6.51( 1 H, dd, J=3.2Hz and 8.8Hz). 6.73( 1 H, d, J=8.8Hz), 6.82(1 H, d, J=3.2Hz), 7.43(2H, s). % Yield: 94 INTERMEDIATE 39

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4- (trifluoromethyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1.14(6H, d, J=7.2Hz), 1.33 (3H, t, J=7.2Hz), 3.24-

3.27( I H, m), 3.77(3H, s), 4.26-4.31 (2H, q, J=7.2Hz), 4.57(2H, s), 6.30-6.33( 1 H, dd, J=3.2Hz and 8.8Hz), 6.67( 1 H, d, J=8.8Hz), 6.70( 1 H, d, J=3.2Hz), 7.22(2H, s), 7.51(2H, d, J=8.4Hz), 7.56 (2H, d, J=8.4Hz).

% Yield: 91

INTERMEDIATE 40

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-rnethoxyphenoxy)phenyl)-2-methyl benzamido) acetate ¹ H NMR (CDCl₃, 400MHz): U 8(6H, d, J= 6.8Hz), 1.30- l .35(3H, m), 2.41(3H. s), 3.21 -3.28( I H, m), 3.77(3H, s), 4.27-4.30(2H, m), 4.58(2H, s). 6.32(1 H, d, J=7.2Hz). 6.60(1 H, s), 6.67( I H, d, J=8.8Hz), 7.07-7.08(2H, m), 7.12-7.18(4H, m). % Yield: 79 INTERMEDIATE 41

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-metho.\yphenoxy)phenyl)-3-methyl benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1.16(6H, d, J=6.8Hz), 1.32 (3H, t, J=7.2Hz), 2.30(3 H, s),

3.23-3.30( 1 H, m). 3.78(3H, s), 4.24-4.29(2H, q, J=7.2Hz), 4.56 (2H, s), 6.33-6.35( I H, dd, J=2.8Hz and 8.8Hz), 6.67(1 H, d, J=8.8Hz), 6.75(1 H, d, J=3.2Hz), 7.08-7.16(3H, m), 7.20(2H, s), 7.27 ( I H, s).

% Yield: 98

INTERMEDIATE 42

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) cyclopropane carboxamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.05-1.07(2H, m), 1.08-1.10(2H, m), 1.19(6H, d, J=6.8Hz), 1 .29(3H, t, J=7.2Hz), 1.42-1.45( 1 H, m), 3.27-3.30( I H, m), 3.78(3H, s), 4.19- 4.25(2H, q, J=7.2Hz), 4.37(2H, s), 6.39-6.42( 1 H, dd, J=3.2Hz and 8.8Hz), 6.70( 1 H, d, J=8.8Hz), 6.88( 1 H, d, J=3.2Hz), 7.72(2H, s). % Yield: 95

INTERMEDIATE 43

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[l , r-biphenyl]-3-yl)oxy)phenyl)-4-methoxy benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1.3(3H, t, J=7.2Hz), 3.73(3H, s), 3.76(3H, s), 4.22- 4.28(2H, q, J=7.2Hz), 4.55(2H, s), 6.70-6.73(4H, m), 6.89(1 H, d, J=9.6Hz), 7.34(3H, d,

J=6.4Hz), 7.39-7.43(4H, m), 7.49(2H, d, J=7.2Hz).

% Yield: 79

INTERMEDIATE 44

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methoxy benzamido) acetate

¹H NMR (CDCl₃, 400MHz): 1.14(6H, d, J=6.8Hz), 1.33(3H, t, J=7.2Hz), 3.22-3.29(1 H, m), 3.74(3H, s), 3.77(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.57(2H, s), 6.25-6.27(1 H, dd, J=2.8Hz and 8.8Hz), 6.61 ( 1 H, d, J=2.0Hz), 6.66( 1 H, d, J=8.8Hz), 6.71(1 H, d, J=8.0Hz), 6.90(1 H, t, J=7.6Hz), 7.24-7.28(2H, m), 7.46(2H, s). % Yield:79

INTERMEDIATE 45 Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-(l , r-biphenyl]-3-yl)oxy)phenyl)-3-methoxy benzamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.31(3H, t, J=7.2Hz), 3.71(3H, s), 3.76(3H, s), 4.23- 4.29(2H, q, J=7.2Hz), 4.55(2H. s), 6.66-6.69(2H, m), 6.80-6.83(2H, m), 6.87( 1 H, d, J=8.4Hz), 6.96-6.97( I H, m), 7.01 -7.03( I H, m), 7.33-7.35( 1 H, m), 7.38-7.42(4H, in), 7.46-7.48(2H, m). % Yield:84

INTERMEDIATE 46

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl)-4-methyl benzamido) acetate 1H NMR (CDCI₃, 400MHz): 0.81(3H, t, J=7.2Hz), 1.13(3H, d, J=6.8Hz), 1.31(3H, t, J=6.8Hz), 1.45-1.52(2H, m), 2.3 1 (3H, s), 3.03-3.08( 1 H, m), 3.77(3H, s), 4.23-4.29(2H, q, J=7.2Hz), 4.56(2H, s), 6.44-6.47( I H, dd, J=3.2Hz and 8.8Hz), 6.61( I H. d, J=3.2Hz), 6.71 (1 H, d, J=8.8Hz), 7.07(2H, d, J=8.0Hz), 7.19(2H, s), 7.28(2H, d, J=8.0Hz). % Yield:91 INTERMEDIATE 47

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[l , r-biphenyl]-3-yl)oxy)phenyl)-2-methoxy benzamido) acetate

¹H NMR (CDCI₃, 400MHz): I .32(3H, t, J=7.2Hz), 3.66(3H, s), 3.75(3H, s), 4.24-

4.29(2H, q, J=7.2Hz), 4.56 (2H, s), 6.51(2H, d, J=8.4Hz), 6.65-6.68( 1 H, dd, J=2.8Hz and 8.8Hz), 6.82( I H, d, J=7.6Hz), 6.87(1 H, d, J=7.2Hz), 6.99-7.01 ( 1 H, m), 7.05-

7.1 1(1H, m), 7.35(1 H, d, J=9.2Hz), 7.39-7.44(6H, m).

% Yield: 98

INTERMEDIATE 48

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[l,l'-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.30(3H, t, J=7.0 Hz), 2.57(3H, s), 3.76(3H, s), 4.23- 4.28(2H, q, J=7.2Hz), 4.55(2H, s), 6.68(1 H, d, J=3.2Hz), 6.70-6.73(1 H, dd, J=3.2Hz and 8.8Hz), 6.89(1 H, d, J=8.8Hz), 6.98(2H, d, J=8.0Hz), 7.23(2H, s), 7.3 I -7.35( 1H, m), 7.39-7.41 (2H, m), 7.42(2H, s), 7.48(2H, d, J=8.8Hz). % Yield: 73 INTERMEDIATE 49 Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l , r-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetate

¹H NMR (CDCI₃, 400MHz): I .3O(3H, t, J=7.20Hz), 2.25(3H, s), 3.76(3H, s), 4.22- 4.28(2H, q, J=7.2Hz), 4.55(2H, s), 6.70( I H, d, J=3.2Hz), 6.72-6.75( 1 H, dd, J=3.2Hz and9.2Hz), 6.88(1 H, d, J=9.2Hz), 6.98(2H, d, J=7.6Hz), 7.19(2H, s), 7.25(1H, d, J=8.8Hz), 7.3 l-7.35(2H, m), 7.38-7.42(2H, m), 7.46-7.48(2H, m). % Yield:92

INTERMEDIATE 50

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-methoxy benzamido) acetate 1H NMR (CDCI₃, 400MHz): 1.16(6H, d, J=6.8Hz), 1.32(3H, t, J=5.0Hz), 3.23-3.30(1 H, m), 3.75(3H, s), 3.78(3H, s), 4.24-4.30(2H, q, J=7.2Hz), 4.56(2H, s), 6.31-6.34(IH, dd, J=3.2Hz and 8.8Hz), 6.68( 1 H, d, J=8.8Hz), 6.73(1 H, d, J=3.2Hz), 6.87-6.90(2H, m), 6.96-6.97( 1 H, m), 7.14-7.18(1 H, m), 7.43(2H, s). % Yield:94 INTERMEDIATE 51

Ethyl 2-(4-chloro-N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.15(6H, d, J=5.2Hz), 1.32(3H, t, J=6.0Hz), 3.23-3.30(1 H, m), 3.78(3H, s), 4.24-4.30(2H, q, J=7.2Hz), 4.55(2H, s), 6.37-6.40(1 H, dd, J=3.2Hz and 9.2Hz), 6.69-6.72(2H, m), 7.25-7.27(4H, m), 7.32-7.35(2H, m). % Yield: 95 INTERMEDIATE 52

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methyl benzamido) acetate 1H NMR (CDCI₃, 400MHz): 1.14(6H, d, J=6.8Hz), 1.29-1.30(3H, m), 2.42(3H, s), 3.23-3.28(1H, m), 3.78(3H, s), 4.29-4.31(2H, q, J= 7.2Hz), 4.60(2H, s), 6.31(1 H, d, J=7.2Hz), 6.59(1 H, s), 6.68( 1 H, d, J=8.8Hz), 7.09-7.19(4H, m), 7.39(2H, s). % Yield: 74 INTERMEDIATE 53

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-2-methyl benzamido) acetate 1H NMR (CDCl₃. 400MHz): 1.27-1.29(3H, m), 2.39(3H, s), 3.75(3H, s), 4.22-4.29(2H, m), 4.57(2H, s), 6.55-6.65(2H, m), 6.86( 1 H, d, J=8.8Hz), 6.94 ( I H, bs), 7.05(3H, bs),

7.33-7.40(5H, m), 7.42-7.46(2H,m).

% Yield: 82

INTERMEDIATE 54 Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-2'-methyl-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): l .33(3H, t, J=7.0Hz), 1.72(3H, s), 3.75(3H, s), 4.25-

4.29(2H, m), 4.60(2H, s), 6.38-6.41 (I H, dd, J=2.8Hz and 8.8Hz), 6.55-6.57(2H, m),

6.66( 1 H, d, J=7.6Hz), 6.89(1 H, d, J=2.8Hz), 6.95(1 H, t, J=7.4Hz), 7.00(1 H, d, J=7.6Hz), 7.06-7.08(1 H, m), 7.28-7.34(3H, m), 7.39-7.41(2H, m), 7.59(1 H, d,

J=2.8Hz).

% Yield: 33

INTERMEDIATE 55

Ethyl 2-(2-chloro-N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.14(6H, d, J=8.8Hz), I .33(3H, t, J=8.6Hz), 3.21 -3.28(1 H, m), 3.77(3H, s), 4.27-4.33(2H, q, J=7.2Hz), 4.59(2H, s), 6.27-6.30(1 H, dd, J=3.2Hz and 8.8Hz), 6.57(1 H, d, J=3.2Hz), 6.67( 1 H, d, J=8.8Hz), 7. I 7-7.21(2H, m), 7.22-7.30(2H, m), 7.52(2H, s). % Yield: 96

INTERMEDIATE 56

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl)-3-yl)oxy)pheny l)-4-

(trifluoromethyl) benzamido) acetate

¹H NMR (CDCI₃, 400 MHz): 1.28(3H, t, J= 7.2Hz), 3.75(3H, s), 4.24-4.30 (2H, q, J= 6.8Hz), 4.56(2H, s), 6.61 -6.64(1H, dd, J=3.2Hz and 8.8Hz), 6.75(1 H, d, J=3.2Hz), 6.85-6.87(1H, d, J=8.8Hz), 7.21(2H, s), 7.31-7.35( 1H, m), 7.38-7.42(2H, m), 7.46- 7.48(2H, m), 7.50-7.53(4H, m). % Yield: 76

INTERMEDIATE 57

Ethyl 2-(N-(3,5-dibromo-4-((2',6-dimethoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate 1H NMR (CDCI₃, 400MHz): 1.31(3H, t, J=7.2Hz), 3.53(3H, s), 3.77(3H, s), 4.23- 4.29(2H, q, J=7.2Hz), 4.61(2H, s), 6.5O-6.53( 1 H, dd, J=2.8Hz and 8.8Hz), 6.59- 6.63(2H, m), 6.72(1 H, d, J=8.4Hz), 6.79-6.80(2H, m), 7.08( I H, d, J=2.4Hz), 7.16- 7.18( 1 H, m), 7.29-7.33(2H, m), 7.35-7.36(1 H, m), 7.4 I -7.43(2H, m). 7.47( 1 H, d, J=2.8Hz). % Yield: 49

INTERMEDIATE 58

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-

(trifluoromethyl) benzamido) acetate

¹H NMR (CDCI₃, 400 MHz): 1.14(6H, d, J=6.8Hz), 1.33(3H, t, J=7.2Hz), 3.24- 3.28(1 H, m), 3.78(3H, s), 4.26-4.32(2H, q, J=7.2Hz), 4.58(2H, s), 6.28-6.31 (1H, dd,

J=3.2Hz and 8.8Hz), 6.67-6.69(2H, m), 7.43(2H, s), 7.5 1(2H, d, J=8.4Hz), 7.56(2H, d,

J=8.4Hz)

% Yield: 98

INTERMEDIATE 59 Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-

(trifluoromethyl) benzamido) acetate

¹H NMR (CDCI₃, 400MHz): I .32(3H, t, J=7.2Hz), 3.76(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.57(2H, s), 6.58-6.61 ( 1 H, dd, J=3.2Hz and 8.8Hz), 6.73( 1 H, d, J=3.2Hz), 6.86(1 H, d, J=9.2Hz), 7.33-7.35( I H. m), 7.38-7.42(4H, m), 7.46-7.48(6H, m). % Yield: 92

INTERMEDIATE 60

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3,5-bis

(trifluoromethyl) benzamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.17(6H, d, J=6.8Hz), 1.34(3H, t, J=7.0Hz), 3.25-3.28(1 H, m), 3.78(3H, s), 4.27-4.32(2H, q, J=7.2 Hz), 4.58(2H, s), 6.16-6.19(1H, dd, J=3.2Hz and 8.8Hz), 6.63(1 H, d, J=8.8Hz), 6.87(1 H, d, J=2.8Hz), 7.87(3H, s). % Yield: 90 INTERMEDIATE 61

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l , r-biphenyl]-3-yl)oxy)phenyl)-3,5-bis (trifluoromethyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1.33(3H, t, J=7.2Hz), 3.76(3H, s), 4.26-4.31 (2H, q, J=7.2 Hz), 4.57(2H, s), 6.51 -6.54( I H, dd, J=2.8Hz and 8.8Hz), 6.83( 1 H, d, J=8.8Hz),

6.85( 1 H, d, J=3.2Hz), 7.26-7.27(2H, m), 7.33-7.35(1 H, m), 7.39(2H, t, J=7.6Hz), 7.47- 7.49(2H, m), 7.84(I H, s), 7.86(2H, s). % Yield: 69 INTERMEDIATE 62 Ethyl 2-(N-(3,5-dibromo-4-((2'-fluoro-6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1.31 (3H, t, J=7.2Hz), 3.77(3H, s), 4.24-4.29(2H, q,

J=7.2Hz), 4.61 (2H, s), 6.45-6.48( I H, dd, J=2.8Hz and 8.8Hz), 6.61(1 H, d, J=9.2Hz),

6.65(1 H, d, J=2.8Hz), 6.85-6.87( 1 H, m), 6.97(2H, t, J=7.6Hz), 7.07-7.08( 1H, m), 7.30- 7.34(3H, m), 7.38-7.41(3H, m), 7.55( 1 H, d, J=2.4Hz).

% Yield:73

INTERMEDIATE 63

Ethyl 2-(N-(3,5-dichloro-4-(3-(N,N-diethylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate 1H NMR (CDCI₃, 400MHz): 1 .09(6H, t, J=7.2Hz), 1.33(3H, t, J=7.2Hz), 3.29-3.35(4H, q, J=7.2Hz), 3.89(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.59(2H, s), 6.91 -6.99(2H, m),

7.20(2H, s) 7.26-7.27(1 H, m), 7.34-7.39(5H, m).

% Yield: 98

INTERMEDIATE 64 Ethyl 2-(N-(3,5-dibromo-4-(3-(N,N-diethylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate

¹H NMR (CDCI₃, 400 MHz): 1.08(6H, t, J=7.2Hz), 1.34(3H, t, J=6.8Hz), 3.29-3.35(4H, q, J=7.2Hz), 3.89(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.59(2H, s), 6.91(1 H, d, J=8.8Hz),

6.93-6.96(1 H, dd, J=2.8Hz and 8.8Hz), 7.24(1 H, d, J=2.8Hz), 7.37-7.38(5H, m), 7.40(2H, s).

% Yield: 93

INTERMEDIATE 65 Ethyl 2-(N-(3,5-dibromo-4-(4-methoxy-3-(piperidin- I -ylsιιlfonyl) phenoxy) phenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400 MHz): 1.32(3H, t, J=7.2Hz), I .24- I .34(6H, m), 3.15(4H, t,

J=5.0Hz), 3.88(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.58(2H, s), 6.93-7.00(2H, m), 7.17( 1 H, d, J=3.2Hz), 7.32-7.38(5H, m), 7.40(2H. s).

% Yield: 80

INTERMEDIATE 66

Ethyl 2-(N-(3,5-dibromo-4-(3-(N-cyclohexylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate 1H NMR (CDCI₃, 400MHz): 1.06-1.18(6H, m), I .33(3H, t, J=7.2Hz), 1.64-1.70(4H, m), 3.06-3.08( 1 H, m), 3.95(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.59(2H, s), 6.97(1H, d,

J=9.2Hz), 7.00-7.03( I H, dd, J=2.4Hz and 8.8 Hz), 7.18(I H, d, J=2.8Hz), 7.3 l-7.38(5H, m), 7.40(2H, s).

% Yield: 76 INTERMEDIATE 67

Ethyl 2-(N-(3,5-dichloro-4-(3-(diethyIcarbamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate

¹H NMR (CDCI₃ , 400 MHz): 0.97(3H, t, J=7.0Hz), 1.21-1.26(6H, m), 3.08-3.13(2H, q,

J=7.2Hz), 3.43-3.64(2H, m), 3.78(3H, s), 4.24-4.30(2H, q, J=7.2Hz), 4.57(2H, s), 6.52( 1 H, d, J=2.8Hz), 6.75-6.78( 1 H, dd, J=2.8Hz and 8.8Hz), 6.82( I H, d, J=8.8Hz),

7.19(2H, s), 7.25-7.27(2H, m), 7.28-7.33(3H, m).

% Yield: 55

INTERMEDIATE 68

Ethyl 2-(N-(3,5-dichloro-4-(4-methoxy-3-(piperidine- l -carbonyl) phenoxy) phenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 1.37(3H, t, J=7.2Hz), 1.49-1.78(6H, m), 3.10-3.15(2H, m), 3.76-3.79(2H, m), 3.81 (3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.57(2H, s), 6.57(1 H, d,

J=3.2Hz), 6.74-6.82(2H, m), 7.19(2H, s), 7.27-7.33(2H, m), 7.34-7.37(3H, m).

% Yield: 94 INTERMEDIATE 69

Ethyl 2-(TSI-(3,5-dibromo-4-(4-methoxy-3-(piperidine-l -carbonyl) phenoxy) phenyl) benzamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.33(3H, t, J=7.2Hz), 1.6-1.64(6H, m), 3.14-3.19(2H, m),

3.67-3.72(2H, m), 3.79(3H, s), 4.25-4.31(2H, q, J=7.2Hz), 4.58(2H, s), 6.54(1H, d, J=2.8Hz), 6.73-6.76( I H, dd. J=3.2Hz and 8.8Hz), 6.82( I H, d, J=8.8Hz), 7.27-7.29(2H, m), 7.33-7.34(3H, m), 7.35(2H, s).

% Yield: 95

INTERMEDIATE 70 Ethyl 2-(N-(3,5-dibromo-4-(3-(diethylcarbamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate

¹ H NMR (CDCI₃, 400MHz): 0.98(3H, t, J=7.2Hz), 1.21 - 1.25(6H, m), 3.08-3.14(2H, q,

J=6.4 Hz), 3.43( I H, bs), 3.65(3H, bs), 3.78(3H, s), 4.25-4.30(2H, q, J=7.2Hz), 4.57(2H, s), 6.50(1 H, d, J=2.8Hz), 6.73-6.76(1 H, dd, J=2.8Hz and 8.8Hz), 6.82( 1 H, d, J=8.8Hz), 7.26-7.28(2H, m), 7.32-7.36(3H, m), 7.39(2H, s).

% Yield: 72

INTERMEDIATE 71

Ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate 1H NMR (CDCI₃, 400MHz): 1.31(3H, t, J=7.2 Hz), 3.68 (3H, s), 4.23-4.29(2H, q,

J=7.2Hz), 4.56(2H, s), 6.63(1 H, m), 6.91 (2H, d, J= 1.6Hz), 7.17-7.23 (3H, m), 7.32 (2H, d, J=6.8 Hz), 7.38(2H, s), 7.40-7.42 (2H, dd, J= 1.6Hz and 6.8 Hz), 7.72-7.75 (2H, dd,

J=1.6Hz and 6.8 Hz).

% Yield: 62 INTERMEDIATE 72

Ethyl 2-(N-(3,5-dibromo-4-(3-((4-chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido)acetate

¹ H NMR (CDCI₃, 400MHz): 1.31(3H, t, J=7.2 Hz), 4.24-4.29(2H, q, J=7.2Hz),

4.55(2H, s), 5.87( I H, d, J=3.6Hz), 6.40(1 H, d, J=2.8Hz), 6.47-6.50 (I H, dd, J=3.2Hz and 9.2Hz), 6.77( 1 H, d, J=8.8Hz), 7.19 ( I H, bs), 7.24 ( I H, bs), 7.28-7.31 (3H, m), 7.32-

7.34(4H, m), 7.38(2H, s)

% Yield: 86

INTERMEDIATE 73

Ethyl 2-(N-(3,5-dibromo-4-(3-(3-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate

¹H NMR (CDCl₃, 400MHz): 1.32(3H, t, J=7.2Hz), 3.69(3H, s), 4.23-4.29(2H, q, J=7.2Hz), 4.56(2H, s), 6.65-6.67(1 H, m), 6.93-6.94(2H, m), 7.20-7.26(3H, m), 7.32- 7.40(5H, m), 7.52-7.54 (I H, m), 7.76(2H, s). % Yield :60

INTERMEDIATE 74

Ethyl 2-(N-(3,5-dibromo-4-(3-((3-chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate 1H NMR (CDCI₃, 400MHz): 1.32(3H, t, J=7.0Hz), 4.24-4.30(2H, q, J=7.2Hz), 4.56(2H, s), 5.87( I H, d, J=3.6Hz), 6.40(1 H, d, J=2.8Hz), 6.51-6.54( 1 H, dd, J=2.8Hz and 9.2Hz),

6.78(1 H, d, J=8.8Hz), 7.09( I H, s), 7.21 -7.24(2H, m), 7.26-7.30(3H, m). 7.32-7.36(3H, m), 7.38(2H, s).

% Yield: 68 INTERMEDIATE 75

Ethyl 2-(N-(3,5-dibromo-4-(3-(4-fluorobenzoyl)-4-methoxy phenoxy) phenyl) benzam ido)acetate

¹H NMR (CDCl₃, 400MHz): I .31(3H, t, J=7.2Hz), 3.69(3H, s), 4.23-4.29(2H, q,

J=7.2Hz), 4.56(2H, s), 6.63(1 H, m), 6.88-6.93(2H, m), 7.1 1(2H, t, J=8.8Hz), 7.17- 7.26(3H, m), 7.28-7.33(2H, m), 7.38(2H, s), 7.81-7.84(2H, m).

% Yield:73

INTERMEDIATE 76

Ethyl 2-(N-(3,5-dibromo-4-(3-((4-fluorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) pheny l)benzam ido)acetate 1H NMR (CDCl₃, 400MHz): l .32(3H, t, J=7.2Hz), 4.24-4.29(2H, q, J=7.2Hz), 4.55(2H, s), 5.90( 1 H, d, J=3.2Hz), 6.39(1 H, d, J=2.8Hz), 6.47-6.50( I H, dd, J=3.2Hz and 8.8Hz),

6.78( I H, d, J=8.8Hz), 7.03(2H, t, J=8.8Hz), 7.22-7.27(2H, m), 7.28-7.35(5H, m),

7.37(2H, s).

% Yield: 97 INTERMEDIATE 77

Ethyl 2-(N-(3,5-dibromo-4-(3-(3-fluorobenzoyl)-4-methoxy phenoxy) phenyl) benzam ido)acetate

¹H NMR (CDCI₃, 400MHz): 1.31 (3H, t, J=7.2Hz), 3.69(3H, s), 4.23-4.29(2H, q,

J=7.2Hz), 4.56(2H, s), 6.65(1 H, m), 6.92(2H, d, J= 1.6Hz), 7.18-7.22(2H, m), 7.23- 7.29(3H, m), 7.39-7.44(2H, m), 7.47-7.51(1 H, m), 7.56(1 H, d, J=8.0Hz).

% Yield: 72

INTERMEDIATE 78

Ethyl 2-(N-(3,5-dibromo-4-(3-((3-fluorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzam ido)acetate ¹H NMR (CDCI₃, 400MHz): 1.3 1 (3H, t, J=7.2Hz), 4.24-4.29(2H, q, J=7.2Hz), 4.55(2H, s), 5.87( I H, d, J=3.2Hz), 6.41 ( 1 H, d. J=3.2Hz), 6.49-6.52( 1 H, dd, J=3.2Hz and 8.8Hz),

6.76-6.78( 1 H, m), 6.97-7.02( I H, m), 7.07( I H. d, J=9.6Hz), 7.1 1 ( 1 H, d, J=7.6Hz),

7.14( 1 H. s), 7.22-7.26(1 H, m), 7.28-7.35(4H, m), 7.40(2H, s). % Yield: 90

[NTERMEDIATE 79

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl)moφholine-4- carboxam ido)acetate

¹H NMR (CDCI₃, 400MHz): 0.88(3H, t, J=6.8Hz), 1.14(3H, d, J=7.2 Hz), 1.29(3H, t, J=7.2Hz), 1.46-1.60(2H, m), 3.04-3.09(1 H, m), 3.29(4H, t, J=4.8 Hz), 3.58(4H, t, J=4.6

Hz), 3.77(3H, s), 4.20-4.25(2H, q, J=7.2Hz), 4.37(2H, s), 6.45-6.48( 1 H, dd, J=3.2Hz and 8.8Hz), 6.72(1 H, d, J=8.8Hz), 6.74( 1 H, d, J=2.8Hz), 7.16(2H, s).

% Yield: 87

INTERMEDIATE 80 Ethyl 2-(N-(3,5-dibroιno-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)ιnoφholine-4- carboxam ido)acetate

¹ H NMR (CDCI₃, 400MHz): 0.86(3H, t, J=7.4Hz), 1.14(3H, d, J=6.8Hz), 1.31(3H, t,

J=7.2Hz), 1.48-1.50(2H, m), 3.04-3.09( 1 H, m), 3.29(4H, t, J=4.8Hz), 3.58(4H, t,

J=4.6Hz), 3.77(3H, s), 4.20-4.25(2H, q, J=7.2Hz), 4.37(2H, s), 6.43-6.46(I H, dd, J=3.2Hz and 8.8Hz), 6.71 ( 1 H, d, J=2.8Hz), 6.72( 1 H, d, J=8.8Hz), 7.38(2H, s).

% Yield: 97

INTERMEDIATE 81

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ l, r-biphenyl]-3-yl)oxy)phenyl)moφholine-

4-carboxam ido)acetate 1 H NMR (CDCI₃, 400MHz): I .29(3H, t, J=7.2Hz). 3.28(4H, t, J=4.8Hz), 3.56(4H, t,

J=4.6Hz), 3.77(3H, s), 4.19-4.24(2H, q, J=7.2Hz), 4.36(2H, s), 6.74-6.77(2H, m),

6.90(1 H, d, J=9.2Hz), 7.17(2H, s), 7.30-7.33(I H, m), 7.39(2H, t, J=7.4Hz), 7.47-

7.49(2H, m).

% Yield: 83 INTERMEDIATE 82

Ethyl 2-(lM-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dichlorophenyl)moφholine-4- carboxamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.29(3H, t, J=7.2Hz), 3.27(4H, t, J=4.8Hz), 3.57(4H, t,

J=4.8 Hz), 3.76(3H, s), 3.93(2H, s), 4.20-4.25(2H, q, J=7.2Hz), 4.35(2H, s), 6.51- 6.54(1 H, dd, J=3.2Hz and 8.8Hz), 6.64( 1 H, d, J=2.8Hz), 6.74( I H, d, J=8.8Hz), 7.13(2H, s), 7.16-7.18(4H, m), 7.24-7.28( 1 H, m). % Yield:97 INTERMEDIATE 83 Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)morpholine-4- carboxam ido)acetate

¹H NMR (CDCI₃, 400MHz): 1. I 7(6H, d, J=6.8Hz), 1.29(3H, t, J=7.2Hz), 3.24-3.31( 1 H, m), 3.29(4H, t, J=4.8Hz), 3.59(4H, t, J=4.6Hz), 3.78(3H, s), 4.2 I -4.26(2H, q, J=7.2Hz), 4.38(2H, s), 6.42-6.45( 1 H, dd, J=3.2Hz and 8.8Hz), 6.71(1 H, d, J=9.2Hz), 6.81(1 H, d, J=3.2Hz), 7.17(2H, s). % Yield: 95 INTERMEDIATE 84

Ethyl 2-( 1 -(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3- isopropylureido)acetate 1H NMR (DMSO-D₆, 400MHz): 1.03(6H, d, J=6.8Hz), 1.16(3H, t, J=7.2Hz), 3.72(3H, s), 3.74-3.79( 1 H, m), 4.06-4.12(2H, q, J=6.8Hz), 4.34(2H, s), 6.31 (1 H, d, J=8.0Hz), 6.80-6.83( 1 H, dd, J=3.2Hz and 8.8Hz), 6.84( 1 H, d, J=2.8Hz), 7.06(I H, d, J=8.8Hz), 7.29-7.34(1 H, m), 7.36-7.40(2H, m), 7.42-7.44(2H, m), 7.47(2H, s). % Yield: 98 INTERMEDIATE 85

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-hydroxy piperidine-1 -carboxamido) acetate

¹ H NMR (DMSO-D₆, 400MHz): 1.09(6H, d, J=6.8Hz), 1. I 7(3H, t, J=7.2Hz), 1.21-

1.22(2H. m), l .57- l .60(2H, m), 2.82-2.88(2H, m), 3.4 I -3.44(2H, m), 3.15-3.20( 1 H, m), 3.73(3H, s), 4.05-4.1 1 (2H, q, H=7.2Hz), 4.36(2H, s), 4.71( 1 H, d, J=4.0Hz), 6.39-

6.42(2H, dd, J=2.8Hz and 8.8Hz), 6.68(1 H, d, J=3.2Hz), 6.85( 1 H, d, J=8.8Hz),

7.54(2H, s).

% Yield: 95

INTERMEDIATE 86 Ethyl 2-(3-cyclohexyl-l-(3,5-dichloro-4-(3-isopropyl-4-methoxy phenoxy) phenyl) ureido) acetate

¹H NMR (CDCl₃, 400MHz): 1.20(6H, d, J=6.8Hz), 1.29(3H, t, J=7.0Hz), 1.31 - 1.36(4H, m), 1.41 -1.66 (4H, m), 1.93-2.04 (2H, m), 3.25-3.32(1 H, m), 3.62-3.66(1 H, m), 3.79 (3H, s), 4.20-4.27(2H, m), 4.32(2H, s), 6.44-6.47( I H, dd, J=3.2Hz and 8.8Hz), 6.71 (I H, d, J=8.8Hz), 6.86 ( I H. d, J= 3.2Hz), 7.45(2H, s). % Yield: 87 INTERMEDIATE 87 Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)morpholine- 4-carboxamido) acetate

¹H NMR (CDCI₃, 400MHz): 1.28(3H, t, J=7.0Hz), 3.27(4H, t, J=4.6Hz), 3.55(4H, t, J=4.6Hz), 3.77(3H, s). 4.19-4.24(2H, q, J=7.2Hz), 4.36(2H, s), 6.73-6.75(2H, m), 6.89- 6.91 ( 1 H, dd, J=2.0Hz and 7.6Hz), 7.30-7.33( I H, m), 7.34-7.41 (4H, m), 7.49(2H, d, J=7.2Hz). % Yield: 92 INTERMEDIATE 88

Ethyl 2-(l-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-isopropylureido) acetate 1H NMR (CDCl₃, 400MHz): 1.12(6H, d, J=6.8Hz), 1.19(6H, d, J=6.8Hz), 1.31(3H, t, J=7.8Hz), 3.25-3.32(1 H, m), 3.79(3H, s), 3.94-3.99(1 H, m), 4.20-4.25(2H, q, J=7.2Hz), 4.32(2H, s), 6.44-6.47( 1 H, dd, J=3.2Hz and 8.8Hz), 6.71(1 H, d, J=9.2Hz), 6.87(1 H, d, J=2.8Hz), 7.45(2H, s). % Yield: 99 INTERMEDIATE 89

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methyl piperazine-1-carboxamido) acetate

¹H NMR (CD₃OD, 400MHz): 1.14(6H, d, J=6.8Hz), 1.25-1.28(3H, m), 1.96(1 H, m),

2.33(3H, s), 2.38(1 H, m), 2.43-2.45(4H, m), 2.69-2.70( 1 H, m), 3.19-3.21(1 H, m), 3.27- 3.30(1 H, m), 3.78(3H, s), 4.19-4.20(2H, m), 4.40(2H, s), 6.50-6.51(1 H, m), 6.71 (1 H, d,

J=2.8Hz), 6.82(1 H, d, J=8.8Hz), 7.37(2H, s).

% Yield: 96

INTERMEDIATE 90

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methyl piperazine-1-carboxamido) acetate

¹H NMR (CDCl₃, 400MHz): 1.17(6H, d, J=6.8Hz), 1.29(3H, t, J=6.2Hz), 2.26(3H, s), 2.99(4H, t, J=4.8Hz), 3.23-3.30(1 H, m), 3.32(4H, t, J=4.6Hz), 3.79(3H, s), 4.20- 4.25(2H, q, J=7.2Hz), 4.36(2H, s), 6.42-6.45(1 H, dd, J=3.2Hz and 8.8Hz), 6.71 ( I H, d, J=8.8Hz), 6.78( 1 H, d, J=2.8Hz), 7.36(2H, s). % Yield: 80 INTERMEDIATE 91 N-(3,5-dichloro-4-((6-hydroxy-[ l, l '-biphenyl]-3-yl)oxy)phenyl)-N-(2-oxo-2- (((tetrahydro-2H-pyran-2-yl)oxy) amino)ethyl)benzamide

¹H NMR (CDCl₃, 400MHz): 1.20-1.27(3H, m), 1.71 - 1.72(3H, m), 3.65-3.67(1 H, m), 3.98( 1 H, bs), 4.43( 1 H, bs), 5.01 (2H, s), 6.56(1 H, d, J=2.8Hz), 6.67-6.70( 1 H, dd, J=2.8Hz and 8.8Hz), 6.89(1 H, d, J=8.8Hz), 7.14-7.32(6H, m), 7.41 -7.43(3H, m), 7.48- 7.52(3H, m). % Yield: 99 Activity data: In-vitro studies

In vitro Thyroid hormone receptor α (TR-α) and Thyroid hormone receptor β (TR-β) activities were determined as per the general protocol described in Bioorganic and Medicinal Chemistry Letters 18 (2008) 3919-3924 and the results of representative compounds are provided in tables 1 and 2 below as a proof of the efficacies of the novel class of compounds disclosed above. Table 1: In vitro EC50 for selected compounds of formula (I) for TR-α, TR-β

Table 2- In vitro % activity of selected compounds of Formula (I) for TR-α and TR-O with respect to T3

Table 2- continued.

Table 2- continued

* Fold Induction vv.r.t T₃ ( 100 nm)

The data above clearly indicates that several of the novel compounds of the present invention are selective to TR-beta receptor and therefore have potential therapeutically beneficial properties. In-vivo studies: (A) Efficacy Studies in Cholesterol fed Rats for Cholesterol Reduction

Cholesterol lowering effect of T₃ and selected compounds disclosed in the present invention and change in heart rate in cholesterol-fed rats (treated for 7 days) was determined according to the general protocol described in PNAS, ,vol. 100 (17) 10067-10072 and Endocrinology 145(4): 1656-1661. The results of representative compounds are provided in Table 3. Many of the compounds were found to be reducing cholesterol and having very little effect on the heart weight. Therefore, these compounds have the potential to be further developed as Thyroid receptor modulators for the treatment of human and other animals in need of such treatment. Table 3: In vivo efficacy of the selected compounds of formula (I) in Cholesterol fed Rats

(B) Portal-systemic cannulated rat model:

Liver selectivity was determined using Portal-systemic cannulated rat model. Method: Sprague Dawley rats of age 8- i O weeks weighing >275 g were used for the procedure. The animals were cannulated permanently at portal vein and carotid artery. From the same animal 0.3 mL blood was collected in EDTA tubes from portal venous cannula and carotid arterial cannula at the specified time-points starting from 5 min upto 24 hours simultaneously (with no cross-overs). The AUC were calculated using the portal cannula samples for hepatic and carotid cannula samples for systemic pharmacokinetics. The Eh, hepatic extraction ratio, is calculated using the formula: Eh = l -(AUC0-inf systemic/A UCO-inf portal).

Several compounds represented by structural formula (I) showed the hepatic extraction ratio (Eh) greater than 0.4 which is considered as the index showing more liver selectivity.

Claims

We claim-

I . A compound of formula (I), tautomers or pharmaceutically salts thereof

(I) wherein R = ORi, NHRi _, wherein R| is selected from H or groups selected from (C_rC₆)alkyl, Ar(C|-C₆)alkyl groups, each of these groups are further substituted by suitable substituents; R₂ represents hydrogen, hydroxyl, halo, acyl, oxo or optionally substituted groups selected from (C| -C₆)alkyl, alkoxy, (C₃-C₇)cycloalkyl, aryl, heteroaryl, aryloxy, aralkyl, aralkoxy, carboxylic acid and its derivatives selected from (C|-C₃)alkyl esters and amides, sulfenyl derivatives, sulfonyl derivatives or R₂ is selected from the groups representing -CONR₅R^ , -SO₂N R₅R₆, wherein R₅ and RO are same or different and at each occurrence are independently selected from H, or groups selected from (C|-C₆)alkyl, (C₃-C₇)cycloalkyl, bicycloalkyl, aryl groups, each of these groups are further substituted by suitable substituents; or the groups R₅ and R₆ together with the nitrogen atom to which they are attached forms a five to eight membered cyclic ring which further optionally contains one or more heteroatoms selected from N, S, O; R₃, R₄ may be same or different and at each occurrence are independently selected from H, halogen or (C| -C₆)alkyl groups, which is further substituted with suitable substituents; 'X' represents O, -CH₂-, CO; 'Z' represents either a bond or suitable linker selected from NH or -(CH₂)_n wherein 'n' represents integer 0-2; ¹Y' represents groups selected from alkyl aryl, heteroaryl, heterocyclyl or cycloalkyl groups, each of these groups are further substituted by suitable substituents; Ry is selected from H or groups selected from (C|-C₆)alkyl, (C₃- C₇)cycloalkyl, acyl, aryl, aralkyl, heteroaryl groups, each of these groups being further substituted by suitable substituents; Rg is selected from ORg, NHR₉ or

NHOH wherein, R₉ at each occurrence is selected from H or groups selected from

(C|-C₆)alkyl, which is further substituted with suitable substituents.

2. The compound as claimed in claim 1 wherein R₂ is selected from (C|-C6)alkyl, (C₃- C₇)cycloalkyl, aryl, aralkyl, carboxamide and sulfonamide or acyl groups.

3. The compound as claimed in claim 1 wherein ¹Z' represents either a bond or the group NH.

4. The compound as claimed in claim 1 wherein R₇ represents H or (C|-C₆)alkyl.

5. The compound as claimed in claim 1 wherein Rg is selected from OR₉, or NHOH wherein R₉ is as defined in claim 1 .

6. The compound as claimed in claim I wherein 'X' represents O or CH₂.

7. The compound of any preceding claims wherein the substituents on R₂ is selected from hydroxy, halo or . groups selected from (Ci-C₆)alkyl, (C|-C₆)haloalkyl, aryl or heteroaryl groups, each of these groups is further substituted by suitable substituents.

8. The compound as claimed in any preceding claims wherein the substituents on alkyl, aryl, heteroaryl or cycloalkyl groups as defined earlier is selected from hydroxyl, halo, cyano, optionally substituted groups selected from (C_rC₆)alkyl, haloalkyl, alkoxy, oxo, aryl, aryloxy, aralkyl, acyl, alkylthio, thioalkyl groups.

9. The compound as claimed in Formula (I) according to any of the preceding claims is selected from

2-(N-(3,5-dichloro-4-((6-hydroxy-[ l , l '-biphenyl]-3- yl)oxy)phenyl)benzamido) acetic acid;

2-(N-(3,5-dichloro-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-hydroxy benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2- phenylacetamido) acetic acid; 2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzamido)acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)acetic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)-2- phenylacetamido)acetic acid; 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-phenyl acetamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[l , l'-biphenyl]-3-yl)oxy)phenyl)benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)-2-phenyl acetamido) acetic acid;

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzamido)acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-2-phenyl acetamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , l'-biphenyl]-3-yl)oxy)phenyl)thiophene-2- carboxamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)thiophene-2-carbox amido)acetic acid; 2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)benzamido) propanoic acid;

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)thiophene-2-carbox amido)acetic acid;

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)furan-2-carbox amido)acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)furan-2-carbox amido)acetic acid; 2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dimethylphenyl)benzamido)acetic acid;

2-(N-(4-(4-hydroxy-3-isopropylphenoxy)-3,5-dimethylphenyl)benzamido)acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido) propanoic acid; 2-(M-(3.5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido) butanoic acid;

2-(N-(3.5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)benzamido)-2-methyl propanoic acid; 2-(N-(3,5-dibromo-4-((6-hydroλy-[l, l'-biphenyl]-3-yl)oxy)phenyl)benzamido) propanoic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromophenyl)benzamido)acetic acid;

2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromopheny!)benzamido)propanoic acid; 2-(N-(3,5-dibromo-4-(3-ethyl-4-hydroxyphenoxy)phenyl)benzamido)acetic acid;

2-(N-(4-((6-hydroxy-[ 1 , 1 '-bipheny l]-3-yl)oxy)-3,5-dimethylpheny l)benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(tert-butyl)-4-hydroxyphenoxy)phenyl)benzamido)acetic acid; 2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dibromophenyl)thiophene-2-carbox amido)acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl) cyclohexane carboxamido) acetic acid;

2-(3-chloro-N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methyl benzamido) acetic acid; 2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl) cyclohexane carbox amido) acetic acid;

2-(N-(3,5-dichIoro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-(trifluoromethyI) benzamido) acetic acid; 2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-methyl benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-methyl benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl) cyclopropane carboxamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-hydroxy benzamido) acetic acid;

2-(N-(3.5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-hydroxy benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ l , l'-biphenyl]-3-yl)oxy)phenyl)-3-hydroxy benzamido) acetic acid;

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)-4-methyl benzamido) acetic acid; 2-(N-(3,5-dibromo-4-((6-hydroxy-[ l , l'-biphenyl]-3-yl)oxy)phenyl)-2-hydroxy benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetic acid;

2-(N-(3,5-dichIoro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-methy I benzamido) acetic acid;

2-(4-chloro-N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-2-methyl benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , l '-biphenyl]-3-yl)oxy)phenyl)-2-methyl benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-2'-methyl-[l , r-biphenyl]-3-yl)oxy)phenyl) benzamido) acetic acid; 2-(2-chloro-N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-((6-hydroxy-[ l , l '-biphenyl]-3-yl)oxy)phenyl)-4-(trifluoro methyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-((2',6-dihydroxy-[ l , l '-biphenyl]-3- yl)oxy)phenyl)benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-(trifluoromethyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-(trifIuoro methyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-((6-hydroxy-[ 1 , l '-biphenyl]-3-yl)oxy)phenyl)-3,5-bis(trifluoro methyl) benzamido)acetic acid; 2-(N-(3,5-dibromo-4-((2'-fluoro-6-hydroxy-[ l, l '-biphenyl]-3-yl)oxy)phenyl) benzamido)acetic acid;

2-(N-(3,5-dichloro-4-(3-(N,N-diethylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(N,N-diethylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzam ido) acet ic ac id ;

2-(M-(3,5-dibromo-4-(4-hydroxy-3-(piperidin- l -ylsulfonyl) phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(N-cyclohexylsulfamoyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(diethylcarbamoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-(piperidine- 1 -carbony I) phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-(piperidine-l -carbonyl) phenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(diethylcarbamoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-((4-chlorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(3-chlorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid:

2-(N-(3,5-dibromo-4-(3-((3-chlorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(4-fluorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(3,5-dibromo-4-(3-((4-fluorophenyl)(hydroxy)methyl)-4-hydroxyphenoxy) phenyl) benzamido) acetic acid; 2-(N-(3,5-dibromo-4-(3-(3-fluorobenzoyl)-4-hydroxy phenoxy) phenyl) benzamido) acetic acid;

2-(N-(4-(3-(sec-butyl)-4-hydroxyphenoxy)-3,5-dichlorophenyl)moφholine-4- carbox amido) acetic acid;

2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)morpholine-4- carbox amido) acetic acid;

2-(N-(3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)morpholine-4- carboxamido) acetic acid; 2-(N-(4-(3-benzyl-4-hydroxyphenoxy)-3,5-dichlorophenyl)moφholine-4-carbox amido) acetic acid;

2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)moφholine-4- carboxamido) acetic acid;

2-( 1 -(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3- phenylureido)acetic acid;

2-(l-(3,5-dichloro-4-((6-hydroxy-[l,r-biphenyl]-3-yl)oxy)phenyl)-3-isopropyl ureido)acetic acid; 2-(N-(3.5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4- hydroxypiperidine- 1 -carbox amido) acetic acid;

2-(3-cyclohexyl- l -(3,5-dichloro-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) ureido) acetic acid; 2-(N-(3.5-dibromo-4-((6-hydroxy-[ l , l '-biρhenyl]-3-yl)oxy)phenyl)morpholine-4- carboxamido) acetic acid;

2-(l-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3-isopropyl ureido) acetic acid;

2-( 1 -(3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido) acetic acid;

2-(l -(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-3- phenylureido)acetic acid;

2-( 1 -(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido)acetic acid; 2-(N-(3,5-dichIoro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methylpiperazine-

1 -carboxamido) acetic acid;

2-(3-cyclohexyl-l -(3,5-dibromo-4-(4-hydroxy-3-isopropyl phenoxy) phenyl) ureido) acetic acid;

2-(N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-4-methylpiperazine- 1 -carboxam ido) acetic acid ;

2-( I -(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-isopropyl ureido) acetic acid;

2-(l -(3,5-dibromo-4-(3-(sec-butyl)-4-hydroxyphenoxy)phenyl)-3- phenylureido)acetic acid; 2-(N-(3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)phenyl)- 4- hydroxypiperidine-1 -carboxamido) acetic acid;

N-(3,5-dibromo-4-((6-hydroxy-[ 1 , 1 '-bipheny l]-3-yl)oxy)phenyl)-N-(2-(hydroxyl amino)-2-oxoethyl) benzamide; N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-N-(2-(hydroxyamino)- 2-oxoethyl)benzamide;

10. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) as claimed in any of the preceding claims and a pharmaceutically acceptable carrier diluent or excipients.

1 1. A pharmaceutical composition according to claim I O which is used for the treatment of obesity and dyslipidemia.

12. A method of treating disorders caused by dyslipidemia or obesity comprising administering to a patient in need thereof an effective amount of a compound of formula (I) according to any of the preceding claims or its pharmaceutical composition according to any of the preceding claims.

13. The use of a compound of formula (I) or its pharmaceutical composition according to any of the preceding claims for the manufacture of a medicament for the treatment of obesity and dyslipidemia.

14. A medicine for the treatment of disorders caused by dyslipidemia or obesity which comprises administering therapeutically effective amount of compound of formula (I) or its pharmaceutical composition as defined in any of the preceding claims to a patient or subject in need thereof.

15. The compound of any of the preceding claims or pharmaceutical compositions containing the compound of any preceding claims wherein the compounds are preferably targeted to the liver.

16. The compound of formula (I) suitable for preparation of further compounds of formula (I) selected from:

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l , r-biphenyl]-3-yl)oxy)phenyl)-4- methoxy benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxy phenoxy) phenyl) benzamido) acetate; Ethyl2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-phenyl acetamido) acetate; Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5- dichlorophenyl)benzamido)acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl) benzamido) acetate; Ethyl2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dichlorophenyl)-2-phenyl acetamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methoxy benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)-2-phenyl acetamido) acetate;

Ethyl2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-2-phenyl acetamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3- yl)oxy)phenyl)thiophene-2-carboxamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)thiophene-2- carboxamido) acetate; Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl) benzamido) propanoate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)thiophene-2- carboxamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)furan-2- carboxamido) acetate; Ethyl 2-(N-(3.5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy) phenyl) benzamido) propanoate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)furan-2- carboxamido) acetate; Ethyl 2-(N-(4-(3-(sec-bιιtyl)-4-methoxyphenoxy)-3,5-dimethylphenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl) benzamido) propanoate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl) benzamido) butanoate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)benzamido)-2- methyl propanoate; Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ l , r-biphenyl]-3-yl)oxy) phenyl) benzamido) propanoate;

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5- dibromophenyl)benzamido)acetate;

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dibromophenyl) benzamido) propanoate;

Ethyl 2-(N-(3,5-dibromo-4-(3-ethyl-4-methoxyphenoxy)phenyl)benzamido)acetate;

Ethyl 2-(N-(4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)-3,5-dimethylphenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(tert-butyl)-4-methoxyphenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dibromophenyl)thiophene-2- carboxamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) cyclohexane carboxamido) acetate; Ethyl 2-(3-chloro-N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3.5-dibromo-4-(3-isopropyl-4-methoxypheno\y)phenyl)-3-methyl benzamido) acetate; Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4- (trifluoromethyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3- methylbenzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) cyclopropane carboxamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methoxy benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ U '-biphenyl]-3-yl)oxy)phenyl)-3- methoxy benzamido) acetate;

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyl)-4-methyl benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-2- methoxy benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ l , r-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-methyl benzamido) acetate; Ethyl 2-(lM-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-methoxy benzamido) acetate;

Ethyl 2-(4-chloro-N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-2-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ I , I '-biphenyl]-3-yl)oxy)phenyl)-2-methyl benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-2'-methyl-[ 1 , 1 '-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate;

Ethyl 2-(2-chloro-N-(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-4-

(trifluoromethyl) benzamido) acetate; Ethyl 2-(N-(3,5-dibromo-4-((2',6-dimethoxy-[ l, r-biphenyl]-3-yl)oxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[l ,r-bipheny!]-3-yl)oxy)phenyl)-4- (trifluoro methyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3,5- bis(trifluoro methyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[l,l'-biphenyl]-3-yl)oxy)phenyl)-3,5-bis (trifluoromethyl) benzamido) acetate ; Ethyl 2-(N-(3,5-dibromo-4-((2'-fluoro-6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dichloro-4-(3-(N,N-diethylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-(3-(N,N-diethylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ; Ethyl 2-(N-(3,5-dibromo-4-(4-methoxy-3-(piperidin- 1 -ylsulfonyl) phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-(N-cyclohexylsulfamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ; Ethyl 2-(N-(3,5-dichloro-4-(3-(diethylcarbamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dichloro-4-(4-methoxy-3-(piperidine- l -carbonyl) phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(4-methoxy-3-(piperidine- l -carbonyl) phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-(diethylcarbamoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-(4-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ; Ethyl 2-(N-(3,5-dibromo-4-(3-((4-chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido)acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-(3-chlorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-((3-chlorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-(4-fluorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido) acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-((4-fluorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido) acetate ; Ethyl 2-(N-(3,5-dibromo-4-(3-(3-fluorobenzoyl)-4-methoxy phenoxy) phenyl) benzamido)acetate ;

Ethyl 2-(N-(3,5-dibromo-4-(3-((3-fluorophenyl)(hydroxy)methyl)-4-hydroxy phenoxy) phenyl) benzamido)acetate ;

Ethyl 2-(N-(4-(3-(sec-butyl)-4-methoxyphenoxy)-3,5-dichlorophenyI)morpholine- 4-carboxamido) acetate ; Ethyl 2-(N-(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyI)moφholine- 4-carboxamido) acetate ;

Ethyl 2-(N-(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3- yl)oxy)phenyl)moφholine-4-carboxamido) acetate ; Ethyl 2-(N-(4-(3-benzyl-4-methoxyphenoxy)-3,5-dichloropheny!)moφholine-4- carboxamido) acetate ;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)morpholine-4- carboxamido)acetate;

Ethyl 2-( I -(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3- phenylureido)acetate;

Ethyl 2-( I -(3,5-dichloro-4-((6-methoxy-[ l , 1 '-bipheny l]-3-yl)oxy)pheny!)-3- isopropyl ureido) acetate;

Ethyl 2-(N-(3,5-dibroιno-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-hydroxy piperidine- 1 -carboxamido) acetate; Ethyl 2-(3-cyclohexyl- l -(3,5-dichloro-4-(3-isopropyl-4-methoxy phenoxy) phenyl) ureido) acetate;

Ethyl 2-(N-(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3- yl)oxy)phenyl)moφholine-4-carboxamido)acetate ;

Ethyl 2-( I -(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-isopropyl ureido) acetate ;

Ethyl 2-( 1 -(3,5-dichloro-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido) acetate;

Ethyl 2-( 1 -(3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-3-phenyl ureido) acetate; Ethyl 2-( 1 -(3,5-dibromo-4-((6-methoxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-3-phenyl ureido) acetate;

Ethyl 2-(N-(3,5-dichloro-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methyl piperazine-1 -carboxamido) acetate ;

Ethyl 2-(3-cyclohexyl-l -(3,5-dibromo-4-(3-isopropyl-4-methoxy phenoxy) phenyl) ureido)acetate; Ethyl 2-(N-(3.5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)phenyl)-4-methyl piperazine-1-carboxamido) acetate ;

Ethyl 2-( I -(3,5-dibromo-4-((6-methoxy-[ I , I '-biphenyl]-3-yl)oxy)phenyl)-3- isopropyl ureido) acetate; Ethyl 2-( 1 -(3,5-dibromo-4-(3-(sec-butyl)-4-methoxyphenoxy)phenyl)-3-phenyl ureido) acetate;

N-(3,5-dichloro-4-((6-hydroxy-[ 1 , 1 '-biphenyl]-3-yl)oxy)phenyl)-N-(2-oxo-2- (((tetrahydro-2H-pyran-2-yl) oxy)amino)ethyl)benzamide ;

N-(3,5-dibromo-4-((6-hydroxy-[l, l'-biphenyl]-3-yl)oxy)phenyl)-N-(2-oxo-2- (((tetrahydro-2H-pyran-2-yl)oxy)amino)ethyl)benzamide;

N-(3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenyl)-N-(2-oxo-2- (((tetrahydro-2H-pyran-2-yl)oxy)amino)Ethyl)benzamide.

17. A process for preparing compounds of formula (I) wherein R? is alkyl, aryl, R₅R₆NCO- R₅R₆NSO₂- etc, Z= -(CH₂)n-, R₈=OH, comprising the steps of: i) reducing suitable biaryl ether of formula 2j wherein 'PG' represents suitable protecting groups to give corresponding amine of formula 3

ii) reacting the amine of formula 3 with suitable alkyl haloacetate in suitable base(s) in suitable solvents to give a compound of formula 4j_wherein 'Ak' represents suitable alkyl group;

iii) reacting the compound of formula 4 with CICO(CH₂)_nY, wherein 'Y' is as defined earlier, in presence of suitable base in inert solvents to give compound of formula 5.

iv) deprotection and hydrolysis of compound of formula 5 to give compound of formula (1)