(EXTRACTED FROM WIPO PAGE)
NOVEL COMPOUNDS SUITABLE FOR THE TREATMENT OF
DYSLIPIDEMIA
FIELD OF INVENTION
The present invention relates to compounds of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.
The present invention is directed towards compounds which can be used to treat diseases such as hyperlipidemia and also have a beneficial effect on cholesterol.

The compounds of the general formula (I) lower or modulate triglyceride levels and/or cholesterol levels and/or low-density lipoproteins (LDL) and raises the high-density lipoproteins (HDL) plasma levels, lower blood glucose and hence are useful in combating different medical conditions, where such lowering of LDL (and/or raising of HDL) is beneficial. Thus, it could be used in the treatment and/or prophylaxis of obesity, hyperlipidemia, hypercholesteremia, hypertension, atherosclerotic disease events, vascular restenosis, diabetes and many other related conditions.
The compounds of general formula (I) are useful to prevent or reduce the risk of developing atherosclerosis, which leads to diseases and conditions such as artereosclerotic cardiovascular diseases, stroke, coronary heart diseases, cerebrovascular diseases, peripheral vessel diseases and related disorders.
These compounds of general formula (I) are useful for the treatment and/or prophylaxis of metabolic disorders loosely defined as Syndrome X. The characteristic features of Syndrome X include initial insulin resistance followed by hyperinsulinemia, dyslipidemia and impaired glucose tolerance. The glucose intolerance can lead to non-insulin dependent diabetes mellitus (NIDDM, Type 2 diabetes), which is characterized by hyperglycemia, which if not controlled may lead to diabetic complications or metabolic disorders caused by insulin resistance. Diabetes is no longer considered to be associated only with glucose metabolism, but it affects anatomical and physiological parameters, the intensity of which vary depending upon stages/duration and severity of the diabetic state. The compounds of this invention are also useful in prevention, halting or slowing progression or reducing the risk of the above mentioned disorders along with the resulting secondary diseases such as cardiovascular diseases, like arteriosclerosis, atherosclerosis; diabetic retinopathy, diabetic neuropathy and renal disease including diabetic nephropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis and end stage renal diseases, like microalbuminuria and albuminuria, which may be result of hyperglycemia or hyperinsulinemia.
The compounds of the present invention can be useful as aldose reductase inhibitors; for improving cognitive functions in dementia, and in the treatment and/or prophylaxis of disorders such as psoriasis, polycystic ovarian syndrome (PCOS), cancer, osteoporosis, leptin resistance, inflammation and inflammatory bowel diseases, wound healing, xanthoma, pancreatitis, myotonic dystrophy, endothelial cell dysfunction and hyperlipidemia.
BACKGROUND OF THE INVENTION
Higher LDL cholesterol levels in the plasma increase cardiovascular risk and reduction in the levels of LDL would decrease CVD risk by a comparable percentage (PNAS, 2009, 106, 9546-9547). Clearance of LDL cholesterol from plasma is through the action of LDL receptors in the liver and LDL receptors are cell surface glycoproteins that bind to apoliporpotein B100 (apoBlOO) on LDL particles with high affinity and mediate their endocytic uptake (Journal of Biological Chemistry, 2009, 284, 10561-10570). Defect in hepatic cholesterol clearance and elevated levels of plasma LDL cholesterol that result from the mutations cause familial hypercholesterolemia. Such mutations are identified in the human LDL receptor and later in apolipoprotein-B (Nature Structural and Molecular Biology, 2007, 14, 413-419). Recently, mutations within certain subtypes of the pro-protein convertasesubtilisin/ gene such as the subtype nine (hereinafter “the gene”) were found to represent a third class of mutations associated with autosomal dominant hypercholesterolemia (ADH). The discovery, etiology and functions of this subtype gene is discussed in details in Nature Genetics, 2003, 34, 154-156, Trends in Biochemical Sciences, 2008, 33, 426-434 etc.. Several missense mutations (S127R, D129G, F216L, D374H, D374Y) are associated with hypercholesterolemia and premature atherosclerosis (J Lipid Res. 2008, 49, 1333-1343). Loss-of-function mutations (R46L, L253F, A433T) lead to elevated receptor abundance, enhancing clearance of LDL cholesterol from the circulation and reducing cardiovascular risk (Nature Structural and Molecular Biology, 2007, 14, 413-419).
Detailed molecular mechanisms explaining the association of LDLR and the particular subtype gene and LDLR degradation is not very clear (Drug News Perspectives, 2008, 21, 323-330). Because of inhibition of LDLR recycling, number of LDL receptors on the cell surface are decreased and this increases plasma LDL levels (PNAS, 2009, 106, 9546-9547).
Various approaches for inhibiting this particular subtype gene are reported, including gene silencing by siRNA or antisense oligonucleotides, mAh disrupting protein-protein interactions or by peptides; all the above-mentioned strategies have shown lowering of LDL cholesterol which may be effective therapy for treating hypercholesterolemia (Biochemical Journal, 2009, 419, 577-584; PNAS, 2008, 105, 11915-11920; Journal of Lipid Research, 2007, 48, 763-767; PNAS, 2009, 106, 9820-9825). However, very little success has been reported in trying to inhibit this subtype gene by using small molecules. Such small molecule inhibitors have their obvious clinical and therapeutic benefits over the other known approaches as
discussed above. We herein disclose novel small molecules which have shown to inhibit this particular gene in in-vitro studies and therefore provide an alternate beneficial approach for treating patients in need of such therapy.
We have disclosed earlier compounds which inhibits this particular gene in patent applications no. WO2015107541, WO2014192023, WO2012090220, W02014002105. Inhibitors of this gene have been disclosed by few companies in application no WO2014150395, WO2014150326, WO 2014151936,
W02016021706, W02016055901, WO2017222953, W02017034990,
WO2017034997, WO2017034994, WO2018165718, WO2018053517,
W02018057409, W02020110009, W02020150473, W02020150474, WO
2020028723.
EMBODIMENTS OF THE INVENTION
The main objective of the present invention is to provide novel heterocyclic derivatives represented by the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them or their mixtures thereof.
In an embodiment of the present invention is provided a process for the preparation of novel heterocyclic derivatives represented by the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts.
In a further embodiment of the present invention is provided pharmaceutical compositions containing compounds of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, or their mixtures in combination with suitable pharmaceutical excipients such as carriers, solvents, diluents and other media normally employed in preparing such compositions.
In a further embodiment of the present invention is provided a method for treatment of diseases such as dyslipidemia, hyperlipidemia etc. by providing therapeutically effective amount of the compounds of formula (I) or their pharmaceutically acceptable salts or their suitable pharmaceutical compositions.
The above and other embodiments are described in details hereinafter.
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention relates to compounds of the general formula
(I),

their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them wherein
‘Cy’ represents heterocyclic groups selected from saturated or partially unsaturated or unsaturated, monocyclic or bicyclic or spirocyclic groups containing 0-4 heteroatoms selected from O, N or S.
Ύ at each occurance independently represents either a bond, or may be selected from O, S(0)o, CO, (Ci-C3)alkyl, C(0)NR5, NR5 or SO2NR5; wherein R5 represents H, (Ci-C6)alkyl, (C3-C6)cycloalkyl;
‘Q’ represents O, S(0)0 or NR7 wherein R7 represents H, (Ci-Ce)alkyl, (C3-C6)cycloalkyl, acyl, -C(0)OR6, wherein IC5 represents (Ci-C6) linear or branced alkyl;
‘o’ represents integers from 0-2;
‘m’ and ‘n’ represents integers from 0-4;
‘X’ at each occurance independently represents represents either C or N;
Ri hydrogen, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, perhaloalkyl, alkoxy, haloalkoxy, perhaloalkoxy, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocylyl, heterocyclylalkyl, heterocycloxy, heterocyclylalkoxy, heterocyclylalkoxyacyl, carboxylic acid and its derivatives such as esters and amides, carbonylamino, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkylsulfonyl, hydroxyl, sulfonic acid and its derivatives;
R2 represents hydrogen, or substituted or unsubstituted groups selected from alkyl, haloalkyl, perhaloalkyl, cycloalkyl, deuterated alkyl, alkynyl, alkenyl, aryl, aralkyl, heterocylyl, heterocyclylalkyl, heterocyclylalkoxyacyl, Acyl, carbonylamino, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfonyl, alkylthioalkyl, alkylsulfmylalkyl, alkylsulfonylalkyl, alkylcarboxylic acid;
R3 and R4 independently represents hydrogen, halo, cyano, hydroxy or substituted or unsubstituted groups selected from alkyl, haloalkyl, perhaloalkyl, alkoxy, haloalkoxy, perhaloalkoxy, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocylyl, heterocyclylalkyl, heterocycloxy, heterocyclylalkoxy, heterocyclylalkoxyacyl, carboxylic acid and its derivatives such as esters and amides, carbonylamino, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkylsulfonyl, hydroxyl, sulfonic acid and its derivatives.
When ‘Cy’ is substituted, the substituents at each occurrence may be independently selected from hydroxyl, oxo, halo, thiol, nitro, amino, cyano, formyl, or substituted or unsubstituted groups selected from amidino, alkyl, haloalkyl, perhaloalkyl, alkoxy, haloalkoxy, perhaloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, alkoxy, alkenoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocylyl, heterocyclylalkyl, heterocycloxy, heterocyclylalkoxy, heterocyclylalkoxyacyl, acyl, acyloxy, acylamino, monosub stituted or disubstituted amino, arylamino, aralkylamino, carboxylic acid and its derivatives such as esters and amides, carbonylamino, hydroxyalkyl, aminoalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, cycloalkylthio, arylthio, heterocyclylthio, alkylsulfmyl, cycloalkylsulfmyl, arylsulfmyl, heterocyclylsulfmyl, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, heterocyclylsulfonyl, alkylsulfonylamino, cycloalkylsulfonylamino, arylsulfonyl amino, heterocyclylsulfonylamino, alkylsulfonyloxy,
cycloalkylsulfonyloxy, arylsulfonyloxy, heterocyclylsulfonyloxy, alkoxycarbonylamino, aryloxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino, alkoxyamino, hydroxyl amino, sulfmyl derivatives, sulfonyl derivatives, sulfonic acid and its derivatives.
When the substituents on any of ‘Cy’ or Ri, are further substituted, the substituents may be selected from one or more groups described above.
In a preferred embodiment, ‘Cy’ is saturated or partially unsaturated or unsaturated monocyclic or bicyclic, or spirocyclic groups containing 0-3 N, O, S atoms such as pyrrolidinyl, piperidinyl, piperazinyl, diazepinyl, oxazolyl, oxadiazolyl, indolinyl, pyridothienyl, hexahydrocyclopenta[c]pyrrol, hexahydropyrrolo[3,4-c]pyrrol, dihydropyrrolo[3,4-c]pyrazol, 5H-imidazo[4,5-c]pyridine, 5,6-dihydropyridin-, hexahydrocyclopenta[c]pyrrol, 3,9-diazaspiro[5.5]undecan, tetrahydropyrrolo[3,4-c] pyrrol, 3,4-dihydroisoquinolin-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-, 3,6-diazabicyclo[3.1.1] heptan, dihydrothieno[3,2-c]pyridine, dihydrothiazolo[5,4-cjpyridine, diazaspiro[4.5]decan and the like.
In another preferred embodiment, Ύ is selected form a bond, O, S(0)0, CO, C(0)NR5, wherein R5 represents H.
The various groups, radicals and substituents used anywhere in the specification are described in the following paragraphs.
In a further 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, «-propyl, zso-propyl, «-butyl, sec-butyl, /c/7-butyl, amyl, /-amyl, «-pentyl, «-hexyl, and the like;
- the “alkenyl” group used either alone or in combination with other radicals, is selected from a radical containing from two to six carbons, more preferably groups selected from vinyl, allyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4- pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl and the like; the “alkenyl” group includes dienes and trienes of straight and branched chains;
- the “cycloalkyl”, or “alicyclic” group used either alone or in combination with other radicals, is selected from a cyclic radical containing three to six carbons, more preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like;
- the “cycloalkenyl” group used either alone or in combination with other radicals, are preferably selected from cyclopropenyl, 1-cyclobutenyl, 2-cylobutenyl, 1- cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2- cyclohexenyl, 3-cyclohexenyl and the like; The terms “bicycloalkenyl” means more than one cycloalkenyl groups fused together;
- 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, «-propoxy, /.vo-propoxy, «-butoxy, /-butoxy, /.vo-butoxy, pentyloxy, hexyloxy, and the like;
- the “cycloalkoxy” group used either alone or in combination with other radicals, is selected from a cyclic radical containing three to seven carbons, more preferably cyclopropyl oxy, cyclobutylxoy, cyclopentyloxy, cyclohexyloxy and the like; The terms “bicycloalkyloxy” means more than one cycloalkyl groups fused together;
- the “alkenoxy” group used either alone or in combination with other radicals, is selected from groups containing an alkenyl radical, as defined above, attached to an oxygen atom, more preferably selected from vinyloxy, allyloxy, butenoxy, pentenoxy, hexenoxy, and the like;
- 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(Ci-C6)alkyl such as fluoromethyl, difluorom ethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, mono or polyhalo substituted methyl, ethyl, propyl, butyl, pentyl or hexyl groups;
- the “haloalkoxy” group is selected from suitable haloalkyl, as defined above, directly attached to an oxygen atom, more preferably groups selected from fluoromethoxy, chloromethoxy, fluoroethoxy, chloroethoxy and the like;
- 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 an aryl radical, as defined above, attached directly to an oxygen atom, more preferably groups selected from phenoxy, naphthyloxy, tetrahydronaphthyl oxy, biphenyloxy, and the like;
- the “heterocyclyl” or “heterocyclic” group used either alone or in combination with other radicals, is selected from suitable aromatic or non-aromatic radicals containing one or more hetero atoms selected from O, N or S. The non-aromatic radicals may be saturated, partially saturated or unsaturated 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, morpholinyl, 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, thieno piperidinyl, and the like; the aromatic radicals, may be selected from suitable single or fused mono, bi or tricyclic aromatic heterocyclic radicals containing one or more hetero atoms selected from O, N or S, more preferably the groups are selected from pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, isothiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, benzofuranyl, benzothienyl, indolinyl, indolyl, azaindolyl, azaindolinyl, pyrazolopyrimidinyl, azaquinazolinyl, pyridofuranyl, pyridothienyl, thienopyrimidyl, quinolinyl, pyrimidinyl, pyrazolyl, quinazolinyl, pyridazinyl, triazinyl, benzimidazolyl, benzotriazolyl, phthalazynil, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl, benzoxazolyl, benzothiazolyl hexahydrocyclopenta[c]pyrrol, hexahydropyrrolo[3,4-c]pyrrol, dihydropyrrolo[3,4-c]pyrazol, 5H-imidazo[4,5-c]pyridine, 5,6-dihydropyridin-, hexahydrocyclopenta[c]pyrrol, 3,9-diazaspiro[5.5]undecan, tetrahydropyrrolo[3,4-c]pyrrol, 3,4-dihydroisoquinolin- 3, 3a, 6, 6a- tetrahydrocyclopenta[c]pyrrol-, 3 ,6-diazabicyclo[3.1.1 Jheptan, dihydrothieno[3,2-c]pyridine, dihydrothiazolo[5,4-c]pyridine, diazaspiro[4.5]decan and the like;
- the groups “heterocycloxy”, “heterocylylalkoxy” are selected from suitable heterocyclyl, heterocylyl alkyl groups respectively, as defined above, attached to an oxygen atom;
- 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, /.vo-butanoyl, pentanoyl, hexanoyl, heptanoyl, benzoyl and the like, which may be substituted;
- the “acyloxy” group used either alone or in combination with other radicals, is selected from a suitable acyl group, as defined above, directly attached to an oxygen atom, more preferably such groups are selected from acetyloxy, propionyloxy, butanoyloxy, /.vo-butanoyl ox y, benzoyloxy and the like;
- the “acylamino” group used either alone or in combination with other radicals, is selected from a suitable acyl group as defined earlier, attached to an amino radical, more preferably such groups are selected from CH3CONH, C2H5CONH, C3H7CONH, C4H9CONH, C6H5CONH and the like, which may be substituted;
- the “mono-substituted amino” group used either alone or in combination with other radicals, represents an amino group substituted with one group selected from (Ci-C6)alkyl, substituted alkyl, aryl, substituted aryl or arylalkyl groups as defined earlier, more preferably such groups are selected from methylamine, ethylamine, «-propylamine, //-butylamine, //-pentylamine and the like;
- the ‘di substituted amino” group used either alone or in combination with other radicals, represents an amino group, substituted with two radicals that may be same or different selected from (Ci-Ce)alkyl, substituted alkyl, aryl, substituted aryl, or arylalkyl groups, as defined above, more preferably the groups are selected from dimethylamino, methyl ethyl amino, diethylamino, phenylmethyl amino and the like;
- the “arylamino” used either alone or in combination with other radicals, represents an aryl group, as defined above, linked through amino having a free valence bond from the nitrogen atom, more preferably the groups are selected from phenylamino, naphthylamino, N-methyl anilino and the like;
- the “oxo” or “carbonyl” group used either alone (-C=0-) or in combination with other radicals such as alkyl described above, for e.g. “alkylcarbonyl”, denotes a carbonyl radical (-C=0-) 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 m ethoxy carbonyl, ethoxycarbonyl, and the like, which may optionally be substituted; aryloxycarbonyl group such as phenoxycarbonyl, napthyloxycarbonyl, and the like, which may optionally be substituted; aralkoxy carbonyl group such as benzyloxy carbonyl, 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; heterocyclyloxy carbonyl, 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=0), wherein the amino group is mono- or di- substituted or unsubstituted, more preferably the groups are selected from methyl amide, dimethyl amide, ethyl amide, diethyl amide, and the like;
- the “aminocarbonyl” group used either alone or in combination with other radicals, may be selected from ‘aminocarbonyl’, ‘aminocarbonylalkyl”, “n- alkylaminocarbonyl”, “N-arylaminocarbonyl”, “N,N-dialkylaminocarbonyl”, “N- alkyl-N-arylaminocarbonyl”, “N-alkyl-N-hydroxyaminocarbonyl”, and “N- alkyl-N-hydroxyaminocarbonylalkyl”, each of them being optionally substituted. The terms “N-alkylaminocabonyl” and “N,N-dialkylaminocarbonyl” denotes aminocarbonyl radicals, as defined above, which have been substituted with one alkyl radical and with two alkyl radicals, respectively. Preferred are “lower alkylaminocarbonyl” having lower alkyl radicals as described above attached to aminocarbonyl radical. The terms “N-arylaminocarbonyl” and “N-alkyl-N- arylaminocarbonyl” denote amiocarbonyl radicals substituted, respectively, with one aryl radical, or one alkyl, and one aryl radical. The term “aminocarbonylalkyl” includes alkyl radicals substituted with aminocarbonyl radicals;
- the “hydroxyalkyl” group used either alone or in combination with other radicals, is selected from an alkyl group, as defined above, substituted with one or more hydroxy radicals, more preferably the groups are selected from hydroxymethyl, hydroxy ethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl and the like;
- the “aminoalkyl” group used alone or in combination with other radicals, denotes an amino (-NH2) moiety attached to an alkyl radical, as defined above, which may be substituted, such as mono- and di-substituted aminoalkyl. The term “alkylamino” used herein, alone or in combination with other radicals, denotes an alkyl radical, as defined above, attached to an amino group, which may be substituted, such as mono- and di-substituted alkylamino;
- the “alkoxyalkyl” group used alone or in combination with other radicals, denotes an alkoxy group, as defined above, attached to an alkyl group as defined above, more preferably the groups may be selected from methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl 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,
- 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 “alkoxycarbonylamino” group used alone or in combination with other radicals, is selected from a suitable alkoxycarbonyl group, as defined above, attached to an amino group, more preferably methoxycarbonyl amino, ethoxycarbonylamino, and the like;
- the “arylthio” group used either alone or in combination with other radicals, denotes a an aryl 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 phenylthio, naphthylthio, tetrahydronaphthylthio, indanethio, biphenylthio, and the like;
- the “heterocyclylthio” group used either alone or in combination with other radicals, denotes an heterocyclyl 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 aziridinylthio, azetidinylthio, pyrrolidinylthio, imidazolidinylthio, piperidinylthio, piperazinylthio, 2- oxopiperidinylthio, 4-oxopiperidinylthio, 2-oxopiperazinylthio, 3- oxopiperazinylthio, morpholinylthio, thiomorpholinylthio, 2-oxomorpholinylthio, azepinylthio, diazepinylthio, oxapinylthio, thiazepinylthio, oxazolidinylthio, thiazolidinylthio, dihydrothiophenethio, dihydropyranthio, dihydrofuranthio, dihydrothiazolethio, benzopyranylthio, benzopyranonylthio, benzodihydrofuranylthio, benzodihydrothienylthio, pyrazolopyrimidonylthio, azaquinazolinoylthio, thienopyrimidonylthio, quinazolonylthio, pyrimidonylthio, benzoxazinylthio, benzoxazinonylthio, benzothiazinylthio, benzothiazinonylthio, thieno piperidinylthio, pyridylthio, thienylthio, furylthio, pyrrolylthio, oxazolylthio, thiazolylthio, isothiazolylthio, imidazolylthio, isoxazolylthio, oxadiazolylthio, thiadiazolylthio, triazolylthio, tetrazolylthio, benzofuranylthio, benzothienylthio, indolinylthio, indolylthio, azaindolylthio, azaindolinylthio, pyrazolopyrimidinylthio, azaquinazolinylthio, pyridofuranylthio, pyridothienylthio, thienopyrimidylthio, quinolinylthio, pyrimidinylthio, pyrazolylthio, quinazolinylthio, pyridazinylthio, triazinylthio, benzimidazolylthio, benzotriazolylthio, phthalazynilthio, naphthylidinylthio, purinylthio, carbazolylthio, phenothiazinylthio, phenoxazinylthio, benzoxazolylthio, benzothiazolylthio and the like;
- the “alkoxycarbonylamino” group used alone or in combination with other radicals, is selected from a suitable alkoxycarbonyl group, as defined above, attached to an amino group, more preferably methoxycarbonyl amino, ethoxycarbonylamino, and the like;
the “aminocarbonylamino”, “alkylaminocarbonylamino”,
“dialkylaminocarbonylamino” groups used alone or in combination with other radicals, is a carbonylamino (-CONH2) group, attached to amino(NH2),
alkylamino group or dialkylamino group respectively, where alkyl group is as defined above;
- the “amidino” group used either alone or in combination with other radicals, represents a -C(=NH)-NH2 radical; the “alkylamidino” group represents an alkyl radical, as described above, attached to an amidino group;
- the “alkoxyamino” group used either alone or in combination with other radicals, represents a suitable alkoxy group as defined above, attached to an amino group;
- the “hydroxyamino” group used either alone or in combination with other radicals, represents a -NHOH moiety, and may be optionally substituted with suitable groups selected from those described above;
- the “sulfenyl” group or “sulfenyl derivatives” used alone or in combination with other radicals, represents a bivalent group, -SO- or RxSO, where Rx 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 -S02-, or RxS02-, where Rx is as defined above. More preferably, the groups may be selected from “alkylsulfonyl” wherein suitable alkyl radicals, selected from those defined above, is attached to a sulfonyl radical, such as methylsulfonyl, ethylsulfonyl, propyl sulfonyl and the like, “arylsulfonyl” wherein an aryl radical, as defined above, is attached to a sulfonyl radical, such as phenyl sulfonyl and the like.
The term "combination therapy" means the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.
The phrase "therapeutically effective" is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder. This amount will achieve the goal of reducing or eliminating the said disease or disorder.
The term "therapeutically acceptable" refers to those compounds (or salts, prodrugs, tautomers, zwitterionic forms, etc.) which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and are effective for their intended use.
As used herein, reference to "treatment" of a patient is intended to include prophylaxis. The term "patient" means all mammals including humans. Examples of patients include humans, cows, dogs, cats, goats, sheep, pigs, and rabbits. Preferably, the patient is a human.
Suitable groups and substituents on the groups may be selected from those described anywhere in the specification.
Particularly useful compounds may be selected from-
(4-(3 -hydroxy ox etan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3-m ethoxy ox etan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
N-(4-(3 -hydroxy ox etan-3-yl)phenyl)- l-(4-(trifluoromethyl)phenyl)piperidine-4-carboxamide;
N-(4-(3 -hydroxy ox etan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl)piperi dine- 1-carboxamide;
N-(4-(3-m ethoxy oxetan-3 -yl)phenyl)-4-(4-(tri fluoromethyl)phenyl)piperi dine- 1-carboxamide;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperazin-l-yl) methanone;
3-(4-((4-(4-(trifluoromethyl)phenyl)piperazin-l-yl)sulfonyl)phenyl)oxetan-3-ol;
3-(4-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)phenyl)oxetan-3-ol;
1-(4-(3-m ethoxy oxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl)piperi dine;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(4- (trifluoromethyl)phenyl)hexahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(4- (trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3 -(2-hydroxy ethoxy)ox etan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
2-((3-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl) phenyl)oxetan-3 -yl)oxy)acetic acid;
(4-(3 -fluoro-5 -(trifluoromethyl)phenyl)piperidin- 1 -yl)(4-(3 -hydroxy oxetan-3 -yl) phenyl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(3 -(4-methyl - 1 H-imidazol- 1 -yl)-5 -(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
3-(4-(3-(3-fluoro-4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5-yl)phenyl)oxetan-3-ol;
3-(4-((l-(4-(trifluoromethyl)phenyl)piperidin-4-yl)oxy)phenyl)oxetan-3-ol;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno
[3,2-c]pyridin-5(4H)-yl)methanone;
(l-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl) (4-(3 -hydroxy ox etan-3 -yl)phenyl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(l -methyl-3 -(4-(trifluoromethyl)phenyl)-4, 6-dihydropyrrolo [3,4-c]pyrazol-5(lH)-yl)methanone;
(4-(3-hydroxyox etan-3-yl)phenyl)(2 -methyl-3 -(4-(trifluoromethyl)phenyl)-2, 6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethoxy)phenyl)piperidin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(p-tol yl)piperi din- l-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(3-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(p-tolyl)piperi din- l-yl)methanone;
(4-(3 -chloro-4-methoxyphenyl)piperidin- 1 -yl)(4-(3 -hydroxy oxetan-3 -yl)phenyl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-methoxyphenyl)piperidin-l-yl)methanone;
(4-(3-fluoro-4-methoxyphenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl) methanone;
(4-(3 -chi oro-4-methylphenyl)piperi din- l-yl)(4-(3 -hydroxy ox etan-3-yl)phenyl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(3 -methoxy-4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
(4-(3 -fluoro-4-(trifluoromethyl)phenyl)piperidin- 1 -yl)(4-(3 -hydroxy oxetan-3 -yl) phenyl)methanone;
(4-(3 -chi oro-4-(trifluoromethyl)phenyl)piperi din- l-yl)(4-(3 -hydroxy ox etan-3 -yl) phenyl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(2-(trifluorom ethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
2-((3-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl)phenyl)oxetan-3-yl) oxy)acetic acid;
3 -(4-(4-(4-(trifluorom ethyl )phenyl)piperi dine- l-carbonyl)phenyl)ox etan-3 -yl acetate; (4-(3-m ethoxy ox etan-3 -yl)phenyl)(4-(3-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3 -fluoro-4-(trifluoromethyl)phenyl)piperidin- 1 -yl)(4-(3 -methoxy oxetan-3 -yl) phenyl) methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(4-(3-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3 -methoxy ox etan-3 -yl)phenyl)(4-(2-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3 -ethoxy ox etan-3 -yl)phenyl)(4-(3-fluoro-4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-isopropoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-isobutoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-(cyclopropylmethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperi din- 1-yl) methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(5-(3-hydroxyoxetan-3-yl)pyridin-3-yl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(3-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(3-(3-methoxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
N-(3 -(3 -hydroxy ox etan-3 -yl)phenyl)-4-(4-(trifluoromethyl)phenyl)piperi dine- 1-carboxamide;
(4-(3-m ethoxy ox etan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperazin-l-yl) methanone;
3-(4-((4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)sulfonyl)phenyl)oxetan-3-ol;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(4- (trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(3 -(3 -m ethoxy ox etan-3 -yl)phenyl)(5-(4- (trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3-m ethoxy ox etan-3 -yl)phenyl)(5-(4- (trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3 -ethoxy ox etan-3 -yl)phenyl)(5 -(4- (trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(4-(difluoromethyl) phenyl) piperidin-l-yl)(3-(3-(methoxy-d3) oxetan-3-yl) phenyl)methanone;
N-(4-(3-m ethoxy oxetan-3-yl) phenyl)- l-(4-(trifluorom ethyl) phenyl) piperidine-4-carboxamide;
(4-(3-hydroxy-l,l-dioxidothietan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo [3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3 -hydroxy- 1,1-dioxidothi etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl) phenyl)(4-(4-hydroxyphenyl) piperidin- 1 -yl)methanone; (4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-phenylpiperi din- l-yl)methanone;
(4-(4-(difluoromethyl)phenyl)piperidin-l-yl)(3-(3-methoxyoxetan-3-yl)phenyl) methanone;
(4-(4-(difluoromethyl)phenyl)piperidin- 1 -yl)(3 -(3 -hydroxy oxetan-3 -yl)phenyl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(2-methoxypyridin-4-yl)-4-(4-(trifluoromethyl) phenyl)piperazin-l-yl)methanone;
(4-(4-(difluoromethyl)phenyl)piperidin-l-yl)(4-(3-methoxyoxetan-3-yl)phenyl) methanone;
(4-(4-(difluorom ethyl)phenyl)piperi din- l-yl)(4-(3 -hydroxy oxetan-3 -yl)phenyl) methanone;
(4-(3-(but-2-yn-l-yloxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-1-yl) methanone;
N-(4-(3-hydroxyoxetan-3-yl)phenyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)oxazole- 4-carboxamide;
(4-(3 -(prop-2 -yn-l-yloxy)oxetan-3-yl)phenyl)(4-(4-(trifluorom ethyl )phenyl) piperidin-l-yl) methanone;
4-(4-(3-methoxyoxetan-3-yl)phenyl)-l-(4-(trifluoromethyl)phenyl)piperidin-4-ol; N-(4-(3-methoxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrole-2(lH)-carboxamide;
N-(4-(3-hydroxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrole-2(lH)-carboxamide;
(4-(3-(methoxy-d3)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
5-(3-hydroxyoxetan-3-yl)-2-(4-(4-(trifluoromethyl) phenyl) piperidin-l-yl) benzoic acid;
3-(3-hydroxyoxetan-3-yl)-5-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)benzoic acid;
(3-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-l,4,6,7-tetrahydro- 5H-imidazo[4,5-c]pyridin-5-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-l,4,6,7-tetrahydro- 5H-imidazo[4,5-c]pyridin-5-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)-2-morpholinophenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3-yl)-2-(piperazin-l-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
l-(4-(3 -ethoxy ox etan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl)piperi dine;
3-(3-morpholino-5-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)phenyl)oxetan-3-ol; /er/-butyl4-(5-(3-hydroxyoxetan-3-yl)-2-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl) phenyl)piperazine-l-carboxylate;
(4-hydroxy-4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl) phenyl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)-5,6-dihydropyridin-1 (2H)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(l-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo [3,4-c] pyrazol-5(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-2,6-dihydropyrrolo
[3,4-c]pyrazol-5(4H)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-2,6-dihydropyrrolo
[3,4-c]pyrazol-5(4H)-yl)methanone;
(4-(3 -hydroxy ox etan-3-yl)phenyl)(5-m ethoxy-5 -(4-(trifluoromethyl)phenyl) hexahydrocyclopentafc] pyrrol-2(lH)-yl)methanone;
(5-methoxy-5-(4-(trifluoromethyl)phenyl)hexahydrocyclopenta[c]pyrrol-2(lH)-yl)(4-(3-methoxyoxetan-3-yl)phenyl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,5-dihydropyrrolo
[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,5-dihydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3 -(3 -m ethoxy ox etan-3 -yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3 ,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
3-(4-((5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)sulfonyl) phenyl)ox etan-3 -ol;
(4-(3-hydroxyoxetan-3-yl)phenyl)(9-(4-(trifluoromethyl)phenyl)-3,9-diazaspiro [5.5]undecan-3 -yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(9-(4-(trifluoromethyl)phenyl)-3,9-diazaspiro [5.5]undecan-3 -yl)methanone;
(4-(3-m ethoxy ox etan-3-yl)phenyl)(9-(4-(trifluoromethyl)phenyl)-3,9-diazaspiro [5.5]undecan-3 -yl)methanone;
(4-(3 -hydroxy ox etan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)pyrrolidin-l-yl) methanone;
((5-(4-fluorophenyl)-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-2(lH)-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(5-hydroxy-5-(4-(trifluoromethyl)phenyl)hexahydrocyclopenta[c]pyrrol-2(lH)-yl)(4- (3-hydroxyoxetan-3-yl)phenyl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(6-(4-(trifluoromethyl)phenyl)-3, 4-dihydroisoquinolin-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)indolin-l-yl) methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(3-(4-methyl-lH-imidazol-l-yl)-4-(trifluorom ethyl) phenyl)piperidin-l-yl)methanone;
2,2-dimethyl-7-((3-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl)phenyl) oxetan-3-yl)oxy)heptanoic acid;
(4-(methoxymethyl)-4-(4-(trifluorom ethyl )phenyl)piperidin- l-yl)(4-(3-m ethoxy oxetan-3-yl) phenyl)methanone;
(4-(hydroxymethyl)-4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3 -yl) phenyl)methanone;
l-(4-(3-m ethoxy oxetan-3-yl )benzoyl)-4-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid;
methyl l-(4-(3 -hydroxy oxetan-3-yl)benzoyl)-4-(4-(trifluoromethyl)phenyl) piperidine-4-carboxylate;
l-(4-(3 -hydroxy oxetan-3-yl )benzoyl)-4-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid;
(4-(3-chloro-4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-methoxyoxetan-3-yl) phenyl)methanone;
l-(4-(3 -hydroxy oxetan-3-yl )benzoyl)-4-(4-(trifluoromethyl)phenyl)piperidine-4-carbonitrile;
l-(4-(3-m ethoxy oxetan-3-yl )benzoyl)-4-(4-(trifluoromethyl)phenyl)piperidine-4-carbonitrile;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-methoxy-4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
(4-methoxy-4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-methoxyoxetan-3-yl) phenyl)methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(3 -(trifluoromethyl)phenyl)piperidin- 1 -yl) methanone;
(4-(3 -fluoro-4-(trifluoromethyl)phenyl)piperidin- 1 -yl)(3 -(3 -hydroxy oxetan-3 -yl) phenyl) methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(2-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
3-(3-(3-(4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5-yl)phenyl)oxetan-3-ol;
5-(3-(3-methoxyoxetan-3-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)-l,2,4-oxadiazole; 3-(4-(3-(4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5-yl)phenyl)oxetan-3-ol;
5-(4-(3-methoxyoxetan-3-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)-l,2,4-oxadiazole; (4-(3 -hydroxy ox etan-3-yl)phenyl)(4-(4-((trifluoromethyl)thio)phenyl)piperi din- 1-yl) methanone;
(4-(3-m ethoxy ox etan-3-yl)phenyl)(4-(4-((trifluoromethyl)thio)phenyl)piperi din- 1-yl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(p-tolyl)-3,3a,6,6a-tetrahydrocyclopenta[c] pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(methylthio)phenyl)-3,3a,4,6a-tetrahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(6-(4-(trifluoromethyl)phenyl)-3,6-diazabicyclo [3.1.1] heptan-3-yl)methanone;
(4-(3-(cyclopropylmethoxy)oxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-(methoxy-d3)oxetan-3-yl)phenyl)(5-(4-(trifluorom ethyl )phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-isobutoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo [3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3 -i sopropoxyoxetan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3-(2-methoxyethoxy)oxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
3-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl) phenyl)oxetan-3-yl acetate;
3-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl) phenyl)oxetan-3-yl pivalate;
tert-butyl 4-hydroxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine- 1 -carbonyl)phenyl) piperidine- 1-carboxylate;
(4-(4-hydroxypiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(4-hydroxytetrahydro-2H-pyran-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperi din- 1-yl) methanone;
(4-(4-methoxytetrahydro-2H-pyran-4-yl)phenyl)(4-(4-(trifluorom ethyl )phenyl) piperi din- 1-yl) methanone;
(4-(4-methoxypiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-hydroxythietan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3-hydroxythietan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo [3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3-methoxythietan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3-ethoxythietan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(3-methoxythietan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo [3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3-ethoxythietan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo
[3,4-c]pyrrol-2(lH)-yl)methanone;
/er/-butyl 3 -hydroxy-3 -(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl) phenyl)pyrrolidine-l-carboxylate;
(4-(3-hydroxypyrrolidin-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-methoxypyrrolidin-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
tert-butyl 3 -hydroxy-3 -(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl) phenyl)azetidine- 1 -carboxylate;
(4-(3-hydroxyazeti din-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl) methanone;
(4-(4-(methoxy-d3)piperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
tert-butyl 4-methoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl) phenyl )piperi dine- 1 -carboxylate;
l-(4-methoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl)phenyl) piperidin- 1 -yl)ethan- 1 -one;
ethyl 4-m ethoxy-4-(4-(4-(4-(trifluorom ethyl )phenyl)piperidine-l -carbonyl )phenyl) piperidine- 1 -carboxylate;
(4-(4-methoxy-l-methylpiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin- 1-yl) methanone;
tert-butyl 4-ethoxy-4-(4-(4-(4-(trifluorom ethyl )phenyl)piperi dine- 1 -carbonyl )phenyl) piperidine- 1 -carboxylate;
(4-(4-ethoxypiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
l-(4-ethoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl )phenyl) piperidin- 1-yl) ethan-l-one;
ethyl 4-ethoxy-4-(4-(4-(4-(trifluorom ethyl )phenyl)piperidine-l -carbonyl )phenyl) piperidine- 1 -carboxylate;
(4-(4-ethoxy-l-methylpiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
tert-butyl 4-hydroxy-4-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c] pyrrole-2-carbonyl)phenyl)piperidine-l -carboxylate;
tert-butyl 4-methoxy-4-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)phenyl)piperidine- 1 -carboxylate;
(4-(4-methoxypiperidin-4-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(4-methoxy-l-(2,2,2-trifluoroethyl)piperidin-4-yl)phenyl)(4-(4-(trifluoromethyl) phenyl)piperidin-l-yl)methanone;
(4-(4-ethoxy-l-(2,2,2-trifluoroethyl)piperidin-4-yl)phenyl)(4-(4-(trifluoromethyl) phenyl)piperidin-l-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno [3,2-c] pyridin-5(4H)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno
[3,2-c]pyridin-5(4H)-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothiazolo [5,4-c] pyridin-5(4H)-yl)methanone;
N-(4-(3-hydroxyoxetan-3-yl)phenyl)-2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxamide;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothiazolo [5,4-c] pyridin-5(4H)-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno [3,2-c] pyridin-5(4H)-yl)methanone;
(l-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl) (3 -(3 -hydroxy ox etan-3 -yl)phenyl)methanone;
(3-(3-ethoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo [3,4-c] pyrrol-2(lH)-yl)methanone;
ethyl 2-((3-(3-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)phenyl)oxetan-3-yl)oxy)acetate;
(3-(3-isobutoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo [3,4-c] pyrrol-2(lH)-yl)methanone;
(3-(3-(cyclopropylmethoxy)oxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
N-(3-(3-hydroxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo [3,4-c] pyrrole-2(lH)-carboxamide;
N-(3-(3-methoxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo [3,4-c] pyrrole-2(lH)-carboxamide;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)-l,4-diazepan-l-yl) methanone;
(4-(3 -m ethoxy ox etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)- 1 ,4-diazepan- 1 -yl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(8-(4-(trifluoromethyl)phenyl)-2,8-diazaspiro[4.5] decan-2-yl)methanone;
4-(3-hydroxyoxetan-3-yl)-N-(l-(4-(trifluoromethyl)phenyl)pyrrolidin-3-yl) benzamide;
(4-(3-(2-hydroxyethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-1-yl) methanone;
(4-(3-(2-(ethylthio)ethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperi din- 1-yl) methanone;
(4-(3-(2-(ethylsulfonyl)ethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperi din- 1-yl )methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-(methylthio)phenyl)piperi din- 1-yl) methanone;
(4-(3-m ethoxy ox etan-3 -yl)phenyl)(4-(4-(methylthio)phenyl)piperi din- 1-yl) methanone;
(4-(4-hydroxypiperidin-4-yl)phenyl)(4-(4-(methylthio)phenyl)piperidin-l-yl) methanone;
(4-(4-methoxypiperidin-4-yl)phenyl)(4-(4-(methylthio)phenyl)piperidin-l-yl) methanone;
(3 -(3 -(methoxy-d3)ox etan-3 -yl)phenyl)(5-(4-(trifluorom ethyl )phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3 -(3 -i sopropoxyoxetan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
N-(3 -(3 -hydroxy ox etan-3-yl)-5-morpholinophenyl)-l-(4-(trifluoromethyl)phenyl) piperidine-4-carboxamide;
methyl 4-(5-hydroxy-2-(4-(3-hydroxyoxetan-3-yl)benzoyl)octahydrocyclopenta[c] pyrrol-5-yl)benzoate;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(4-methoxyphenyl)-3 ,3 a,4, 6a-tetrahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(2-(methylthio)ethoxy)phenyl)-3,3a,4,6a-tetrahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
N-(3 -(3 -hydroxy ox etan-3 -yl)-5-(4-methylpiperazin- 1 -yl)phenyl)- 1 -(4-(trifluoromethyl)phenyl)piperidine-4-carboxamide;
(4-(3 -m ethoxy ox etan-3 -yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3 ,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(5-hydroxy-5-(6-methoxypyridin-3-yl)hexahydrocyclopenta[c]pyrrol-2(lH)-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone;
3-(4-((l-(4-(trifluoromethyl)phenyl)piperidin-4-yl)amino)phenyl)oxetan-3-ol;
In another embodiment compounds are selected from following:
tert-butyl 4-methoxy-4-(4-(4-(5-(trifluoromethyl)pyridin-2-yl)piperidine-l -carbonyl) phenyl )piperi dine- 1 -carboxylate;
(4-(4-methoxypiperidin-4-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)piperidin-l-yl)methanone;
(4-(3-m ethoxy ox etan-3 -yl)phenyl)(5-(6-(trifluoromethyl)pyri din-3 -yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(5-(trifluoromethyl)pyridin-2-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3-(3-methoxyoxetan-3-yl)phenyl)(5-(5-(trifluoromethyl)pyridin-2-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(5-(5-(trifluoromethyl)pyridin-2-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(5 -(trifluoromethyl)pyridin-2-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)piperidin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)piperidin-l-yl) methanone;
(4-(3-m ethoxy ox etan-3 -yl)phenyl)(4-(6-(trifluoromethyl)pyri din-3 -yl)piperi din- 1-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(6-(trifluoromethyl)pyri din-3 -yl)piperidin- 1-yl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(6-(trifluoromethyl)pyridin-3-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl) phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl) piperazin-1-yl)methanone;
(4-(3-hydroxyoxetan-3-yl) phenyl)(4-(6-(trifluoromethyl) pyri din-3 -yl) piperazin-1-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-l-yl) methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-l-yl) methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-l-yl) methanone;
(3 -(3 -m ethoxy ox etan-3 -yl)phenyl)(4-(5 -(trifluoromethyl)pyridin-2-yl)piperazin- 1 -yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(2-(trifluoromethyl)pyridin-4-yl)piperazin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(2-(trifluoromethyl)pyridin-4-yl)piperidin-l-yl) methanone.
The novel compounds of this invention may be prepared using the reactions and techniques as shown in scheme below and described in this section. The reactions are performed in solvents appropriate to the reagents and materials employed and are suitable for the transformations being affected. It is understood by those skilled in the art that the nature and order of the synthetic steps presented may be varied for the purpose of optimizing the formation of the compounds of the present invention. It will also be well appreciated that one or more of the reactants may be protected and deprotected for facile synthesis by techniques known to persons skilled in the art. It will also be appreciated that one or more of the compounds of the present invention may exist in stereoisomeric and/or diastereomeric forms. Such stereoisomers and/or diastereoisomers as well as their optical antipodes are to be construed to be within the scope of the present invention. It will also be well appreciated that one or more of these compounds may be converted to their salts and other derivatives based on the specific groups present on the compounds, which can be well comprehended by persons skilled in the art. Such salts and/or other derivatives, as the case may be should also be construed to be within the scope of the present invention.
The compounds of general formula (la) & (lb) wherein Ύ’ represents C=0, and all other symbols are as defined earlier, may be prepared by reactions outlined in Scheme 1 below which comprises:
Scheme:!

i. Reacting the acids of general formula II wherein all the symbols are as defined earlier and compounds of general formula III wherein all the symbols are as defined earlier, using suitable metal alkyls such as //-butyllithium, .s-butyl lithium and the like to prepare compounds of general formula IV wherein the symbols are as defined earlier. The reaction may be carried out in presence of suitable solvent(s) such as tetrahydrofuran, diethylether and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of -78 °C to 28 °C and the reaction time may range from 1 to 48 hours;
ii. The compounds of formula (la) wherein all the symbols are as defined earlier may be prepared by coupling reaction of acids of general formula IV wherein all the symbols are as defined earlier and amine of general formula V wherein all the symbols are as defined earlier under suitable conditions in presence of reagents(s) such as N-(3-dimethylaminopropyl)-N’-ethylcarbodimide hydrochloride (EDC) & 1-Hydroxybenzotriazole (HOBT), l-[Bis(dimethylamino)methylene]-lH- l,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), N,N,N',N'- Tetramethyl-0-(lH-benzotriazol-l-yl)uronium hexafluorophosphate (HBTU) and the like. The reaction may be carried in presence of suitable organic bases such as triethyl amine, diisopropyl ethyl amine, pyridine N-ethylmorpholine and the like. The reaction may be carried out in presence of suitable solvent(s) such as dimethylformamide (DMF), dimethylacetamide (DMA), dichloromethane and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours.
iii. Reacting the compounds of general formula (la) wherein all the symbols are as defined earlier and the compounds of general formula VI wherein ‘L’ represents suitable leaving group and all other symbols are as defined earlier, using suitable inorganic base(s) such as NaOH, KOH, K2C03, Cs2C03, NaH, KH and the like or organic base(s) such as pyridine, triethyl amine, diisopropyl ethylamine and the like to prepare compounds of general formula (lb) wherein the symbols are as defined earlier. The reaction may be carried out neat or in presence of suitable protic solvent(s) such as methanol, ethanol, butanol and the like or suitable aprotic solvent(s) such as dimethyl formamide, tetrahydrofuran, dichloromethane and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours;
The compounds of general formula (Ic), (Id) & (Ie) wherein Ύ represents - C(0)NH- and all other symbols are as defined earlier, may be prepared by reactions outlined in Scheme 2 below which comprises:
Scheme:2

i. Reacting the compounds of general formula VII wherein all the symbols are as defined earlier and compounds of general formula III wherein all the symbols are as defined earlier, using suitable metal alkyls such as //-butyllithium, .s- butyllithium and the like to prepare compounds of general formula VIII wherein the symbols are as defined earlier. The reaction may be carried out in presence of suitable solvent(s) such as tetrahydrofuran, diethylether and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of -78 °C to 28 °C and the reaction time may range from 1 to 48 hours;
ii. Reacting the compounds of general formula VIII wherein the symbols are as defined earlier and the compounds of general formula VI wherein ‘L’ represents suitable leaving group and all other symbols are as defined earlier, using suitable inorganic base(s) such as NaOH, KOH, K2CO3, CS2CO3, NaH, KH and the like or organic base(s) such as pyridine, triethyl amine, diisopropyl ethylamine and the like to prepare compounds of general formula IX wherein all the symbols are as defined earlier. The reaction may be carried out neat or in presence of suitable protic solvent(s) such as methanol, ethanol, butanol and the like or suitable aprotic solvent(s) such as dimethyl formamide, tetrahydrofuran, di chi orom ethane and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours;
iii. Reacting the Compounds of formula VIII and IX wherein all the symbols are as defined earlier and ammonia solution, using suitable reagents such copper (II) oxide and the like to prepare corresponding compounds of general formula X &
XI wherein all the symbols are as defined earlier. The reaction may be carried out neat or in presence of suitable solvent(s) such as methanol, ethanot, toluene and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of 100 °C to 200 °C under microwave irradiation and the reaction time may range from 1 to 5 hours;
iv. The compounds of formula (Ic) and (Id) wherein all the symbols are as defined earlier may be prepared by reacting reaction of corresponding aryl amine of general formula X and XI wherein all the symbols are as defined earlier and corresponding cyclic amine of general formula V wherein all the symbols are as defined earlier under suitable conditions in presence of reagents(s) such as phosgene, triphosgene, Carbonyldiimidazole and the like. The reaction may be carried in presence of organic base(s) such as trimethylamine, diisopropylamine, pyridine and the like using suitable solvent(s) such as dimethyl formamide, tetrahydrofuran, dichloromethane, acetonitrile and the like or mixtures thereof. The reaction may be carried out at a temperature in the range 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours;
v. The compounds of formula (Ie) wherein all the symbols are as defined earlier may be prepared by coupling reaction of acids of general formula XII wherein all the symbols are as defined earlier and amine of general formula X wherein all the symbols are as defined earlier under suitable conditions in presence of reagents(s) such as N-(3-dimethylaminopropyl)-N’-ethylcarbodimide hydrochloride (EDC) & 1-Hydroxybenzotriazole (HOBT), l-[Bis(dimethylamino)methylene]-lH- l,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), N,N,N',N'- Tetramethyl-0-(lH-benzotriazol-l-yl)uronium hexafluorophosphate (HBTU) and the like. The reaction may be carried in presence of suitable organic bases such as triethyl amine, diisopropyl ethyl amine, pyridine, N-ethylmorpholine and the like. The reaction may be carried out in presence of suitable solvent(s) such as DMF, DMA, dichloromethane and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours.
vi. Reacting the compounds of general formula (Ie) wherein the symbols are as defined earlier and the compounds of general formula VI wherein ‘L’ represents suitable leaving group and all other symbols are as defined earlier, using suitable inorganic base(s) such as NaOH, KOH, K2C03, Cs2C03, NaH, KH and the like or organic base(s) such as pyridine, triethyl amine, diisopropyl ethylamine and the like to prepare compounds of general formula (If) wherein all the symbols are as defined earlier. The reaction may be carried out neat or in presence of suitable protic solvent(s) such as methanol, ethanol, butanol and the like or suitable aprotic solvent(s) such as dimethyl formamide, tetrahydrofuran, dichloromethane and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours;
The compounds of general formula (If) & (Ig) wherein Ύ represents a bond and all other symbols are as defined earlier, may be prepared by reactions outlined in Scheme 2 below which comprises:
Scheme 3:

i. Buchwald coupling of the compounds of general formula V wherein the symbols are as defined earlier and dibromo compounds of general formula VII wherein all othe symbols are as defined earlier, in presence of palladium catalysts such as palladium(II) acetate, tris(dibenzylideneacetone)dipalladium(0), [1,1'- Bis(diphenylphosphino)ferrocene]dichloropalladium(II),
Bis(triphenylphosphine) palladium(II) dichloride,
Tetrakis(triphenylphosphine)palladium(0) and the like using suitable base(s) such as /-BuONa, /-BuOK and the like to prepare compounds of general formula XIII wherein all the symbols are as defined earlier. The reaction may be carried out neat or in presence of suitable solvent(s) such as toluene, xylene, dimethyl formamide, tetrahydrofuran, dichloromethane and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours;
ii. Reacting the compounds of general formula XIII wherein all the symbols are as defined earlier and compounds of general formula III wherein all the symbols are as defined earlier, using suitable metal alkyls such as n-butyllithium, s- butyllithium and the like to prepare compounds of general formula (Ig) wherein the symbols are as defined earlier. The reaction may be carried out in presence of suitable solvent(s) such as tetrahydrofuran, diethylether and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of -78 °C to 28 °C and the reaction time may range from 1 to 48 hours; iii. Reacting the compounds of general formula (Ig) wherein the symbols are as defined earlier and the compounds of general formula VI wherein ‘L’ represents suitable leaving group and all other symbols are as defined earlier, using suitable inorganic base(s) such as NaOH, KOH, K2CO3, CS2CO3, NaH, KH and the like or organic base(s) such as pyridine, tri ethyl amine, diisopropyl ethylamine and the like to prepare compounds of general formula (Ih) wherein all the symbols are as defined earlier. The reaction may be carried out neat or in presence of suitable protic solvent(s) such as methanol, ethanol, butanol and the like or suitable aprotic solvent(s) such as dimethyl formamide, tetrahydrofuran, dichloromethane and the like or suitable mixtures thereof. The reaction may be carried out at a temperature in the range of 0 °C to reflux temperature of the solvent(s) used and the reaction time may range from 1 to 48 hours.
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.
' H NMR spectral data given in the examples (vide infra) are recorded using a 400 MHz spectrometer (Bruker AVANCE-400) and reported in d scale.
Exameple 1 : (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

Step-a: Preparation of 4-(3-hydroxyoxetan-3-yl)benzoic acid:
To a solution of 4-bromobenzoic acid (1.860 g, 9.25 mmol) in THF (25 ml), N- butyllithium (2.5 M in hexane) (8.14 ml, 20.35 mmol) was added dropwise under nitrogen atmosphere at -78 °C over a period of 30 minutes. The reaction mixture was stirred at the same temperature for 30 min. A solution of oxetan-3-one (1 g, 13.88 mmol) in THF (5 ml) was added dropwise at -78 °C. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 hrs under nitrogen atmosphere. The reaction mixture was poured into saturated aqueous NH C1 solution (20 mL), acidified with dil. HC1 and extracted with ethyl acetate (3 x 25 ml). The combined organic layers was washed with water & brine, dried over Na2S0 and evapourated under vacuum. The crude product was purified by triturating with diethyl ether to obtain pure 4-(3-hydroxyoxetan-3-yl)benzoic acid (410 mg, 23% Yield) as off white solid.
¾ NMR (DMSO-d6) d : 4.68 (d, J = 6.8 Hz, 2H), 4.80 (d, J = 6.8 Hz, 2H), 6.53 (s,
1H), 7.74 (d, J= 6.8 Hz, 2H), 7.98 (d, J = 6.8 Hz, 2H), 12.93 (br s, 1H); MS (ESI, pos. ion) m/z: 195.04 [M+H]
Step b: Preparation of /tvV-butyl 4-hydroxy-4-(4-(trifluoromethyl) phenyl) piperidine- 1-carboxylate.
To, a solution of l-bromo-4-(trifluoromethyl)benzene (5.0 g, 22.22 mmol) in THF (50 ml), N-butyllithium(2.5M in hexane) (18.67 ml, 46.7 mmol) was added dropwise maintaining the reaction temperature below -70 °C over a period of 20 min and stirred for 30 min at -78 °C under nitrogen atmosphere. A solution of tert- butyl 4-oxopiperidine-l-carboxylate (4.43 g, 22.22 mmol) in THF (20 ml) was added drop wise to the reaction mixture under nitrogen atmosphere at -78 °C over a period of 10 min. The reaction mixture was stirred under nitrogen atmosphere at 27 °C for 3 hrs. The reaction mixture was poured into saturated ammonium chloride solution (250 mL) and extracted with ethyl acetate (3 x 100 mL). The combined organic extract was washed with water (3 x 150 mL) & brine (150 mL), dried over Na2S0 and evapourated under vacuum. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 10% EtOAc in Hexane as an eluent to yield pure fe/V-butyl 4-hydroxy-4-(4-(trifluoromethyl)phenyl) piperidine-1-carboxylate (2.8 g, 8.11 mmol, 36.5% yield) as off white solid.
¾ NMR (DMSO-de) d : 1.42 (s, 9H), 1.58 (d, J = 12.4 Hz, 2H), 1.79-1.87 (m, 2H), 3.13 (br s, 2H), 3.87 (br s, 2H), 5.32 (s, 1H), 7.67-7.72 (m, 4H).
Step c: Preparation of 4-(4-(trifluoromethyl)phenyl)piperidin-4-ol hydrochloride HC1 in 1,4-dioxane (10 ml) was added to a solution of tert- butyl 4-hydroxy-4-(4-(trifluoromethyl)phenyl)piperidine-l-carboxylate (1.1 g, 3.19 mmol) in 1,4-Dioxane (10 ml) under nitrogen atmosphere at 27 °C. The reaction mixture was stirred under nitrogen atmosphere at 27 °C for 12 hrs. Solvent was removed under vacuum and the residue was diluted with diethyl ether (10 ml) and stirred for 30 min to get pure 4-(4-(trifluoromethyl)phenyl)piperidin-4-ol hydrochloride as off white solid.
¾ NMR (DMSO-de) d : 1.48 (d, J= 12.0 Hz, 2H), 1.76-1.83 (m, 2H), 2.66-2.74 (m, 2H), 2.88-2.95 (m, 2H), 5.01 (s, 1H), 7.67-7.70 (m, 4H).
Step d: Preparation of 4-(4-(trifluoromethyl)phenyl)-l,2,3,6-tetrahydropyridine 4-methylbenzenesulfonate.
/’am-Toluenesulfonicacid (PTSA) (5.43 g, 28.5 mmol) was added to a solution of 4-(4-(trifluoromethyl)phenyl)piperidin-4-ol (1.4 g, 5.71 mmol) in Toluene (25 ml) under nitrogen atmosphere at 27 °C and the reaction mixture was refluxed for 12 hrs. The reaction mixture was cooled to ambient temperature and was poured into ice cold water (100 mL). Off white solid sepereated was filtered through Buchner funnel, washed with water and dried over P205 under vacuum to yield 4-(4-(trifluoromethyl)phenyl)-l,2,3,6-tetrahydropyridine 4-methylbenzenesulfonate (1.3 g, 5.05 mmol, 88 % yield) as off white solid.
¾ NMR (DMSO-d6) d: 2.27 (s, 3H), 2.67-2.71 (m, 2H), 3.35 (br s, 2H), 3.81 (br s, 2H), 6.36 (s, 1H), 7.11 (d, J= 7.6 Hz, 2H), 7.48 (d, J= 8.0 Hz, 2H), 7.70 (d, J= 8.8 Hz, 2H), 7.75 (d, J= 8.4 Hz, 2H), 8.81 (br s, 2H).
Step e: Preparation of 4-(4-(trifluoromethyl)phenyl)piperidine 4-methylbenzenesulfonate.
A solution of 4-(4-(trifluoromethyl)phenyl)-l,2,3,6-tetrahydropyridine (5.0 g, 22.00 mmol) in MeOH (100 ml) was added to a suspention of Pd/C (10%) (1.5 gm) in MeOH (10 ml) and the mixture was hydrogenated on a parr apparatus at 50 psi hydrogen pressure and 27 °C temperature for 3 hrs. The reaction mixture was filtered through celite bed and the filtrate was evoparated in rotavapour under reduced pressure to obtained 4-(4-(trifluoromethyl)phenyl)piperidine ( 5 gm, 99% yield) as white solid.
¾ NMR DMSO-d6) ό : 1.74-1.85 (m, 2H), 1.94-1.98 (m, 2H), 2.29 (s, 3H), 2.94-3.07 (m, 3H), 3.34-3.41 (m, 2H), 7.12 (d, J= 8.0 Hz, 2H), 7.45-7.50 (m, 4H), 7.71 (d, J = 8.0 Hz, 2H), 8.30 (br s, 1H), 8.56 (br s, 2H).
Step-f: Preparation of (4-(3 -hydroxy oxetan-3-yl)phenyl)(4-(4-(trifluorom ethyl) phenyl)piperidin-l-yl)methanone.
To a solution of 4-(4-(trifluorom ethyl )phenyl)piperidine 4-methylbenzenesulfonate (200 mg, 0.872 mmol) in DMF (3.0 ml), 4-(3-hydroxyoxetan-3-yl)benzoic acid (152 mg, 0.785 mmol) and HOBT (200 mg, 1.309 mmol) were added followed by addition of EDC (201 mg, 1.047 mmol) and N-ethylmorpholine (0.331 ml, 2.62 mmol) under nitrogen atmosphere at 27 °C. The reaction mixture was stirred under nitrogen atmosphere at 27 °C for 2 hrs. The reaction mixture was poured into ice cold water (50 mL) and extracted with ethyl acetate (3 x 25 mL). The combined organic layers was washed with water (3 x 25 mL) & brine (25 mL), dried over Na2S0 and evaporated in rotavapor under vacuum to yield crude product as thick liquid. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 50% EtOAc in Hexane as an eluent to yield (4-(3-hydroxyoxetan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin- 1 -yl)methanone (130mg, 0.316 mmol, 36% yield) as white solid.
¾ NMR (CDCI3) ό : 1.64 (br s, 2H), 1.83 (br s, 2H), 2.01 (br s, 1H), 2.82-3.02 (m, 2H), 3.17 (br s, 1H), 3.58 (s, 1H), 3.92 (br s, 1H), 4.84 (d, J= 7.2 Hz, 2H), 4.95 (d, J = 12 Hz, 2H), 7.34-7.43 (m, 4H), 7.59-7.66 (m, 4H).
ESI-MS: m/z 406.15 (M+H)+, 100%.
Example 2: (4-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

O
To a suspention of sodium hydride (8.88 mg, 0.185 mmol) in THF (2 ml), a solution of (4-(3 -hydroxy oxetan-3-yl)phenyl)(4-(4-(trifluorom ethyl )phenyl)piperi din- 1-yl)methanone (50 mg, 0.123 mmol) in THF (0.5 ml) was added dropwise at 0-10 °C over a period of 10 min and reaction mixture was stirred for 30 min. Iodom ethane (9.25 mΐ, 0.148 mmol) was added to the reaction mixture and continued to stirr at 28 °C for 3 hrs. The reaction mixture was poured into ice cold water (15 mL) and extracted with ethyl acetate (3 x 15 mL). The combined organic layers was washed with water (2 x 20 mL) & brine (20 mL), dried over Na2S04 and evaporated under vacuum. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 30% EtOAc in Hexane as an eluent to yield pure (4-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone (45mg, 0.105 mmol, 85 % yield) as pale yellow solid.
¾ NMR (DMSO-d6) d : 1.61-1.72 (m, 3H), 1.88 (br s, 1H), 2.87-2.98 (m, 2H), 3.05 (s, 3H), 3.19 (br s, 1H), 3.70 (br s, 1H), 4.65 (br s, 1H), 4.76-4.81 (m, 4H), 7.50-7.55 (m, 6H), 7.67 (d, J= 8.0 Hz, 2H).
ESI-MS: m/z 420 (M+H)+, 100%.
Example 3: N-(4-(3-hydroxyoxetan-3-yl)phenyl)-l-(4-(trifluoromethyl)phenyl) piperidine-4-carboxamide

Step a: Preparation of Ethyl l-(4-(trifluorom ethyl )phenyl)piperidine-4-carboxylate To a solution of l-bromo-4-(trifluoromethyl)benzene (3 g, 13.33 mmol) in Toluene (20 ml), ethyl piperidine-4-carboxylate (3.35 g, 21.33 mmol) was added followed by addition of sodium /er/-butoxide (1.922 g, 20.00 mmol), BINAP (0.249 g, 0.400 mmol) and Pd2(dba)3 (0.122 g, 0.133 mmol) under nitrogen atmosphere at 28 °C. The reaction mixture was stirred under nitrogen atmosphere at 120 C for 16 hrs. Reaction mixture was cooled to room temperature and filtered througt celite. The filtrate was diluted with ethyl acetate (40 mL) and water (40 mL). Organic layer was seperated and aq. layer was extracted with ethyl acetate (2 x 20 mL). The combined organic layers was washed with water (2 x 60 mL) and brine (60 mL), dried over Na2S04 and evapourated on rotavapor under vacuum to yield crude product as an oil. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 10% EtOAc in Hexane as an eluent to obtained ethyl l-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylate (1.608 g, 40% yield) as light yellow oil.
¾ NMR (CDCI3) d : 1.29 (t, J= 7.2 Hz, 3H), 1.81-1.91 (m, 2H), 2.02-2.07 (m, 2H), 2.47-2.55 (m, 1H), 2.89-2.95 (m, 2H), 3.74-3.79 (m, 2H), 4.18 (q, J= 7.2 Hz, 2H), 6.94 (d, J= 8.4 Hz, 2H), 7.48 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z 302.12 (M+H)+, 100%.
Step b: Preparation of l-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid To a solution of ethyl l-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylate (1.2 g, 3.98 mmol) in THF (5 ml) and MeOH (5 ml), a solution of Lithium hydroxide monohydrate (0.334 g, 7.97 mmol) in water (5 mL) was added and the reaction mixture was stired at ambient temperature for 3 hr. Reaction mixture was concentrated under vacuum, diluted with cold water (15 mL) and was acidified with dil HC1 (pH 3-4) with vigorous stirring. The white solid obtained was filtered, washed with water and dried over P205 under vacuum to yield l-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid (1 g, 92 % yield) as off white solid.
¾ NMR (DMSO-de) d : 1.61-1.66 (m, 2H), 1.86-1.88 (m, 2H), 2.44-2.49 (m, 1H), 2.88-2.99 (m, 2H), 3.78-3.82 (m, 2H), 7.05 (d, J = 8.8Hz, 2H), 7.55 (d, J = 8.8Hz, 2H), 12.30 (br s, 1H). ESI-MS: m/z 302.12 (M+H)+, 100%.
Step c : Preparation of N-(4-(3 -hydroxy oxetan-3-yl)phenyl)-l-(4-(trifluorom ethyl) phenyl) piperidine-4-carboxamide.
To a solution of l-(4-(trifluoromethyl)phenyl)piperidine-4-carboxylic acid (0.220 g, 0.805 mmol) in DMF (4 ml), HATU (0.490 g, 1.288 mmol) was added followed by addition of 3-(4-aminophenyl)oxetan-3-ol (0.146 g, 0.886 mmol) and DIPEA (0.337 ml, 1.932 mmol) under nitrogen atmosphere at 28 °C. The reaction mixture was stirred at 70 °C under nitrogen atmosphere for 16 h. Then it was cooled to room temperature, poured into ice cold water (25 ml) and extracted with ethyl acetate (3 x 25 ml). The combine organic extract was washed with water (3 x 30 mL) and brine (20 mL), dried over Na2SC>4 and evapourated under vacuum to yield crude product as thick liquid. The crude product was purified by triturating with ethyl acetate to obtained pure N-(4-(3-hydroxyoxetan-3-yl)phenyl)-l-(4-(trifluoromethyl)phenyl) piperidine-4-carboxamide (0.2 g, 58.4% Yield) as off white solid.
¾ NMR (DMSO-de) d : 1.66-1.76 (m, 2H), 1.86-1.89 (m, 2H), 2.56-2.63 (m, 1H), 2.85-2.91 (m, 2H), 3.93-3.97 (m, 2H), 4.66 (d, J = 6.4 Hz, 2H), 4.75 (d, J= 6.4 Hz, 2H), 6.27 (s, 1H), 7.08 (d, J = 8.8 Hz, 2H), 7.48-7.52 (m, 4H), 7.63 (d, J = 8.8 Hz, 2H). 9.97 (s, 1H).
ESI-MS: m/z 421.15 (M+H)+, 100%.
Example 4: N-(4-(3-hydroxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl) piperidine-l-carboxamide

To a solution of 3-(4-aminophenyl)oxetan-3-ol (100 mg, 0.605 mmol) in THF (3.0 ml), an other solution of triphosgene (59.3 mg, 0.200 mmol) in THF (1.0 ml) was added followed by addition of a solution of 4-(4-(trifluoromethyl)phenyl)piperidine (180 mg, 0.787 mmol) and diisopropylethylamine (0.317 ml, 1.816 mmol) in acetonitrile (3.00 ml) under nitrogen atmosphere at 0 °C. The reaction mixture was stirred at 27 °C for 12 hrs under nitrogen atmosphere. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (2 x 25 mL). The combined organic layers was washed with water (2 x 25 mL) and brine (50 mL), dried over sodium sulfate and evaporated on rotavapor under vacuum to yield crude product as colorless liquid. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 50% EtOAc in Hexane as an eluent to yield pure N-(4-(3-hydroxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl)piperidine-l -carboxamide (120mg, 42% yield) as off white solid.
¾ NMR (DMSO-d6) ό : 1.55-1.65 (m, 2H), 1.82-1.84 (m, 2H), 2.84-2.92 (m, 3H), 4.28-4.31 (m, 2H), 4.67 (d, J= 6.8 Hz, 2H), 4.72 (d, J = 6.8 Hz, 2H), 6.20 (s, 1H), 7.40 (d, J= 8.8 Hz, 2H), 7.43-7.53 (m, 4H), 7.67 (d, J= 8.4 Hz, 2H), 8.51 (s, 1H). ESI-MS: m/z 421 (M+H)+, 100%.
Example 5: N-(4-(3-methoxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl) piperidine-l-carboxamide

Step a: Preparation of 3-(4-bromophenyl)-3-methoxyoxetane.
To a suspension of NaH (27.2 mg, 0.568 mmol) in THF (1.0 ml) was added 3-(4-bromophenyl) oxetan-3-ol (100 mg, 0.437 mmol) in small portions under nitrogen atmosphere at 27 °C and stirred for 30 min. Iodomethane (0.033 ml, 0.524 mmol) was added drop wise and continued to stirr for further 2 hr. The reaction mixture was poured into ice cold water (20 mL) and extracted with ethyl acetate (2 x 15 mL). The combined organic layer was washed with water (2 x 15 mL) & brine (15 mL), dried over NaiSCL and evaporated on rotavapor under vacuum to yield 3-(4-bromophenyl)-3-methoxyoxetane (106 mg, 0.437 mmol, 100% yield) as yellow liquid.
XH NMR (CDCI3) S: 3.16 (s, 3H), 4.79 (d, J= 7.6 Hz, 2H), 4.93 (d, J= 7.2 Hz, 2H), 7.30 (d, J= 8.8 Hz, 2H), 7.54 (d, J= 8.4 Hz, 2H).
Step b: Preparation of 4-(3-methoxyoxetan-3-yl) aniline.
A solution of 3-(4-bromophenyl)-3-methoxyoxetane (200mg, 0.823 mmol) in saturated NH4OH solution (1.0 ml) was placed into microwave vial. Copper (II) oxide (65.4 mg, 0.823 mmol) was added at 27 °C. The reaction mixture was stirred under microwave radiation at 100 °C and 40 psi pressure for 1 hr. The reaction mixture was diluted with ethyl acetate (10 ml) and filtered through celite bed. The filtrate was dried over NaiSCE and evaporated under reduced pressure to obtain crude product as thick liquid. The crude product was used for next step without purification.
Step c: Preparation of N-(4-(3-methoxyoxetan-3-yl)phenyl)-4-(4- (trifluoromethyl)phenyl)piperidine-l -carboxamide.
The title product was systhesized from 3-(4-bromophenyl)-3-methoxyoxetane and 4-(4-(trifluoromethyl)phenyl)piperidine following the procedure described in example

Step a : Preparation of /cvV-butyl 4-(4-(trifluoromethyl)phenyl)piperazine-l-carboxylate.
To, a solution of l-bromo-4-(trifluoromethyl)benzene (5.0 g, 22.22 mmol) in toluene (4.0 ml), /er/-butyl piperazine- 1-carboxylate (6.21 g, 33.3 mmol), Pd2(dba)3 (1.017 g, 1.11 mmol), BINAP (1.384 g, 2.22 mmol) and potassium /er/-butoxide (7.48 g, 66.7 mmol) were added under nitrogen atmosphere at 27 °C. The reaction mixture was stirred under nitrogen atmosphere at 80 °C for 3 hrs. The reaction mixture was cooled to room temperature and was filtered through celite bed. The filtrate was evoparated under reduced pressure. The residue was purified by column chromatography using 100-200 mesh silica gel column and 5% EtOAc in Hexane as an eluent to yield fe/V-butyl 4-(4-(trifluoromethyl)phenyl)piperazine-l-carboxylate (3.0 g, 41 % yield) as white solid.
¾ NMR (DMSO-d6) 0: 1.42 (s, 9H), 3.25-3.28 (m, 4H), 3.44-3.47 (m, 4H), 7.07 (d, J= 8.8 Hz, 2H), 7.52 (d, J= 8.8 Hz, 2H).
Step b : Preparation of l-(4-(trifluoromethyl)phenyl)piperazine hydrochloride.
To a solution of fe/V-butyl 4-(4-(trifluoromethyl)phenyl)piperazine- 1-carboxylate (100 mg, 0.303 mmol) in 1,4-Dioxane (1.0 ml), HC1 in 1,4-dioxane (1.0 ml) was added and stirred at 27 °C for 12 hr. Solvent was removed from the reaction mixture under vacuum and the residue was triturated with diethyl ether (3 ml) to obtained 1-(4-(trifluoromethyl)phenyl) piperazine hydrochloride (80 mg, 99% yield) as off white solid.
¾ NMR (DMSO-d6) ό : 3.33 (br s, 4H), 3.54 (br s, 4H), 3.98 (br s, 1H), 7.14 (d, J =
8.8 Hz, 2H), 7.57 (d, J= 8.4 Hz, 2H).
Step c : Preparation of (4-(3 -hydroxy oxetan-3-yl)phenyl)(4-(4-(trifluorom ethyl) phenyl) piperazin-l-yl) methanone.
The title compound was prepared by coupling read on of l-(4-(trifluoromethyl)phenyl)piperazine hydrochloride (250mg, 0.825 mmol) and 4-(3-hydroxyoxetan-3-yl)benzoic acid (160 mg, 0.825 mmol) following the procedure described in step f of example 1 (60mg, 0.139 mmol, 17% yield, white solid)
¾ NMR (DMSO-de) S: 3.40 (br s, 2H), 3.60 (br s, 4H), 3.80 (br s, 2H), 4.70 (d, J =
6.8 Hz, 2H), 4.80 (d, J= 6.8 Hz, 2H), 6.47 (s, 1H), 7.08 (d, J = 8.8 Hz, 2H), 7.48-7.54 (m, 4H), 7.70 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z, 407 (M+H)+, 100%.
Example 7 : 3-(4-((4-(4-(trifluoromethyl)phenyl)piperazin-l-yl)sulfonyl)phenyl) oxetan-3-ol

Step a : Preparation of l-((4-bromophenyl)sulfonyl)-4-(4-(trifluoromethyl) phenyl) piperazine.
To a solution of 4-(4-(trifluoromethyl)phenyl)piperidine (500 mg, 2.181 mmol) in dichloromethane (5.0 ml), triethylamine (0.912 ml, 6.54 mmol) was added followed by drop wise addition of 4-bromobenzene-l-sulfonyl chloride (446 mg, 1.745 mmol) under nitrogen atmosphere at 0-10 °C over a period of 10 min. The reaction mixture was stirred under nitrogen atmosphere at 27 °C for lhr. The reaction mixture was poured into ice cold water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layers was washed with water (2 x 50 mL) & brine (50 mL), dried over NaiSCL and evaporated on rotavapor under vacuum to yield crude product as thick liquid. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 6% EtOAc in Hexane as an eluent to yield l-((4-bromophenyl) sulfonyl)-4-(4-(trifluorom ethyl )phenyl)piperidine (400 mg, 41% yield) as white solid.
H NMR (CDCI3) ό: 1.85-1.92 (m, 4H), 2.37-2.43 (m, 2H), 2.53 (br s, 1H), 3.96-3.99 (m, 2H), 4.28 (d, J= 7.6 Hz, 2H), 7.58 (d, J= 8.0 Hz, 2H), 7.67-7.74 (m, 4H).
Step b: Preparation of 3-(4-((4-(4-(trifluoromethyl) phenyl) piperidin-l-yl) sulfonyl) phenyl)oxetan-3 -ol .
A solution of l-((4-bromophenyl)sulfonyl)-4-(4-(trifluoromethyl)phenyl)piperidine (100 mg, 0.223 mmol) in THF (3.0 ml) was cooled to -78 °C and n-butyllithium (2.5M in hexane) (0.167 ml, 0.335 mmol) was added drop wise maintaining the temperature at -78 °C over a period of 15 min. The reaction mixture was stirred for further 15 min and 3-oxetanone (19.29 mg, 0.268 mmol) was added under nitrogen atmosphere at -78 °C and continued to stirr for 1 hr. The reaction mixture was poured into saturated solution of NH4CI (25 mL) and extracted with ethyl acetate (2 x 15 mL). The combined organic layers was washed with water (2 x 15 mL) & brine (20 mL), dried over NaiSCL and evaporated on rotavapor under vacuum. The residue was purified by column chromatography 230-400 mesh silica gel column and 15%
EtOAc in Hexane as an eluent to yield pure 3-(4-((4-(4-(trifluoromethyl) phenyl) piperidin-l-yl)sulfonyl)phenyl)oxetan-3-ol ( 50 mg, 31% Yield) as off white solid.
3.27 (m, 4H), 3.36-3.38 (m, 4H), 4.72 (d, J= 7.6 Hz, 2H), 5.06 (d, J = 7.6 Hz, 2H), 6.26 (s, 1H), 7.06 (d, J = 8.8 Hz, 2H), 7.49-7.53 (m, 3H), 7.58 (d, J= 7.6 Hz, 1H), 7.67-7.71 (m, 1H), 7.86-7.89 (m, 1H).
ESI-MS: m/z 443 (M+H)+, 50%.
Example 8: 3-(4-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)phenyl)oxetan-3-ol

Step a: Preparation of l-(4-bromophenyl)-4-(4-(trifluoromethyl)phenyl)piperidine.
To a solution of 4-(4-(trifluorom ethyl )phenyl)piperidine 4-methylbenzenesulfonate (0.5g, 1.246 mmol) in Toluene (10 ml), were added 1,4-dibromobenzene (1.469 g, 6.23 mmol) and potassium /t'/7-but oxide (0.419 g, 3.74 mmol) followed by addition of Pdi(dba)3 (0.114 g, 0.125 mmol) and BINAP (0.155 g, 0.249 mmol) under nitrogen atmosphere at 27 °C. The reaction mixture was stirred at 90 °C for 18 hr. The reaction mixture was diluted with ethyl acetate (20 ml) and filtered through celite bed. The filtrate was evaporated on rotavapour under reduced pressure to obtain crude product as an oil. The crude product was purified by column chromatography using 100-200 mesh silica gel and 10% EtOAc in Hexane as an eluent to yield pure l-(4-bromophenyl)-4-(4-(trifluorom ethyl )phenyl)piperidine (300mg, 0.781 mmol, 62.7 % yield) as off white solid.
¾ NMR (DMSO-£¾) S: 1.71-1.81 (m, 2H), 1.86-1.89 (m, 2H), 2.76-2.85 (m, 3H), 3.81-3.84 (m, 2H), 6.95 (d, J= 9.2 Hz, 2H), 7.35 (d, J= 9.2 Hz, 2H), 7.51 (d, J= 8.4 Hz, 2H), 7.67 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z, 384.26 & 386.15 (M+H)+, 100%.
Step b: Preparation of 3-(4-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)phenyl)oxetan-3-ol.
To a solution of l-(4-bromophenyl)-4-(4-(trifluoromethyl)phenyl)piperidine (220mg, 0.573 mmol) in THF (10 ml), n-BuLi (0.458 ml, 1.145 mmol) was added dropwise under nitrogen atmosphere at -78 °C over a period of 10 minute and the reaction mixture was stirred for further 15 min at the same temperature. A solution of oxetanone (83 mg, 1.145 mmol) in THF (0.5 ml) was added drop wise to reaction mixture at -78 °C and the reaction mixture was stirred for lhr. The reaction mixture was poured into saturated solution of aqueous NH4CI (25 mL) and extracted with ethyl acetate (2 x 20 mL). The combined organic phase was washed with water (2 x 20 mL) & brine (20 mL), dried over sodium sulphate and evaporated on rotavapor under vacuum to yield crude product as thick liquid. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 20% EtOAc in Hexane as an eluent to yield pure 3-(4-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)phenyl)oxetan-3-ol (lOOmg, 0.253 mmol, 44.3 % yield) as off white solid.
H NMR (DMSO-£¾) S: 1.77-1.91 (m, 4H), 2.67-2.81 (m, 3H), 3.84 (d, J= 12.4 Hz, 2H), 4.66 (d , J= 6.4 Hz, 2H), 4.71 (d , J= 6.8 Hz, 2H), 6.14 (s, 1H), 7.01 (d , J= 8.8 Hz, 2H), 7.43 (d, J= 6.8 Hz, 2H), 7.52 (d, J= 8.0 Hz, 2H), 7.67 (d, J= 8.0 Hz, 2H). ESI-MS: m/z, 378.13 (M+H)+, 100%.
Example 9: l-(4-(3-methoxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl) piperidine

To a suspension of NaH (25.4 mg, 0.530 mmol) in THF (3.0 ml), 3-(4-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)phenyl)oxetan-3-ol (lOOmg, 0.265 mmol) was added in small portions under nitrogen atmosphere at 27 °C and the reaction mixture was stirred for 15 minutes. Iodomethane (0.020 ml, 0.318 mmol) was added to the reaction mixture under nitrogen atmosphere and was continued to stir for 12hr. The reaction mixture was poured into ice cold water (10 mL) and extracted with ethyl acetate (2 x 10 mL). The combined organic layer was washed with water (2 x 15 mL) & brine (20 mL), dried over NaiSCL and evaporated on rotavapor under vacuum to yield crude product as thick liquid. The crude product was purified by column chromatography using 100-200 mesh silica gel column and 15% EtOAc in Hexane as an eluent to yield pure l-(4-(3-methoxyoxetan-3-yl) phenyl)-4-(4-(trifluoromethyl) phenyl) piperidine (102mg, 0.254 mmol, 96 % yield) as off white solid.
2.02 (m, 4H), 2.73-2.76 (m, 1H), 2.88 (t, J= 12.0 Hz, 2H), 3.13 (s, 3H), 3.89 (d, J= 12.4 Hz, 2H), 4.87 (d , J= 7.2 Hz, 2H), 4.91 (d, J= 7.2 Hz, 2H), 7.01 (d, J= 8.8 Hz, 2H), 7.35 (d, J= 8.8 Hz, 2H), 7.39 (d, J= 8.4 Hz, 2H), 7.60 (d, J= 8.0 Hz, 2H).
ESI-MS: m/z, 392.12 (M+H)+, 100%.
Example 10: (4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone

Step a : Preparation of 2-benzyl-l,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrol-5-yl trifluoromethane sulfonate.
To a solution of 2-benzylhexahydrocyclopenta[c]pyrrol-5(lH)-one (lOOmg, 0.464 mmol) in THF (5.0 mL), an other solution of lithium bis(trimethylsilyl)amide in THF (1.0 M, 0.6 mL) was added dropwise at -78 °C over a period of 15 min under nitrogen atmosphere and the mixture was continued to stir at -78 °C for 30 min. A solution of l,l,l-trifluoro-N-phenyl-N((trifluoromethyl)sulfonyl) methanesulfonamide (166 mg, 0.464 mmol) in THF (1.5 mL) was added dropwise to the reaction mixture and continued to stir for an additional 1 hr at -78 °C and was then allowed to stir at 28 °C for 2 h. The mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography using 0-50% Ethyl acetate in hexane gradient system as an eluent to give 2-benzyl-l,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrol-5-yl trifluoromethane sulfonate as a clear, viscous oil (lOOmg, 62% yield).
¾ NMR (CDCI3) d 2.35-2.37 (m, 2H), 2.78-2.80 (m, 4H), 3.60-3.64 (m, 2H), 5.56 (s, 1H), 7.3-7.4 (m, 5H).
ESI-MS: m/z 347.99 (M+H)+, 100%.
Step b : Preparation of 2-benzyl-5-(4-(trifluoromethyl)phenyl)-l,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrole.
To a mixture of 2-benzyl-l,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrol-5-yl trifluoromethanesulfonate (lOOmg, 0.263 mmol), 4-trifluoromethylphenylboronic acid (50m g, 0.263 mmol) and 2M aqueous solution of NaiCCL (2.5 mL) in DMF (5.0 mL) was added PdCl2(PPh )2 (2.15 mg, 2.63 pmol) under nitrogen atmosphere at 28 °C. The mixture was stirred at 80 °C for 3 hrs under nitrogen atmosphere. The reaction mixture was cooled to ambient temperature, diluted with water (50 mL) and extracted with ethyl acetate (3 c 20 mL). The combined organic extracts were washed with water (50 mL) & brine (50 mL), dried over Na2S0 and concentrated under reduced pressure. The residue was purified by flash column chromatography using 0-50% Ethyl acetate in hexanes as eluent to give 2-benzyl-5-(4-(trifluoromethyl)phenyl)-l,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrole, viscous oil (90 mg, 94% yield):
¾ NMR (CDCfi) d 2.35-2.37 (m, 2H), 2.57-2.60 (m, 1H), 2.82-2.85 (m, 2H), 2.95-2.98 (m, 2H), 3.6 (s, 2H), 6.18 (s, 1H), 7.2-7.25 (m, 1H), 7.27-7.30 (m, 4H), 7.33-7.57(m, 4H).
ESI-MS: m/z 344.14 (M+H)+, 100%.
Step c : Preparation of 5-(4-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrole. A solution of 2-benzyl-5-(4-(trifluoromethyl)phenyl)-l,2,3,3a,4,6a-hexahydrocyclopenta [c] pyrrole (90 mg, 0.262 mmol) in MeOH (20 ml) was added to a suspention of Pd/C (10%) (50 mg) in MeOH (2 mL). The reaction mixture was hydrogenated under 40 psi preuure of hydrogen gas using Parr Shaker apparatus at ambient temperature for 16 hrs. The mixture was filtered through Celite, washed with methanol and the filtrate was concentrated under reduced pressure to give 5-(4-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrole (65 mg, 97% yield) as a clear, viscous oil.
H NMR (CDCfi) d: 1.25-1.27 (m, 2H), 2.11-2.13 (m, 1H), 2.31-2.35 (m, 1H), 2.83-2.87 (m, 2H), 2.88-2.90 (m, 1H), 3.10-3.19 (m, 1H), 3.31-3.34 (m, 1H), 3.36-3.38 (m, 1H), 3.63-3.65 (m, 1H), 7.33 (d, J= 8.0 Hz, 2H), 7.56 (d, J= 8.0 Hz, 2H).
ESI-MS: m/z 256.13 (M+H)+, 100%.
Step d : Preparation of (4-(3 -hydroxy oxetan-3-yl)phenyl)(5 -(4- (trifluoromethyl)phenyl) hexahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone.
The title compound was prepared by coupling reacion of 5-(4-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrole (0.065g, 0.25mmol) and 4-(3-hydroxyoxetan-3-yl)benzoic acid (0.08g, 0.25mmol) according to the procedure mentioned in step f of example 1 (60 mg, 55% yieldO as white solid.
H NMR (CDCfi) ό: 1.25-1.27 (m, 2H), 2.11-2.13 (m, 1H), 2.31-2.35 (m, 1H), 2.83-2.87 (m, 2H), 2.88-2.90 (m, 1H), 3.10-3.19 (m, 1H), 3.31-3.34 (m, 1H), 3.36-3.38 (m, 1H), 3.63-3.65 (m, 1H), 3.75-3.78 (m, 1H), 4.85 (d, J= 7.6 Hz, 2H), 4.94 (d, J = 7.6 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.49-7.50 (m, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.64-7.66 (m, 1H).
ESI-MS: m/z 432.18 (M+H)+, 100%.
Example 11 : (4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo [3,4-c] pyrrol-2(lH)-yl)methanone

Step a: Preparation of 2-benzyl-5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c] pyrrole.
To a mixture of 2-benzyloctahydropyrrolo[3,4-c]pyrrole. (0.475g, 2.34 mmol), 1-bromo-4-(trifluoromethyl)benzene (0.634g, 2.82 mmol), (2,2 -bis(diphenylphosphino)-l,l'-binaphthyl) (0.146 g, 0.235 mmol), and sodium tert-butoxide (0.451 g, 4.70 mmol) in toluene (10 mL) was added Tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (0.251 g, 0.235 mmol) under nitrogen atmosphere at 28 °C. The mixture was stirred at 110 °C for 16 hrs. The reaction mixture was cooled to ambient temperature, filtered through celite bed and was washed with ethyl acetate. The combined filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography using 0-100% Ethyl acetate in hexane as eluent to give 2-benzyl-5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole (0.320 gm, 40% yield) as white solid.
¾ NMR (DMSO-de) d : 1.74-1.78 (m, 2H), 1.94-1.98 (m, 2H), 2.33 (s, 2H), 2.94-3.01 (m, 4H), 3.41-3.60 (m, 2H), 7.11 (d, =8.0 Hz, 2H), 7.45-7.47 (m, 4H), 7.70 (d, .7=8 0 Hz, 2H).
ESI-MS: m/z 347.17 [M+H]f 100%.
Step b : Preparation of 2-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c] pyrrole.
A solution of 2-benzyl-5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole (0.320g, 0.92 mmol) in methanol (15 ml) was added to a suspention of Pd/C (10%) (50 mg) in methanol (5 ml). A solution of ammonium formate ( 0.582 g, 9.2 mmol) in 0.6ml of water was added dropwise to the reaction mixture with stirring at 28 °C. The mixture was refluxed for 3 hours. Reaction mixture was cooled ambient temperature, filtered through celite bed and washed with methanol. The combined filterate was concentrated in vacuum and the residue was taken up into water, adjusted to pH 9-10 with saturated sodium bicarbonate solution. The resulting solid was filtered, washed with water and dried over P205 under vacuum to yield 2-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole (220 mg, 84% yield ) as off white solid.
¾ NMR (DMSO-de) d 2.68 (br s, 1H), 3.04-3.08 (m, 4H), 3.28-3.32 (m, 1H), 3.65-3.69 (m, 4H), 6.64 (d, J= 6.8Hz, 2H), 7.44 (d, J= 8.8Hz, 2H).
ESI-MS: m/z 257.12 [M+H]f 100%.
Step c : Preparation of (4-(3 -hydroxy oxetan-3-yl)phenyl)(5-(4-(trifluorom ethyl) phenyl)hexahydro pyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone.
The title compound was prepared from 2-(4-(trifluoromethyl)phenyl) octahydropyrrolo[3,4-c]pyrrole (200 mg, 0.78 mmol) and 4-(3 -hydroxy ox etan-3-yl)benzoic acid (151 mg, 0.78 mmol) following the procdure described in step-f, Example 1 to yield the product (215 mg, 64% yield) as off white solid.
¾ NMR (DMSO-de) d : 2.50-2.51 (m, 2H), 3.04-3.09 (m, 1H), 3.34-3.39 (m, 2H), 3.45-3.47 (m, 2H), 3.50-3.51 (m, 1H), 3.75-3.76 (m, 1H), 3.80-3.85 (m, 1H), 4.67 (d, J= 8.0 Hz, 2H), 4.78 (d, J= 8.0 Hz, 2H), 6.45 (s, 1H), 6.62 (d, J= 8.4 Hz, 2H), 7.45 (d, J= 8.0 Hz, 2H), 7.55 (d, J= 8.0 Hz, 2H), 7.64 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z 433.10 (M+H)+, 100%.
Example 12: (4-(3-(2-hydroxyethoxy)oxetan-3-yl)phenyl)(5-(4-(trifluoromethyl) phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone

Step a: Preparation of Ethyl 2-((3-(4-(5-(4-(trifluoromethyl)phenyl) octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)phenyl)oxetan-3-yl)oxy)acetate.
The title compound was prepared from (4-(3 -hydroxy ox etan-3-yl)phenyl)(5 -(4-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone (1 gm, 2.31 mmol) and ethyl bromoacetate (0.309 ml, 2.77 mmol) using the procdure described in example 2 to yield the product (1 gm, 83% yield) as off white solid. The product was directly used for the next step without further purification.
Step b: Preparation of (4-(3-(2-hydroxyethoxy)oxetan-3-yl)phenyl)(5-(4- (trifluoromethyl)phenyl)hexahydro pyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone.
To an ice cold soltuin of ethyl 2-((3-(4-(5-(4-(trifluoromethyl)phenyl) octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)phenyl)oxetan-3-yl)oxy)acetate (900 mg, 1.78 mmol) in THF (20 ml), lithiumaluminiumhydride (81 mg, 2.14 mmol) wad added in small portions over a period of 10 min under niotrogen atmosphere at 0 °C and stirred for further 10 min. Excess LiAlH was quenched by addition of saturated sodium sulfate soltion untill white solid seperated out. The solid was filtered and washed with ethyl acetate (50 ml). The combined filtrate was dried over sodium sulfate and evaporated on rotavapor under vacuum to yield the product (770 mg, 91% yield) as off white solid.

3.20 (m, 3H), 3.32-3.80 (m, 4H), 3.40-3.42 (m, 1H), 3.71-3.85 (m, 5H), 4.00-4.02 (m, 1H), 4.84 (d, J= 7.2 Hz, 2H), 4.97 (d, J= 7.2 Hz, 2H), 6.56 (d, J= 8.8 Hz, 2H), 7.47 (d, J= 8.4 Hz, 2H), 7.51 (d , J= 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H).
ESI-MS: m/z 477.23 (M+H)+, 100%.
Example 13 : 2-((3-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo [3,4-c] pyrrole-2-carbonyl)phenyl)oxetan-3-yl)oxy)acetic acid

To a solution of l-((4-bromophenyl)sulfonyl)-4-(4-(trifluoromethyl)phenyl) piperazine (product of step a, example 6) (lOOmg, 0.193 mmol) in THF (2.0 ml) and MeOH (0.6 ml), a solution of lithium hydroxide (23 mg, 0.96 mmol) in water (0.6 ml) was added and the reaction mixture was stirred for 12 hrs at 28 °C. Solvent was evaporated under vacuum, the residue was diluted with water (20 ml) and neutralized by adding dilute HC1. The solid separated was filtered, washed with water and dried over P205 under vacuum to yield title product (85 mg. 89% Yield) as off white solid. ¾ NMR (DMSO-de) d : 3.03-3.16 (m, 2H), 3.33-3.36 (m, 5H), 3.43-3.45 (m, 2H), 3.48-3.50 (m, 2H), 3.80-3.81 (m, 1H), 3.83-4.0 (m, 1H), 4.66 (d, J = 7.2 Hz, 2H), 4.88 (d, J= 7.2 Hz, 2H), 6.61 (d, J= 8.8 Hz, 2H), 7.45 (d, J= 8.8 Hz, 2H), 7.57 (d, J = 8.4 Hz, 4H).
ESI-MS: m/z 491.16 (M+H)+, 100%.
Example 14: (4-(3-fluoro-5-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone

The title compound was synthesized according to the procedure given in Example 1 by using 3-Bromo-5-fluorobenzotrifluoride as a starting material.
¾ NMR (DMSO-d6) d : 1.57-1.85 (m, 4H), 2.89-3.10 (m, 1H), 3.21-3.23 (s, 2H), 3.71 (s, 1H), 4.52-4.71 (m, 3H), 4.79 (d, J= 6.8 Hz, 2H), 6.45 (s, OH), 7.47 (d, J = 7.2 Hz, 2H), 7.52-7.69 (m, 5H).
ESI-MS: m/z, 424.15 (M+H)+, 100%.
Example 15: (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(3-(4-methyl-lH-imidazol-l-yl)-5-(trifluoromethyl)phenyl)piperidin-l-yl)methanone

To a solution of 4-Methylimidazole (65.9 mg, 0.803 mmol) in N-Methyl-2-pyrrolidinone (1.0 ml), sodium hydride (57.8 mg, 1.205 mmol) was added and the reaction mixture was stirred at 30 °C for 30 min. To this (4-(3-fluoro-5-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone (170 mg, 0.402 mmol) (Example 14) was added in small portions under nitrogen atmosphere. The reaction mixture was stirred at 30 °C for 20 hours and then was further stirred at 80 °C for additional 5 hours. The reaction mixture was poured into water (25 mL) and extracted with ethyl acetate (2 x 25 mL). The combined organic layer was washed with water (3 x 15 mL) & brine (15 mL), dried over sodium sulfate and evaporated on rotavapour under vacuum to yield crude product as thick liquid. The crude product was purified by column chromatography using 230-400 mesh silica gel column and 1-5% methanol in chloroform as eluent to yield pure (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(3-(4-methyl-lH-imidazol-l-yl)-5-(trifluoromethyl)phenyl)piperidin-l-yl)methanone (60 mg, 28.6 % yield) as white solid
H NMR (DMSO-de) S: 1.47-1.95 (m, 4H), 2.19 (s, 3H), 2.67 (s, 2H), 2.81-3.20 (m, 1H), 3.47-3.51 (m, 1H), 4.52-4.60 (m, 1H), 4.70 (d, J= 5.6 Hz, 2H), 4.78 (d, J= 6.0 Hz, 2H), 6.43 (s, OH), 7.16 (s, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.66-7.75 (m, 4H), 7.84-7.90 (m, 2H).
ESI-MS: m/z, 486.26 (M+H)+, 100%.
Example 16: 3-(4-(3-(3-fluoro-4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5-yl)phenyl) oxetan-3-ol

Step a: Preparation of (Z)-3-fluoro-N'-((4-(3 -hydroxy oxetan-3-yl )benzoyl)oxy)-4-(trifluoromethyl)benzimidamide.
To a solution of 4-(3-hydroxyoxetan-3-yl)benzoic acid (219 mg, 1.125 mmol) and HBTU (469 mg, 1.238 mmol) in N,N-dimethylformamide (2.0 ml), Diisopropylethylamine (0.590 ml, 3.38 mmol) was added and the reaction mixture was stirred at 30°C for 5 min. 3-Fluoro-N-hydroxy-4-(trifluoromethyl)benzimidamide (250 mg, 1.125 mmol) was added and the reaction
mixture was stirred overnight at 30 °C. The reaction mixture was poured into water (50 mL). Solid separated was filtered through Buchner funnel, washed with water and dried over P2O5 under vacuum to yield (Z)-3-fluoro-N'-((4-(3 -hydroxy ox etan-3-yl)benzoyl)oxy)-4-(trifluoromethyl)benzimidamide (400 mg, 89 % yield) as Pale brown solid which was directly used in the next step without purification.
Step b: Preparation of 3-(4-(3-(3-fluoro-4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5 -yl)phenyl)oxetan-3 -ol .
A solution of (Z)-3-fluoro-N'-((4-(3-hydroxyoxetan-3-yl)benzoyl)oxy)-4-(trifluoromethyl) benzimidamide (400 mg, 1.004 mmol) in Dimethylformamide (5.0 ml) was heated under nitrogen atmosphere at 120 °C for 5 hours. Solvent was evaporated from the reaction mixture under reduced pressure, residue was dissolved in ethyl acetate (25 ml) and washed with IN HC1 (10 ml), NaHC03 (10 ml) & brine ( 20 ml). The organic phase was dried over sodium sulfate and evaporated under reduced pressure to yield crude product as tick liquid. The crude product was purified by column chromatography using 230-400 mesh silica gel column and 25% Ethyl acetate in hexane as eluent to yield pure 3-(4-(3-(3-fluoro-4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5-yl)phenyl)oxetan-3-ol (200 mg, 51.8 % yield) as white solid.
¾ NMR (CDCI3) ό : 4.71 (d, J = 6.8 Hz, 2H), 4.85 (d, J = 6.8 Hz, 2H), 6.67 (s, -OH), 7.92 (d, J= 8.4 Hz, 2H), 8.03-8.07 (m, 1H), 8.13 (d, J= 9.6 Hz, 2H), 8.25 (d, J = 8.4 Hz, 2H).
ESI-MS: m/z, 381.12 (M+H)+, 100%.
Example 17 : 3-(4-((l-(4-(trifluoromethyl)phenyl)piperidin-4-yl)oxy)phenyl) oxetan-3-ol

Step a: Preparation of l-(4-(trifluoromethyl)phenyl)piperidin-4-ol.
To a solution of l-bromo-4-(trifluoromethyl)benzene (5.56 g, 24.72 mmol) in
Toluene (20 ml), piperidin-4-ol (3 g, 29.7 mmol) was added followed by addition of sodium /ert-butoxide (3.56 g, 37.10 mmol), BINAP (0.462 g, 0.741 mmol) &
Pd2(dba)3 (0.226 g, 0.247 mmol) under nitrogen atmosphere at rt. The reaction mixture was stirred under nitrogen atmosphere at 120 C for 16 hrs. After completion of reaction, reaction mixture was cooled to ambient temperature and filtered through celite bed. The filtrate was diluted with ethyl acetate (40 mL) and water (40 mL). Organic layer was seperated and aqeous layer was extracted with ethyl acetate (2 x 20 mL). The combined organic layer was washed with water (2 x 60 mL) & brine (60 mL), dried over Na2S04 and evapourated on rotavapor under vacuum to yield crude product as an oil. The crude product was purified by column chromatography usingl 00-200 mesh silica gel column and 20 % Ethyl acetate in n-hexane as eluent to obtained l-(4-(trifluoromethyl)phenyl)piperidin-4-ol (3.9 g, 64% yield) as thick liquid.
¾ NMR (CDCI3) ό : 1.54 (s, 1H), 1.64-1.72 (m, 2H), 1.99-2.05 (m, 2H), 3.03-3.09 (m, 2H), 3.65-3.71 (m, 2H), 3.90-3.96 (m, 1H), 6.95 (d, J= 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H).
ESI-MS: m/z 246.1 (M+H)+, 100%.
Step b: Preparation of 4-(4-bromophenoxy)-l-(4-(trifluoromethyl)phenyl)piperidine.
To a suspention of sodium hydride (0.245 g, 5.10 mmol) in DMF (4 ml), a solution of l-(4-(trifluoromethyl)phenyl)piperidin-4-ol (0.5 g, 2.039 mmol) in DMF (0.5 ml) was added dropwise at 0-10 °C over a period of 10 min and reaction mixture was stirred for 30 min. l-bromo-4-fluorobenzene (0.428 g, 2.447 mmol) was added to the reaction mixture and stirred at 120 °C for 8 hrs. The reaction mixture was poured into ice cold water (25 mL) and precipitated solid was collected by filtration. Then it was washed with hexane and dried over P2O5 overnight to obtain 4-(4-bromophenoxy)-l-(4-(trifluoromethyl)phenyl)piperidine (0.648 g, 79% yield) as off white solid.

1.97 (m, 2H), 2.06-2.12 (m, 2H), 3.23-3.29 (m, 2H), 3.56-3.62 (m, 2H), 4.47-4.52 (m, 1H), 6.83 (d, J= 8.8 Hz, 2H), 6.97 (d, J= 8.8 Hz, 2H), 7.40 (d, J= 8.4 Hz, 2H), 7.51 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z 400.2 (M)+, 100%.
Step c: Preparation of 3-(4-((l-(4-(trifluoromethyl)phenyl)piperidin-4-yl)oxy) phenyl)oxetan-3 -ol .
A solution of 4-(4-bromophenoxy)-l-(4-(trifluoromethyl)phenyl)piperidine (0.640 g, 1.599 mmol) in THF (8 ml) was cooled to -78 °C and n-butyllithium (2.5M in hexane) (1.599 ml, 4.00 mmol) was added drop wise maintaining the temperature at -78 °C over a period of 15 min. The reaction mixture was stirred further for 15 min and a solution of oxetan-3-one (0.173 g, 2.399 mmol) in THF (1 ml) was added under nitrogen atmosphere at -78 °C. The reaction mixture was stirred at -78 °C for 3 hr. The reaction mixture was poured into saturated NH C1 solution (25 mL) and extracted with ethyl acetate (2 x 20 mL). The combined organic layers was washed with water (2 x 15 mL) & brine (20 mL), dried over NaiSCL and evaporated on rotavapor under vacuum. The residue was purified by column chromatography using 100-200 mesh silica gel column and 20% Ethyl acetate in Hexane as eluent to yield 3-(4-((l-(4-(trifluoromethyl)phenyl)piperidin-4-yl)oxy)phenyl)oxetan-3-ol (127 mg, 20% Yield) as off white solid.
H NMR (CDCI3) ό : 1.92-2.00 (m, 2H), 2.06-2.15 (m, 2H), 2.75 (brs, 1H), 3.25-3.31 (m, 2H), 3.58-3.64 (m, 2H), 4.54-4.59 (m, 1H), 4.91-4.94 (m, 4H), 6.96-7.01 (m, 4H), 7.49-7.54 (m, 4H).
ESI-MS: m/z, 394.30 (M+H)+, 100%.
Example 18: (4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)methanone

Step a: Preparation of /er/-butyl 2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate.
To a stirred solution of te/V-butyl 2-bromo-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate (0.5 g, 1.571 mmol) in DMF (10 mL), Dichlorobis(triphenylphosphine)-palladium(II) (0.110 g, 0.157 mmol) was added and the mixture was heated at 90 °C for 1 hour. (4-(Trifluoromethyl)phenyl)boronic acid (0.298 g, 1.571 mmol) was added and the reaction mixture was further stirred for 30 min at the same temperature. Then a solution of potassium bicarbonate (0.944 g, 9.43 mmol) in water (4.00 mL) was added and stirring was continued for 3 h at 90 °C. The reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (2 x 15 mL). The combined organic extract was washed with water (30 mL) & brine (30 mL),
dried over Na2S0 and evaporated on rotavapor under vacuum. The residue was purified by column chromatography using 100-200 mesh silica gel column and 10% Ethyl acetate in Hexane as eluent to yield tert-butyl 2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate (390 mg, 64.7% Yield) as off white solid.
XH NMR (CDCI3) ό: 1.52 (s, 9H), 2.89 (brs, 2H), 3.77 (brs, 2H), 4.53 (brs, 2H), 7.10 (s, 1H), 7.61-7.66 (m, 4H).
Step b: Preparation of 2-(4-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrothieno[3,2-cjpyridine hydrochloride.
The title product was synthesized form /er/-butyl 2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate following the procedure discribed in step b of example 6, (311 mg, 91.0% Yield).
¾ NMR (DMSO-i¾) d: 3.09 (t, J = 6.0 Hz, 2H), 3.44 (t, J = 6.0 Hz, 2H), 4.28 (s, 2H), 7.51 (s, 1H), 7.78 (d, J= 8.4 Hz, 2H), 7.82 (d, J= 8.4 Hz, 2H), 9.36 (brs, 2H) .
Step c: Preparation of (4-(3 -hydroxy oxetan-3-yl )phenyl)(2-(4- (trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)methanone.
The title product was synthesized form 2-(4-(trifluoromethyl)phenyl)-4, 5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride and 4-(3 -hydroxy ox etan-3-yl)benzoic acid using the procedure discribed in step f of Example 1, (110 mg, 60.4% Yield)
XH NMR (DMSO-i¾) d: 2.93 (brs, 2H), 3.65 (brs, 1H), 3.94 (brs, 1H), 4.55 (brs, 1H), 4.71 (d, J = 6.8 Hz, 2H), 4.81 (d, J = 6.8 Hz, 3H), 6.41 (s, 1H), 7.50-7.56 (m, 3H), 7.70-7.81 (m, 6H).
ESI-MS: m/z, 460.08 (M+H)+, 30%.
Example 19: (l-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone

Step a: Preparation of tert- butyl l-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate.
To a stirred solution of tert- butyl l-benzyl-3-bromo-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate (1.5 g, 3.97 mmol) in DMF (30 mL), dichlorobis(triphenylphosphine)-palladium(II) (0.278 g, 0.397 mmol) was added and the mixture was heated to 90 °C for an hour. (4-(trifluoromethyl)phenyl)boronic acid (0.828 g, 4.36 mmol) was added and the reaction mixture was further stirred for 30 min. Then a solution of potassium bicarbonate (2.382 g, 23.79 mmol) in Water (12 mL) was added and stirring was continued for 3 h at 90 °C. The reaction mixture was diluted with water (40 mL) and extracted with ethyl acetate (2 c 30 mL). The combined organic extracts were washed with water (50 mL) & brine (50 mL), dried over Na2S04 and evaporated on rotavapor under vacuum. The residue was purified by column chromatography using 100-200 silica gel column and 8% ethyl acetate in hexane as eluent to yield tert-butyl l-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate (1.56 g, 89% Yield) as thick gum. H NMR (CDCf) d: 1.53 (d, J= 8.0 Hz, 9H), 4.48-4.60 (m, 4H), 5.32-5.37 (m, 2H), 7.08-7.09 (m, 2H), 7.27-7.35 (m, 3H), 7.43 (d, J= 7.6 Hz, 2H) 7.67-7.71 (m, 2H).
ESI-MS: m/z, 444.14 (M+H)+, 100%.
Step b: Preparation of l-benzyl-3-(4-(trifluoromethyl)phenyl)-l,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole 2,2,2-trifluoroacetate.
Trifluoroacetic acid (0.174 mL, 2.255 mmol) was added to a solution of /er/-butyl 1-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate (0.1 g, 0.225 mmol) in dicholoromethane (30 ml) under nitrogen atmosphere at ambient temperature and stirred for 2 hr. Solvent was evaporated on rotavapor under vacuum and the residue was diluted with diisopropylether (5 ml) and stirred for 30 min to obtain pure l-benzyl-3-(4-(trifluoromethyl)phenyl)-l, 4,5,6-tetrahydropyrrolo[3,4-c]pyrazole 2,2,2-trifluoroacetate (102 mg, 99% Yield) as thick liquid.
ESI-MS: m/z, 344.10 (M+H)+, 100%.
Step c: Preparation of (l-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone. The title product was synthesized form 1 -benzyl-3 -(4-(trifluoromethyl)phenyl)-l,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole 2,2,2-trifluoroacetate and 4-(3-hydroxyoxetan-3-yl)benzoic acid using the procedure discribed in step f of Example 1, (55 mg, 46.3% Yield)
¾ NMR (DMSO-i¾) ό : 4.66-4.72 (m, 5H), 4.78-4.81 (m, 3H), 5.45 (d, J= 7.6 Hz, 2H), 6.47 (d, J= 10.4 Hz, 1H), 7.01-7.04 (m, 2H), 7.24-7.29 (m, 3H), 7.62-7.79 (m 7H), 7.85 (d, J= 8.0 Hz, 1H).
ESI-MS: m/z, 520.13 (M+H)+, 100%.
Example 20: (4-(3-hydroxyoxetan-3-yl)phenyl)(l-methyl-3-(4-(trifluoromethyl) phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl)methanone
Step a: Preparation
3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate.
A solution of tert- butyl l-benzyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate (0.8 g, 1.804 mmol) in EtOH (15 ml) was added to a suspention of Pd(OH)2 (20%) (0.6 g, 0.854 mmol) in EtOH (10 ml) and the reaction mixture was hydrogenated in Paar hydrogenation apparatus under 50 psi hydrogen pressure at ambient temperature for 24 hrs. The reaction mixture was filtered through celite bed and the filtrate was evoparated on rotavapour under reduced pressure to obtained /cvV-butyl 3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate (100 mg, 15.69% yield) as sticky solid which was directly used for the next step without purification.
Step b: Preparation of /cvV-butyl l-methyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate and /er/-butyl 2-methyl-3-(4-(trifluoromethyl)phenyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate.
To a suspention of NaH (0.019 g, 0.425 mmol) in THF (2 ml), a solution of tert- butyl 3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate (0.1 g, 0.283 mmol) in THF (2 ml) was added dropwise at 0-10 °C followed by addition of iodomethane (0.027 ml, 0.425 mmol) and the reaction mixuture was stirred at 55 °C for 16 hrs. The reaction mixture was poured into ice cold water (10 mL) and extracted with ethyl acetate (2 x 10 mL). The combined organic layer was washed with water (2 x 15 mL) & brine (15 mL), dried over NaiSCL and evaporated under vacuum to obtain mixture of /cvV-butyl 1 -methyl-3 -(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(lH)-carboxylate and /ert-butyl 2-methyl-3-(4-(trifluoromethyl)phenyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate (100 mg, 98% yield) as thick liquid which was directly used for the next step without purification.
Step c: Preparation of l-methyl-3-(4-(trifluoromethyl)phenyl)-l,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole hydrochloride and 2-methyl-3-(4-(trifluorom ethyl) phenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole hydrochloride.
HC1 in 1,4-dioxane (3 ml) was added to a solution of mixture of products of step b (0.230 g, 0.626 mmol) in dichloromethane (3 ml) under nitrogen atmosphere at 27 °C. The reaction mixture was stirred at ambient temperarure for 3 hrs. Solvent was removed under vacuum and the residue was triturated in diethylether (4 ml) to obtained mixture of l-methyl-3-(4-(trifluoromethyl)phenyl)-l,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole hydrochloride and 2-methyl-3-(4-(trifluoromethyl)phenyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole hydrochloride (190 mg, 100% Yield) as off white solid.
ESI-MS: m/z, 268.10 (M+H)+, 100%.
Step d: Preparation of (4-(3-hydroxyoxetan-3-yl)phenyl)(l-methyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl)methanone.
To a solution of product of step c (0.180 g, 0.593 mmol) in DMF (3 ml), 4-(3-hydroxyoxetan-3-yl)benzoic acid (0.127 g, 0.652 mmol) and HBTU (0.462 g, 0.889 mmol) was added followed by addition of DIPEA (0.311 ml, 1.778 mmol) under nitrogen atmosphere at 27 °C. The reaction mixture was stirred under nitrogen atmosphere for 16 hrs. The reaction mixture was poured into ice cold water (15 mL) and extracted by ethyl acetate (3 x 10 mL). The combined organic layer was washed with water (3 x 25 mL) & brine (25 mL), dried over NaiSCL and evaporated on rotavapor under vacuum to yield crude product as thick liquid. The crude product was purified by preparative HPLC to yield (4-(3 -hydroxy oxetan-3 -yl)phenyl)(l-methyl-3-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl)methanone (30 mg, 10.88%) as off white solid.
¾ NMR (DMSO-i¾) ό : 3.93 (s, 3H), 4.68-4.72 (m, 6H), 4.77-4.82 (m, 2H), 6.65 (brs, 1H), 7.62-7.75 (m, 6H), 7.81-7.91 (m, 2H).
ESI-MS: m/z, 444.17 (M+H)+, 100%.
Example 21 : (4-(3-hydroxyoxetan-3-yl)phenyl)(2-methyl-3-(4-(trifluoromethyl) phenyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)methanone

The title compound is isolated during preparative HPLC of mixture obtained in step d of Example 20 as off white solid (32 mg, 12 % yield).
¾ NMR (DMSO-i¾) ό : 3.78-3.90 (m, 3H), 4.71-4.74 (m, 3H), 4.81-4.83 (m, 4H), 4.89 (s, 1H), 6.50-6.5 l(m, 1H), 7.65-7.74 (m, 6H), 7.78 (d, J= 8.4 Hz, 1H), 7.88 (d, J= 8.0 Hz, 1H).
ESI-MS: m/z, 444.17 (M+H)+, 100%.
The following examples were prepared following the general procedures given in the Examples 1-21 with suitable modifications, alterations and other process variations which are within the scope of a person skilled in the art
Example 22: (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethoxy)phenyl) piperidin-l-yl)methanone

¾ NMR (DMSO-de) d : 1.58-1.85 (m, 4H), 2.85-2.91 (m, 2H), 3.10-3.16 (m, 1H), 3.66-3.74 (m, 1H), 4.64-4.67 (m, 1H),4.70 (d , J= 6.8 Hz, 2H), 4.79 (d, J= 6.8 Hz, 2H), 6.43 (s, 1H), 7.30 (d , J= 8.0 Hz, 2H), 7.43 (d, J= 8.8 Hz, 2H), 7.47 (d, J= 8.0 Hz, 2H), 7.68 (d, J= 8.8 Hz, 2H).
ESI-MS: m/z 422.14 (M+H)+, 40%.
Example 23: (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(p-tolyl)piperidin-l-yl) methanone

¾ NMR (DMSO-d6) d : 1.54-1.82 (m, 4H), 2.26 (s, 3H), 2.73 - 2.89 (m, 2H), 3.14 (brs, 1H), 3.69 (bs, 1H), 4.63 (brs, 1H), 4.70 (d, J= 6.8 Hz, 2H), 4.79 (d, J= 6.4 Hz, 2H), 6.43 (s, 1H), 7.10-7.17 (m, 4H), 7.46 ( d, J= 8.0 Hz, 2H), 7.68 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z, 452.17 (M+H)+, 100%.
Example 24 : (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(3-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

¾ NMR (DMSO-de) S: 1.64-1.87 (m, 4H), 2.87 - 2.99 (m, 2H), 3.16 (brs, 1H), 3.71 (brs, 1H), 4.69 - 4.71 (m, 3H), 4.79 (d , J= 6.4 Hz, 2H), 6.43 (s, 1H), 7.49 (d , J= 8.4 Hz, 2H), 7.53-7.69 (m, 6H).
ESI-MS: m/z, 406.13 (M+H)+, 100%.
Example 25: (3-(3-hydroxyoxetan-3-yl)phenyl)(4-(p-tolyl)piperidin-l-yl) methanone

¾ NMR (DMSO-de) d: 1.58-1.83 (m, 4H), 2.26 (s, 3H), 2.74 - 2.89 (m, 2H), 3.15 (brs, 1H), 3.68 (bs, 1H), 4.64 - 4.68 (m, 3H), 4.79 (d, J= 6.4 Hz, 2H), 6.44 (s, 1H), 7.09-7.17 (m, 4H), 7.35-7.38 (m, 1H), 7.48 (d, J= 7.6 Hz, 1H), 7.70 (s, 1H), 7.95 (s, 1H).
ESI-MS: m/z, 352.17 (M+H)+, 100%.
Example 26: (4-(3-chloro-4-methoxyphenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone

¾ NMR (DMSO-d6) ό : 1.54-1.81 (m, 4H), 2.74 - 2.80 (m, 2H), 3.15 (brs, 1H), 3.64 (brs, 1H), 3.82 (s, 3H), 4.59-4.62 (m , 1H), 4.69 (d, J= 6.8 Hz, 2H), 4.79 (d , J= 6.8 Hz, 2H), 6.44 (s, 1H), 7.07 (d, J= 8.4 Hz, 1H), 7.22 (dd, J= 8.4 & 2.0 Hz, 1H), 7.35 (d, J= 2.0 Hz, 1H), 7.47 (dd, J= 6.8 & 2.0 Hz, 2H), 7.68 (dd, J= 6.4 & 1.6 Hz, 2H). ESI-MS: m/z, 402.13 (M+H)+, 100%.
Example 27 : (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-methoxyphenyl)piperidin-l-yl)methanone

¾ NMR (DMSO-de) ό : 1.56-1.82 (m, 4H), 2.67 - 2.89 (m, 2H), 3.14 (brs, 1H), 3.72 (s, 4H), 4.62-4.64 (m, 1H), 4.69 (d, J= 6.4 Hz, 2H), 4.79 (d, J= 6.4 Hz, 2H), 6.43 (s, 1H), 7.85 (d, J= 8.4 Hz, 2H), 7.19 (d , J= 8.4, 2H), 7.46 (d , J= 8.0 Hz, 2H), 7.67 (d, J= 8.0 Hz, 2H).
ESI-MS: m/z, 338.17 (M+H)+, 100%.
Example 28 : (4-(3-fluoro-4-methoxyphenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone

H NMR (DMSO-d6) ό: 1.60-1.83 (m, 4H), 2.77 bs, 2H), 3.11-3.14 (brs, 1H), 3.73 (s, 1H), 3.80 (s, 3H), 4.70 (bs, 3H), 4.79 (s, 2H), 6.43 (s, 1H), 7.15-7.35 (m, 3H), 7.47 (s, 2H), 7.67 (s, 2H).
ESI-MS: m/z, 386.17 (M+H)+, 100%.
Example 29 : (4-(3-chloro-4-methylphenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone

¾ NMR (DMSO-de) d: 1.65-2.06 (m, 4H), 2.44 (s, 3H), 2.65-2.90 (m, 2H), 3.14 (brs, 1H), 3.87 (s, 1H), 3.82-3.95 (m, 5H), 7.02 (d, J= 8.0 Hz, 1H), 7.12-7.28 (m, 2H), 7.44 (d, J= 9.6 Hz, 2H), 7.64 (d, J= 8.0 Hz, 2H).
ESI-MS: m/z, 386.14 (M+H)+, 100%.
Example 30 : (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(3-methoxy-4-(trifluoromethyl) phenyl)piperidin-l-yl)methanone

H NMR (DMSO-d6) S: 1.68-1.95 (m, 4H), 2.80-3.00 (brs, 2H), 3.25 (brs, 1H), 3.81 (s, 1H), 3.92 (s, 3H), 4.69-4.71 (m, 3H), 4.79 (d , J= 6.8 Hz, 2H), 6.44 (s, 1H), 7.32 (t, J= 7.60 Hz, 1H), 7.48-7.54 (m, 3H), 7.68 (d, J= 8.4 Hz, 2H), 7.76 (d, J= 7.2 Hz, 1H).
ESI-MS: m/z, 336.12 (M+H)+, 100%.
Example 31 : (4-(3-fluoro-4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone

^NMR (CDCI3) ό : 1.76-2.00 (m, 4H), 2.90 (brs, 1H), 3.21-3.32 (m, 1H), 3.90 (brs, 1H), 4.14 (brs, 1H), 4.79-4.94 (m, 5H), 7.13-7.50 (m, 5H), 7.62 (d, J= 6.8 Hz, 2H). ESI-MS: m/z, 424.10 (M+H)+, 100%.
Example 32: (4-(3-chloro-4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone

H NMR (DMSO-d6) ό: 1.53-1.86 (m, 4H), 2.85 (brs, 1H), 2.96 (brs, 1H), 3.15-3.25 (m, 1H), 3.71 (brs, 1H), 4.61-4.80 (m, 3H), 4.90 (d, J= 13.2 Hz, 2H), 6.43 (s, 1H), 7.48-7.56 (m, 3H), 7.67-7.80 (m, 3H), 7.88 (d, J= 9.6 Hz, 1H).
ESI-MS: m/z, 440.07 (M+H)+, 100%.
Example 33 : (4-(3-hydroxyoxetan-3-yl)phenyl)(4-(2-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

^NMR (CDCI3) d : 1.64-2.06 (m, 4H), 2.90 (brs, 1H), 3.21-3.27 (m, 2H), 3.91 (brs, 1H), 4.84 (d, J = 7.2 Hz, 2H), 4.87-4.96 (m, 3H), 7.29-7.38 (m, 1H), 7.43-7.67 (m, 7H).
ESI-MS: m/z, 406.20 (M+H)+, 100%.
Example 34: (4-(3-hydroxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

¾ NMR (DMSO-de) ό : 1.61-1.91 (m, 4H), 2.92-2.97 (m, 2H), 3.17 (brs, 1H), 3.71 (brs, 1H), 4.67-4.71 (m, 3H), 4.80 (d, J= 6.4 Hz, 2H), 6.44 (s, 1H), 7.48 (d, J= 8.4 Hz, 2H), 7.52 (d, J= 8.4 Hz, 2H), 7.66-7.69 (m, 4H).
ESI-MS: m/z, 406.20 (M+H)+, 100%.
Example 35: 2-((3-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl) phenyl)oxetan-3-yl)oxy)acetic acid

¾ NMR (DMSO-d6) S: 1.23-1.79 (m, 4H), 2.88-2.97 (m, 2H), 3.14 (brs, 1H), 3.45 (s, 2H), 3.83 (brs, 1H), 4.70 (d, J= 6.8 Hz, 3H), 4.89 (d, J= 7.2 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.54 (d, J= 8.0 Hz, 2H), 7.60 (d, J= 8.4 Hz, 2H) 7.67 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z 464.18 (M+H)+, 100%.
Example 36: 3-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl)phenyl) oxetan-3-yl acetate

¾ NMR (DMSO-d6) ό : 1.62-1.76 (m, 3H), 1.88 (br s, 1H), 2.16 (s, 3H), 2.92-2.98 (m, 2H), 3.19 (br s, 1H), 3.68 (br s, 1H), 4.64 (br s, 1H), 4.83 (d , J = 8.0 Hz, 2H), 4.95 (d, J= 8.0 Hz, 2H), 7.49-7.59 (m, 6H), 7.67 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z 448 (M+H)+, 100%.
Example 37 : (4-(3-methoxyoxetan-3-yl)phenyl)(4-(3-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

^NMR (CDCI3) ό : 1.61-2.06 (m, 4H), 2.86-2.93 (m, 2H), 3.18 (brs, 4H), 3.95 (brs, 1H), 4.83 (d, J= 7.2 Hz, 2H), 4.90-4.97 (m, 3H), 7.42-7.57 (m, 8H).
ESI-MS: m/z, 420.21 (M+H)+, 100%.
Example 38: (4-(3-fluoro-4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-methoxyoxetan-3-yl)phenyl)methanone

¾ NMR (CDCI3) ό : 1.64-2.06 (m, 4H), 2.94-3.00 (brs, 1H), 3.17 (s, 3H), 3.21-3.28 (m, 2H), 3.95 (brs, 1H), 4.83 (d, J = 7.2 Hz, 2H), 4.90-4.97 (m, 3H), 7.22-7.28 (m, 1H), 7.44-7.56 (m, 6H).
ESI-MS: m/z, 438.19 (M+H)+, 100%.
Example 39: (4-(3-methoxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

¾ NMR (CDCI3) ό : 1.64-2.06 (m, 4H), 2.86-2.92 (m, 2H), 3.18 (s, 4H), 3.96 (brs, 1H), 4.83 (d, J= 7.2 Hz, 2H), 4.87-4.97 (m, 3H), 7.36 (d, J= 8.0 Hz, 2H), 7.51-7.57 (m, 4H), 7.60 (d, J = 8.4 Hz, 2H).
ESI-MS: m/z, 420.19 (M+H)+, 100%.
Example 40: (4-(3-ethoxyoxetan-3-yl)phenyl)(4-(3-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

H NMR (CDCI3) d : 1.25 (t, J= 6.8 Hz, 3H), 1.61-2.02 (m, 4H), 2.87-2.93 (m, 2H), 2.99-3.05 (m, 1H), 3.26 (q, J= 7.2 Hz, 2H), 3.96 -4.01 (m, 1H), 4.83 (d, J= 6.8 Hz, 2H), 4.90-4.99 (m, 3H), 7.37-7.62 (m, 8H).
ESI-MS: m/z, 434.22 (M+H)+, 100%.
Example 41: (4-(3-methoxyoxetan-3-yl)phenyl)(4-(2-(trifluoromethyl)phenyl) piperidin-l-yl)methanone
o
¾ NMR (DMSO-de) S: 1.65-1.80 (m, 4H), 2.87 (brs, 1H), 3.05 (s, 3H), 3.19-3.23 (m, 2H), 3.70 (brs, 1H), 4.68 (brs, 1H), 4.76-4.81 (m, 4H), 7.41-7.44 (m, 1H), 7.64-7.69 (m, 2H),7.54 (s, 4H), 7.75 (d, J= 7.6 Hz, 1H);
ESI-MS: m/z, 420.20 (M+H)+, 100%
Example 42: (4-(3-ethoxyoxetan-3-yl)phenyl)(4-(3-fluoro-4-(trifluoromethyl) phenyl) piperidin-l-yl)methanone

¾ NMR (CDCI3) ό : 1.13 (t, J = 6.8 Hz, 3H), 1.68-1.85 (m, 4H), 2.91 (brs, 1H), 3.17-3.33 (m, 4H), 3.72 (brs, 1H), 4.65 (brs, 1H), 4.75-4.81(m, 4H), 7.38-7.42 (m, 1H), 7.51-7.55 (m, 4H), 7.63-7.67 (m, 1H), 7.78-7.81 (m, 1H).
ESI-MS: m/z, 452.18 (M+H)+, 100%.
Example 43: (4-(3-ethoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

¾ NMR (DMSO-d6) ό : 1.18 (t, J= 6.8 Hz, 3H), 1.61-1.71 (m, 3H), 1.88 (br s, 1H), 2.88-2.98 (m, 2H), 3.17-3.22 (m, 3H), 3.70 (br s, 1H), 4.74 (br s, 1H), 4.75-4.81 (m, 4H), 7.49-7.55 (m, 6H), 7.67 (d, J= 8.0 Hz, 2H).
ESI-MS: m/z 434 (M+H)+, 100%.
Example 44: (4-(3-isopropoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

0
¾ NMR (DMSO-de) d: 0.95 (d, J = 6.0 Hz, 6H), 1.62-1.72 (m, 2H), 1.88-1.91 (m, 2H), 2.87-2.98 (m, 2H), 3.03 (br s, 1H), 3.40-3.51 (m, 1H), 3.70 (br s, 1H), 4.65 (br s, 1H), 4.81 (s, 4H), 7.50-7.57 (m, 6H), 7.67 (d, J= 8.4 Hz, 2H).
ESI-MS: m/z 448 (M+H)+, 100%.
Example 45: (4-(3-isobutoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

O
¾ NMR (CDCI3) S: 0.95 (d, J = 6.4 Hz, 6H), 1.70 (br s, 1H), 1.84-1.94 (m, 3H), 2.01 (br s, 1H), 2.87-2.93 (m, 2H), 2.97 (d, J= 6.4 Hz, 2H), 3.19 (br s, 1H), 3.98 (br s, 1H), 4.81 (d, J= 7.2 Hz, 2H), 4.96 (br s, 1H), 4.99 (d, J= 11.2 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.50-7.57 (m, 4H), 7.60 (d, J= 8.0 Hz, 2H).
ESI-MS: m/z 462 (M+H)+, 100%.
Example 46: (4-(3-(cyclopropylmethoxy)oxetan-3-yl)phenyl)(4-(4- (trifluoromethyl)phenyl)piperidin-l-yl)methanone

, 2H), 0.85-0.90 (m, 1H), 1.03-1.10 (m, 2H), 1.12 (br s, 2H), 1.61-1.70 (br s, 3H), 2.01 (br s, 1H), 2.86-2.96 (m, 2H), 3.04 (d, J = 6.8 Hz, 2H), 3.19 (br s, 1H), 3.95 (br s, 1H), 4.81 (d , J = 6.8 Hz, 2H), 4.93 (br s, 1H), 4.99 (d, J= 7.2 Hz, 2H), 7.36 (d, J= 8.4 Hz, 2H), 7.50-7.65 (m, 2H).
ESI-MS: m/z 460 (M+H)+, 100%.
Example 47 : (3-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

¾ NMR (DMSO-de) d: 1.65-1.89 (m, 4H), 2.89-2.98 (m, 2H), 3.16-3.20 (m, 1H), 3.70-3.76 (m, 1H), 4.62-4.70 (m, 3H), 4.79 (d, J= 6.8 Hz, 2H), 6.45 (s, 1H), 7.38 (d, J= 7.6 Hz, 1H), 7.54 (d, J= 7.6 Hz, 1H), 7.53 (d, J= 8.4Hz, 2H), 7.63-7.71 (m, 4H). ESI-MS: m/z 406.15 (M+H)+, 100%.
Example 48: (3-(3-hydroxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

¾ NMR (DMSO-d6) ό : 1.66-2.03 (m, 4H), 2.86-2.92 (m, 2H), 3.19 (brs, 1H), 3.70 (brs, 1H), 4.64-4.70 (m, 3H), 4.80 (d, J = 6.8 Hz, 2H), 6.45 (s, 1H), 7.32-7.39 (m, 1H), 7.47-7.54 (m, 4H), 7.63-7.71 (m, 3H).
ESI-MS: m/z, 406.22 (M+H)+, 100%.
Example 49: (5-(3-hydroxyoxetan-3-yl)pyridin-3-yl)(4-(4-(trifluoromethyl) phenyl)piperidin-l-yl)methanone

¾ NMR (DMSO-de) ό : 1.82-1.87 (m, 3H), 2.04 (bs, 1H), 2.88-2.94 (m, 2H), 3.15-3.28 (m, 1H), 3.88-3.90 (m, 1H), 4.85 (d, J = 7.2 Hz, 2H), 4.88-4.96 (m, 1H), 4.97 (d , J= 7.2 Hz, 2H), 7.35 (d, J= 8.0 Hz, 2H), 7.60 (d, J= 8.0 Hz, 2H), 8.06 (s, 1H), 8.64 (d, J= 1.6 Hz, 1H), 8.98 (d, J= 2.0 Hz, 1H).
ESI-MS: m/z 407.1 (M+H)+, 100%.
Example 50: (3-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone
¾ NMR (DMSO-d6) d : 1.67-1.91
-2.97 (m, 2H), 3.04 (s, 3H), 3.18-3.22 (m, 1H), 3.63-3.69 (m, 1H), 4.65-4.69 (m, 1H), 4.77 (d, J= 7.2 Hz, 2H),4.80 (d, J= 7.2 Hz, 2H), 7.43-7.48 (m, 2H), 7.52-7.55 (m, 4H), 7.67 (d, J= 8 Hz, 2H).
ESI-MS: m/z 420.15 (M+H)+, 100%.
Example 51: (3-(3-methoxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone

H NMR (CDCI3) ό: 1.65-2.06 (m, 4H), 2.86-2.92 (m, 2H), 3.11-3.18 (m, 4H), 3.91 (brs, 1H), 4.83 (d, J = 6.8 Hz, 2H), 4.90-4.97 (m, 3H), 7.36 (d, J = 8.0 Hz, 2H), 7.43-7.49 (m, 1H), 7.51-7.61 (m, 5H).
ESI-MS: m/z, 420.19 (M+H)+, 100%.
Example 52: N-(3-(3-hydroxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl) piperidine-l-carboxamide

H NMR (DMSO-d6) ό: 1.56-1.65 (m, 2H) 1.8 (d, J = 12.0 Hz, 2H), 2.86-2.92 (m, 3H), 4.31 (d , J = 13.2 Hz, 2H), 4.66 (d, J = 6.8 Hz, 2H), 4.76 (d, J = 6.4 Hz, 2H), 6.28 (s, 1H), 7.16 (d, J = 7.6 Hz, 1H), 7.48-7.53 (m, 3H), 7.67 (d, J = 8.0 Hz, 2H), 7.72 (d, J= 2.0 Hz, 1H), 8.59 (s, 1H).
ESI-MS: m/z 421 (M+H)+, 100%.
Example 53: (4-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperazin-l-yl)methanone

¾ NMR (DMSO-de) ό : 3.05 (s, 3H), 3.36 (br s, 4H), 3.61-3.66 (m, 2H), 3.76 (br s, 2H), 4.76-4.81 (m, 4H), 7.08 (d, J= 8.8 Hz, 2H), 7.45-7.56 (m, 6H).
We claim:
1. Compounds of general formula (I)

their tautomer forms, their stereosiomers, their pharmaceutically acceptable salts and pharmaceutical compositions containing them wherein
‘Cy’ is selected from heterocyclic groups selected from saturated or partially unsaturated or unsaturated, monocyclic or bicyclic or spirocyclic groups containing 0-4 heteroatoms selected from O, N or S;
Ύ is selected from either a bond, or O, S(0)0, CO, (Ci-C3)alkyl, C(0)NR5, NR5 or SO2NR5; wherein R5 represents H, (Ci-Ce)alkyl, (C3-Cr,)cycloalkyl;
‘Q’ selected from O, S(0)0 or NR7 wherein R7is selected from H, (Ci-C6)alkyl, (C3-Ce)cycloalkyl, acyl, -C(0)0R5, wherein , represents (Ci-Cr,) linear or branched alkyl;
‘o’ selected from integers from 0-2;
‘m’ and ‘n’ selected from integers from 0-4;
‘p’ selected from integers from 1-4
‘X’ at each occurrence independently selected from either C or N;
Ri is selected from hydrogen, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, perhaloalkyl, alkoxy, haloalkoxy, perhaloalkoxy, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocylyl, heterocyclylalkyl, heterocycloxy, heterocyclylalkoxy, heterocyclylalkoxyacyl, carboxylic acid and its derivatives such as esters and amides, carbonylamino, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkylsulfonyl, hydroxyl, sulfonic acid and its derivatives;
R2 is selected from hydrogen, or substituted or unsubstituted groups selected from alkyl, haloalkyl, perhaloalkyl, cycloalkyl, deuterated alkyl, alkynyl, alkenyl, aryl, aralkyl, heterocylyl, heterocyclylalkyl, heterocyclylalkoxyacyl, acyl, carbonylamino, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfonyl, alkylthioalkyl, alkylsulfmylalkyl, alkylsulfonylalkyl, alkylcarboxylic acid;
R3 and R4 independently selected from hydrogen, halo, cyano, hydroxy or substituted or unsubstituted groups selected from alkyl, haloalkyl, perhaloalkyl, alkoxy, haloalkoxy, perhaloalkoxy, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocylyl, heterocyclylalkyl, heterocycloxy, heterocyclylalkoxy, heterocyclylalkoxyacyl, carboxylic acid and its derivatives such as esters and amides, carbonylamino, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkylsulfonyl, hydroxyl, sulfonic acid and its derivatives.
2. Compound of formula (I) as claimed in claim 1, wherein ‘Cy’ is selected from pyrrolidinyl, piperidinyl, piperazinyl, diazepinyl, oxazolyl, oxadiazolyl, indolinyl, pyridothienyl, hexahydrocyclopenta[c]pyrrol, hexahydropyrrolo[3,4-c]pyrrol, dihydropyrrolo[3,4-c]pyrazol, 5H- imidazo[4,5-c]pyridine, 5,6-dihydropyridin-, hexahydrocyclopenta[c]pyrrol, 3,9-diazaspiro[5.5]undecan, tetrahydropyrrolo[3,4-c]pyrrol, 3,4- dihydroisoquinolin- 3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-, 3,6- diazabicyclo[3.1.1 Jheptan, dihydrothieno[3 ,2-c]pyridine, dihydrothiazolo[5,4-c]pyridine, diazaspiro[4.5]decan heterocycles.
3. Compound of genral formula (I) as claimed in claim 1, wherein Ύ’ is selected form a bond, O, S(0)0, CO, C(0)NR5, wherein R5 represents H.
4. Compound of general formula (I) as claimed in claim 1, wherein compound is selected from:
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1- yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l- yl)methanone;
N-(4-(3 -hydroxy ox etan-3 -yl)phenyl)- 1 -(4-(trifluoromethyl)phenyl) piperidine-4-carboxamide;
N-(4-(3-hydroxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl) piperidine- 1 -carboxamide;
N-(4-(3-methoxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl) piperidine- 1 -carboxamide;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperazin-l- yl)methanone;
3-(4-((4-(4-(trifluoromethyl)phenyl)piperazin-l-yl)sulfonyl)phenyl)oxetan-3- ol;
3 -(4-(4-(4-(trifluoromethyl)phenyl)piperidin- 1 -yl)phenyl)oxetan-3 -ol ;
1-(4-(3-m ethoxy oxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl)piperi dine; (4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-(2-hydroxyethoxy)ox etan-3 -yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
2-((3-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2- carbonyl)phenyl)oxetan-3-yl)oxy)acetic acid;
(4-(3 -fluoro-5 -(trifluorom ethyl )phenyl)piperi din- 1 -yl)(4-(3 -hydroxy ox etan-3 - yl)phenyl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(3-(4-methyl-lH-imidazol-l-yl)-5- (trifluoromethyl)phenyl)piperidin-l-yl)methanone;
3-(4-(3-(3-fluoro-4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5- yl )phenyl)ox etan-3 -ol;
3-(4-((l-(4-(trifluoromethyl)phenyl)piperidin-4-yl)oxy)phenyl)oxetan-3-ol;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7- dihydrothieno[3,2-c]pyridin-5(4H)-yl)methanone;
(1 -benzyl-3 -(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone;
(4-(3 -hydroxy ox etan-3-yl)phenyl)(l -methyl-3 -(4-(trifluoromethyl)phenyl)- 4.6-dihydropyrrolo[3,4-c]pyrazol-5(lH)-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(2-methyl-3 -(4-(trifluoromethyl)phenyl)- 2.6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethoxy)phenyl)piperidin- 1-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(p-tolyl)piperi din- l-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(3-(trifluoromethyl)phenyl)piperi din- 1-yl)methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(p-tolyl)piperidin- 1 -yl)methanone;
(4-(3-chloro-4-methoxyphenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl) phenyl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-methoxyphenyl)piperidin-l-yl) methanone;
(4-(3 -fluoro-4-methoxyphenyl)piperidin- 1 -yl)(4-(3 -hy droxy ox etan-3 -yl) phenyl)methanone;
(4-(3 -chi oro-4-methylphenyl)piperi din- l-yl)(4-(3-hy droxy oxetan-3-yl) phenyl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(3 -methoxy-4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
(4-(3 -fluoro-4-(trifluorom ethyl )phenyl)piperi din- 1 -yl)(4-(3 -hydroxy ox etan-3 -yl)phenyl) methanone;
(4-(3 -chi oro-4-(trifluoromethyl)phenyl)piperi din- l-yl)(4-(3 -hydroxy oxetan-3-yl)phenyl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(2-(trifluoromethyl)phenyl)piperi din- 1-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperi din- 1-yl)methanone;
2-((3-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl)phenyl)oxetan- 3-yl)oxy)acetic acid;
3 -(4-(4-(4-(tri fluoromethyl)phenyl)piperi dine- l-carbonyl)phenyl)ox etan-3 -yl acetate;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(3-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3-fluoro-4-(trifluorom ethyl )phenyl)piperi din- l-yl)(4-(3 -methoxyoxetan-3-yl)phenyl) methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3 -ethoxy oxetan-3-yl)phenyl)(4-(3-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(2-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3 -ethoxy oxetan-3 -yl)phenyl)(4-(3 -fluoro-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
(4-(3 -ethoxy oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl) methanone;
(4-(3-isopropoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3-isobutoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3-(cyclopropylmethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl) phenyl)piperidin-l-yl) methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperi din- 1-yl)methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperi din- 1-yl)methanone;
(5 -(3 -hydroxy ox etan-3 -yl)pyri din-3 -yl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
(3-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(3-(3-methoxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
N-(3-(3-hydroxyoxetan-3-yl)phenyl)-4-(4-(trifluoromethyl)phenyl) piperidine- 1 -carboxamide;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperazin-l-yl)methanone;
3 -(4-((4-(4-(trifluoromethyl)phenyl)piperi din- l-yl)sulfonyl)phenyl)ox etan-3 -ol;
(3-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(3-(3-methoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(4-(4-(difluoromethyl) phenyl) piperidin-l-yl)(3-(3-(methoxy-d3) oxetan-3-yl)phenyl) methanone;
N-(4-(3 -m ethoxy oxetan-3 -yl) phenyl)- 1 -(4-(trifluorom ethyl) phenyl) piperidine-4-carboxamide;
(4-(3 -hydroxy- 1, 1-dioxidothi etan-3 -yl) phenyl)(5-(4-(trifluoromethyl) phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3 -hydroxy- 1, 1-dioxidothi etan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
(4-(3-hydroxyoxetan-3-yl) phenyl)(4-(4-hydroxyphenyl) piperidin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-phenylpiperi din- l-yl)methanone;
(4-(4-(difluoromethyl)phenyl)piperidin-l-yl)(3-(3-methoxyoxetan-3-yl) phenyl)methanone;
(4-(4-(difluoromethyl)phenyl)piperidin-l-yl)(3-(3-hydroxyoxetan-3-yl) phenyl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(2-methoxypyridin-4-yl)-4-(4-(trifluoromethyl)phenyl)piperazin- 1 -yl)methanone;
(4-(4-(difluoromethyl)phenyl)piperidin-l-yl)(4-(3-methoxyoxetan-3-yl) phenyl)methanone;
(4-(4-(difluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxyoxetan-3-yl) phenyl)methanone;
(4-(3-(but-2-yn-l-yloxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
N-(4-(3-hydroxyoxetan-3-yl)phenyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl) oxazole-4-carboxamide;
(4-(3 -(prop-2 -yn-l-yloxy)oxetan-3-yl)phenyl)(4-(4-(trifluorom ethyl )phenyl) piperidin-l-yl)methanone;
4-(4-(3-m ethoxy oxetan-3-yl)phenyl)-l-(4-(trifluoromethyl)phenyl)piperi din- 4-01;
N-(4-(3-methoxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrole-2(lH)-carboxamide;
N-(4-(3-hydroxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrole-2(lH)-carboxamide;
(4-(3-(methoxy-d3)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
5-(3-hydroxyoxetan-3-yl)-2-(4-(4-(trifluoromethyl) phenyl) piperidin-l-yl) benzoic acid;
3 -(3 -hydroxy ox etan-3 -yl)-5 -(4-(4-(trifluoromethyl)phenyl)piperidin- 1 -yl) benzoic acid;
(3-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-l, 4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-l, 4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)-2-morpholinophenyl)(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)-2-(piperazin-l-yl)phenyl)(4-(4-(trifluorom ethyl) phenyl)piperidin-l-yl)methanone;
l-(4-(3 -ethoxy ox etan-3 -yl)phenyl)-4-(4-(trifluoromethyl)phenyl)piperi dine;
3-(3-morpholino-5-(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)phenyl) oxetan-3-ol;
/er/-butyl 4-(5-(3-hydroxyoxetan-3-yl)-2-(4-(4-(trifluoromethyl)phenyl) piperidine-l-carbonyl)phenyl)piperazine-l-carboxylate;
(4-hydroxy-4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3 -hydroxy oxetan-3-yl)phenyl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)-5,6-dihydropyridin-l(2H)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl) phenyl)(l-(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c] pyrazol-5(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-2,6-dihydropyrrolo[3,4-c] pyrazol-5(4H)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-2,6-dihydropyrrolo[3,4-c] pyrazol-5(4H)-yl)methanone;
(4-(3 -hydroxy ox etan-3-yl)phenyl)(5-methoxy-5-(4-(trifluorc>methyl)phenyl) hexahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
(5-methoxy-5-(4-(trifluoromethyl)phenyl)hexahydrocyclopenta[c]pyrrol-2
(lH)-yl)(4-(3-methoxyoxetan-3-yl)phenyl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,5-dihydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,5-dihydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,4,5,6-tetrahydropyrrolo [3,4-c]pyrrol-2(lH)-yl)methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl)-3 ,4,5,6-tetrahydropyrrolo [3,4-c]pyrrol-2(lH)-yl)methanone;
(3 -(3 -methoxyoxetan-3 -yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3 ,4,5,6-tetrahydropyrrolo [3,4-c]pyrrol-2(lH)-yl)methanone;
3-(4-((5-(4-(trifluoromethyl)phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl) sulfonyl) phenyl)oxetan-3-ol;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(9-(4-(trifluoromethyl)phenyl)-3, 9-diazaspiro[5.5]undecan-3-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(9-(4-(trifluoromethyl)phenyl)-3,9-diazaspiro[5.5]undecan-3-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(9-(4-(trifluoromethyl)phenyl)-3,9-diazaspiro[5.5]undecan-3-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(3-(4-(trifluoromethyl)phenyl)pyrrolidin-l-yl)methanone;
((5-(4-fluorophenyl)-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-2(lH)-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3, 4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(5-hydroxy-5-(4-(trifluoromethyl)phenyl)hexahydrocyclopenta[c]pyrrol-2(lH)-yl)(4-(3-hydroxyoxetan-3-yl)phenyl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(6-(4-(trifluoromethyl)phenyl)-3, 4-dihydroisoquinolin-2 (lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)indolin-l-yl) methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(3-(4-methyl-lH-imidazol-l-yl)-4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
2,2-dimethyl-7-((3-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l-carbonyl)phenyl)oxetan-3-yl)oxy)heptanoic acid;
(4-(m ethoxymethyl)-4-(4-(trifluorom ethyl )phenyl)piperidin-l-yl)(4-(3-methoxyoxetan-3-yl)phenyl)methanone;
(4-(hydroxymethyl)-4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-hydroxy ox etan-3 -yl) phenyl)methanone;
l-(4-(3 -methoxyoxetan-3 -yl)benzoyl)-4-(4-(trifluoromethyl)phenyl) piperidine-4-carboxylic acid;
methyl l-(4-(3-hydroxyoxetan-3-yl)benzoyl)-4-(4-(trifluoromethyl)phenyl) piperidine-4-carboxylate;
l-(4-(3-hydroxyoxetan-3-yl)benzoyl)-4-(4-(trifluoromethyl)phenyl) piperidine-4-carboxylic acid;
(4-(3 -chi oro-4-(trifluoromethyl)phenyl)piperi din- l-yl)(4-(3-m ethoxy ox etan-3-yl)phenyl) methanone;
l-(4-(3-hydroxyoxetan-3-yl)benzoyl)-4-(4-(trifluoromethyl)phenyl) piperidine-4-carbonitrile;
l-(4-(3-m ethoxy oxetan-3-yl)benzoyl)-4-(4-(trifluoromethyl)phenyl) piperidine-4-carbonitrile;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-methoxy-4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
(4-methoxy-4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)(4-(3-methoxyoxetan-3-yl)phenyl)methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(3 -(trifluoromethyl)phenyl)piperidin- 1 -yl)methanone;
(4-(3 -fluoro-4-(trifluorom ethyl )phenyl)piperi din- 1 -yl)(3 -(3 -hydroxy ox etan-3 -yl)phenyl) methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(2-(trifluoromethyl)phenyl)piperi din- 1-yl)methanone;
(4-(3 -ethoxy oxetan-3 -yl)phenyl)(3-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
3-(3-(3-(4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5-yl)phenyl)oxetan-3-ol; 5 -(3 -(3 -m ethoxy oxetan-3 -yl)phenyl)-3 -(4-(trifluoromethyl)phenyl)- 1,2,4-oxadiazole;
3-(4-(3-(4-(trifluoromethyl)phenyl)-l,2,4-oxadiazol-5-yl)phenyl)oxetan-3-ol; 5 -(4-(3 -m ethoxy oxetan-3 -yl)phenyl)-3 -(4-(trifluoromethyl)phenyl)- 1,2,4-oxadiazole;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(4-((trifluoromethyl)thio)phenyl) piperidin-l-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(4-((trifluoromethyl)thio)phenyl) piperidin-l-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(p-tolyl)-3,3a,6,6a-tetrahydrocyclopenta
[c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(methylthio)phenyl)-3,3a,4,6a-tetrahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(6-(4-(trifluoromethyl)phenyl)-3, 6-diazabicycl[3.1. l]heptan-3-yl)methanone;
(4-(3-(cy cl opropylmethoxy)ox etan-3 -yl)phenyl)(5-(4-(trifluorom ethyl) phenyl)hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-(methoxy-d3)oxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3 -i sobutoxy oxetan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3 -i sopropoxy oxetan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-(2-methoxyethoxy)ox etan-3 -yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
3-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)phenyl)oxetan-3-yl acetate;
3-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)phenyl) oxetan-3-yl pivalate;
tert-butyl 4-hy droxy-4-(4-(4-(4-(trifluorom ethyl )phenyl)piperi dine- 1-carbonyl)phenyl) piperidine- 1-carboxylate;
(4-(4-hydroxypiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(4-hydroxytetrahydro-2H-pyran-4-yl)phenyl)(4-(4-(trifluoromethyl) phenyl)piperidin-l-yl)methanone;
(4-(4-methoxytetrahydro-2H-pyran-4-yl)phenyl)(4-(4-(trifluorom ethyl) phenyl)piperidin-l-yl)methanone;
(4-(4-methoxypiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3-hydroxythietan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3-hydroxythietan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxythietan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(3-ethoxythietan-3-yl)phenyl)(4-(4-(trifluorom ethyl )phenyl)piperi din- 1-yl)methanone;
(4-(3-methoxythietan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-ethoxythietan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
/c/7-butyl 3 -hydroxy-3 -(4-(4-(4-(trifluorom ethyl)phenyl)piperi dine- 1-carbonyl)phenyl) pyrrolidine- 1 -carboxylate;
(4-(3-hydroxypyrrolidin-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-1-yl) methanone;
(4-(3-methoxypyrrolidin-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
tert-butyl 3 -hydroxy-3 -(4-(4-(4-(trifluorom ethyl )phenyl)piperi dine- 1 -carbonyl)phenyl)azetidine- 1-carboxylate;
(4-(3-hydroxyazeti din-3 -yl)phenyl)(4-(4-(tri fluoromethyl)phenyl)piperi din- 1-yl)methanone;
(4-(4-(methoxy-d3)piperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
tert-butyl 4-methoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine- 1 -carbonyl)phenyl)piperidine- 1-carboxylate;
l-(4-methoxy-4-(4-(4-(4-(trifluorom ethyl )phenyl)piperi dine- 1 -carbonyl) phenyl )piperi din- 1 -yl)ethan- 1 -one;
ethyl 4-methoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl) phenyl )piperi dine- 1 -carboxylate;
(4-(4-methoxy-l-methylpiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
tert-butyl 4-ethoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl) phenyl piperidine- 1-carboxylate;
(4-(4-ethoxypiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl)piperidin-l-yl)methanone;
1-(4-ethoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl) phenyl )piperi din- 1 -yl)ethan- 1 -one;
ethyl 4-ethoxy-4-(4-(4-(4-(trifluoromethyl)phenyl)piperidine-l -carbonyl) phenyl )piperi dine- 1 -carboxylate;
(4-(4-ethoxy-l-methylpiperidin-4-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl)methanone;
tert-butyl 4-hydroxy-4-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo
[3, 4-c]pyrrole-2-carbonyl)phenyl)piperi dine- 1-carboxylate;
tert-butyl 4-methoxy-4-(4-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo
[3, 4-c]pyrrole-2-carbonyl)phenyl)piperi dine- 1-carboxylate;
(4-(4-methoxypiperidin-4-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(4-methoxy-l-(2,2,2-trifluoroethyl)piperidin-4-yl)phenyl)(4-(4- (trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(4-(4-ethoxy-l-(2,2,2-trifluoroethyl)piperidin-4-yl)phenyl)(4-(4- (trifluoromethyl)phenyl)piperidin-l-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c] pyridin-5(4H)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c] pyridin-5(4H)-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothiazolo[5,4-c] pyridin-5(4H)-yl)methanone;
N-(4-(3-hydroxyoxetan-3-yl)phenyl)-2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxamide;
(4-(3-hydroxyoxetan-3-yl)phenyl)(2-(4-(trifluoromethyl)phenyl)-6,7-dihydrothiazolo[5,4-c] pyridin-5(4H)-yl)methanone;
(3-(3-hydroxyoxetan-3-yl)phenyl)(3-(4-(trifluoromethyl)phenyl)-6,7-dihydrothieno[3,2-c] pyridin-5(4H)-yl)methanone;
(1 -benzyl-3 -(4-(trifluoromethyl)phenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1 H)-yl)(3 -(3 -hydroxy oxetan-3 -yl)phenyl)methanone;
(3-(3-ethoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
ethyl 2-((3-(3-(5-(4-(trifluoromethyl)phenyl)octahydropyrrolo[3,4-c]pyrrole- 2-carbonyl)phenyl)oxetan-3-yl)oxy)acetate;
(3 -(3 -i sobutoxy oxetan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
(3-(3-(cyclopropylmethoxy)oxetan-3-yl)phenyl)(5-(4-(trifluoromethyl) phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
N-(3-(3-hydroxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrole-2(lH)-carboxamide;
N-(3-(3-methoxyoxetan-3-yl)phenyl)-5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrole-2(lH)-carboxamide;
(4-(3 -hydroxy ox etan-3-yl)phenyl)(4-(4-(trifluorc>methyl)phenyl)- 1,4- diazepan-l-yl)methanone;
(4-(3 -methoxyoxetan-3 -yl)phenyl)(4-(4-(trifluoromethyl)phenyl)- 1,4- diazepan-l-yl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(8-(4-(trifluoromethyl)phenyl)-2,8- diazaspiro[4.5 ] decan-2-yl)methanone;
4-(3 -hydroxy ox etan-3 -yl)-N-( 1 -(4-(trifluoromethyl)phenyl)pyrroli din-3 -yl) benzamide;
(4-(3-(2-hydroxyethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
(4-(3-(2-(ethylthio)ethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl)phenyl) piperidin-l-yl) methanone;
(4-(3-(2-(ethylsulfonyl)ethoxy)oxetan-3-yl)phenyl)(4-(4-(trifluoromethyl) phenyl)piperidin-l-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(4-(m ethylthio)phenyl)piperi din- 1-yl) methanone;
(4-(3 -methoxyoxetan-3 -yl)phenyl)(4-(4-(methylthio)phenyl)piperi din- 1-yl) methanone;
(4-(4-hydroxypiperidin-4-yl)phenyl)(4-(4-(methylthio)phenyl)piperidin-l-yl) methanone;
(4-(4-methoxypiperidin-4-yl)phenyl)(4-(4-(methylthio)phenyl)piperidin-l-yl) methanone;
(3-(3-(methoxy-d3)oxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3 -(3 -i sopropoxyoxetan-3 -yl)phenyl)(5 -(4-(trifluoromethyl)phenyl) hexahydropyrrolo[3,4-c] pyrrol-2(lH)-yl)methanone;
N-(3 -(3 -hydroxy ox etan-3 -yl)-5-morpholinophenyl)-l-(4-(trifluorom ethyl) phenyl)piperidine-4-carboxamide;
methyl 4-(5-hydroxy-2-(4-(3-hydroxyoxetan-3-yl)benzoyl) octahydrocyclopenta[c]pyrrol-5-yl)benzoate;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(4-methoxyphenyl)-3 ,3 a,4, 6a- tetrahydrocyclopenta [c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(4-(2-(methylthio)ethoxy)phenyl)- 3,3a,4,6a-tetrahydrocyclopenta[c]pyrrol-2(lH)-yl)methanone;
N-(3 -(3 -hydroxy ox etan-3 -yl)-5-(4-methylpiperazin- 1 -yl)phenyl)- 1 -(4- (trifluoromethyl) phenyl)piperidine-4-carboxamide;
(4-(3-methoxyoxetan-3-yl)phenyl)(5-(4-(trifluoromethyl)phenyl)-3,4,5,6- tetrahydropyrrolo [3,4-c]pyrrol-2(lH)-yl)methanone;
(5-hydroxy-5-(6-methoxypyridin-3-yl)hexahydrocyclopenta[c]pyrrol-2(lH)- yl)(4-(3 -hydroxy ox etan-3 -yl)phenyl)methanone;
3-(4-((l-(4-(trifluoromethyl)phenyl)piperidin-4-yl)amino)phenyl)oxetan-3-ol; 5. Compounds selected from:
/er/-butyl 4-methoxy-4-(4-(4-(5-(trifluoromethyl)pyridin-2-yl)piperidine-l- carbonyl)phenyl) piperidine- 1-carboxylate;
(4-(4-methoxypiperidin-4-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2- yl)piperidin-l-yl) methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(5-(6-(trifluoromethyl)pyri din-3 -yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(5-(trifluoromethyl)pyridin-2-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3-(3-methoxyoxetan-3-yl)phenyl)(5-(5-(trifluoromethyl)pyridin-2-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(5-(5-(trifluoromethyl)pyri din-2 -yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(5 -(5 -(trifluoromethyl)pyridin-2-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(5-(trifluoromethyl)pyri din-2 -yl) piperidin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl) piperidin-l-yl) methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(6-(trifluoromethyl)pyri din-3 -yl) piperidin-l-yl) methanone;
(4-(3 -hydroxy ox etan-3 -yl)phenyl)(4-(6-(trifluorom ethyl)pyri din-3 -yl) piperidin-l-yl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(5-(6-(trifluoromethyl)pyridin-3-yl) hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)methanone;
(4-(3 -hydroxy ox etan-3 -yl) phenyl)(4-(5 -(trifluorom ethyl) pyridin-2-yl) piperazin- 1 -yl)methanone;
(4-(3-hydroxyoxetan-3-yl) phenyl)(4-(6-(trifluorom ethyl) pyri din-3 -yl) piperazin- 1-yl) methanone;
(4-(3-methoxyoxetan-3-yl)phenyl)(4-(5-(trifluoromethyl)pyri din-2 -yl) piperazin- 1-yl) methanone;
(4-(3-ethoxyoxetan-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl) piperazin- 1-yl) methanone;
(3 -(3 -hydroxy ox etan-3 -yl)phenyl)(4-(5 -(trifluorom ethyl)pyridin-2-yl) piperazin- 1-yl) methanone;
(3 -(3 -methoxyoxetan-3 -yl)phenyl)(4-(5 -(trifluoromethyl)pyri din-2 -yl) piperazin- 1-yl) methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(2-(trifluoromethyl)pyridin-4-yl) piperazin- 1 -yl)methanone;
(4-(3-hydroxyoxetan-3-yl)phenyl)(4-(2-(trifluoromethyl)pyridin-4-yl) piperidin-l-yl) methanone.
6. A pharmaceutical composition comprising a therapeutically effective amount of compound of formula (I) as claimed in any of preceeding claims and suitable pharmaceutically acceptable excipients.
7. A pharmaceutical composition comprising compounds of formula (I) in combination with one or more pharmaceutically active agents selected from group comprising insulin, insulin derivatives and mimetics, insulin secretagogues, insulin sensitizers, biguanide agents, alpha-glucosidase inhibitors, insulinotropic sulfonylurea receptor ligands, meglitinides, GLP-1 (glucagon like peptide-1), GLP- 1 analogs, dipeptidyl peptidase IV(DPP-IV) inhibitors, GPR- 1 19 activators, sodium-dependent glucose co-transporter (SGLT2) inhibitors, PPAR modulators, non-glitazone type PPAR. delta agonist, HMG-CoA reductase inhibitors, cholesterol-lowering drugs, rennin inhibitors, anti-thrombotic and anti-platelet agents and anti-obesity agents or pharmaceutically acceptable salts thereof.
8. The use of compounds as claimed in any of preceeding claims or their pharmaceutical compositions for the treatment of hyperlipidemia, and other disorders related to hyperlipidemia.
9. Method of treating hyperlipidemia and disorders related to hyperlipidemia comprising the administering to a patient in need thereof an effective amount of a compound as claimed in any of above claims or pharmaceutical composition thereof.