FIELD OF THE INVENTION

The present invention describe novel compounds of formula (I) as autotaxin (ATX) inhibitors for the treatment and prophylaxis of conditions or a disorder caused by autotaxin (ATX) activation or increased concentration of lysophosphatidic acid (LPA) and also a pharmaceutical composition containing the same. Invention also describe pharmaceutically acceptable salts, enantiomers, tautomeric forms, their diastereomers.and pharmaceutical composition of novel autotaxin (ATX) inhibitors.

BACKGROUND OF THE INVENTION

ATX enzyme is important for converting Lysophosphatidylcholine (LPC) into LPA, as a bioactive signaling molecule. ATX is a secreted enzyme of the ectonucleotide phosphatase family, also known as Ectonucleotide Pyrophosphatase/ Phosphodiesterase 2 (ENPP-2 or NPP2). ATX plays important role in driving pathological conditions, including fibrosis, arthritic inflammation, neurodegeneration, neuropathic pain and cancer. LPA is a bioactive lipid that affects migration, proliferation and survival of various cell types. LPA mediates variety of cellular and biological actions through LPA receptors (LPAR). The LPA shows broad tissue expression and it can couple to at least six distinct G proteins, known as LPAR1-6, which in turn, feed into multiple effector systems (Yung, Y.C. et al., J. Lipid Res. 2014, 55, 1192 and Kihara, Y. et al., Exp. Cell Res. 2015, 333, 171). Since the LPA level in plasma is highly related to the activity of ATX, it is believed that ATX is an important supply source of extracellular LPA.

Inhibition of ATX has been shown to reduce LPA levels in pathological settings. Reduction of LPA may provide therapeutic benefits in diseases with unmet need, including cancer, lymphocyte homing chronic inflammation, neuropathic pain, fibrotic diseases such as Idiopathic Pulmonary Fibrosis (IPF), thrombosis and cholestatic pruritus which caused and / or propagated by increased LPA levels and / or activation of ATX.

IPF is characterized as a progressive scarring of lung tissue which leads to worsening lung function and is ultimately fatal within 3-5 years from the onset of symptoms. There were no treatment options for IPF until 2014, when the FDA approved Nintedanib (Ofev) and Pirfenidone (Esbriet) (King, T, E. et al., Lancet 2011, 378, 1949; Richeldi, L. at el., N. Engl. J. Med. 2014, 370, 2071; Roth, G. J. et al., J. Med. Chem. 2009, 52, 4466; J. Med. Chem. 2015, 58, 1053; Hilberg, F. et al., Drugs Future 2010, 35, 5; and King, T. E. et al., N. Engl. J. Med. 2014, 370, 2083). Despite this advancement, there remains a need for additional medicines to treat IPF. Patients with IPF have elevated levels of LPA in their bronchoalveolar lavage fluid (BALF) and exhaled breath condensate. FPAR1 has been identified to be the predominant FPA receptor (Tager, A. M. et al., Nat. Med. 2008, 14, 45 and Montesi, S. B. et al., BMC Pulm. Med. 2014). In the lung fibroblasts of an IPF patient, FPAR1 was found to be responsible for enhanced fibroblast cell migration and vascular leak. It is therefore envisaged that FPAR1 antagonists will be a potential drug target for the treatment of IPF. In recent years, several FPAR1 antagonists have been reported, and some of these compounds are currently being evaluated for the treatment of IPF (Budd, D. C et al.., Future Med. Chem. 2013, 5, 1935; Qian, Y. et al., J. Med. Chem. 2012, 55, 7920 and Terakado, M. et al., ACS Med. Chem. Fett. 2016, 7, 913).

Fibrosis can develop in the liver, kidney, lung, dermis, vasculature, gut and other sites. Fibrosis develops due to action of pathways including growth factors, cytokines, integrin and lipids. ATX, FPA and FPAR pathways have been implicated in fibrotic disease. Increased levels of ATX, FPA and FPARs observed in various rodent models of fibrosis and in patient fluids and biopsy tissues. FPA can induce proliferative, survival and chemotactic responses in cells known to be critical in fibrotic disease, including: fibroblasts, smooth muscle cells, macrophages, epithelial and endothelial cells and leukocytes. Inhibitors of FPARs indicate that antagonism of receptors within this pathway blocked or reversed fibrosis in the lung, liver, kidney and skin in rodents. Accordingly in fibrotic diseases, it is desirable to lower FPA levels. This can be accomplished through inhibition of enzymes involved in FPA biosynthesis, such as ATX.

Various publications refer to compounds that are capable of inhibiting ATX, including: WO2019228403, WO2019108943, WO 2019029620, WO2019223721, W02019158107, WO2018153312, WO2017152062, W02017050791, W02017050792, W02017050747, W02017050732, WO2015144605, W02015042052, WO2014139882, WO2014139978, WO 2014097151, WO2014048865, WO2014202458, WO 2010130944, WO2013186159. There is an unmet need for ATX inhibitors for use in the treatment and / or prophylaxis of physiological and / or pathophysiological conditions such as cancer, chronic inflammation, neuropathic pain, fibrotic diseases, thrombosis which are caused, medicated and / or propagated by increased FPA levels and / or the activation of ATX. SUMMARY OF THE INVENTION

The present invention describe novel compounds as autotaxin (ATX) inhibitors for treatment and prophylaxis of conditions or a disorder caused by ATX activation or increased concentration of LAP and also a pharmaceutical composition containing the same.

The present invention includes certain substituted compounds described herein, their salts, preparations thereof, pharmaceutical compositions and formulations thereof and methods of treating diseases such as therewith. The present invention includes novel compounds of formula (I) their pharmaceutically acceptable salts, tautomeric forms, enantiomers and their diastereomers. In some embodiments, compounds of the present invention are inhibitors of ATX. Embodiments of the present invention include the compounds herein, pharmaceutically acceptable salts thereof, any physical forms thereof including solvates and hydrates, preparation of the compounds, intermediates and pharmaceutical compositions and formulations thereof.

EMBODIMENT(S) OF THE INVENTION An embodiment of the present invention provides novel compounds represented by the general formula (I), their pharmaceutically acceptable salts, tautomeric forms, enantiomers and their diastereomers.

In a further embodiment of the present invention is provided pharmaceutical compositions containing novel compounds of the general formula (I), their tautomeric forms, their enantiomers, their diastereomers, their stereoisomers, their pharmaceutically acceptable salts, or their mixtures in combination with suitable excipients.

In a still further embodiment is provided the use of novel compounds of the present invention as ATX inhibitors, by administering a therapeutically effective and non-toxic amount of novel compounds of general formula (I) or their pharmaceutically acceptable compositions to the mammals. In a still further embodiment is provided a process for preparing the novel compounds of the general formula (I). DESCRIPTION OF THE INVENTION

Accordingly, the present invention relates to the novel compounds of the formula (I) represents below and their pharmaceutically acceptable salts, tautomeric forms, enantiomers and their diastereomers; Wherein,

A is

4-10 membered mono, bi or spirocyclic heterocycloalkyl containing one or more hetereoatoms independently selected from O, N, and S;

5-6 membered heterocycloalkenyl containing 1 double bond, one or more heteroatom independently selected from O, N, and S;

5-6 membered heteroaryl containing one or more heteroatom independently selected from O, N, and S;

X is -C(0)0-, -NR ^a -C(0)-, -C(O)-, S(0) ₂ -, -S(0) ₂ NR ^a -;

Ri is selected from (Ci-C ₆ )alkyl, (C ₂ -C ₆ )alkenyl, (C ₂ -C ₆ )alkynyl, haloalkyl, cycloalkyl, carbocycle, heterocyclyl, heteroaryl, aryl, arylalkyl, heterocycloalkyl, heteroarylalkyl, arylalkoxy, aryloxy, heteroaryloxy, heterocycloxy, arylalkenyl, arylalkynyl, arylcycloalkyl, wherein each of these groups, wherever applicableis further substituted with substituent(s) independently selected from halo, hydroxyl, (Ci-C ₆ )alkyl, (Ci-C ₆ )alkoxy, (Ci-C ₆ )acyloxy, haloalkyl, -N0 ₂ , -OCF ₃ , -CN, -(CR ^b R ^c )) _r NR ^d R ^e , -COOR ^d , -S(0) ₂ NR ^d R ^e , -S(0) ₂ (CR ^b R ^c ) _r , - C(0)NR ^d R ^e ; R ₂ selected from H, (C ₁ -C ₆ )alkyl, halo, haloalkyl, -(CR ^f R ^g ) _s -COOR ^h , -(CR ^f R ^g ) _s -OR ^h , -S(0) ₂ -(CR ^f R ^g ) _s , -S(0) ₂ -NR ^h R', (C ₃ -C ₇ )cycIoaIkyI, heterocyclyl or aryl; m, n, p and q are independently selected from 0, 1, 2 or 3;

Y is absent, or is selected from -H, -(CR ^ab R ^ac ) _r , -(CR ^ab R ^ac ) _r C(0)-, -C(0)-(CR ^ab R ^ac ) _r , - C(0)-C(0)-, -C(0)NR ^ad R ^ae -, -(CR ^ab R ^ac ) _t C(0)NR ^ad R ^ae -, -(CR ^ab R ^ac ) _t C(0)0R ^ad -, -C(O)- (CR ^ab R ^ac ) _t -OR ^ad -, -(CR ^ab R ^ac ) _t -OR ^ad -, -S(0) ₂ -, -S(0) ₂ NR ^ad R ^ae -, -S(0) ₂ _(CR ^ab R ^ac ) _r ;

B is absent or is

4-10 member mono, bi or spirocyclic heterocycloalkyl containing one or more hetereoatoms independently selected from O, N, and S; - 5-6 membered heterocycloalkenyl containing 1 double bond containing one or more heteroatom independently selected from O, N, and S;

5-10 membered heteroaryl containing one or more heteroatom independently selected from O, N, and S ;

Aryl, arylalkyl,

R ₃ , R ₅ , and R ₆ are independently selected from H, (CY jalkyl, halo, haloalkyl, - (CR ^af R ^ag ) _v -COOR ^ah , -(CR ^af R ^ag ) _v -CONR ^ah R ^ai , -(CR ^af R ^ag ) _v -OR ^ah , -(CR ^af R ^ag ) _v -NR ^ah R ^ai , -S(0) ₂ - (CR ^af R ^ag ) _v , -S(0) ₂ -NR ^ah R ^ai , (C ₃ -C ₇ )cycloalkyl, heterocyclyl, aryl; R ₄ & R ₇ are independently selected from, H, (Ci-C ₆ )alkyl, halo, haloalkyl, -ORA -CN, - NR^R^, (C ₃ -C ₇ )cycloalkyl, aryl;

R ^a , R ^b , R ^c , R ^d , R ^e , R ^f , R ^s , R ^h , R\ R ^ab , R ^ac , R ^ad , RA R ^af , R ^ag , R ^ah , and R ^ai are independently selected from H, (Ci-C ₆ )alkyl, halo, haloalkyl, cycloalkyl, aryl or arylalkyl; r, s, t and v represents integers from 0-6.

In one of the preferred embodiment, A is selected from the following structures: In one of the preferred embodiment, B is selected from the following structures:

-5 _* C»- , oi- o ¾-O- _¾ ^« -Ό+ _R . + jo *·

In one of the preferred embodiment, present invention relates to novel compounds of the formula (I) is represented by (I-a) and (I-b) provided below their pharmaceutically acceptable salts, tautomeric forms, enantiomers and their diastereomers; (I-a) and (I-b)

For both compounds of formula (I-a) and (I-b),

A is selected from 4-10 membered mono, bi or spirocyclic heterocycloalkyl containing one or more hetereoatoms independently selected from O, N, and S.

In another preferred embodiment A is selected from following structures: X is selected from -C(0)0-, -NR ^a -C(0)-, -C(O)-, S(0) ₂ -, -S(0) ₂ NR ^a -;

In yet another preferred embodiment X is selected from -C(0)0- and -C(O)-.

Ri is selected from (Ci-C ₆ )alkyl, (C ₂ -C ₆ )alkenyl, (C ₂ -C ₆ )alkynyl, haloalkyl, cycloalkyl, carbocycle, heterocyclyl, heteroaryl, aryl, arylalkyl, heterocycloalkyl, heteroarylalkyl, arylalkoxy, aryloxy, heteroaryloxy, heterocycloxy, arylalkenyl, arylalkynyl, arylcycloalkyl, wherein each of these groups, wherever applicable, is further substituted with substituent(s) independently selected from halo, hydroxyl, (C _r C _{( )} alkyl, (CY jalkoxy, (C ₁ -C ₆ )acyloxy, haloalkyl, -N0 ₂ , -OCF ₃ , -CN, -(CR ^b R ^c )) _r NR ^d R ^e , -COOR ^d , -S(0) ₂ NR ^d R ^e , - S(0) ₂ (CR ^b R ^c ) _r , -C(0)NR ^d R ^e groups;.

In a preferred embodiment, R _| is selected from aryl or phenyl group, arylalkyl, arylalkoxy group optionally substituted with one or more halo, hydroxyl, (CYQjalkyl, (CYQjalkoxy, (C ₁ -C ₆ )acyloxy, haloalkyl, -N0 ₂ , -OCF ₃ , -CN, -(CR ^b R ^c )) _r NR ^d R ^e , -COOR ^d , -S(0) ₂ NR ^d R ^e , - S(0) ₂ (CR ^b R ^c ) _r and -C(0)NR ^d R ^e substituents; R ₂ is selected from H, alkyl, halo and haloalkyl;

In a preferred embodiment, R ₂ is H. is absent, or is selected from -H, -(CR ^ab R ^ac ) _r , -(CR ^ab R ^ac ) _r C(0)-, -C(0)-(CR ^ab R ^ac ) _r , -C(O)- C(O)-, -C(0)NR ^ad R ^ae -, -(CR ^ab R ^ac ) _t _C(0)NR ^ad R ^ae -, -(CR ^ab R ^ac ) _t _C(0)0R ^ad -, -C(0)-(CR ^ab R ^ac ) _t - OR ^ad -, -(CR ^ab R ^ac ) _t -OR ^ad -, -S(0) ₂ -, -S(0) ₂ NR ^ad R ^ae -, -S(0) ₂ _(CR ^ab R ^ac ) _r ;

In a preferred embodiment, Y is selected from -(CR ^ab R ^ac ) _t -C(0)-, -C(0)-(CR ^ab R ^ac ) _t - and - (CR ^ab R ^ac ) _t _C(0)0R ^ad -.

B is absent or is

4-10 member mono, bi or spirocyclic heterocycloalkyl containing one or more hetereoatoms independently selected from O, N, and S;

5-6 membered heterocycloalkenyl containing 1 double bond containing one or more heteroatom independently selected from O, N, and S;

5-6 membered heteroaryl containing one or more heteroatom independently selected from O, N, and S;

Aryl, arylalkyl, or selected from the following structures: In another preferred embodiment, B is absent or is selected from:

4-10 member monocyclic heterocycloalkyl containing one or more hetereoatoms independently selected from O, N, and S;

5-6 membered heteroaryl containing one or more heteroatom independently selected from O, N, and S.

In yet another preferred embodiment, B is absent or selected from the following structures:

R ₃ , R ₅ , and R ₆ are independently selected from H, (Q-Q alkyl, halo, haloalkyl, - (CR ^af R ^ag ) _v -COOR ^ah , -(CR ^af R ^ag ) _v -CONR ^ah R ^ai , -(CR ^af R ^ag ) _v -OR ^ah , -(CR ^af R ^ag ) _v -NR ^ah R ^ai , -S(0) ₂ - (CR ^af R ^ag ) _v , -S(0) ₂ -NR ^ah R ^ai , (C ₃ -C ₇ )cycloalkyl, heterocyclyl, aryl; In a preferred embodiment, R ₃ , R ₅ , and R ₆ are independently selected from H, (CVQjalkyl, haloalkyl.

R ₄ & R ₇ are independently selected from, H, (Q-C ₆ )alkyl, halo, haloalkyl, -OR' ¹ , -CN, - NR^R^, (C ₃ -C ₇ )cycloalkyl, aryl; In a preferred embodiment, R ₄ & R ₇ are independently selected from haloalkyl and -OR" ¹ .

R ^a , R ^b , R ^c , R ^d , R ^e , R ^f , R ^s , R ^h , R ¹ , R ^ab , R ^ac , R ^ad , R ^ae , R ^af , R ^ag , R ^ah , and R ^ai are independently selected from H, (Q-Qjalkyl, halo, haloalkyl, cycloalkyl, aryl or arylalkyl; In another preferred embodiment R ^a , R ^b , R ^c , R ^d , R ^e , R ^f , R ^g , R ^h , R\ R ^ab , R ^ac , R ^ad , R ^ae , R ^af , R ^ag , R ^ah , and R ^ai are independently selected from H and (Q-C ₆ )alkyl. r, s, t and v represents integers from 0-6.

In a preferred embodiment, the groups, radicals described above may be selected from: “Alkyl”, as well as other groups having the prefix “alk”, such as alkoxy and alkanoyl, means carbon chain which may either be linear or branched, and combinations thereof, unless the carbon chain is defined otherwise. Examples of alkyl group include but not limited to methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert.-butyl, pentyl, hexyl etc.

Where the specified number of carbon atoms permits e.g. from C _{3 10} , the term alkyl also includes cycloalkyl groups, and combinations of linear or branched alkyl chains combined with cycloalkyl structures.

“Cycloalkyl” is the subset of alkyl and means saturated carbocyclic ring having a specified number of carbon atoms, preferably 3-6 carbon atoms. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl etc. A cycloalkyl group generally is monocyclic unless otherwise stated. Cycloalkyl groups are saturated unless and otherwise stated.

“Aryl” means a mono- or polycyclic aromatic ring system containing carbon ring atoms. The preferred aryls are monocyclic or bicyclic 6-10 membered aromatic ring systems. Phenyl and naphthyl are preferred aryls.

“Heterocycloalkyl” means, a mono or polycyclic non-aromatic/saturated ring system containing carbon atoms and one or more heteroatoms selected from nitrogen, sulfur and oxygen. Examples of heterocycloalkyl include oxirane, oxetane, tetrahydrofuran, tetrahydro-2H-pyran, thietane, tetrahydrothiophene, tetrahydro-2H-thiopyran, azetidine, pyrrolidone, piperidine, azepane, diazetidine, imidazolidine, piperazine, diazepane, diazocane, triazinane, oxaziridine, oxazetidine, oxazolidine, morpholine, oxazepane, oxazocane, thiazetidine, thiazolidine, thiomorpholine, thiazepane, and thiazocane.

“Heterocycloalkenyl” means, a mono or polycyclic partially unsaturated ring system /containing double bond, containing carbon atoms and one or more heteroatoms selected from nitrogen, sulfur and oxygen. Examples of heterocycloalkenyl include cyclobutenyl, cyclopentenyl, and cyclohexenyl,

“Heteroaryl” means an aromatic or partially aromatic heterocycle that contains at least one ring heteroatom selected from nitrogen, sulfur and oxygen. Examples of heteroaryl include furanyl, pyranyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, benzofuranyl, indolyl, indazolyl, quinolinyl, benzothiazolyl, benzooxazolyl, benzoimidazolyl, and benzotriazolyl. Suitable groups and substituents on the groups may be selected from those described anywhere in the specification.

The term "substituted," as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. The term "substituted," as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound.

“Pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of the basic residues. Such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 1, 2-ethanedisulfonic, 2- acetoxybenzoic, 2-hydroxyethanesulfonic, acetic, ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric, eidetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicyclic, stearic, subacetic, succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, and toluenesulfonic.

In general, the term “cation” includes H, Na, K, Mg, Ca, NH ₄ ⁺ , (CH ₃ CH ₂ )3N ⁺ etc.

The term ‘optional’ or ‘optionally’ means that the subsequent described event or circumstance may or may not occur, and the description includes instances where the event or circumstance occur and instances in which it does not. For example, ‘optionally substituted alkyl’ means either ‘alkyl’ or ‘substituted alkyl’. Further an optionally substituted group means unsubstituted. Unless otherwise stated in the specification, structures depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. In the following examples molecules with a single chiral center, unless otherwise noted, exist as a racemic mixture. Those molecules with two or more chiral centers, unless otherwise noted, exist as a racemic mixture of diastereomers. Single enantiomers/diastereomers may be obtained by methods known to those skilled in the art. Particularly useful compounds may be selected from but not limited to the following;

Table: 1

Following is a list of abbreviations used in the description of the preparation of the compounds of the present invention:

ACN : Acetonitrile

BOC : tert-Butyloxy carbonyl

Cs ₂ C0 : Cesium carbonate

CDI : Carbonyl diimidazole

DCM : Dichloro methane

DIEA : Diisopropyl ethyl amine

DIPE : Diisopropyl ether

DMA : N,N-DimethyI acetamide

DMF : N,N-DimethyI formamide

DMSO : Dimethyl sulfoxide

EtOH : Ethanol

EtOAc : Ethyl acetate h : hours

HBTU :0-(BenzotriazoI-l-yI)-A,AA^' A'-tetramethyluronium hexafluorophosphate

HCI : Hydrochloric acid

H ₂ 0 ₂ : Hydrogen peroxide

HPLC : High performance liquid chromatography

IPA : Isopropyl alcohol K ₂ C0 ₃ : Potassium carbonate

MeOH : Methanol

MsCl : Methane sulfonylchloride

Mel : Methyl iodide NaBH ₄ : Sodium borohydride Na ₂ C0 ₃ : Sodium carbonate NaOH : Sodium hydroxide Na ₂ S0 ₄ : Sodium sulfate NaHC0 ₃ : Sodium bicarbonate/sodium hydrogen carbonate NMP : N-Methyl-2-pyrrolidone NaN ₃ : Sodium azide NaCN : Sodium cyanide POCl ₃ : Phosphorous oxychloride PTSA : -Tolucnc sulphonic acid fBuOK : Potassium to -butoxidc TEA : Triethylamine TFA : Trifluoro acetic acid THF : Tetrahydrofuran

TFC : Thin layer chromatography

The novel compounds of the present invention were prepared using the reactions and techniques described below, together with conventional techniques known to those skilled in the art of organic synthesis, or variations thereon as appreciated by those skilled in the art. The reactions can be performed in solvents appropriate to the reagents and materials employed and are suitable for the transformations being effected. Preferred methods include, but not limited to those described below, where all symbols are as defined earlier unless and otherwise defined below.

The compounds of the formula (I) can be prepared as described in general scheme-1 below along with suitable modifications/variations which are well within the scope of a person skilled in the art. Substituted bicyclic acids (II) can be treated with diversified amines (III) in an appropriate solvent to give compound (IV) under the condition of coupling reaction to prepare amide linkage or can be prepared by the method reported in literature along with their suitable modifications as may be necessary. Deprotection of Boc. group of compound (IV) can be accomplished by using appropriate acids like HC1, HBr, and TFA in a suitable solvent to give compound (V). N-alkylation or N-acylation of compound (V) using alkyl halides or acyl halides of the type (VI) can be carried out preferably with base like K ₂ C0 or Cs ₂ C0 in a suitable solvents like ACN, acetone and DMF or can be prepared by the conventional methods reported in literature or conventional techniques known to those skilled in the art of organic synthesis to furnish compounds of formula (I). General Scheme-1:

General Methods

Melting points were recorded on a scientific melting point apparatus and are uncorrected. IR spectra were recorded as neat (for oils) or on KBr pellet (for solid) on FT-IR 8300 Shimadzu and are reported in wavenumbers v (cm ¹ ). NMR spectra were measured on a Varian Unity 400 (' i at 400 MHz, ¹³ C at 100 MHz), magnetic resonance spectrometer. Spectra were taken in the indicated solvent at ambient temperature. Chemical shifts (d) are given in parts per million (ppm) with tetramethylsilane as an internal standard. Multiplicities are recorded as follows: s = singlet, d = doublet, t = triplet, q = quartet, br = broad. Coupling constants (/ values) are given in Hz. Mass spectra are recorded on Perkin - Elmer Sciex API 3000. ESI-Q-TOF-MS measurements were performed with a micrOTOF- Q II (Bruker Daltonics) mass spectrometer. HPLC analysis were carried out at lhiac 220 nm using column ODS C-18, 150 mm x 4.6 mm x 4 pm on AGILENT 1100 series. Reactions were monitored using thin layer silica gel chromatography (TLC) using 0.25 mm silica gel 60F plates from Merck. Plates were visualized by treatment with UV, acidic p-anisaldehyde stain, KMn0 ₄ stain with gentle heating. Products were purified by column chromatography using silica gel 100-200 mesh and the solvent systems indicated.

All reactions involving air or moisture sensitive compounds were performed under nitrogen atmosphere in flame dried glassware. Tetrahydrofuran (THF) and diethyl ether (Et ₂ 0) were freshly distilled from sodium/ benzophenone under nitrogen atmosphere.

Other solvents used for reactions were purified according to standard procedures. Starting reagents were purchased from commercial suppliers and used without further purification unless otherwise specified. Synthesis of Compound-49 [ 3,5-dichlorobenzyl (3R)-3-(2-(3-(3-hydroxyazetidin-l-yl)-3- oxopropyl)octahydrocyclopenta[c ]pyrrole-5-carboxamido )pyrrolidine-l -carboxylate ]

Synthesis of compound-49 (3,5-dichlorobenzyl (3R)-3-(2-(3-(3-hydroxyazetidin-l-yl)-3- oxopropyl)octahydrocyclopenta[c]pyrrole-5-carboxamido)pyrrol idine-l-carboxylate) was carried out as shown in Scheme-2 and the stepwise procedure is depicted below: Scheme-2: Step-1: Preparation of 3,5-dichlorobenzyl (R)-3-aminopyrrolidine-l-carboxylate (2)

To a solution of (3,5-dichloro phenyl) methanol (1.25 g, 7.09 mmol) in DMF was added I,G-carbonyldiimidazole (1.15 g, 7.09 mmol) at room temperature and stirred for 30 min. To the reaction mixture was added (tert -butyl (R)-pyrrolidin-3-ylcarbamate (1) (1.2 g, 6.44 mmol) in portions and stirred for lh at RT. Reaction was poured onto cold water and extracted with EtOAc (2 x 100 ml). Combined organic layer was washed with water (1 x 150 ml) and brine (1 x 100 ml), dried over anhydrous Na ₂ S0 ₄ and evaporated to dryness under reduced pressure to get 3,5-dichlorobenzyl (R)-3-((tert- butoxycarbonyl)amino)pyrrolidine-l-carboxylate as a solid (2.4 g). To the product thus obtained was added DCM (48 ml) followed by TFA (5.5 ml) at RT. Reaction mixture was stirred for 3h at RT. Reaction mixture was then treated with saturated NaHC0 _(aq) solution (100 ml). Layers were separated and organic layer was washed with water (100 ml) and brine solution (100 ml), dried over Na ₂ S0 ₄ , filtered, and concentrated to provide 3,5- dichlorobenzyl (R)-3-aminopyrrolidine-l-carboxylate (2) as a white solid (1.7 g, 91.4 % yield). H NMR: (CDC1 _3, 400 MHz): d 7.31 (t, 1H, /= 2.0Hz), 7.28-7.26 (m, 2H), 5.13 (s, 2H), 3.68-3.57 (m, 3H), 3.52-3.45 (m, 1H), 3.19-3.11 (m, 1H), 2.14-2.04 (m, 1H), 1.77-

1.65 (m, 1H); ESI-MS: (+ve mode) 289.04 (M+H) ⁺ (100 %). Step-2: _ tot-butyl 5-(((R)-l-(((3,5-dichlorobenzyl)oxy)carbonyl)pyrrolidin-3- vDcarbamoyl) hexahydrocvclopentalclpyrrole-2(lH)-carboxylate (4)

To a mixture of 3,5-dichlorobenzyl (R) -3 -aminopyrrolidine-1 -carboxylate (2) (1.5 g, 5.19 mmol), 2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5-carbo xylic acid (3) (1.46 g, 5.71 mmol) and DIEA (2.72 ml, 15.56 mmol) in DMF (30 ml) were added HBTU (2.36 g, 6.23 mmol) in portions at 0°C-5°C. After lh reaction mixture was gradually brought to RT and stirred for 18h. To the reaction mixture was added EtOAc (75 ml) and water (150 ml) were added. Layers were separated, and the aqueous layer was extracted with EtOAc (2 X 75 ml). The combined EtOAc layer were washed with water (2 x 150 ml) followed by brine (150 ml), dried over Na ₂ S0 ₄ , filtered, and concentrated to provide crude compound. Purified it by column chromatography to obtain tert- butyl 5-(((R)-l-(((3,5- dichlorobenzyl)oxy)carbonyl)pyrrolidin-3-yl)carbamoyl) hexahydrocyclopenta[c]pyrrole- 2(1 H) -carboxylate (4) (2.6 g, 95.2 % yield). ¹ H NMR: (CDCI ₃ , 400 MHz); d 7.36 (d, 1H, J = 2.0Hz), 7.28-7.25 (m, 2H), 5.08 (s, 2H), 4.68-4.65 (m, 1H), 4.31-4.25 (m, 1H), 3.72-3.67 (m, 1H), 3.53-3.50 (m, 4H), 3.32-3.25 (m, 1H), 3.12-3.07 (m, 2H), 2.96-2.92 (m, 1H),

2.78-2.76 (m, 2H), 2.23-2.17 (m, 1H), 2.10-2.01 (m, 2H), 1.97-1.81 (m, 1H), 1.80-1.76 (m, 1H), 1.46 (s, 9H). ESI-MS: (+ve mode) 426.13 (M-Boc) ⁺ (100 %).

Step-3: 3.5-dichlorobenzyl (3R)-3-(octahvdrocvclopentalclpyrrole-5-carboxamido ^' ) pyrrolidine- 1 -carboxylate (5)

To a solution of tert-butyl 5-(((R)-l-(((3,5-dichlorobenzyl)oxy)carbonyl)pyrrolidin-3- yl)carbamoyl) hexahydrocyclopenta[c]pyrrole-2(lH)-carboxylate (4) (2.7 g, 5.13 mmol) in DCM (54 ml) was added TFA (3.95 ml, 51.32 mmol) at RT. Reaction mixture was stirred for 3h at RT. Reaction mixture was then treated with saturated NaHC03(aq) solution (100 ml). Layers were separated and organic layer was washed with water (100 ml) and brine solution (75 ml), dried over Na2S04, filtered, and concentrated to provide 3,5- dichlorobenzyl (3R)-3-(octahydrocyclopenta[c]pyrrole-5-carboxamido)pyrrolid ine- 1 - carboxylate (5) (2.28 g, 82.2 % yield).1H NMR: (CDCI3, 400 MHz); d 7.48 (d, 1H, J = 2.0Hz), 7.45-7.42 (m, 2H), 5.08 (s, 2H), 4.69-4.67 (m, 1H), 4.32-4.25 (m, 1H), 3.74-3.67 (m, 1H), 3.56-3.49 (m, 4H), 3.32-3.24 (m, 1H), 3.12-3.07 (m, 2H), 2.96-2.92 (m, 1H),

2.78-2.76 (m, 2H), 2.23-2.18 (m, 1H), 2.10-2.01 (m, 2H), 1.98-1.81 (m, 1H), 1.80-1.76 (m, 1H). ESI-MS: (+ve mode) 427.12 (M)+ (100 %). Step-4: 3,5-dichlorobenzyl (3R ^' )-3-(2-(3-(3-hvdroxyazetidin-l-yl ^' )-3-oxopropyl ^' ) octahydrocyclopcn talc I pyrrolc-5-carhoxamido) pyrrolidine- 1 -carboxyl ate (Compound-49 ^' )

To a stirred solution of 3,5-dichlorobenzyl (3R)-3-(octahydrocyclopenta[c]pyrrole-5- carboxamido)pyrrolidine-l-carboxylate (5) (2.0 g, 4.71 mmol) in acetonitrile (40 ml), 3- chloro-l-(3-hydroxyazetidin-l-yl)propan-l-one (6) (1.46 g, 7.04 mmol) and K ₂ C0 ₃ (1.94 g, 14.08 mmol) were added and the mixture was heated to 60 °C. The reaction mass was filtered through celite and washed with ACN (2 x 20 ml). Combined filtrate was evaporated under reduced pressure and residue thus obtained was purified by column chromatography to provide the title compound 3,5-dichlorobenzyl (3R)-3-(2-(3-(3- hydroxyazetidin- 1 -yl)-3-oxopropyl)octahydrocyclopenta[c]pyrrole-5- carboxamido)pyrrolidine-l-carboxylate (Compound-49) as a white solid (2.46 g, 94.6 % yield). ¾ NMR: (CDCI ₃ , 400 MHz); d 7.48 (d, 1H, J= 2.0Hz), 7.45-7.42 (m, 2H), 5.08 (s, 2H), 4.69-4.67 (m, 1H), 4.32-4.25 (m, 1H), 3.74-3.67 (m, 1H), 3.56-3.49 (m, 4H), 3.32- 3.24 (m, 1H), 3.12-3.07 (m, 2H), 2.96-2.92 (m, 1H), 2.78-2.76 (m, 2H), 2.64-2.61 (m, 2H), 2.52-2.49 (m, 3H), 2.23-2.18 (m, 2H), 2.10-2.01 (m, 3H), 1.98-1.81 (m, 3H), 1.80-1.76 (m,

2H). ESI-MS: (+ve mode) 553.19 (M+H) ⁺ (100 %).

Synthesis of intermediate 3 [2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5- carboxylic acid]

Synthesis of substituent R ₃ (2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5- carboxylic acid) was carried out as shown in Scheme-3 and the stepwise procedure is depicted below: Scheme-3: 10 11 3

Step-1: tot-butyl 5-hvdroxyhexahvdrocvclopentalclpyrrole-2(lH)-carboxylate (8)

To a solution of teri-butyl 5-oxohexahydrocyclopenta[c]pyrrole-2(lH)-carboxylate (7) (20 g, 88.8 mmol) (Bahekar Rajesh H. et al., 2017, 21(2), 266-272) in MeOH (200 ml) was added NaBH ₄ (5.04 g, 133.21 mmol) in small portions at temperature below 5°C. The reaction mixture was stirred for 3h and then concentrated under reduced pressure. Residue was dissolved in DCM (200 ml) and washed it with IN HC1 (135 ml). Organic layer was washed with water (100 ml) and brine solution (75 ml), dried over Na ₂ S0 ₄ , filtered, and concentrated to provide teri-butyl 5-hydroxyhexahydrocyclopenta[c]pyrrole-2(lH)- carboxylate (8) as white solid (19.45 g, 96.4% yield). 'H NMR: (CDC1 _3, 400 MHz): d 4.31 (qint, 1H, / = 6.4Hz), 3.50 (dd, 2H, /, = 8.0Hz, J ₂ = 11.2Hz), 3.36 (dd, 2H, /, = 3.6Hz, J ₂ = 11.2Hz), 2.64-2.60 (m, 2H), 2.21-2.14 (m, 2H), 1.45-1.48 (m, 12H); ESI-MS: (+ve mode) 172.1 (M-OtBu) ⁺ (80 %).

Step-2: _ fert-butyl _ 5-((methylsulfonyl)oxy)hexahvdrocvclopentalclpyrrole-2(lH)- carboxylate (9)

To a solution of teri-butyl 5-hydroxyhexahydrocyclopenta[c]pyrrole-2(lH)-carboxylate (8) (20 g, 88.0 mmol), dissolved in DCM (200 ml) was added TEA (24.53 ml, 176.0 mmol) followed by MsCl (8.23 ml, 105.6 mmol) dropwise at 0-5 °C. Reaction mixture was stirred for 3h at 25 °C. Reaction mixture was washed sequentially with saturated NaHC0 _3(aq) solution (150 ml), water and brine (150 ml each) organic layer was separated, dried and evaporated to dryness under reduced pressure to get teri-butyl 5- ((methylsulfonyl)oxy)hexahydrocyclopenta[c]pyrrole-2(lH)-car boxylate (9) as a thick oil (26.3 g, 97.8% yield) which gets solidify at RT over the time. Product was used as such in next reaction step without any purification. 'H NMR: (CDCK 400 MHz): d 5.14-5.09 (m, 1H), 3.55-3.50 (m, 2H), 3.36-3.31 (m, 2H), 3.01 (s, 3H), 2.70-2.65 (m, 2H), 2.38-2.30 (m, 2H), 1.90-1.84 (m, 2H), 1.47(s, 9H); ESI-MS: (+ve mode) 250.07 (M-/Bu) ⁺ (90%). Step-3: tot-butyl 5-cvanohexahvdrocvclopentalclpyrrole-2(lH)-carboxylate (10)

To a solution of tot-butyl 5-((methylsulfonyl)oxy)hexahydrocyclopenta[c]pyrrole-2(lH)- carboxylate (9) (10 g, 32.74 mmol) in DMSO (10 ml) was added 18-CROWN-6 (0.606 g, 2.29 mmol followed by NaCN (8.02 g, 164.0 mmol). Reaction mixture was heated at 80°C for 5h. The reaction mixture cooled at room temperature, diluted with water (500 ml), extracted with ethyl acetate (200 ml X 3), and combined organic layer was washed with water (200 ml), brine (100 ml), dried over Na ₂ S0 ₄ and evaporated to dryness under reduced pressure to get tert- butyl 5-cyanohexahydrocyclopenta[c]pyrrole-2(lH)-carboxylate (10) as a light yellow oil (7.58g, 97.9% yield). Product was used for next reaction step without any purification. 'H NMR: (CDC1 _3, 400 MHz): d 3.53-3.51 (m, 2H), 3.17-3.12 (m, 2H), 3.02-2.96 (m, 1H), 2.91-2.86 (m, 2H), 2.22-2.15 (m, 2H), 1.96-1.91 (m, 2H), 1.46 (s, 9H); ESI-MS: (+ve mode) 181.1 (M-/Bu) ⁺ (100%). Step-4: 2-( tot-butyl ) 5-mcthyl 2,5( 1 H l-dicarhoxylatc (11 )

To a cold solution of tot-butyl 5-cyanohexahydrocyclopenta[c]pyrrole-2(lH)-carboxylate (4.5 g, 19.04 mmol) in MeOH (45.0 ml) was passed HCl _(g) for an hour maintaining temperature 0°C-5°C. Reaction mixture was gradually brought to room temperature and stirred for 2h. Reaction mixture was then concentrated and dried in vacuo, residue thus obtained was dissolved in mixture of Water (22.50 ml) and Acetonitrile (45 ml). Charged slowly Na ₂ C0 (6.05 g, 57.1 mmol) to it followed by dropwise addition of BOC- Anhydride (6.63 ml, 28.6 mmol) maintaining temperature 0°C-5°C. Reaction mixture was stirred overnight at RT, concentrated in vacuum to remove acetonitrile. Obtained residue was dissolved in ethyl acetate (100 ml), washed with water (50 ml) and brine (50 ml) solution, Removal of solvent under reduced pressure provided crude product which was purified by flash column chromatography(Gradient: 0 to 30% ethyl acetate in Hexane). The desired product 2-(tor-butyl) 5-methyl hexahydrocyclopenta[c]pyrrole-2,5(lH)- dicarboxylate (ll)_was isolated as colorless thick oil (3.78 g, 73.7 % yield). 'H NMR: (CDCI3 _, 400 MHz): d 4.08 (s, 3H), 3.51-3.45 (m, 2H), 3.12-3.07 (m, 2H), 2.96-2.92 (m, 1H), 2.78-2.76 (m, 2H), 2.10-2.01 (m, 2H), 1.82-1.78 (m, 2H), 1.44 (s, 9H); ESI-MS: (+ve mode) 170.1 (M-Boc) ⁺ (90%). Step-5: 2-(tert-butoxycarbonyl)octahvdrocvclopentaic]pyrrole-5-carbo xylic acid (3)

To a stirred solution of 2-(to -butyl) 5-methyl hexahydrocyclopenta[c]pyrrole-2,5(lH)- dicarboxylate (11) (2.5 g, 9.28 mmol) in MeOH (25 ml) was added 5M NaOH _{(aq )} (5.57 ml, 27.8 mmol) at temperature 0°C-5°C. Reaction mixture was gradually brought to ambient temperature and stirred overnight. Reaction mixture was then concentrated in vacuum to remove methanol, residue obtained was dissolved in water (25 ml) and acidified to 4 pH using citric acid solution. The aqueous mixture was extracted with DCM (25 ml X 3) and combined organic layer was washed with brine (25 ml), dried over Na ₂ S0 ₄ . The solvent was removed in vacuo to afford 2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5- carboxylic acid (3) as colourless thick oil (2.35 g, 9.20 mmol, 99 % yield), which on standing get solidified. 'H NMR: (CDC1 _3, 400 MHz): d 9.13 (bs, 1H), 3.55-3.49 (m, 2H), 3.28-3.25 (m, 1H), 3.13-3.07 (m, 1H), 2.97-2.91 (m, 1H), 2.80-2.78 (m, 1H), 2.65-2.64 (m, 1H), 2.25-2.16 (m, 1H), 2.14-2.11 (m, 1H), 2.09-1.76 (m, 2H), 1.46 (s, 9H); ESI-MS: (+ve mode) 200.11 (M-OtBu) ⁺ (90%). Following specific novel compounds of general formula (I) of the present invention are prepared by using methods depicted in general scheme-1 and scheme-2.

Compound-3:3,5-dichlorobenzyl-(3R)-3-(2-(2-ethoxy-2-oxoet hyl)octahydrocyclo- penta[c]pyrrole-5-carboxamido) pyrrolidine- 1 -carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.32 (d, 1H, J = 2.3Hz), 7.26-7.25 (m, 2H), 5.08 (s, 2H), 4.52-4.46 (m, 2H), 4.28-4.14 (m, 2H), 4.12-4.07 (m, 3H), 3.70-3.61 (m, 2H), 3.59-3.58 (m, 2H), 3.34-3.27 (m, 3H), 3.24-3.16 (m, 2H), 2.19-2.15 (m, 3H), 1.90-1.84 (m, 3H), 1.39- 1.32 (m, 4H). ESI-MS: (+ve mode) 512.43 (M+H) ⁺ (100 %).

Compound-7:3,5-dichlorobenzyl-(3R)-3-(2-(2-(3-hydroxyazet idin-l-yl)-2-oxoethyl) octahydrocyclopenta[c]pyrrole-5-carboxamido)pyrrolidine-l-ca rboxylate ¾ NMR: (CDCI ₃ , 400 MHz); d 7.54 (d, 1H, / = 2.0Hz), 7.46-7.41 (m, 2H), 6.35-6.28 (m, 1H), 5.08 (s, 2H), 4.99-4.97 (m, 1H), 4.96-4.95 (m, 1H), 4.69-4.67 (m, 1H), 4.46-4.38 (m, 1H), 4.26-4.24 (m, 1H), 3.98-3.92 (m, 1H), 3.81-3.78 (m, 1H), 3.67-3.52 (m, 2H), 3.36- 3.29 (m, 1H), 3.20-3.11 (m, 1H), 2.95-2.92 (m, 1H), 2.89-2.75 (m, 2H), 2.67-2.61 (m, 2H),

2.55-2.44 (m, 2H), 2.34-2.31 (m, 1H), 2.23-2.18 (m, 1H), 2.11-2.01 (m, 2H), 1.98-1.81 (m, 2H), 1.80-1.76 (m, 2H). ESI-MS: (+ve mode) 539.14 (M+H) ⁺ (100 %).

Compound-8:3,5-dichlorobenzyl-(3S)-3-(2-(2-(3-hydroxyazet idin-l-yl)-2- oxoethyl)octahydro cyclopenta[c]pyrrole-5-carboxamido)pyrrolidine-l-carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.54 (d, 1H, / = 2.0Hz), 7.46-7.42 (m, 2H), 6.35-6.27 (m, 1H), 5.08 (s, 2H), 4.99-4.97 (m, 1H), 4.96-4.95 (m, 1H), 4.69-4.67 (m, 1H), 4.48-4.38 (m, 1H), 4.26-4.24 (m, 1H), 3.98-3.90 (m, 1H), 3.81-3.78 (m, 1H), 3.68-3.52 (m, 2H), 3.37- 3.29 (m, 1H), 3.20-3.11 (m, 1H), 2.95-2.92 (m, 1H), 2.89-2.75 (m, 2H), 2.67-2.61 (m, 2H),

2.55-2.44 (m, 2H), 2.34-2.31 (m, 1H), 2.23-2.18 (m, 1H), 2.10-2.01 (m, 2H), 1.98-1.81 (m, 2H), 1.80-1.76 (m, 2H). ESI-MS: (+ve mode) 539.17 (M+H) ⁺ (100 %).

Compound- 14: 3,5-dichlorobenzyl (3R)-3-(2-(2-((S)-3-hydroxy pyrrolidin-l-yl)-2- oxoethyl) octahydrocyclopenta [c]pyrrole-5-carboxamido)pyrrolidine-l-carboxylate ¾ NMR: (CDCI3, 400 MHz); d 7.56 (d, 1H, / = 2.2Hz), 7.47-7.43 (m, 2H), 5.94-5.86 (m, 1H), 5.08 (s, 2H), 4.49-4.37 (m, 1H), 4.28-4.16 (m, 1H), 3.90-3.87 (m, 2H), 3.77-3.68 (m, 1H), 3.38-3.31 (m, 3H), 3.18-3.11 (m, 2H), 2.92-2.90 (m, 2H), 2.76-2.69 (m, 2H), 2.61- 2.57 (m, 2H), 2.30-2.27 (m, 1H), 1.92-1.81 (m, 7H), 1.74-1.69 (m, 2H), 1.53-1.49 (m, 2H), 1.33-1.27 (m, 1H). ESI-MS: (+ve mode) 553.80 (M+H) ⁺ (100 %).

Compound- 17:3, 5-dichlorobenzyl-(3R)-3-(2-(2-(4-hydroxypiperidin-l-yl)-2-ox oethyl) octahydrocyclopenta[c]pyrrole-5-carboxamido)pyrrolidine-l-ca rboxylate ¾ NMR: (CDCI3, 400 MHz); d 7.54 (d, 1H, J = 2.0Hz), 7.46-7.42 (m, 2H), 5.94-5.86 (m,

1H), 5.08 (s, 2H), 4.49-4.37 (m, 1H), 4.28-4.16 (m, 1H), 3.90-3.87 (m, 2H), 3.77-3.68 (m, 1H), 3.52-3.42 (m, 2H), 3.38-3.31 (m, 3H), 3.18-3.11 (m, 2H), 2.92-2.90 (m, 2H), 2.76- 2.69 (m, 2H), 2.61-2.57 (m, 2H), 2.30-2.27 (m, 1H), 1.90-1.81 (m, 7H), 1.72-1.69 (m, 2H), 1.51-1.48 (m, 2H), 1.33-1.27 (m, 1H). ESI-MS: (+ve mode) 567.21 (M+H) ⁺ (100 %).

Compound-33: 3,5-dichlorobenzyl (3R)-3-(2-(2-(2,6-dihydropyrrolo [3,4-c]pyrazol- 5(4H)-yl)-2-oxoethyl)octahydrocyclopenta[c]pyrrole-5-carboxa mido)pyrrolidine-l- carboxylate

¾ NMR: (DMSO, 400 MHz); d 12.71 (s, 1H), 8.09 (s, 1H), 7.56-7.50 (m, 2H), 7.43-7.40 (m, 2H), 5.15-5.05 (m, 2H), 5.08 (s, 2H), 4.67-4.62 (m, 2H), 4.36-4.18 (m, 3H), 3.56-3.53

(m, 1H), 3.48-3.43 (m, 2H), 3.31-3.27 (m, 2H), 2.79-2.72 (m, 2H), 2.68-2.63 (m, 2H), 2.56-2.53 (m, 2H), 1.77-1.71 (m, 2H), 1.54 (m, 4H). ESI-MS: (+ve mode) 575.19 (M+H) ⁺ (100 %). Compound-34: 3,5-dichlorobenzyl (3R)-3-(2-(2-(2-methyl-2,6-dihydropyrrolo[3,4- c] pyr azol-5 (4H) -yl) -2 -oxoethyl) octahydrocyclopentafc] pyrrole-5 -carboxamido) pyrrolidine- 1 -carboxylate ¾ NMR: (DMSO, 400 MHz); d 8.09 (s, 1H), 7.56-7.50 (m, 2H), 7.43-7.40 (m, 2H), 5.15-

5.05 (m, 2H), 5.08 (s, 2H), 4.67-4.62 (m, 2H), 4.36-4.18 (m, 3H), 3.83 (s, 3H), 3.56-3.53 (m, 1H), 3.48-3.43 (m, 2H), 3.31-3.27 (m, 2H), 2.79-2.72 (m, 2H), 2.68-2.63 (m, 2H), 2.56-2.53 (m, 2H), 1.77-1.71 (m, 2H), 1.54 (m, 4H). ESI-MS: (+ve mode) 589.20 (M+H) ⁺ (100 %). Compound-35:3,5-dichlorobenzyl-(3R)-3-(2-(2-(2-isopropyl-2,6 -dihydropyrrolo[3,4-c] pyrazol-5(4H)-yl)-2-oxoethyl) octahydrocyclopenta[c]pyrrole-5-carboxamido) pyrrolidine- 1 -carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.32-7.25 (m, 4H), 5.84-5.82 (m, 1H), 5.08 (s, 2H), 4.67- 4.51 (m, 3H), 4.48-4.46 (m, 2H), 3.75-3.68 (m, 1H), 3.54-3.52 (m, 2H), 3.31-3.27 (m, 2H),

2.79-2.72 (m, 2H), 2.68-2.63 (m, 2H), 2.56-2.53 (m, 2H), 2.19-2.16 (m, 1H), 1.97-1.85 (m, 6H), 1.77-1.71 (m, 2H), 1.54 (d, 6H, J = 6.8Hz). ESI-MS: (+ve mode) 617.23 (M+H) ⁺ (100 %). Compound-41: 3,5-dichlorobenzyl (3R)-3-(2-(2-(5,6-dihydro-[l,2,4]triazolo[4,3- a]pyrazin-7(8H)-yl)-2-oxoethyl)octahydrocyclopenta[c]pyrrole -5- carboxamido)pyrrolidine- 1 -carboxylate ¾ NMR: (CDCI ₃ , 400 MHz); d 8.04-7.97 (m, 1H), 7.62 (d, 1H, / = 2.5Hz), 7.46-7.42 (m, 3H), 5.84-5.82 (m, 1H), 5.07 (s, 2H), 4.67-4.51 (m, 3H), 4.48-4.46 (m, 2H), 3.75-3.68 (m, 1H), 3.54-3.52 (m, 2H), 3.31-3.27 (m, 2H), 2.79-2.72 (m, 2H), 2.68-2.63 (m, 2H), 2.56- 2.53 (m, 2H), 2.19-2.16 (m, 2H), 1.97-1.94 (m, 2H), 1.91-1.85 (m, 4H), 1.39-1.36 (m, 2H).

ESI-MS: (+ve mode) 519.20 (M+H) ⁺ (100 %).

Compound-44:3,5-dichlorobenzyl-(3R)-3-(2-(2-oxo-2-(3-(tri fluoromethyl)-5,6-dihydro- [l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)ethyl)octahydrocyclop enta[c]pyrrole-5- carboxamido)pyrrolidine- 1 -carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.54 (d, 1H, / = 2.0Hz), 7.46-7.42 (m, 2H), 5.84-5.82 (m, 1H), 5.08 (s, 2H), 4.67-4.51 (m, 3H), 4.48-4.46 (m, 2H), 3.75-3.68 (m, 1H), 3.54-3.52 (m, 2H), 3.31-3.27 (m, 2H), 2.79-2.72 (m, 2H), 2.68-2.63 (m, 2H), 2.56-2.53 (m, 2H), 2.19-

2.16 (m, 2H), 1.97-1.94 (m, 2H), 1.91-1.85 (m, 4H), 1.74-1.71 (m, 2H). ESI-MS: (+ve mode) 658.18 (M+H) ⁺ (100 %).

Compound-49:3,5-dichlorobenzyl-(3R)-3-(2-(3-(3-hydroxyaze tidin-l-yl)-3- oxopropyl)octahydrocyclopenta[c]pyrrole-5-carboxamido)pyrrol idine-l-carboxylate ¾ NMR: (CDCI ₃ , 400 MHz); d 7.56 (d, 1H, / = 2.1Hz), 7.47-7.42 (m, 2H), 6.35-6.28 (m, 1H), 5.08 (s, 2H), 4.99-4.97 (m, 1H), 4.96-4.95 (m, 1H), 4.70-4.67 (m, 1H), 4.46-4.38 (m,

1H), 4.26-4.24 (m, 1H), 3.98-3.92 (m, 1H), 3.81-3.78 (m, 1H), 3.67-3.52 (m, 2H), 3.36- 3.29 (m, 1H), 3.20-3.11 (m, 1H), 2.95-2.92 (m, 1H), 2.89-2.75 (m, 4H), 2.67-2.61 (m, 2H),

2.55-2.44 (m, 2H), 2.34-2.31 (m, 1H), 2.23-2.18 (m, 1H), 2.11-2.01 (m, 2H), 1.97-1.90 (m, 2H), 1.80-1.76 (m, 2H). ESI-MS: (+ve mode) 553.68 (M+H) ⁺ (100 %).

Compound-67:3,5-dichlorobenzyl (3R)-3-(2-(2-(3-hydroxyazetidin-l-yl)-2-oxoethyl)-N- methyloctahydro cyclopenta[c] pyrrole-5-carboxamido)pyrrolidine-l-carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.54 (d, 1H, / = 2.0Hz), 7.46-7.41 (m, 2H), 6.35-6.28 (m, 1H), 5.08 (s, 2H), 4.99-4.97 (m, 1H), 4.96-4.95 (m, 1H), 4.69-4.67 (m, 1H), 4.46-4.38 (m,

1H), 4.26-4.24 (m, 1H), 3.98-3.92 (m, 1H), 3.81-3.78 (m, 1H), 3.67-3.52 (m, 2H), 3.36- 3.29 (m, 1H), 3.27 (s, 3H), 3.20-3.11 (m, 1H), 2.95-2.92 (m, 1H), 2.89-2.75 (m, 2H), 2.67-

2.61 (m, 2H), 2.55-2.44 (m, 2H), 2.34-2.31 (m, 1H), 2.23-2.18 (m, 1H), 2.11-2.01 (m, 2H), 1.98-1.81 (m, 2H), 1.80-1.76 (m, 2H). ESI-MS: (+ve mode) 553.804 (M+H) ⁺ (100 %).

Compound-69:3,5-dichlorobenzyl-(3R)-3-(2-(2-(3-hydroxyaze tidin-l-yl)-2-oxoethyl) octahydrocyclopenta[c]pyrrole-5-carboxamido)pyrrolidine- 1 -carboxylate ¾ NMR: (CDCI ₃ , 400 MHz); d 7.54 (d, 1H, / = 2.0Hz), 7.46-7.41 (m, 2H), 6.35-6.28 (m, 1H), 5.08 (s, 2H), 4.99-4.97 (m, 1H), 4.96-4.95 (m, 1H), 4.69-4.67 (m, 1H), 4.46-4.38 (m, 1H), 4.26-4.24 (m, 1H), 3.98-3.92 (m, 1H), 3.81-3.78 (m, 1H), 3.67-3.52 (m, 2H), 3.36- 3.29 (m, 1H), 3.20-3.11 (m, 1H), 2.95-2.92 (m, 1H), 2.89-2.75 (m, 2H), 2.67-2.61 (m, 2H), 2.55-2.44 (m, 2H), 2.34-2.31 (m, 1H), 2.23-2.18 (m, 1H), 2.11-2.01 (m, 2H), 1.98-1.81 (m,

2H), 1.80-1.76 (m, 2H). ESI-MS: (+ve mode) 507.23 (M+H) ⁺ (100 %).

Compound-77:N-((R)-l-(3-(3,5-dichlorophenyl)propanoyl)pyr rolidin-3-yl)-2-(2-(3- hydroxyazetidin-l-yl)-2-oxoethyl )octahydrocyclopenta[c]pyrrole-5-carboxamide ¾ NMR: (CDCI ₃ , 400 MHz); d 8.06-8.01 (m, 1H), 7.41 (d, 1H, J = 2.0Hz), 7.39-7.34 (m,

2H), 6.35-6.28 (m, 1H), 5.69 (s, 1H), 4.99-4.97 (m, 1H), 4.96-4.95 (m, 1H), 4.69-4.67 (m, 1H), 4.46-4.38 (m, 1H), 4.26-4.24 (m, 2H), 3.98-3.92 (m, 1H), 3.81-3.78 (m, 1H), 3.67- 3.52 (m, 2H), 3.36-3.29 (m, 1H), 3.20-3.11 (m, 1H), 2.95-2.92 (m, 2H), 2.89-2.75 (m, 2H), 2.67-2.61 (m, 2H), 2.55-2.44 (m, 2H), 2.34-2.31 (m, 1H), 2.23-2.18 (m, 1H), 2.11-2.01 (m, 2H), 1.98-1.81 (m, 2H), 1.80-1.76 (m, 2H). ESI-MS: (+ve mode) 537.20 (M+H) ⁺ (100 %).

Compound-86:3,5-dichlorobenzyl4-(2-(2-(3-hydroxyazetidin- l-yl)-2-oxoethyl)octahydro- cyclopenta[c]pyrrole-5-carboxamido)piperidine- 1 -carboxylate ¾ NMR: (CDCI ₃ , 400 MHz); d 7.32 (s, 1H), 7.24 (s, 2H), 5.89-5.87 (d, 1H, J = 7.6Hz),

5.07 (s, 2H), 4.68-4.65 (m, 1H), 4.41-4.37 (m, 1H), 4.28-4.24 (m, 1H), 4.11-4.08 (m, 3H), 3.96-3.89 (m, 2H), 3.14-3.10 (m, 1H), 2.99-2.89 (m, 3H), 2.79-2.76 (m, 3H), 2.69-2.58 (m, 2H), 2.46-2.41 (m, 2H), 2.33-2.16 (m, 4H), 1.95-1.93 (m, 2H), 1.74-1.71 (m, 2H), 1.27- 1.22 (m, 1H). ESI-MS: (+ve mode) 553.19 (M+H) ⁺ (100 %). Compound- 100:3, 5-dichlorobenzyl-4-(2-(2-morpholino-2-oxoethyl)-octahydrocyc lo- penta[c]pyrrole-5 -carboxamido) piperidine- 1 -carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.34 (s, 1H), 7.24 (s, 2H), 5.89-5.87 (d, 1H, / = 7.6Hz), 5.07 (s, 2H), 4.68-4.65 (m, 1H), 4.41-4.37 (m, 1H), 4.28-4.24 (m, 1H), 4.11-4.08 (m, 3H),

3.96-3.89 (m, 2H), 3.14-3.10 (m, 1H), 2.99-2.89 (m, 3H), 2.79-2.76 (m, 3H), 2.69-2.58 (m, 4H), 2.46-2.41 (m, 4H), 2.33-2.16 (m, 4H), 1.95-1.93 (m, 2H), 1.74-1.71 (m, 2H), 1.27- 1.22 (m, 1H). ESI-MS: (+ve mode) 567.80 (M+H) ⁺ (100 %). Compound-110: 3,5-dichlorobenzyl 4-(2-(2-(2-isopropyl-2, 6-dihydro pyrrolo[3,4- c]pyrazol-5(4H)-yl)-2-oxoethyl)octahydrocyclopenta[c]pyrrole -5-carboxamido)piperidine- 1 -carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.33 (s, 1H), 7.28-7.21 (m, 2H), 5.63-5.59 (d, 1H, J = 7.6Hz), 5.07 (s, 2H), 4.68-4.62 (m, 1H), 4.57-4.53 (m, 1H), 4.52-4.48 (m, 2H), 4.11-4.08

(m, 3H), 3.96-3.89 (m, 1H), 3.30-3.27 (m, 1H), 2.97-2.79 (m, 2H), 2.79-2.76 (m, 4H), 2.58-2.54 (m, 2H), 2.06-2.01 (m, 3H), 2.33-2.16 (m, 4H), 1.96-1.93 (m, 5H), 1.54-1.50 (m, 6H), 1.29-1.26 (m, 2H). ESI-MS: (+ve mode) 631.24 (M+H) ⁺ (100 %).

Compound- 143 : 3 ,5-dichlorobenzyl-4-(2-(2-(3-hydroxyazetidin- 1 -yl)-2-oxoethyl)-N - methyloctahydrocyclopenta[c]pyrrole-5-carboxamido)piperidine -l -carboxylate ¾ NMR: (CDCI ₃ , 400 MHz); d 7.58 (s, 1H), 7.43-7.40 (m, 2H), 5.69-5.63 (d, 1H, J = 7.6Hz), 5.08 (s, 2H), 4.68-4.65 (m, 1H), 4.41-4.37 (m, 1H), 4.28-4.24 (m, 1H), 4.11-4.08 (m, 3H), 3.96-3.89 (m, 2H), 3.14-3.10 (m, 1H), 2.99-2.89 (m, 3H), 2.84 (s, 3H), 2.79-2.76 (m, 3H), 2.69-2.58 (m, 2H), 2.46-2.41 (m, 2H), 2.33-2.16 (m, 3H), 1.95-1.93 (m, 2H), 1.74-1.71 (m, 2H), 1.27-1.22 (m, 1H). ESI-MS: (+ve mode) 567.21 (M+H) ⁺ (100 %).

Compound- 144:3, 5-dichlorobenzyl-(3R)-3-(2-(2-(3-hydroxyazetidin-l-yl)-2-oxo ethyl) octahydrocyclopenta[c]pyrrole-5-carboxamido)piperidine-l-car boxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.33 (s, 1H), 7.28-7.25 (m, 2H), 5.93 (d, 1H, J = 7.2Hz), 5.09 (s, 2H), 4.65-4.64 (m, 1H), 4.38-4.29 (m, 1H), 4.28-4.25 (m, 1H), 4.13-4.11 (m, 1H),

3.99-3.97 (m, 1H), 3.89-3.88 (m, 1H), 3.73-3.68 (m, 1H), 3.37-3.29 (m, 2H), 3.18-3.11 (m, 1H), 2.97-2.92 (m, 1H), 2.89-2.74 (m, 3H), 2.67-2.62 (m, 2H), 2.55-2.44 (m, 2H), 2.26- 2.21 (m, 7H), 1.98-1.81 (m, 1H), 1.73-1.61 (m, 2H). ESI-MS: (+ve mode) 539.17 (M+H) ⁺ (100 %). Compound- 153:N-(l-(3-(3, 5-dichlorophenyl)propanoyl)piperidin-4-yl)-2-(2-(3-hydroxy- azetidin-l-yl)-2-oxoethyl)octahydro cyclopenta[c]pyrrole-5-carboxamide

¾ NMR: (CDCI ₃ , 400 MHz); d 7.77 (s, 1H), 7.41 (s, 2H), 5.09 (s, 2H), 4.68-4.65 (m, 1H), 4.41-4.37 ( _m , m _), 4.28-4.24 (m, 1H), 4.11-4.08 (m, 3H), 3.96-3.89 (m, 2H), 3.14-3.10 (m, 1H), 2.99-2.89 (m, 3H), 2.79-2.76 (m, 3H), 2.69-2.58 (m, 2H), 2.46-2.41 (m, 2H), 2.33-

2.16 (m, 4H), 1.95-1.93 (m, 2H), 1.74-1.71 (m, 2H), 1.27-1.18 (m, 4H). ESI-MS: (+ve mode) 551.21 (M+H) ⁺ (100 %). Compound- 157:N-(l-(2-(3,5-dichlorophenoxy)acetyl)piperidin-4-yl)-2-(2 -(3-hydroxy- azetidin-l-yl)-2-oxoethyl)octahydro cyclopenta[c]pyrrole-5-carboxamide

¾ NMR: (CDCI ₃ , 400 MHz); d 7.81 (s, 1H), 7.13-7.04 (m, 3H), 5.89-5.87 (d, 1H, J = 7.6Hz), 5.07 (s, 2H), 4.69-4.65 (m, 1H), 4.41-4.38 (m, 1H), 4.28-4.24 (m, 1H), 4.11-4.08

(m, 3H), 3.96-3.89 (m, 2H), 3.14-3.10 (m, 1H), 2.98-2.89 (m, 3H), 2.79-2.76 (m, 3H), 2.69-2.58 (m, 2H), 2.46-2.41 (m, 2H), 2.33-2.16 (m, 3H), 1.95-1.93 (m, 2H), 1.74-1.71 (m, 2H), 1.29-1.23 (m, 1H). ESI-MS: (+ve mode) 553.27 (M+H) ⁺ (100 %).

Compound-165: 3,5-dichlorobenzyl-5-(2-(2-(3-hydroxyazetidin-l-yl)-2- oxoethyl)octahydro cyclopenta[c]pyrrole-5-carboxamido)hexahydrocyclopenta[c]pyr role- 2(1 H)-carboxylate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.32 (s, 1H), 7.24 (s, 2H), 5.89-5.87 (d, 1H, / = 7.6Hz), 5.07 (s, 2H), 4.68-4.65 (m, 1H), 4.41-4.37 (m, 1H), 4.28-4.24 (m, 1H), 4.11-4.08 (m, 3H), 3.96-3.89 (m, 2H), 3.14-3.10 (m, 1H), 2.99-2.89 (m, 2H), 2.79-2.76 (m, 3H), 2.69-2.58 (m,

2H), 2.46-2.41 (m, 2H), 2.33-2.16 (m, 4H), 1.95-1.93 (m, 2H), 1.74-1.71 (m, 2H), 1.27- 1.22 (m, 1H). ESI-MS: (+ve mode) 579.21 (M+H) ⁺ (100 %).

Compound- 169:3, 5-dichlorobenzyl-4-(2-(2-(3-hydroxyazetidin-l-yl)-2-oxoethyl )- octahydrocyclopenta[c]pyrrole-5-carbonyl)piperazine-l-carbox ylate ¾ NMR: (CDCI ₃ , 400 MHz); d 7.34 (s, 1H), 7.28 (s, 2H), 5.10 (s, 2H), 4.68-4.65 (m, 1H), 4.41-4.37 ( _m , m _), 4.28-4.24 (m, 1H), 4.11-4.08 (m, 3H), 3.96-3.89 (m, 2H), 3.14-3.10 (m, 1H), 2.99-2.89 (m, 3H), 2.79-2.76 (m, 3H), 2.69-2.58 (m, 2H), 2.46-2.41 (m, 4H), 2.33- 2.16 (m, 4H), 1.95-1.93 (m, 2H), ESI-MS: (+ve mode) 553.19 (M+H) ⁺ (100 %). Compound- 171:3, 5-dichlorobenzyl-5-(2-(2-(3-hydroxyazetidin-l-yl)-2-oxoethyl ) octahydrocyclopenta[c]pyrrole-5-carbonyl)hexahydropyrrolo[3, 4-c]pyrrole-2(lH)- carboxylatc _'

¾ NMR: (CDCI ₃ , 400 MHz); d 7.33 (s, 1H), 7.28-7.25 (m, 2H), 5.10-5.05 (m, 2H), 4.66- 4.64 (m, 1H), 4.44-4.42 (m, 1H), 4.40-4.37 (m, 1H), 4.29-4.11 (m, 1H), 3.91-3.90 (m, 1H),

3.89-3.88 (m, 1H), 3.78-3.72 (m, 3H), 3.68-3.65 (m, 2H), 3.43-3.41 (m, 2H), 3.15-3.12 (m, 1H), 3.03-2.93 (m, 3H), 2.91-2.80 (m, 3H), 2.76-2.74 (m, 1H), 2.44-2.41(m, 1H), 2.34- 2.31 (m, 1H), 2.07-1.97 (m, 3H), 1.72-1.69 (m, 1H), 1.29-1.27 (m, 1H). ESI-MS: (+ve mode) 565.19 (M+H) ⁺ (100 %). Compound- 176:3, 5-dichlorobenzyl-(2-(2-(2-(3-hydroxyazetidin-l-yl)-2-oxoethy l)- octahydrocyclopenta[c]pyrrole-5-carbonyl)octahydrocyclopenta [c]pyrrol-5-yl)carbamate

¾ NMR: (CDCI ₃ , 400 MHz); d 7.35 (s, 1H), 7.26-7.24 (m, 2H), 5.12-5.05 (m, 2H), 4.67- 4.64 (m, 1H), 4.44-4.42 (m, 1H), 4.40-4.37 (m, 1H), 4.29-4.11 (m, 1H), 3.91-3.90 (m, 1H), 3.89-3.88 (m, 1H), 3.78-3.72 (m, 3H), 3.67-3.65 (m, 2H), 3.43-3.41 (m, 2H), 3.15-3.12 (m,

1H), 3.03-2.93 (m, 3H), 2.91-2.80 (m, 3H), 2.75-2.76 (m, 1H), 2.44-2.41(m, 1H), 2.34- 2.31 (m, 1H), 2.11-1.97 (m, 4H), 1.72-1.69 (m, 2H), 1.30-1.27 (m, 2H). ESI-MS: (+ve mode) 579.52 (M+H) ⁺ (100 %). In some embodiments, the present invention includes a pharmaceutical composition comprising the compound of formula (I) or their pharmaceutically acceptable salts, tautomeric forms, enantiomers and their diastereomers, formulated with or without one or more pharmaceutical excipients.

In some embodiments, the present invention includes a method for the treatment of at least one of cancer, chronic inflammation, neuropathic pain, fibrotic diseases mediated in part by ATX comprising administering to a subject in need thereof a therapeutically effective amount of a compound or salt of the novel compound of formula (I).

Biological studies:

ATX Inhibitory activity (IC ₅₀ determination):

ATX Inhibitory activity was determined in a biochemical or whole blood assay as described previously (Bretschneider, T. et al., SLAS Discov 2017, 22, 425). The biochemical reaction consisted of 50 mM Tris (pH 8.0), 3 mM KC1, 1 mM CaCl ₂ , 1 mM Mg Cl ₂ , 0.14 mM NaCl and 0.1% bovine serum albumin, which was supplemented with 5 nM recombinant rat ATX, 5 mM 18:1 LPC and the test compound (0.1 - 10 mM). The reaction was stopped at 2 h by the addition of butanol, prior to the RapidFire -MS-based analysis.

The whole blood assay consisted of 45 pL heparinized mice/ rat whole blood and the test compound (0.12 - 100 mM). The reaction was stopped after 1 h at 37 °C by addition of 100 pL 40 mM disodium hydrogen phosphate buffer containing 30 mM citric acid (pH 4) and 1 pM 17:0 LPA (internal standard). Afterwards the samples were treated as described above and analysed by LC-MS/MS. The data was analyzed using graph pad prism (v 7.03) to arrive at the half-maximal inhibitory concentrations (IC50) of the test compounds.

Mice serum ATX inhibitory activity (IC50) for representative compounds are listed in the

Table 2.

In an embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) and optionally one or more pharmaceutically acceptable excipients. The novel compounds of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients by techniques and processes and concentrations as are well known.

One or more pharmaceutical excipients are selected from known to those skilled in the art such as diluents, carries, lubricants fillers and the like. The pharmaceutical compositions further comprise an effective amount of compounds of formula (I) or pharmaceutically acceptable salts thereof. The dosage of compounds of formula (I) may vary within wide limits and should be adjusted, in each particular case, to the individual conditions. In an embodiment, the compound of formula (I), may be used alone or in any combination with one or more therapeutic agents such as anti-inflammatory agents, antitumor agents, antifibrotic agents, autotaxin inhibitors, immunomodulators and cardiovascular agents and other therapeutic agents which are known to skilled medical practitioner. The selection of such therapeutic agents may be depend upon the type of disease and its severity, condition of patient being treated, and other medications being taken by the patients, etc.

The compounds of formula (I), or pharmaceutical compositions containing them are useful as a medicament for the inhibition of ATX activity and suitable for humans and other warm blooded animals, and may be administered either by oral, topical or parenteral administration.

In some embodiments, the present invention includes a method for the treatment of at least one of cancer, chronic inflammation, neuropathic pain, fibrotic diseases mediated in part by ATX comprising administering to a subject in need thereof a therapeutically effective amount of a compound or salt of the novel compound of formula (I).